Comparison of Outcomes for Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Treated With Induction Chemotherapy Followed By Concurrent Chemoradiation vs. Concurrent Chemoradiation Alone

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Huang, Eugene H.; Liao Zhongxing; Cox, James D.; Guerrero, Thomas M.; Chang, Joe Y.; Jeter, Melinda; Borghero, Yerko; Wei Xiong; Fossella, Frank; Herbst, Roy S.; Blumenschein, George R.; Moran, Cesar; Allen, Pamela K.; Komaki, Ritsuko

2007-01-01

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung

Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma

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Hoebers, Frank J.P.; Heemsbergen, Wilma; Balm, Alfons J.M.; Zanten, Mathilde van; Schornagel, Jan H.; Rasch, Coen R.N.

2007-01-01

Background and purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. Materials and methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m 2 i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). Results: Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p = 0.008), with less renal toxicity (p < 0.001) and less hospital admissions (p < 0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p = 0.06), although this did not lead to an improvement in loco-regional control. Conclusions: Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions

Locally advanced female urethral adenocarcinoma of enteric origin: The role of adjuvant chemoradiation and brief review

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Ling-Ping Chen

2011-04-01

Full Text Available Primary female urethral adenocarcinoma (FUA is rare and has a poor prognosis. The common manifestations include urethrorrhagia, urinary frequency, dysuria, urethral obstructions, focal tenderness, and urinary tract infection. These symptoms are neither diagnostic nor pathognomonic; therefore, a delay in diagnosis and even a misdiagnosis is hardly uncommon. The histogenesis of FUAs may have derived from urethritis glandularis, Mullerian ducts, Skene’s glands, or mixed origins. Tumors of different embryologic origins displayed heterogeneous pathological morphology and immunohistochemistical phenotypes. Because of its rarity and the lack of large-scale studies, there is no current consensus on the optimal treatment of urethral adenocarcinomas. Here, we report two cases of locally advanced FUA of enteric origin. They manifested as slightest warning symptoms of urinary tract infection and stress urinary incontinence, respectively. One patient died of disease progression 2 months after curative operation. The other patient underwent surgery followed by adjuvant irinotecan-containing chemoradiation, and the effect was at least modest. Hence, we recommend adjuvant chemoradiation in locally advanced FUA. Individualizing cancer care of chemoregimens in accordance with the tumor origins may probably be beneficial in FUAs.

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

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Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Volumetric response analysis during chemoradiation as predictive tool for optimizing treatment strategy in locally advanced unresectable NSCLC

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Bral, Samuel; Duchateau, Michael; De Ridder, Mark; Everaert, Hendrik; Tournel, Koen; Schallier, Denis; Verellen, Dirk; Storme, Guy

2009-01-01

Purpose: To study the feasibility of measuring volumetric changes in the primary tumor on megavoltage-computed tomography (MVCT) during chemoradiation and to examine the correlation with local response. Patients and methods: Fifteen consecutive patients with stage III, inoperable, locally advanced non-small cell lung cancer (NSCLC) were treated in a prospective dose escalation study protocol of concurrent chemoradiation. They were monitored for acute toxicity and evaluated with daily MVCT imaging. The volumetric changes were fitted to a negative exponential resulting in a regression coefficient (RC). Local response evaluation was done with positron emission tomography using the radio-labeled glucose analogue F18 fluorodeoxyglucose (FDG-PET). Results: The mean volume decrease (±standard deviation) was 73% (±18%). With a mean treatment time of 42 days this treatment schedule resulted in a mean decrease of 1.74%/day. Of the 13 evaluable patients seven developed a metabolic complete remission (MCR). The mean RC of the patients with MCR is 0.050 versus a mean RC of 0.023 in non-responders (p = 0.0074). Using a proposed cut-off value for the RC of 0.03 80% of the non-responders will be detected correctly while misclassifying 16.4% of patients who will eventually achieve an MCR. The total cumulative percentage of esophageal grade 3 or more toxicity was 46.7%. Conclusion: The RC derived from volumetric analysis of daily MVCT is prognostic and predictive for local response in patients treated with chemoradiation for a locally advanced NSCLC. Because this treatment schedule is toxic in nearly half of the patient population, MVCT is a tool in the implementation of patient-individualized treatment strategies.

A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

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Swisher, Stephen G., E-mail: sswisher@mdanderson.org [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn A. [Headquarters, Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko U. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Wu, Tsung T. [Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Konski, Andre A. [Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Willett, Christopher G. [Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

2012-04-01

Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

[A recent trial of chemo-radiation with S-1 against gastric cancer].

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Saikawa, Yoshiro; Kiyota, Tsuyoshi; Nakamura, Rieko; Wada, Norihito; Yoshida, Masashi; Kubota, Tetsuro; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki

2006-06-01

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer.

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Goguen, Laura A; Posner, Marshall R; Norris, Charles M; Tishler, Roy B; Wirth, Lori J; Annino, Donald J; Gagne, Adele; Sullivan, Christopher A; Sammartino, Daniel E; Haddad, Robert I

2006-06-01

Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. Regional Cancer Center. Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. C-4.

Impact of intensity-modulated and image-guided radiotherapy on elderly patients undergoing chemoradiation for locally advanced head and neck cancer

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Nguyen, N.P.; Chi, A.; Vock, J.

2012-01-01

Purpose: In this work, the treatment tolerance of elderly patients (≥ 70 years) undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed. Patients and methods: A retrospective review of 112 patients undergoing concurrent chemoradiation for locally advanced head and neck cancer was performed. Treatment toxicity, protocol violations, long-term complications, and survival were compared between 85 younger patients (< 70 years) and 27 older patients (≥ 70 years). Results: Grade 3-4 treatment toxicity was observed in 88.2% and 88.8% for younger and older patients, respectively. Mean weight loss and treatment break were 5.9 and 3.9 kg (p = 0.03) and 7.3 and 7.8 days (p = 0.8) for younger and older patients, respectively. Seven patients (8.2%) did not complete treatment in the younger group compared to 1 patient (3.7%) in the older group (p = 0.6). No significant differences in protocol violations and survival were found between the two groups. Conclusion: Compared to younger patients, elderly patients with locally advanced head and neck cancer tolerated chemoradiation with IMRT and IGRT well, and should not be denied curative treatment based solely on age. (orig.)

A rare late complication after concomitant chemoradiation of an oropharyngeal tumor: cervical necrotizing fasciitis

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Karakullukçu, Barış; van der Vlies, Dalith; Hoebers, Frank J. P.

2012-01-01

Chemoradiation is increasingly being used to treat locally advanced head and neck carcinomas. Possible rare complications of this treatment modality have begun to appear, as the number of treated patients increase. In this report, we present a case who underwent chemoradiation due to T3N3M0 tonsil

Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

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Petrović Marina

2009-01-01

Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

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Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.; Bergsland, Emily K.; Dito, Elizabeth R.N.; Schillinger, Brian R.N.; Tempero, Margaret A.

2007-01-01

Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m 2 at 10 mg/m 2 /min) plus cisplatin 20 mg/m 2 on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m 2 orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

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Hurt, Christopher N.; Mukherjee, Somnath; Bridgewater, John; Falk, Stephen; Crosby, Tom; McDonald, Alec; Joseph, George; Staffurth, John; Abrams, Ross A.; Blazeby, Jane M.; Bridges, Sarah; Dutton, Peter; Griffiths, Gareth; Maughan, Tim; Johnson, Colin

2015-01-01

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

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Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Mukherjee, Somnath [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Bridgewater, John [UCL Cancer Institute, London (United Kingdom); Falk, Stephen [Bristol Haematology and Oncology Centre, Bristol (United Kingdom); Crosby, Tom [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); McDonald, Alec [Beatson West of Scotland Cancer Centre, Glasgow, Scotland (United Kingdom); Joseph, George [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); Staffurth, John [Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales (United Kingdom); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Blazeby, Jane M. [Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol (United Kingdom); Bridges, Sarah [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Dutton, Peter [Centre for Statistics in Medicine, University of Oxford, Oxford (United Kingdom); Griffiths, Gareth [Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton (United Kingdom); Maughan, Tim [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Johnson, Colin [University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton (United Kingdom)

2015-11-15

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

A Combined Pharmacokinetic and Radiologic Assessment of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Response to Chemoradiation in Locally Advanced Cervical Cancer

International Nuclear Information System (INIS)

Semple, Scott; Harry, Vanessa N. MRCOG.; Parkin, David E.; Gilbert, Fiona J.

2009-01-01

Purpose: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. Methods and Materials: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic and pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. Results: Pretherapy radiologic parameters and pharmacokinetic K trans correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. Conclusions: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.

Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

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Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Enrica; Fanelli, Mara; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Fattorossi, Andrea

2010-01-01

Purpose: To assess how neoadjuvant chemoradiation regimens modulate the immune system state in tumor-draining lymph nodes (TDLN), in the setting of advanced cervical cancer. Methods and Materials: Tumor-draining lymph nodes of patients undergoing chemotherapy only (nonirradiated, NI-TDLN) and chemoradiation with lower-dose (39.6 Gy, LD-TDLN) and higher-dose radiation (50 Gy, HD-TDLN) were analyzed by multicolor flow cytometry. Results: Enlarging our previous data, LD-TDLN showed features overall indicative of an enhanced antitumor response as compared with NI-TDLN, namely a significant Th1 and Tc1 polarization and a lower amount of the potent CD4 + Foxp3 + CD25 high regulatory T cell (Treg) subset identified by neuropilin-1 expression. Conversely, compared with NI-TDLN, HD-TDLN showed features overall indicative of an impaired antitumor response, namely a significantly inverted CD4/CD8 cell ratio, a higher Nrp1 + Treg frequency, and a higher frequency of CCR4 + Treg, a Treg subset facilitated in migrating out from TDLN to suppress the immune response against distant cancer cells. Moreover, the Th1 and Tc1 polarization induced by LD radiation was lost, and there was an unfavorable tolerogenic/immunogenic dendritic cell ratio compared with LD-TDLN. Conclusions: Even minor differences in radiation dose in neoadjuvant regimens for locally advanced cervical cancer are crucial for determining the balance between a tolerogenic and an efficacious antitumor immune response in TDLN. Because most of the anticancer immune response takes place in TDLN, the present findings also emphasize the importance of chemoradiation protocols in the context of immunotherapeutic trials.

Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

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Miyamoto, David T.; Mamon, Harvey J.; Ryan, David P.

2010-01-01

Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18 had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 ± 0.8, and the mean 6-month weight loss was 5.3 ± 3.8 kg. The mean radiation dose delivered was 48.1 ± 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-∞) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment-related toxicity.

Results of surgical treatment versus chemoradiation therapy in oropharyngeal early tumors

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Chedid, Helma Maria

2009-03-01

Full Text Available Introduction: The epidermoid carcinoma of the upper aerodigestive tract is diagnosed in approximately 40% of the cases of advanced clinical stages. Objective: To evaluate the disease-free interval in patients with clinical stages I and II epidermoid carcinoma who were submitted to surgery or chemoradiation. Method: Retrospective study of the records of 139 patients treated for oropharyngeal epidermoid carcinoma submitted to treatment with curative intent. Among those patients, 38 were classified with early tumors clinical stages I and II. Twenty-seven (71.1% underwent surgical treatment whereas eleven (28.9% were treated with chemoradiation. The mean age was 56.4 years; 31 cases (81.6% were in men and seven (18.4% were in women. Results: Among the eleven patients who were submitted to chemoradiation, 72.7% obtained locoregional control of the disease and their disease-free survival was of 42%. Among the 27 patients operated, 19 remained in Clinical Stages I and II in the histological report and six underwent postoperative radiation therapy. The disease-free interval for two years was of 70%. Conclusion: The patients submitted to the surgery had a better disease-free interval as compared to those submitted to chemoradiation treatment.

NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer

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Tatsuhiro Shibata

2011-09-01

Full Text Available Esophageal squamous cancer (ESC is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22% in advanced ESC tumors and ESC cell lines (3/10. The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT.

Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation

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Shen, Lijun; Zhang, Hui; Liang, Liping; Li, Guichao; Fan, Ming; Wu, Yongxin; Zhu, Ji; Zhang, Zhen

2014-01-01

The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

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Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seok Ah; Lee, Keun Seok; Yun, Tak; Jeong, Seung-Yong; Choi, Hyo Seong; Lim, Seok-Byung; Chang, Hee Jin; Jung, Kyung Hae

2011-01-01

Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m 2 1 week before radiotherapy, and then cetuximab 250 mg/m 2 /week, irinotecan 40 mg/m 2 /week for 5 consecutive weeks and capecitabine 1,650 mg/m 2 /day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

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Pucci, Sabina; Polidoro, Chiara; Joubert, Alessandro; Mastrangeli, Francesca; Tolu, Barbara; Benassi, Michaela; Fiaschetti, Valeria; Greco, Laura; Miceli, Roberto; Floris, Roberto; Novelli, Giuseppe; Orlandi, Augusto; Santoni, Riccardo

2017-01-01

Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively

Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

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Pucci, Sabina, E-mail: sabina.pucci@uniroma2.it; Polidoro, Chiara; Joubert, Alessandro; Mastrangeli, Francesca; Tolu, Barbara; Benassi, Michaela; Fiaschetti, Valeria; Greco, Laura; Miceli, Roberto; Floris, Roberto; Novelli, Giuseppe; Orlandi, Augusto; Santoni, Riccardo

2017-02-01

Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively

Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

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Tiffany A. Pompa

2017-01-01

Full Text Available Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC, the National Comprehensive Cancer Network (NCCN suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles, intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

A STUDY OF COX-2 INHIBITOR CELECOXIB AND CHEMORADIATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

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Kuppa Prakash

2016-08-01

Full Text Available AIMS AND OBJECTIVES To evaluate efficacy of concurrent oral Cox-2 Inhibitor (celecoxib and chemoradiation in locoregional control, distant control, disease free survival and/or overall survival in patients with locally advanced cervical cancer. To determine treatment related toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, intravenous cisplatin and concurrent pelvic radiation therapy. MATERIALS AND METHODS Study was done for a period of 2 years in a tertiary care cancer hospital which caters to the cancer patients. Advanced squamous, adenocarcinoma or adenosquamous carcinoma of uterine cervix, Patients with age <70 years, ECOG performance status 0-2, Normal haematological investigations, Normal renal function test, Normal liver function test, No disease outside of pelvis. RESULTS This prospective study consisted 30 patients, 15 patients on either arm. Overall pooled mean age for both study and comparison group was 50.3 years with a probability value P=0.91 for age. 14 patients (93.33% in both the arms had a performance status of ECOG 0 or 1 and 1 patient in both arms had ECOG PS-2. Stage distribution of the patients in study arm was 3 in IB2, 2 in IIA, 5 in IIB, 4 in III and 1 in stage IVA. In control arm, out of the 15 patients 2 are in IB2, 2 in IIA, 5 in IIB, 5 in III and 1 in stage IVA. The mean probability value was P=0.65 for stage distribution. 15 patients in arm-A (study arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr after pelvic RT on an average of 1 week along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22 and Cox-2 inhibitor oral celecoxib 400 mg twice daily (800 mg/d starting from day 1 to throughout the duration of the chemoradiation. 15 patients in arm-B (Control arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr on an average of 1 week after pelvic RT along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22

Therapeutic Results of Concurrent Chemoradiation in Locally Advanced Uterine Cervical Cancer

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Kang, Seung Hee; Suh, Hyun Suk; Yang, Kwang Mo; Lee, Eung Soo; Park, Sung Kwon

1995-01-01

Purpose : Despite a development for therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate. Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ≥ 5 cm in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiation and 1-2 sessions of intracavitary irradiation, Cisplatinum was administered in bolus injection of 25mg/m 2 at weekly intervals during the course of external radiation therapy. Results : Of the 26 patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5,4 patients, respectively. Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25(68%), partial response(PR) in 8/25(32%). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients(70.8%) maintained local control in the pelvis: 16/17(94.1%) in CR, 1/17(14.3%) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16(59.8) in IIB, 3/5(60.6%) in III, and 1/4(25.0%) in IVA. Overall 5-year survival rate was 55.2%. Ten Patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

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Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer

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Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Eisenberg, Burton L.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

1998-01-01

in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I and II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p = .04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) ≥ 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p = 0.017). Conclusion: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p = 0.04). Older age (≥61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

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Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Leonard, Kara Lynne [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Safran, Howard [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Ng, Thomas [Division of Thoracic Surgery, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Taber, Angela [Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Khurshid, Humera; Birnbaum, Ariel [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Wazer, David E.; DiPetrillo, Thomas [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States)

2016-12-01

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24�

Radiation and chemoradiation treatment of esophagus cancer

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Azhigaliev, N.; Kusherbaev, S.; Abdrakhmanov, Zh.

1988-01-01

Indications and contraindications for radiation treatment of esophagus cancer are presented. The role of chemoradiation among esophagus cancer treatment methods is determined.Thechnical, dosimetric and clinical data are sequently delivered. Preparation of a patient for chemoradiation is described. Recommendations on their most efficient use are given

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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Grassberger, C; Paganetti, H

2016-01-01

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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Grassberger, C; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation

Refining Preoperative Therapy for Locally Advanced Rectal Cancer

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In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

Chemoradiation for adenocarcinoma of the anus

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Papagikos, Michael; Crane, Christopher H.; Skibber, John; Janjan, Nora A.; Feig, Barry; Rodriguez-Bigas, Miguel A.; Hung, Arthur; Wolff, Robert A.; Delclos, Marc; Lin, Edward; Cleary, Karen

2003-01-01

Purpose: To assess the efficacy and limitations of definitive chemoradiation for adenocarcinoma of the anal canal and to propose a treatment strategy that addresses the limitations of treatment. Methods and Materials: Between 1976 and 1998, 16 patients with localized adenocarcinoma of the anal canal were treated with radiotherapy with or without chemotherapy with curative intent. Available histologic slides were reviewed for evidence of primary adenocarcinoma of anal duct origin. The treatment results for these patients were compared with those of a group of patients with epidermoid histologic features who were all treated with definitive chemoradiation (55 Gy with concurrent 5-fluorouracil and cisplatin, n=92) between 1989 and 1998. The hospital records were reviewed for all patients. Patients with epidermoid carcinoma presented with more advanced primary tumors (42% vs. 19% Stage T3 or greater). All adenocarcinoma patients were treated with radiotherapy (median dose 55 Gy): 11 received concurrent 5-fluorouracil-based chemotherapy and 5 received radiotherapy alone. The initial surgical procedures included abdominoperineal resection, excisional biopsies (n=5), and local excision (n=1). Abdominoperineal resection was performed as salvage therapy after local recurrence in 5 patients. The Kaplan-Meier method was used to calculate 5-year actuarial pelvic control, distant disease control, disease-free survival, and overall survival. The median follow-up was 45 months (range 5-196) for patients with adenocarcinoma and 44 months (range 9-115) for patients with epidermoid histologic features. Results: Both local and distant recurrence rates were significantly greater in the adenocarcinoma patients. Of 16 patients with adenocarcinoma, 7 (5-year actuarial rate 54%) had recurrence at the primary site compared with 16 (5-year actuarial rate 18%) of 92 patients with epidermoid histologic features (p=0.004). Distant disease developed in more patients with adenocarcinoma (5-year

Chemoradiation for unresectable gall bladder cancer: time to review historic nihilism?

Science.gov (United States)

Engineer, Reena; Wadasadawala, Tabassum; Mehta, Shaesta; Mahantshetty, Umesh; Purandare, Nilendu; Rangarajan, Venkatesh; Kishore Shrivastava, Shyam

2011-12-01

Treatment of unresectable locally advanced gallbladder cancers (LAGBC) usually consists of various palliative strategies which provide only a modest survival benefit. Here, we present a series of three patients of LAGBC-treated consecutively at our center with preoperative chemoradiation using tomotherapy and concurrent gemcitabine. All three cases were reported to be adenocarcinoma by biopsy or fine-needle aspiration cytology. All the patients underwent positron emission tomography with computerized tomography scan to rule out distant metastasis and also to map the extent of disease for radiotherapy planning. Preoperative chemoradiation consisted of gemcitabine at 300 mg/m(2) weekly and tomotherapy with daily image guidance with MVCT over 5 weeks to a dose of 57 Gy in 25 fractions to the gross tumor and 45 Gy in 25 fractions to the clinical target volume to cover the areas of microscopic spread. Complete metabolic and radiologic response was observed for 2 patients and partial response for 1 patient. Two patients underwent complete surgical excision of which 1 patient had complete pathological response and 1 patient had small residual tumor at the primary and no nodal metastasis. The third patient could not undergo surgery due to medical reasons. The clinical outcome for unresectable LAGBC with preoperative chemoradiation in terms of feasibility, safety, and survival is encouraging. This treatment strategy has a curative potential for the otherwise fatal disease.

The effect of neck dissection on quality of life after chemoradiation.

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Donatelli-Lassig, Amy Anne; Duffy, Sonia A; Fowler, Karen E; Ronis, David L; Chepeha, Douglas B; Terrell, Jeffrey E

2008-10-01

To determine differences in quality of life (QOL) between patients with head and neck cancer who receive chemoradiation versus chemoradiation and neck dissection. A prospective cohort study was conducted at two tertiary otolaryngology clinics and a Veterans Administration hospital. 103 oropharyngeal patients with Stage IV squamous cell carcinoma treated via chemoradiation +/- neck dissection. self-administered health survey to collect health, demographic, and QOL information pretreatment and 1 year later. QOL via SF-36 and HNQoL. Descriptive statistics were calculated for health/clinical characteristics, demographics, and QOL scores. t tests evaluated changes in QOL over time. Sixty-five patients underwent chemoradiation and 38 patients underwent chemoradiation and neck dissection. Only the pain index of the SF-36 showed a significant difference between groups (P < 0.05) with the neck dissection group reporting greater pain. After post-treatment neck dissection, patients experience statistically significant decrement in bodily pain domain scores, but other QOL scores are similar to those of patients who underwent chemoradiation alone.

[The possibility of local control of cancer by neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma].

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Nakagawa, Kei; Katayose, Yu; Rikiyama, Toshiki; Okaue, Adoru; Unno, Michiaki

2009-11-01

Surgical resection is the gold standard of treatment for cholangiocarcinoma. However, there are also many recurrences after operation, because of the anatomical background and the tendency of invasion. We thought that eliminating the remnant of the cancer could yield a better prognosis. Therefore, an introduction of the neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma patient (NACRAC) was planned. The safety of NACRAC was confirmed by a pilot study. The recommended dose of gemcitabine (600 mg/m2) was determined by a phase I study. A phase II study is now being performed for evaluating the effectiveness and safety. NACRAC may control the frontal part of the tumor with difficult distinctions made by MDCT, and abolishing the cancer remnant is expected. The possibility of extended prognosis by NACRAC can be considered.

Efficacy of superselective intra-arterial infusion chemotherapy with concomitant radiotherapy for advanced hypopharyngeal carcinoma

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Bandoh, Nobuyuki; Takahara, Miki; Moriai, Shigetaka; Katayama, Akihiro; Katada, Akihiro; Hayashi, Tatsuya; Harabuchi, Yasuaki; Nagasawa, Kenichi

2008-01-01

Patients with advanced hypopharyngeal carcinoma still have a poor outcome in spite of radical surgery with chemoradiotherapy. We started superselective intra-arterial infusion chemotherapy with concomitant radiotherapy (IA chemoradiation) for advanced hypopharyngeal carcinoma in 2003. The complete response (CR) rate for local and neck lesions was 94.1% and 60%, respectively. After neck dissection the total CR rate was 82.4%. There was no significant difference in survival rates between groups with IA chemoradiation (n=22) and with surgery with preoperative chemoradiotherapy (n=57). However, Kaplan-Meier analysis showed that the cause-specific survival rate in N3 patients and larynx preservation rate was significantly higher in patients treated with IA chemoradiation than in those with surgery with preoperative chemoradiotherapy (p<0.05 and p<0.001). Subjective symptoms are not so severe in patients without the disease after IA chemoradiation. IA chemoradiation is effective for patients with advanced hypopharyngeal carcinoma to maintain quality of life such as voice and swallowing. (author)

Radiation and chemoradiation treatment of esophagus cancer

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Azhigaliev, N.; Kusherbaev, S.; Abdrakhmanov, Zh.

1988-01-01

The theoretical and practical substantiation of dose fractionation regimes in radiation and chemoradiation treatment of esophagus cancer are presented. The indications and contraindications to radiotherapy, radiation reactions and complications resulting from the treatment process are considered. The preparation of patients to the application of chemoradiation treatment methods is described. The recommentations for the improvement of immediate and delayed results of treatment of esophagus cancer patients are given. 99 refs.; 15 figs

Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

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Palta, Manisha; Willett, Christopher G; Czito, Brian G

2014-09-01

There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

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Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p5 cm (p35 days (p5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Chemoradiation therapy of esophageal cancer. Relationship between improvement of dysphagia and treatment outcome

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Mizutani, Yoshihide; Kitahara Tadashi

2004-01-01

The purpose of the study was to determine retrospectively whether the extent of dysphagia influenced the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. 46 patients had dysphagia before treatment, in which 39 patients were treated with a combination of chemotherapy and irradiation. The remaining 7 patients were treated with irradiation alone. Forty six patients were divided into 5 groups according to the dysphagia score standard to obtain a relationship between the extent of dysphagia and the survival rate of the patients after treatment. Thirty out of 46 patients (65.2%) became able to swallow solid food after treatment. In these patients, the median survival period was 12 months and the one-year survival rate was 53.2%. However, dysphagia was not improved in 16 patients and their median survival period was 4 months, the one-year survival rate was 17.9%. The survival rate after treatment was definitely higher in the patients with improvement of dysphagia. Regarding esophageal cancer, the patients with cancer in the upper esophagus had the worse survival rate. Improvement of dysphagia was an important factor to control the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. (author)

Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies

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Algan, Oezer; Coia, Lawrence R; Keller, Steven M; Engstrom, Paul F; Weiner, Louis M; Schultheiss, Timothy E; Hanks, Gerald E

1995-06-15

Purpose: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. Methods and Materials: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT + PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT + E subgroup). Results: The median overall survival was 19 months for the CRT group and 15 months for the CRT + PE group. For the CRT + E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT + PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3-year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT + PE group. Of the 12 patients who underwent esophagectomy (CRT + E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of

Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

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Pablo Palma

Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with

The significance of tumoral ERCC1 status in patients with locally advanced cervical cancer treated with chemoradiation therapy: a multicenter clinicopathologic analysis.

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Doll, Corinne M; Aquino-Parsons, Christina; Pintilie, Melania; Klimowicz, Alexander C; Petrillo, Stephanie K; Milosevic, Michael; Craighead, Peter S; Clarke, Blaise; Lees-Miller, Susan P; Fyles, Anthony W; Magliocco, Anthony M

2013-03-01

ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis. Copyright © 2013. Published by Elsevier

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

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Doll, Corinne M., E-mail: Corinne.Doll@albertahealthservices.ca [Department of Oncology, University of Calgary, Calgary, AB (Canada); Aquino-Parsons, Christina [Department of Radiation Oncology, University of British Columbia, Vancouver, BC (Canada); Pintilie, Melania [Department of Biostatistics, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Klimowicz, Alexander C. [Department of Oncology, University of Calgary, Calgary, AB (Canada); Petrillo, Stephanie K. [Department of Pathology, University of Calgary, Calgary, AB (Canada); Milosevic, Michael [Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON (Canada); Craighead, Peter S. [Department of Oncology, University of Calgary, Calgary, AB (Canada); Clarke, Blaise [Department of Pathology, University of Toronto, Toronto, ON (Canada); Lees-Miller, Susan P. [Departments of Biochemistry and Molecular Biology, and Oncology, University of Calgary, Calgary, AB (Canada); Fyles, Anthony W. [Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON (Canada); Magliocco, Anthony M. [Department of Pathology, Lee Moffitt Cancer Center, Tampa, Florida (United States)

2013-03-01

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

International Nuclear Information System (INIS)

Doll, Corinne M.; Aquino-Parsons, Christina; Pintilie, Melania; Klimowicz, Alexander C.; Petrillo, Stephanie K.; Milosevic, Michael; Craighead, Peter S.; Clarke, Blaise; Lees-Miller, Susan P.; Fyles, Anthony W.; Magliocco, Anthony M.

2013-01-01

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

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Oberholzer, Katja; Menig, Matthias; Kreft, Andreas; Schneider, Astrid; Junginger, Theodor; Heintz, Achim; Kreitner, Karl-Friedrich; Hötker, Andreas M.; Hansen, Torsten; Düber, Christoph; Schmidberger, Heinz

2012-01-01

Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer

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Nguyen, Nam P. [Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, VA North Texas Health Care System, Radiation Oncology Service (140), 4500 S, Lancaster Road, Dallas, TX 72516 (United States)]. E-mail: NamPhong.Nguyen@med.va.gov; Moltz, Candace C. [Audiology and Speech Pathology Service (126), VA North Texas Health Care System, Dallas, TX 75216 (United States); Frank, Cheryl [Audiology and Speech Pathology Service (126), VA North Texas Health Care System, Dallas, TX 75216 (United States); Karlsson, Ulf [Department of Radiation Oncology, East Carolina University, Greenville, NC 27858 (United States); Nguyen, Phuc D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, VA North Texas Health Care System, Radiation Oncology Service (140), 4500 S, Lancaster Road, Dallas, TX 72516 (United States); Vos, Paul [Department of Biostatistics, East Carolina University, Greenville, NC 27858 (United States); Smith, Herbert J. [Radiology Service, VA North Texas Health Care System, Dallas, TX 75216 (United States); Dutta, Suresh [Department of Radiation Oncology, University of Southern California, Los Angeles, CA 90033 (United States); Nguyen, Ly M. [Public Health School, University of Michigan, Ann Arbor, MI 48109 (United States); Lemanski, Claire [Department of Radiation Oncology, Val D' Aurelle, Montpellier (France); Chan, Wayne [Radiation Oncology Service, VAMC, Jackson, MS 39216 (United States); Sallah, Sabah [Division of Hematology/Oncology Research, Novo Nordisk, Athens (Greece)

2006-09-15

Objective: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. Materials and methods: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). Results: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p = 0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p = 0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. Conclusion: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer

International Nuclear Information System (INIS)

Nguyen, Nam P.; Moltz, Candace C.; Frank, Cheryl; Karlsson, Ulf; Nguyen, Phuc D.; Vos, Paul; Smith, Herbert J.; Dutta, Suresh; Nguyen, Ly M.; Lemanski, Claire; Chan, Wayne; Sallah, Sabah

2006-01-01

Objective: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. Materials and methods: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). Results: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p = 0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p = 0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. Conclusion: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

International Nuclear Information System (INIS)

Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 2 = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

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Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Narang, Amol K. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Department of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Reese, Jennifer B. [Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Gearhart, Susan L. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Azad, Nolifer S. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chan, June; Olsen, Leah [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Efron, Jonathan E. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Lawrence, Theodore S.; Ben-Josef, Edgar [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

2013-01-01

Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

International Nuclear Information System (INIS)

Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

2013-01-01

Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (−9.50, P=.0024) but returned to baseline 1 month after the end of treatment (−0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are

Impact of weight loss on survival after chemoradiation for locally advanced head and neck Cancer: secondary results of a randomized phase III trial (SAKK 10/94)

International Nuclear Information System (INIS)

Ghadjar, Pirus; Hayoz, Stefanie; Zimmermann, Frank; Bodis, Stephan; Kaul, David; Badakhshi, Harun; Bernier, Jacques; Studer, Gabriela; Plasswilm, Ludwig; Budach, Volker; Aebersold, Daniel M

2015-01-01

To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival

Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

International Nuclear Information System (INIS)

Trinkaus, Mateya E.; Rischin, Danny; Blum, Rob

2013-01-01

For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ( 18 F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent 18 F-FAZA PET scans and 18 F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment 18 F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P=0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P=0.38). Eight patients with baseline hypoxia had post treatment 18 F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P=0.42). Intra-lesional hypoxia, as detected by 18 F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Rich, T.A.; Skibber, J.M.; Ajani, J.A. [Univ. of Texas M. D. Anderson Cancer Center, Houston, TX (United States)] [and others

1995-07-15

To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m{sup 2}/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. Posttreatment tumor stages were T1-2, N0 in 35%, T3, N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further. 22 refs., 2 figs., 3 tabs.

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

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Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Rischin, Danny [University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology, Melbourne (Australia); Fisher, Richard [Peter MacCallum Cancer Centre, Centre for Biostatistics and Clinical Trials, Melbourne (Australia); Binns, David [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); Scott, Andrew M. [Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Melbourne (Australia); Peters, Lester J. [Peter MacCallum Cancer Centre, Division of Radiation Oncology, Melbourne (Australia)

2005-12-01

The purpose of the study was to evaluate [{sup 18}F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [{sup 18}F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

International Nuclear Information System (INIS)

Hicks, Rodney J.; Rischin, Danny; Fisher, Richard; Binns, David; Scott, Andrew M.; Peters, Lester J.

2005-01-01

The purpose of the study was to evaluate [ 18 F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [ 18 F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

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Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2013-03-01

Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

Cetuximab and chemoradiation for rectal cancer - is the water getting muddy?

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Glynne-Jones, Rob; Mawdsley, Suzy; Harrison, Mark (Mount Vernon Cancer Centre, Northwood, Middlesex (United Kingdom)), E-mail: Rob.glynnejones@nhs.net

2010-04-15

The epidermal growth factor receptor (EGFR) inhibitor cetuximab has been successfully combined with radical radiotherapy in head and neck cancer. In colorectal cancer, increased response rates are achieved by cetuximab and panitumumab within standard chemotherapy schedules, but not in chemoradiation regimens. This review examines the clinical evidence and potential mechanisms for an interaction when EGFR inhibitors are added to fluoropyrimidine-based chemoradiation in rectal adenocarcinoma. Methods. This review was compiled by searching PubMed and Medline for English language articles published until 2009 with established search strategies, supplemented by hand searching of abstracts from the proceedings of relevant international meetings. The primary outcome measure was pathological complete response (pCR). Results. Only 13 publications and three presentations in abstract of 13 phase I/II trials of preoperative chemoradiation with cetuximab in rectal cancer were identified. A total of 316 patients were identified who received cetuximab in combination with radiotherapy and 5-fluorouracil or capecitabine preoperatively. One hundred and thirty eight of these patients received either additional irinotecan or oxaliplatin. One study with panitumumab with safety but no efficacy results was identified, and two studies with gefinitib. The pCR rate ranged from 0-20%. The overall pooled pCR for cetuximab based chemoradiation was 9.1% (29/316). The rate of G3/G4 gastrointestinal toxicity, in terms of diarrhoea, varied from 5-30%, with an overall pooled rate of 47/313 (15%). Discussion. Potential reasons for the disappointing results of EGFR inhibition with fluoropyrimidine-based preoperative chemoradiation include a less critical role of repopulation in rectal adenocarcinoma using a non-curative radiation dose; or antagonistic effects on 5FU-based chemoradiation and oxaliplatin, if some cells arrest in G1 or G2-M and fail to pass through S phase. Conclusion. Cetuximab

Cetuximab and chemoradiation for rectal cancer - is the water getting muddy?

International Nuclear Information System (INIS)

Glynne-Jones, Rob; Mawdsley, Suzy; Harrison, Mark

2010-01-01

The epidermal growth factor receptor (EGFR) inhibitor cetuximab has been successfully combined with radical radiotherapy in head and neck cancer. In colorectal cancer, increased response rates are achieved by cetuximab and panitumumab within standard chemotherapy schedules, but not in chemoradiation regimens. This review examines the clinical evidence and potential mechanisms for an interaction when EGFR inhibitors are added to fluoropyrimidine-based chemoradiation in rectal adenocarcinoma. Methods. This review was compiled by searching PubMed and Medline for English language articles published until 2009 with established search strategies, supplemented by hand searching of abstracts from the proceedings of relevant international meetings. The primary outcome measure was pathological complete response (pCR). Results. Only 13 publications and three presentations in abstract of 13 phase I/II trials of preoperative chemoradiation with cetuximab in rectal cancer were identified. A total of 316 patients were identified who received cetuximab in combination with radiotherapy and 5-fluorouracil or capecitabine preoperatively. One hundred and thirty eight of these patients received either additional irinotecan or oxaliplatin. One study with panitumumab with safety but no efficacy results was identified, and two studies with gefinitib. The pCR rate ranged from 0-20%. The overall pooled pCR for cetuximab based chemoradiation was 9.1% (29/316). The rate of G3/G4 gastrointestinal toxicity, in terms of diarrhoea, varied from 5-30%, with an overall pooled rate of 47/313 (15%). Discussion. Potential reasons for the disappointing results of EGFR inhibition with fluoropyrimidine-based preoperative chemoradiation include a less critical role of repopulation in rectal adenocarcinoma using a non-curative radiation dose; or antagonistic effects on 5FU-based chemoradiation and oxaliplatin, if some cells arrest in G1 or G2-M and fail to pass through S phase. Conclusion. Cetuximab

Radiation dose responses for chemoradiation therapy of pancreatic cancer: an analysis of compiled clinical data using biophysical models.

Science.gov (United States)

Moraru, Ion C; Tai, An; Erickson, Beth; Li, X Allen

2014-01-01

We analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer (LAPC) in order to examine possible benefits from radiation therapy dose escalation. A modified linear quadratic model was used to fit clinical tumor response and survival data of chemoradiation treatments for LAPC reported from 20 institutions. Biophysical radiosensitivity parameters were extracted from the fits. Examination of the clinical data demonstrated an enhancement in tumor response with higher irradiation dose, an important clinical result for palliation and quality of life. Little indication of improvement in 1-year survival with increased radiation dose was observed. Possible dose escalation schemes are proposed based on calculations of the biologically effective dose required for a 50% tumor response rate. Based on the evaluation of tumor response data, the escalation of radiation dose presents potential clinical benefits which when combined with normal tissue complication analyses may result in improved treatment outcome for locally advanced pancreatic cancer patients. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Phase I dose escalating trial of hyperfractinated pre-operative chemoradiation for locally advanced rectal cancer

International Nuclear Information System (INIS)

Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle M.; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

1997-01-01

). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p 2 04). This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

International Nuclear Information System (INIS)

Villar, Alfonso; Martinez, Jose Carlos; Serdio, Jose Luis de

2008-01-01

Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

Science.gov (United States)

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand

International Nuclear Information System (INIS)

Tharavichitkul, Ekkasit; Lorvidhaya, Vicharn; Kamnerdsupaphon, Pimkhuan; Sukthomya, Vimol; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Supawongwattana, Bongkoch; Pukanhaphan, Nantaka; Galalae, Razvan; Chitapanarux, Imjai

2016-01-01

To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6–69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity

Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

International Nuclear Information System (INIS)

Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

2012-01-01

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

Postoperative chemoradiation for resected gastric cancer - is the Macdonald Regimen Tolerable? a retrospective multi-institutional study

International Nuclear Information System (INIS)

Kundel, Yulia; Fenig, Eyal; Sulkes, Aaron; Brenner, Baruch; Purim, Ofer; Idelevich, Efraim; Lavrenkov, Konstantin; Man, Sofia; Kovel, Svetlana; Karminsky, Natalia; Pfeffer, Raphael M; Nisenbaum, Bella

2011-01-01

Postoperative chemoradiation as per Intergroup-0116 trial ('Macdonald regimen') is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0). Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test. Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts. In our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic

Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

International Nuclear Information System (INIS)

Trog, D.; Bank, P.; Wendt, T.G.; Koscielny, S.; Beleites, E.

1999-01-01

Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p 0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [de

Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer

International Nuclear Information System (INIS)

Broek, Guido B. van den; Balm, Alfons J.M.; Brekel, Michiel W.M. van den; Hauptmann, Michael; Schornagel, Jan H.; Rasch, Coen R.N.

2006-01-01

Background and purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. Patients and methods: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. Results: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). Conclusions: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively

Contemporary management of advanced laryngeal cancer.

Science.gov (United States)

Britt, Christopher J; Gourin, Christine G

2017-10-01

The treatment of advanced laryngeal cancer has undergone a paradigm shift in recent years, with an increase in chemoradiation for organ preservation and a decrease in primary surgery. This review will summarize the contemporary management of advanced laryngeal cancer and discuss treatment-related toxicity and strategies to improve outcomes. NA.

Chemoradiation therapy for esophageal cancer

International Nuclear Information System (INIS)

Ohira, Masaichi; Yamashita, Yoshito; Matsumura, Yumiko; Yamazaki, Masanao; Kubo, Naoshi; Hirakawa, Kosei

2002-01-01

The current status and future prospects of chemoradiation therapy (CRT) for esophageal cancer are reviewed herein. In Western countries, CRT is performed for every stage of esophageal cancer and it has been reported that in definitive CRT series the complete response rate is 30 to 50%, the mean survival rate more than twelve months, and the in 2-year survival rate about 30%, while in neoadjuvant CRT series the pathological response rate is 20 to 50%, the mean survival period more than twenty months, and the 3-year survival 30 to 40%. On the other hand, as esophageal cancer is treated mainly by surgery in Japan, CRT is applied in patients with tumors invading adjacent organs, and a high pathological complete response rate is reported in some neoadjuvant studies. Although both definitive and neoadjuvant CRT increases the response rate and improves local tumor control, CRT is associated with substantial mortality and morbidity, especially in neoadjuvant series. More effective and less toxic CRT regimens, using new chemotherapeutic agents such as nedaplatin and paclitaxel and new irradiation protocol such as accelated hyperfractionation, are needed to improve the prognosis of patients with advanced esophageal cancer. (author)

Can we optimize chemo-radiation and surgery in locally advanced stage III non-small cell lung cancer based on evidence from randomized clinical trials? A hypothesis-generating study

International Nuclear Information System (INIS)

De Ruysscher, Dirk; Dehing, Cary; Bentzen, Soren M.; Houben, Ruud; Dekker, Andre; Wanders, Rinus; Borger, Jacques; Hochstenbag, Monique; Boersma, Liesbeth; Geskes, Gijs; Dingemans, Anne-Marie C.; Bootsma, Gerben; Lammering, Guido; Lambin, Philippe

2009-01-01

Purpose: Improved local tumor control (LC) improves survival of patients with non-small cell lung cancer (NSCLC). We estimated the capability of surgical and non-surgical options to improve LC further in this disease. Methods: Eligible studies were phase III trials reporting 2-year survival data as well as the incidence of LC and/or distant metastases. Effect estimates, as well as the statistical uncertainty of these, were combined in order to estimate the benefit in terms of LC from combining multiple modalities. Results: It was estimated that the highest rates of LC can be obtained with high-dose concurrent chemo-radiation followed by surgery. In this situation, escalating the pre-operative radiation dose from 45 to 66 Gy, delivered concurrently with chemotherapy, could increase LC from 58% to 76%. Toxicity may also be higher, but could not be estimated. Without surgery, the gain in LC from concurrent chemo-radiation versus sequential, corresponds to a radiation dose increase from 65 to 72 Gy. Conclusions: We hypothesize that high-dose concurrent chemo-radiation followed by surgery could be superior to other current treatment approaches for selected patients with stage III NSCLC, provided toxicity would be low. At present, high-dose concurrent chemo-radiation followed by surgery should be considered experimental.

Concomitant chemo-radiation in therapeutic management of pancreatic and gastric adenocarcinoma

International Nuclear Information System (INIS)

Mornex, F.; Chauffert, B.

1998-01-01

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5 %. Resection, the gold standard treatment, can be performed in less than 10 % of patients. Following surgery, the median survival is 12 months for the most favorable cancer patients. Concomitant chemo-radiation, as an adjuvant treatment is superior to surgery alone, in terms of survival; controlled trials are currently performed. Neo-adjuvant chemo-radiation is a new approach, potentially able to increase survival and resection rate. This work justifies the role of these schemes, in terms of modalities and potential advantages. A second part is dedicated to gastric carcinoma, with a review of the current results of chemo-radiation, whose efficiency, even though a trend can be observed, remains to be proven. Prospective adjuvant combined treatments are ongoing, in France and in the States. (authors)

Ultrasound elastography in patients with rectal cancer treated with chemoradiation

DEFF Research Database (Denmark)

Rafaelsen, S R; Vagn-Hansen, C; Sørensen, T

2013-01-01

OBJECTIVE: The current literature has described several predictive markers in rectal cancer patients treated with chemoradiation, but so far none of them have been validated for clinical use. The purpose of the present study was to compare quantitative elastography based on ultrasound measurements...... in the course of chemoradiation with tumor response based on T stage classification and the Mandard tumor regression grading (TRG). MATERIALS AND METHODS: We prospectively examined 31 patients with rectal cancer planned for high dose radiochemotherapy. The tumor and the mesorectal fat elasticity were measured...

Analysis of adjuvant treatment with chemoradiation in gastric cancer

International Nuclear Information System (INIS)

Fallas Solis, Elias

2008-01-01

The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference. [es

Chemoradiation of unresectable pancreatic carcinoma: impact of pretreatment hemoglobin level on patterns of failure

Energy Technology Data Exchange (ETDEWEB)

Morganti, A.G.; Macchia, G. [Dept. of Radiation Therapy, Univ. Cattolica del S. Cuore, Campobasso (Italy); Forni, F. [Dept. of Biochemistry and Clinical Biochemistry, Policlinico A. Gemelli, Univ. Cattolica del S. Cuore, Rome (Italy); Valentini, V.; Smaniotto, D.; Trodella, L.; Balducci, M.; Cellini, N. [Dept. of Radiation Therapy, Policlinico A. Gemelli, Univ. Cattolica del S. Cuore, Rome (Italy)

2003-02-01

Aim: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. Patients and Methods: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m{sup 2}/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs cN1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis ({>=} 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs {>=} 40 mm). Results: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb {<=} 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb {<=} 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0.010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb {<=} 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb {<=} 11.5 and > 11.5 g/dl, respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). Conclusion: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

Energy Technology Data Exchange (ETDEWEB)

Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Oh, Jae Hwan [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Jong Hoon; Jang, Hong Seok [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jun-Gi [Department of Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Myung Ah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Gwang-Ju (Korea, Republic of)

2013-05-01

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

Science.gov (United States)

Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

2016-04-01

Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

LENUS (Irish Health Repository)

Abdul-Jalil, K I

2014-01-01

To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative.

Effect of time interval between capecitabine intake and radiotherapy on local recurrence-free survival in preoperative chemoradiation for locally advanced rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Yeon Joo; Kim, Jong Hoon; Yu, Chang Sik; Kim, Tae Won; Jang, Se Jin; Choi, Eun Kyung; Kim, Jin Cheon [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Won Sik [University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

2017-06-15

The concentration of capecitabine peaks at 1–2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals (1,650 mg/m2/day). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

Evaluation of Erosion Resistance of Advanced Turbine Thermal Barrier Coatings

Science.gov (United States)

Zhu, Dongming; Kuczmarski, Maria A.; Miller, Robert A.; Cuy, Michael D.

2007-01-01

The erosion resistant turbine thermal barrier coating system is critical to aircraft engine performance and durability. By demonstrating advanced turbine material testing capabilities, we will be able to facilitate the critical turbine coating and subcomponent development and help establish advanced erosion-resistant turbine airfoil thermal barrier coatings design tools. The objective of this work is to determine erosion resistance of advanced thermal barrier coating systems under simulated engine erosion and/or thermal gradient environments, validating advanced turbine airfoil thermal barrier coating systems based on nano-tetragonal phase toughening design approaches.

Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

International Nuclear Information System (INIS)

Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

2005-01-01

Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

DEFF Research Database (Denmark)

Kirchheiner, Kathrin; Pötter, Richard; Tanderup, Kari

2016-01-01

Purpose This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials In total, 744...... patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during...... at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before...

Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713.

Science.gov (United States)

Leichman, Cynthia Gail; McDonough, Shannon L; Smalley, Stephen R; Billingsley, Kevin G; Lenz, Heinz-Josef; Beldner, Matthew A; Hezel, Aram F; Velasco, Mario R; Guthrie, Katherine A; Blanke, Charles D; Hochster, Howard S

2018-03-01

Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

2016-09-01

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

International Nuclear Information System (INIS)

Seiwert, Tanguy Y.; Melotek, James M.; Blair, Elizabeth A.; Stenson, Kerstin M.; Salama, Joseph K.; Witt, Mary Ellyn; Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison; Lingen, Mark W.; Kocherginsky, Masha; Villaflor, Victoria M.; Cohen, Ezra E.W.; Haraf, Daniel J.; Vokes, Everett E.

2016-01-01

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Esnaola, Nestor F.; Chaudhary, Uzair B.; O'Brien, Paul; Garrett-Mayer, Elizabeth; Camp, E. Ramsay; Thomas, Melanie B.; Cole, David J.; Montero, Alberto J.; Hoffman, Brenda J.; Romagnuolo, Joseph; Orwat, Kelly P.; Marshall, David T.

2014-01-01

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

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Esnaola, Nestor F. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Chaudhary, Uzair B.; O' Brien, Paul [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Garrett-Mayer, Elizabeth [Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Camp, E. Ramsay [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Thomas, Melanie B. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Cole, David J. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Montero, Alberto J. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Hoffman, Brenda J.; Romagnuolo, Joseph [Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Orwat, Kelly P. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States)

2014-03-15

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

Concurrent chemoradiation therapy in stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Kim, I. A.; Choi, I. B.; Kang, K. M.; Jang, J. Y.; Song, J. S.; Lee, S. H.; Kuak, M. S.; Shinn, K. S.

1997-01-01

This study was tried to evaluate the potential benefits of concurrent chemoradiation therapy. Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Complete response rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group. In subgroup analyses for patients with good performance status, CRT group showed significantly higher overall survival rate compared with RT group. The prognostic factors affecting survival rate were performance status and pathologic subtype in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a prognostic factors. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity ahd no significant differences in between CRT group and RT group (16% vs. 6%). The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%). In analyses for relationship of field size and pulmonary toxicity, the patients who treated with field size beyond 200 cm 2 had significantly higher rates of pulmonary toxicities. The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group. Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term

Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer. Prospective randomized trails

International Nuclear Information System (INIS)

Kim, Nam-Kyu; Min, Jin-Sik; Park, Jea-Kun; Yun, Seong-Hyun; Sung, Jin-Sil; Jung, Hyun-Chul; Roh, Jae-Kyung

2001-01-01

during the follow-up periods were 1/14 (7.1%) in the IV arm and 2/14 (14.3%) in the Oral arm, respectively (p=0.307). One local recurrence was observed in the Oral arm. Even though the results were not entirely reliable owing to the small number of patients enrolled, oral doxifluridine-based chemotherapy as preoperative chemoradiation for advanced rectal cancer did not show any significant advantages over intravenous infusion. (author)

Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer

International Nuclear Information System (INIS)

Arcangeli, Giorgio; Saracino, Biancamaria; Arcangeli, Giancarlo; Angelini, Francesco; Marchetti, Paolo; Tirindelli Danesi, Donatella

2002-01-01

Background: The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). Materials and Methods: Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. Results: After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute ≥ Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. Conclusion: This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival

Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

International Nuclear Information System (INIS)

Narang, Amol K; Haddock, Michael G; Donohue, John H; Schulick, Richard D; Wolfgang, Christopher L; Cameron, John L; Herman, Joseph M; Miller, Robert C; Hsu, Charles C; Bhatia, Sumita; Pawlik, Timothy M; Laheru, Dan; Hruban, Ralph H; Zhou, Jessica; Winter, Jordan M

2011-01-01

The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007) and at the Mayo Clinic (n = 130; 1977-2005) were reviewed. Patients with <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis. Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002), node positive status (RR = 3.18, p < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic

Concurrent chemoradiation for unresectable pancreatic cancer

International Nuclear Information System (INIS)

Kim, Yong Bae; Seong, Jin Sil; Song, Si Young; Park, Seung Woo; Suh, Chang Ok

2002-01-01

To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. The patients, who were diagnosed by imaging modalities or by explo-laparotomy were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine 1,000 mg/m 2 or Paclitaxel 50 mg/m 2 weekly and oral 5-FU daily. The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months. Survival was analyzed using the Kaplan-Meier method. Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 60 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to; disease progression for 6 (50%), poor performance status for 4 (33.3%), intercurrent disease for 1 (8.3%), and refusal for 1 (8.3%). Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was 59%. The survival rates were 46.7% and 17.0% at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients (19%), while grade III or IV non-hematologic toxicity was shown in 5 patients (12%). Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient

Acute toxicity of chemoradiation for rectal cancer

International Nuclear Information System (INIS)

Roedel, C.; Fietkau, R.; Keilholz, L.; Grabenbauer, G.G.; Kessler, H.; Martus, P.; Sauer, R.

1997-01-01

Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) ± 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m 2 /d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [de

Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

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Ferrandina, Gabriella, E-mail: gabriella.ferrandina@libero.it [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Gambacorta, Antonietta [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Gallotta, Valerio [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Smaniotto, Daniela [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Fagotti, Anna [Gynecologic Surgery, University of Perugia, Terni (Italy); Tagliaferri, Luca [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Foti, Elvira; Fanfani, Francesco [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Autorino, Rosa [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Scambia, Giovanni [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Valentini, Vincenzo [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy)

2014-11-15

Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m{sup 2}, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m{sup 2}/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: A stepwise developed treatment schedule for advanced head-and-neck cancer

International Nuclear Information System (INIS)

Martinez, Jose Carlos; Villar, Alfonso; Cabezon, Maria Auxiliadora; Serdio, Jose Luis de; Fuentes, Claudio; Espineira, Manuel; Perez, Maria Dolores; Gil, Jose; Artazkoz, Juan Jose; Borque, Carlos; Suner, Marcos; Saavedra, Juan Antonio

2001-01-01

Purpose: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. Methods and Materials: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. Results: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. Conclusions: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions

Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

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Kato, Shingo, E-mail: s_kato@saitama-med.ac.jp [Department of Radiation Oncology, International Medical Center, Saitama Medical University, Saitama (Japan); National Institute of Radiological Sciences of Japan, Chiba (Japan); Ohno, Tatsuya [Gunma University Heavy Ion Medical Center, Gunma University, Gunma (Japan); Thephamongkhol, Kullathorn; Chansilpa, Yaowalak [Division of Radiation Oncology, Department of Radiology, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok (Thailand); Cao, Jianping [School of Radiation Medicine and Public Health, Soochow University, Soochow (China); Xu, Xiaoting [Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Devi, C. R. Beena; Swee, Tang Tieng [Department of Radiotherapy and Oncology, Hospital Umum Sarawak, Kuching (Malaysia); Calaguas, Miriam J.C. [Department of Radiation Oncology, St. Luke' s Medical Center, Quezon City, the Philippines (Philippines); Reyes, Rey H. de los [Department of Obstetrics and Gynecology, Dr Jose R. Reyes Memorial Medical Center, Manila, the Philippines (Philippines); Cho, Chul-Koo [Department of Radiation Oncology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Dung, To Anh [Department of Breast and Gynecology Radiotherapy, National Cancer Institute, Hanoi (Viet Nam); Supriana, Nana [Department of Radiation Therapy, Faculty of Medicine, University of Indonesia, Dr Cipto Mangunkusumo General Hospital, Jakarta (Indonesia); Erawati, Dyah [Division of Radiotherapy, Dr Soetomo General Hospital, Surabaya (Indonesia); Mizuno, Hideyuki [National Institute of Radiological Sciences of Japan, Chiba (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan); Tsujii, Hirohiko [National Institute of Radiological Sciences of Japan, Chiba (Japan)

2013-09-01

Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection - A Matched-Controlled Study.

Science.gov (United States)

Hupkens, Britt J P; Martens, Milou H; Stoot, Jan H; Berbee, Maaike; Melenhorst, Jarno; Beets-Tan, Regina G; Beets, Geerard L; Breukink, Stéphanie O

2017-10-01

Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome. The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group). This was a matched controlled study. This study was conducted at multiple centers. The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years. Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score). The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function. This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study

Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

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Jeong, Jae Ho; Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Yangsoon; Kim, Jihun [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jeong Eun; Kim, Kyu-pyo; Kim, Sun Young [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Jin-hong; Kim, Jong Hoon [Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, In Ja; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon [Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-10-01

Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluated in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.

Dose escalation without split-course chemoradiation for anal cancer: results of a phase II RTOG study

International Nuclear Information System (INIS)

John, Madhu; Pajak, Thomas; Kreig, Richard; Pinover, Wayne H.; Myerson, Robert

1997-01-01

PURPOSE: An attempt at radiotherapy (RT) dose escalation (from 45 Gy to 59.6 Gy) in a Radiation Therapy Oncology Group (RTOG) chemoradiation protocol for advanced anal cancers had resulted in an unexpectedly high 1-year colostomy rate (23%) and local failure (The Cancer Journal from Scientific American 2 (4):205-211, 1996). This was felt to be probably secondary to the split course chemoradiation (CR) that was mandated in the protocol. A second phase of this dose escalation study was therefore undertaken without a mandatory split and with an identical RT dose (59.6 Gy) and chemotherapy. MATERIALS AND METHODS: Twenty patients with anal cancers ≥2 cms were treated with a concurrent combination of 59.6 Gy to the pelvis and perineum (1.8 Gy daily, 5 times per week in 33 fractions over 6 (1(2)) weeks) and two cycles of 5 fluorouracil infusion (1000 mg/m 2 over 24 hours for 4 days) and mitomycin C (10 mg/m 2 bolus). A 10 day rest period was allowed only for severe skin reactions. A comparative analysis was made with the 47 patients in the earlier phase of this study who were treated with the identical chemoradiation course but with a mandatory 2-week break at the 36.00 Gy level. RESULTS: Predominant Grade 3 and 4 toxicities in 18 evaluable patients with dermatitis ((14(18)) or 78%), hematologic ((14(18)) or 78%), infection ((3(18)) or 17%) and gastrointestinal ((5(18)) or 28%). There were no fatalities. Nine patients (50%) completed the planned course without a break; 9 others (50%) had their treatments interrupted for a median of 11 days (range 7-19 days) at a median dose of 41.4 Gy (range 32.4 to 48.6 Gy). This compared to (40(47)) patients (85%) who had a 12 day treatment interruption at 36 Gy total dose in a planned break group. One patient had an abdomino-perineal resection (APR) for persistent disease and another for an anal fissure for (2(18)) or 11% 1-year colostomy rate. This was again favorably comparable to 23% 1-year colostomy rate for the earlier group of

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

International Nuclear Information System (INIS)

Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K.

2004-01-01

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 ∼ 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 ∼ 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (ρ = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively (ρ = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (ρ = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (ρ = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (≥ 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (ρ = 0.02). There were no statistical differences

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

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Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K. [Inha University Medical College, Inchon (Korea, Republic of)

2004-09-15

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 {approx} 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 {approx} 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia ({>=} 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively ({rho} = 0.02). There were

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer

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Jakobsen, Anders; Ploen, John; Vuong, Té

2012-01-01

PURPOSE: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation...

Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach.

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Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

2014-10-01

To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes

Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

International Nuclear Information System (INIS)

Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

2014-01-01

Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283

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Heeger S

2005-10-01

Full Text Available Abstract Background Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. Methods/design The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment. Discussion The primary objective of this study is to evaluate the feasibility and the toxicity profile of

A multidisciplinary treatment strategy for locally advanced rectal cancer

International Nuclear Information System (INIS)

Kimura, F.; Yanagi, Hidenori; Atono, R.

2012-01-01

The aim of this study is to examine the therapeutic effects and adverse events of preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer in different radiation doses and fractions. A total of 142 consecutive patients with locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the rectum were treated with preoperative CRT and were operated radically. 121 patients with resectable cT3 or N1-2 rectal adenocarcinoma were assigned to receive pelvic radiation with single fractions of 2.5 Gy twice daily to a total dose of 25 Gy (Short CRT). Surgery was undergone within two weeks. 21 patients with clinical unresectable or marginally resectable cT4 rectal cancer were assigned to receive preoperative pelvic radiation therapy 45 to 50.4 Gy at 1.8 Gy per day. Surgery was performed 6 to 8 weeks after completion of neoadjuvant therapy (Long CRT). We examined retrospectively the preoperative therapeutic effect and adverse event of Short CRT and Long CRT. Short CRT; Overall R0 resection rate was 98%. Anus preserving rate was 95%. pCR rate was 5%. Median follow-up was 62 months. The actuarial 5-year-local-control rate was 94%. Overall survival for 5 years was 92%. Long neoadjuvant chemoradiation therapy (NCRT); Overall R0 resection rate was 90%. Anus preserving rate was 86%. pCR rate was 24%. Median follow-up was 60 months. The actuarial 5-year-local-control rate was 88%. Overall survival rate for 5 years was 88%. Radiation related adverse event such as pelvic infection and skin trouble was significantly higher in the long CRT group. Local control in primarily resectable rectal cancer after short chemoradiation was excellent. Long chemoradiation for unresectable or marginal cT4 rectum cancer was higher response ratio, but induced more radiation related adverse event than short course CRT. (author)

Role of secondary low energy electrons in radiobiology and chemoradiation therapy of cancer

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Sanche, Léon

2009-05-01

With the chemotherapeutic agent cisplatin bound to DNA, damage to the molecule by electrons of low and high energies increases by factors varying from 1.3 to 4.4. The enhancement in bond dissociation is triggered by modifications of the interaction of low energy electrons with DNA. From our understanding of the latter, the present Letter attempts to explain the basic radiation-damage mechanism responsible for the efficiency of the concomitant chemoradiation treatment of cancer. Such a basic comprehension of the direct effects of radiation may have implications in the design of new chemotherapeutic and radiosensitizing drugs, as well as in the development of more efficient protocols in chemoradiation therapy.

Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided, Intensity Modulated Radiotherapy (IG-IMRT or IG-IMRT Alone for Locally Advanced Non-Small Cell Lung Cancer.

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Alexander Chi

Full Text Available Image-guided (IG intensity-modulated radiotherapy (IMRT enables maximal tumor margin reduction for the sparing of organs at risk (OARs when used to treat locally advanced non-small cell lung cancer (NSCLC with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC.The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both was retrospectively reviewed.After a median follow up of 23.7 months, the median overall survival (OS and progression-free survival (PFS were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed.Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.

Acute insulin resistance mediated by advanced glycation endproducts in severely burned rats.

Science.gov (United States)

Zhang, Xing; Xu, Jie; Cai, Xiaoqing; Ji, Lele; Li, Jia; Cao, Bing; Li, Jun; Hu, Dahai; Li, Yan; Wang, Haichang; Xiong, Lize; Xiao, Ruiping; Gao, Feng

2014-06-01

Hyperglycemia often occurs in severe burns; however, the underlying mechanisms and importance of managing postburn hyperglycemia are not well recognized. This study was designed to investigate the dynamic changes of postburn hyperglycemia and the underlying mechanisms and to evaluate whether early glycemic control is beneficial in severe burns. Prospective, randomized experimental study. Animal research laboratory. Sprague-Dawley rats. Anesthetized rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive vehicle, insulin, and a soluble form of receptor for advanced glycation endproducts treatments. An in vitro study was performed on cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment. We found that blood glucose change presented a distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour postburn, respectively. Acute insulin resistance evidenced by impaired insulin signaling and glucose uptake occurred at 3-hour postburn, which was associated with the second hyperglycemia and positively correlated with mortality. Mechanistically, we found that serum carboxymethyllysine, a dominant species of advanced glycation endproducts, increased within 1-hour postburn, preceding the occurrence of insulin resistance. More importantly, treatment of animals with soluble form of receptor for advanced glycation endproducts, blockade of advanced glycation endproducts signaling, alleviated severe burn-induced insulin resistance. In addition, early hyperglycemic control with insulin not only reduced serum carboxymethyllysine but also blunted postburn insulin resistance and reduced mortality. These findings suggest that severe burn-induced insulin resistance is partly at least mediated by serum advanced glycation endproducts and positively correlated with mortality. Early glycemic control with insulin or inhibition of advanced glycation endproducts with soluble form of receptor

Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

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Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

2015-04-01

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

Chemoradiation therapy efficacy in patients with local cervical cancer

International Nuclear Information System (INIS)

Nemal'tsova, O.A.

2007-01-01

To analyze the efficacy of the original chronomodulation chemoradiation for local cervical cancer (CC) comparing it with the results of the standard treatment protocol and Hydrea administration as a radiomodifier. The use of the original protocol reduced the number of long-term metastases 6.3 times when compared with Hydrea use and 4.5 times when compared with the traditional treatment

Non-small cell lung cancer: current status of chemoradiation for locally advanced disease and an update on susceptibility and prevention

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Byhardt, Roger W.

1996-01-01

Locally advanced, inoperable non-small cell lung cancer (NSCLC) afflicts 40,000 patients yearly. The traditional treatment has been radiation therapy (RT) alone with 5 year survival rates averaging around 5%. Recent reports of randomized clinical trials using combined radiochemotherapy suggest significant improvement in survival compared to RT alone. These trials are difficult to evaluate because of differences in dose, timing and sequencing of both the chemotherapy (CT) and the RT. Dr. Byhardt will give an overview of the significant chemoradiation trials, especially with respect to the factors associated with reduction of local failure and distant metastasis. Dr. Tishler will review the biologic rationale of these regimens and make some prognostications about the potential role of new chemotherapy agents, new developments in RT dose-time-fractionation, and new RT technology in future radiochemotherapy trials. While progress continues to be made using the more traditional cancer treatment modalities, investigations in NSCLC epidemiology and prevention are providing new insights regarding susceptibility, etiology, failure risk stratification, and potential avenues of therapeutic intervention. Dr. Spitz will discuss NSCLC as a paradigm of an environmentally induced disease in which host susceptibility may be determined by genetically determined modulation of environmental exposures. A mutagen sensitivity assay can determine individuals at high risk for developing NSCLC if exposed to carcinogens such as those in cigarette smoke. This susceptibility may have prognostic implications that could influence choice of therapy. Highly susceptible individuals can also be selected for special counseling, smoking cessation, with consideration given to chemoprevention. Dr. Gritz will review major work done in this area

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Bodner, William R. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Halmos, Balazs; Cheng, Haiying; Perez-Soler, Roman [Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Keller, Steven M. [Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Garg, Madhur [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2017-02-01

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for

Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma.

Science.gov (United States)

Wu, Licun; Blum, Walter; Zhu, Chang-Qi; Yun, Zhihong; Pecze, Laszlo; Kohno, Mikihiro; Chan, Mei-Lin; Zhao, Yidan; Felley-Bosco, Emanuela; Schwaller, Beat; de Perrot, Marc

2018-04-27

Cancer cell repopulation during chemotherapy or radiotherapy is a major factor limiting the efficacy of treatment. Cancer stem cells (CSC) may play critical roles during this process. We aim to demonstrate the role of mesothelioma stem cells (MSC) in treatment failure and eventually to design specific target therapies against MSC to improve the efficacy of treatment in malignant mesothelioma. Murine mesothelioma AB12 and RN5 cells were used to compare tumorigenicity in mice. The expression of CSC-associated genes was evaluated by quantitative real-time PCR in both cell lines treated with chemo-radiation. Stemness properties of MSC-enriched RN5-EOS-Puro2 cells were characterized with flow cytometry and immunostaining. A MSC-specific gene profile was screened by microarray assay and confirmed thereafter. Gene Ontology analysis of the selected genes was performed by GOMiner. Tumor growth delay of murine mesothelioma AB12 cells was achieved after each cycle of cisplatin treatment, however, tumors grew back rapidly due to cancer cell repopulation between courses of chemotherapy. Strikingly, a 10-times lower number of irradiated cells in both cell lines led to a similar tumor incidence and growth rate as with untreated cells. The expression of CSC-associated genes such as CD24, CD133, CD90 and uPAR was dramatically up-regulated, while others did not change significantly after chemoradiation. Highly enriched MSC after selection with puromycin displayed an increasing GFP-positive population and showed typical properties of stemness. Comparatively, the proportion of MSC significantly increased after RN5-EOS parental cells were treated with either chemotherapy, γ-ray radiation, or a combination of the two, while MSC showed more resistance to the above treatments. A group of identified genes are most likely MSC-specific, and major pathways related to regulation of cell growth or apoptosis are involved. Upregulation of the gene transcripts Tnfsf18, Serpinb9b, Ly6a

The effect of chemoradiation therapy on pituitary-thyroid system function in children suffering Hodgkin's disease

International Nuclear Information System (INIS)

Konoplya, N.E.; Sachivko, N.V.; Zhavrid, Eh.A.

1997-01-01

The functional status of the thyroid gland was evaluated in 63 children with Hodgkin's disease, aged 4-15 years, before, in the course of and 5 years after chemoradiation therapy. Thyroxin (T4), triiodothyronine (T) and thyroid-stimulating hormone (TSH) in the blood were assayed. The disease was shown to disrupt the pituitary-thyroid system leading to hypothyroidism development which progressed as the disease advanced. While chemotherapy brought the balance between the peripheral thyroid hormone levels and TSH back to normal, thyroid function decrease again following radiotherapy of the neck. The most pronounced and persistent failure of the pituitary-thyroid system was registered with the total target dose of 30 Gy and higher. Irradiation in a dose of 20 Gy caused less disruption and the function was spontaneously restored within 12 months after the treatment

Risk factors for postoperative complications after total laryngectomy following radiotherapy or chemoradiation

DEFF Research Database (Denmark)

Wulff, N B; Kristensen, C.A.; Andersen, E

2015-01-01

OBJECTIVES: To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 143 patients undergoin...

Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study

DEFF Research Database (Denmark)

Mazeron, Renaud; Fokdal, Lars U; Kirchheiner, Kathrin

2016-01-01

Purpose To establish dose volume–effect relationships predicting late rectal morbidity in cervix cancer patients treated with concomitant chemoradiation and MRI-guided adaptive brachytherapy (IBABT) within the prospective EMBRACE study. Material and method All patients were treated with curative ...

Changes of saliva microbiota in nasopharyngeal carcinoma patients under chemoradiation therapy.

Science.gov (United States)

Xu, Yuan; Teng, Fei; Huang, Shi; Lin, Zhengmei; Yuan, Xiao; Zeng, Xiaowei; Yang, Fang

2014-02-01

A growing body of evidence has implicated human oral microbiota in the aetiology of oral and systemic diseases. Nasopharyngeal carcinoma (NPC), an epithelial-originated malignancy, has a complex aetiology not yet fully understood. Chemoradiation therapy of NPC can affect oral microbiota and is usually accompanied by plaque accumulation. Thus, the study aimed to understand the diversity, divergence and development of the oral microbiota in NPC patients and their associated treatment, which might provide useful insights into disease aetiology and treatment side effects. A longitudinal study was designed that included three Chinese adults with NPC. Saliva samples were collected at three time points: prior to the chemoradiation treatment (carcinoma baseline, or CB), 7 months post-treatment (carcinoma-after-therapy phase 1 or CA1) and 12 months post-treatment (carcinoma-after-therapy phase 2 or CA2). Pyrosequencing of the bacterial 16S ribosomal DNA (rDNA) V1-V3 hypervariable region was employed to characterise the microbiota. Saliva samples of three healthy subjects from our former study were employed as healthy controls. Principal coordinates analysis (PCoA), Metastats and random forest prediction models were used to reveal the key microbial members associated with NPC and its treatment programme. (1) In total, 412 bacterial species from at least 107 genera and 13 phyla were found in the saliva samples of the NPC patients. (2) PCoA revealed that not only were the microbiota from NPC patients distinct from those of healthy controls (p<0.001) but also that separation was found on the saliva microbiota between pre- and post-therapy (p<0.001) in the NPC samples. (3) At the genus level and the operational taxonomic unit (OTU) level, Streptococcus was found with lower abundance in NPC samples. (4) Chemoradiation therapy did not incur similar changes in microbiota structure among the three NPC patients; the microbiota in one of them stayed largely steady, while those in the

Five-Year Follow-Up of Concomitant Accelerated Hypofractionated Radiation in Advanced Squamous Cell Carcinoma of the Buccal Mucosa: A Retrospective Cohort Study

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Hassan Iqbal

2015-01-01

Full Text Available In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m2. Five-year overall survival (OS, disease-free survival (DFS, and progression-free survival (PFS were determined. Based on AJCC staging, 7 (11% patients were stage III, 31 (49% stage IV a, and 25 (40% stage IVb at presentation. After IC, 8 (18% patients had complete radiological response, 33 (73% had partial response, and 4 (9% had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62% patients were complete responders and 24 (38% had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.

Uterus necrosis after radiochemotherapy in two patients with advanced cervical cancer

International Nuclear Information System (INIS)

Marnitz, S.; Hinkelbein, W.; Koehler, C.; Schneider, A.; Fueller, J.

2006-01-01

Background: Simultaneous platinum-based radiochemotherapy is the standard of care for patients with advanced or node-positive cancer of the uterine cervix. A large body of literature concerning therapy-related acute and late morbidity is available. Chemoradiation-associated necrosis of the uterus has not been described so far. Case Report: Two patients are reported who were treated by combine chemoradiation between 2004 and 2005 for histologically confirmed cervical cancer following laparoscopic staging. Both patients were diagnosed with squamous cell cancer of the cervix FIGO stage IIB (T2b pN1 pM1 LYM G2) and FIGO IIIA (T3a pN1 MO G2), respectively. External-beam radiotherapy was applied in a 3-D-planned four-field technique, covering pelvic lymph nodes and primary tumor. Simultaneously, cisplatin was given to both patients. Following chemoradiation, both patientsdeveloped pelvic pain and an elevation of C-reactive protein (CRP) in the presence of a normal leukocyte count. Both patients underwent relaparoscopy, and necrosis of the uterus combined with partial necrosis of the bladder was diagnosed in patient 1. Patient 1 underwent total supralevatoric exenteration and patient 2 laparoscopically assisted hysterectomy withbilateral salpingo-oophorectomy. Conclusion: In patients with persisting or incident pelvic pain, questionable findings in imaging techniques and/or elevated inflammation parameters following completion of chemoradiation for cervical cancer, differential diagnosis should include radiogenic necrosis of the uterus and other pelvic organs. Laparoscopy is an ideal technique to exclude or confirm this diagnosis. (orig.)

Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

International Nuclear Information System (INIS)

Marnitz, Simone; Budach, Volker; Weißer, Friederike; Burova, Elena; Gebauer, Bernhard; Vercellino, Filiberto Guiseppe; Köhler, Christhardt

2012-01-01

To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer

International Nuclear Information System (INIS)

Tan, Jennifer; Hui, Andrew C; Heriot, Alexander G.; Mackay, Jack; Lynch, A. Craig; Van Dyk, Sylvia; Bressel, Mathias; Fox, Chris D.; Leong, Trevor; Ngan, Samuel Y.

2013-01-01

This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high-dose-rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control. This is a prospective non-randomised study. Eligible patients were those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high risk of positive resection margins, without evidence of metastasis. Chemoradiation was followed by radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator at time of surgery. There were 15% primary and 85% recurrent cancers. The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%, 22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered patients (90% (95% confidence interval (CI)=73–98)) at a median reported time of 12 weeks (interquartile range (IQR)=10–16) after chemoradiation. Mean IORT procedure and delivery times were 63 minutes (range 22–105 minutes). Ten patients (37% (95% CI=19–58)) experienced grade 3 or 4 toxicities (three wound, four abscesses, three soft tissue, three bowel obstructions, three ureteric obstructions and two sensory neuropathies). Local recurrence-free, failure-free and overall survival rates at 2.5 years were 68% (95% CI=52–89), 37% (95% CI=23–61) and 82% (95% CI=68–98), respectively. The addition of IORT to radical surgery for T4 or recurrent rectal cancer is feasible. It can be delivered safely with low morbidity and good tumour outcomes.

Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

International Nuclear Information System (INIS)

Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

2011-01-01

We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

International Nuclear Information System (INIS)

Aftimos, Philippe G; Nasr, Elie A; Nasr, Dolly I; Noun, Roger J; Nasr, Fady L; Ghosn, Marwan G; El Helou, Joelle A; Chahine, Georges Y

2010-01-01

Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

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Ghosn Marwan G

2010-06-01

Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

Pathological study on preoperative concurrent chemoradiation for advanced hypopharyngeal cancer

International Nuclear Information System (INIS)

Inoue, Toshiya; Nagata, Motoki; Yukawa, Hisaya

2008-01-01

Chemoradiotherapy is frequently applied as the first-line therapy for advanced hypopharyngeal cancer. However, organ-preserving therapy does not allow true pathological assessment of the effectiveness of the therapy. We therefore determined the following treatment modality for advanced hypopharyngeal cancer based on local findings upon the completion of radiotherapy at 40 Gy. Pathological assessments of 33 cases of advanced hypopharyngeal cancer who had undergone extended operation after chemoradiotherapy were performed. The pathological effects were 12 cases of Grade 1, 13 cases of Grade 2 and 8 cases of Grade 3. However, the rate of tumor-free cases was only 60% of the extended operation. In those cases, the local controlled lesions were well, however, distant metastases influenced the outcome; to control distant metastasis is a future issue. Additional studies to select a surgical approach will be needed. (author)

Yellow Rust Resistance in Advanced Lines and Commercial ...

African Journals Online (AJOL)

The objective of this study was to characterize seedling yellow rust resistance in 21 advanced bread wheat lines and 20 cultivars from Ethiopia. Yellow rust infection types (ITs) produced on test wheat lines and cultivars from nine yellow rust races were compared with ITs produced on standard differential lines that differed ...

Resistance Welding of Advanced Materials and Micro Components

DEFF Research Database (Denmark)

Friis, Kasper Storgaard

With the use of the Finite Element Method it has become possible to analyse and better understand complex physical processes such as the resistance welding by numerical simulation. However, simulation of resistance welding is a very complex matter due to the strong interaction between mechanical......, thermal, electrical and metallurgical effects all signifcantly in uencing the process. Modelling is further complicated when down-scaling the process for welding micro components or when welding new advanced high strength steels in the automotive industry. The current project deals with three main themes...... aimed at improving the understanding of resistance welding for increasing the accuracy of numerical simulation of the process. Firstly methods for measuring and modelling mechanical and electrical properties at a wide range of temperatures is investigated, and especially the electrical contact...

SU-E-T-256: Radiation Dose Responses for Chemoradiation Therapy of Pancreatic Cancer: An Analysis of Compiled Clinical Data Using Biophysical Models.

Science.gov (United States)

Moraru, I; Tai, A; Erickson, B; Li, X

2012-06-01

We have analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer in order to examine possible benefits from radiotherapy (RT) dose escalation as well as to propose possible dose escalated fractionation schemes. A modified linear quadratic (LQ) model was used to fit clinical tumor response data from chemoradiation treatments using different fractionations. Biophysical radiosensitivy parameters, a and α/β, tumor potential doubling time, Td, and delay time for tumor doubling during treatment, Tk, were extracted from the fits and were used to calculate feasible fractionation schemes for dose escalations. Examination of published data from 20 institutions showed no clear indication of improved survival with raised radiation dose. However, an enhancement in tumor response was observed for higher irradiation doses, an important and promising clinical Result with respect to palliation and quality of life. The radiobiological parameter estimates obtained from the analysis are: α/β = 10 ± 3 Gy, a = 0.010 ± 0.003 Gŷ-1, Td = 56 ± 5 days and Tk = 7 ± 2 days. Possible dose escalation schemes are proposed based on the calculation of the biologically equivalent dose (BED) required for a 50% tumor response rate. From the point of view of tumor response, escalation of the administered radiation dose leads to a potential clinical benefit, which when combined with normal tissue complication analyses may Result in improved treatments for certain patients with advanced pancreatic cancer. Based on this analysis, a dose escalation trial with 2.25 Gy/fraction up to 69.75 Gy is being initiated for unresectable pancreatic cancer at our institution. Partially supported by MCW Cancer Center Meinerz Foundation. © 2012 American Association of Physicists in Medicine.

A PROSPECTIVE STUDY ON PREOPERATIVE CONCURRENT CHEMORADIATION WITH CAPECITABINE IN STAGE II/III CARCINOMA OF RECTUM

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Anish Kuttappan Soman

2017-09-01

Full Text Available BACKGROUND Fluorouracil (5-FU based chemoradiotherapy represents the standard treatment option for the preoperative treatment of advanced rectal cancer. Capecitabine is an oral precursor of 5-FU with the advantage of delivering the chemotherapy in an outpatient setup. NSABP R-04 & a German phase 3 trial by Hofheinz et al showed that Capecitabine was equivalent to 5-FU. The primary objective of this study was to evaluate pathological response (PR, clinical & surgical outcomes of stage II & III patients treated with chemoradiation with Capecitabine. The secondary objective was to evaluate toxicity and compliance to treatment. MATERIALS AND METHODS This single arm prospective study included 35 patients with stages II & III adenocarcinoma of rectum who after evaluation were treated with pelvic radiotherapy and concurrent Capecitabine. Toxicities were graded using RTOG scoring criteria. Clinical response was assessed after EBRT completion, and patients were referred for surgery after 4-6 weeks. Pathologic response and completeness of resection were assessed from the histopathology report. RESULTS Growth located within 5 cm from anal verge was seen in 24 (68.5% patients and 6 were inoperable upfront. All patients completed the intended preoperative treatment and 88.6% did not have any toxicity related break in RT. Clinical response was seen in 80% of patients after Chemoradiation. Out of 35 treated 80% of them underwent surgery. APR was performed in 64.2% and 35.7% had LAR. Out of 6 upfront inoperable patients, 3 were converted to operable. Out of 23 APR cases, 7 were converted to anterior resection (30.4%, p=0.046. 96% of operated patients had an R0 resection, including all the 3 upfront inoperable patients. Minimal pathologic response was seen in 89.2% of patients and 7.14% had complete pathologic response. There were no Grade 4 or 5 toxicities. Only 2.9% had a Grade 3 event. 45.7% had maximum of Grade 1 events and 48.6% had maximum of Grade 2

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

International Nuclear Information System (INIS)

Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert

2015-01-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m 2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [ 18 F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [ 61 Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

Energy Technology Data Exchange (ETDEWEB)

Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

2015-04-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery

2012-09-15

Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

International Nuclear Information System (INIS)

Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

2009-01-01

Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer

Science.gov (United States)

Rogus-Pulia, Nicole M.; Larson, Charles; Mittal, Bharat B; Pierce, Marge; Zecker, Steven; Kennelty, Korey; Kind, Amy; Connor, Nadine P.

2016-01-01

Purpose Patients treated with chemoradiation for head and neck cancer frequently develop dysphagia. Tissue damage to the oral tongue causing weakness and decreases in saliva production may contribute to dysphagia. Yet, effects of these variables on swallowing-related measures are unclear. The purpose of this study was (1) to determine effects of chemoradiation on tongue pressures, as a surrogate for strength, and salivary flow rates and (2) to elucidate relationships among tongue pressures, saliva production, and swallowing efficiency by bolus type. Methods and Materials 21 patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with 21 healthy control participants who did not receive chemoradiation. Each participant was given a questionnaire to rate dysphagia symptoms. Videofluoroscopic evaluation of swallowing was used to determine swallowing efficiency; the Saxon test measured salivary flow rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue maximum and endurance measures. Results Results revealed significantly lower tongue endurance measures for patients post-treatment as compared to controls (p=.012). Salivary flow rates also were lower compared to pre-treatment (p=.000) and controls (p=.000). Simple linear regression analyses showed that change in salivary flow rate was predictive of change in swallow efficiency measures from pre- to post-treatment for 1mL thin liquid (p=.017), 3mL nectar-thick liquid (p=.026), and 3mL standard barium pudding (p=.011) boluses. Conclusions Based on these findings, it appears that chemoradiation treatment affects tongue endurance and salivary flow rate and these changes may impact swallow efficiency. These factors should be considered when planning treatment for dysphagia. PMID:27492408

Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer.

Science.gov (United States)

Rogus-Pulia, Nicole M; Larson, Charles; Mittal, Bharat B; Pierce, Marge; Zecker, Steven; Kennelty, Korey; Kind, Amy; Connor, Nadine P

2016-10-01

Patients treated with chemoradiation for head and neck cancer frequently develop dysphagia. Tissue damage to the oral tongue causing weakness along with decreases in saliva production may contribute to dysphagia. Yet, effects of these variables on swallowing-related measures are unclear. The purpose of this study was (1) to determine effects of chemoradiation on tongue pressures, as a surrogate for strength, and salivary flow rates and (2) to elucidate relationships among tongue pressures, saliva production, and swallowing efficiency by bolus type. Twenty-one patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with 21 healthy control participants who did not receive chemoradiation. Each participant was given a questionnaire to rate dysphagia symptoms. Videofluoroscopic Evaluation of Swallowing (VFES) was used to determine swallowing efficiency; the Saxon test measured salivary flow rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue maximum and endurance measures. Results revealed significantly lower tongue endurance measures for patients post-treatment as compared to controls (p = .012). Salivary flow rates also were lower compared to pre-treatment (p = .000) and controls (p = .000). Simple linear regression analyses showed that change in salivary flow rate was predictive of change in swallow efficiency measures from pre- to post-treatment for 1 mL thin liquid (p = .017), 3 mL nectar-thick liquid (p = .026), and 3 mL standard barium pudding (p = .011) boluses. Based on these findings, it appears that chemoradiation treatment affects tongue endurance and salivary flow rate, and these changes may impact swallow efficiency. These factors should be considered when planning treatment for dysphagia.

Pseudomembranous colitis within radiotherapy field following concurrent chemoradiation therapy: a case report

Directory of Open Access Journals (Sweden)

Shen BJ

2013-01-01

Full Text Available Bing-Jie Shen,1 Shih-Chiang Lin,2 Pei-Wei Shueng,1,3 Yueh-Hung Chou,4 Li-Ming Tseng,5 Chen-Hsi Hsieh1,6,71Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan; 2Division of Oncology and Hematology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 3Department of Radiation Oncology, National Defense Medical Center, Taipei, Taiwan; 4Department of Anatomical Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan; 5Division of Colorectal Surgery, Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, TaiwanAbstract: Development of nonantibiotic-associated pseudomembranous colitis has been reported in patients receiving chemotherapy. Herein, we report a case of a 70-year-old man with diabetes mellitus and hypertension who received concurrent chemoradiation therapy after surgery for stage III pT3N1M0 rectal cancer. After completion of the therapy, the patient presented with a 2-week history of intermittent watery diarrhea (seven to nine times per day. However, the patient was afebrile and laboratory examination revealed no evidence of leukocytosis. Computed tomography disclosed inflammation of the sigmoid colon, infiltrative changes around the anastomotic site, and edematous changes straddling the serosal surface. Colonoscopic examination revealed multiple whitish patches within the radiation field, a finding suggestive of pseudomembranous colitis. No concomitant antibiotics were used during the period of concurrent chemoradiation therapy. Empirical oral metronidazole (500 mg every 8 hours was administrated for 2 weeks. At the end of this treatment, stool culture was negative for Clostridium difficile. Physicians should be aware of the potential for the development of

Results of using artificial hyperglycemia in chemoradiation treatment of patients with local spread cancer of oral cavity mucous membranes

International Nuclear Information System (INIS)

Puchinina, E.A.

1990-01-01

The comparative estimation of the recent results of chemoradiation therapy using artificial hyperglycemia of 115 patients with local spread cancer of the 3rd and 4th stages of body of the tongue and oral cavity mucous membranes is given. Optimal combinations of irradiation and hyperglycemia are determined. It is shown that the application of artificial hyperglycemia in chemoradiation treatment of cancer of oral cavity mucous membranes is reasonable and it provides an opportunity to improve the results, especially at the 3rd stage of cancer. 15 refs

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

2015-02-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

International Nuclear Information System (INIS)

Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G.; Sridhar, Srinivas

2015-01-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

International Nuclear Information System (INIS)

Haj Mohammad, Nadia; Hulshof, Maarten CCM; Bergman, Jacques JGHM; Geijsen, Debby; Wilmink, Johanna W; Berge Henegouwen, Mark I van; Laarhoven, Hanneke WM van

2014-01-01

Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Haj Mohammad, Nadia [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hulshof, Maarten CCM [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Bergman, Jacques JGHM [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Geijsen, Debby [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Wilmink, Johanna W [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Berge Henegouwen, Mark I van [Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Laarhoven, Hanneke WM van [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2014-01-31

Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

Cervix Regression and Motion During the Course of External Beam Chemoradiation for Cervical Cancer

International Nuclear Information System (INIS)

Beadle, Beth M.; Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Iyer, Revathy B.; Eifel, Patricia J.

2009-01-01

Purpose: To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. Methods and Materials: Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. Results: Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. Conclusions: Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures

Strategies to prevent the occurrence of resistance against antibiotics by using advanced materials.

Science.gov (United States)

Bassegoda, Arnau; Ivanova, Kristina; Ramon, Eva; Tzanov, Tzanko

2018-03-01

Drug resistance occurrence is a global healthcare concern responsible for the increased morbidity and mortality in hospitals, time of hospitalisation and huge financial loss. The failure of the most antibiotics to kill "superbugs" poses the urgent need to develop innovative strategies aimed at not only controlling bacterial infection but also the spread of resistance. The prevention of pathogen host invasion by inhibiting bacterial virulence and biofilm formation, and the utilisation of bactericidal agents with different mode of action than classic antibiotics are the two most promising new alternative strategies to overcome antibiotic resistance. Based on these novel approaches, researchers are developing different advanced materials (nanoparticles, hydrogels and surface coatings) with novel antimicrobial properties. In this review, we summarise the recent advances in terms of engineered materials to prevent bacteria-resistant infections according to the antimicrobial strategies underlying their design.

Adjuvant chemoradiation after laparoscopically assisted radical vaginal hysterectomy (LARVH) in patients with cervical cancer. Oncologic outcome and morbidity

International Nuclear Information System (INIS)

Gruen, Arne; Musik, Thabea; Stromberger, Carmen; Budach, Volker; Marnitz, Simone; Koehler, Christhardt; Schneider, Achim; Fueller, Juergen; Wendt, Thomas

2011-01-01

Compared to laparotomic surgery, laparoscopically assisted radical vaginal hysterectomy (LARVH) offers decreased blood loss during surgery and faster convalescence of the patient postoperatively, while at the same time delivering similar oncologic results. However, there is no data on outcome and toxicity of LARVH followed by (chemo)radiation. A total of 55 patients (range 28-78 years) with cervical cancer on FIGO stages IB1-IIIA (Tables 1 and 2) with risk factors were submitted to either external beam radiotherapy alone [EBRT, n = 8 (14%), including paraaortic irradiation, n = 4 (2.2%); EBRT and brachytherapy (BT), n = 33 (60%); BT alone, n = 14 (25.5%)] or chemoradiation after LARVH. At a median follow-up of 4.4 years, the 5-year disease-free survival (DFS) was 81.8% with 84.5% overall survival (OS). Acute grade 3 side effects were seen in 4 patients. These were mainly gastrointestinal (GI) and genitourinary (GU) symptoms. Grade 4 side effects were not observed. With similar oncologic outcome data and mostly mild side effects, LARVH followed by (chemo)radiation is a valid alternative in the treatment of cervical cancer patients. (orig.)

Rust resistance evaluation of advanced wheat (triticum aestivum l.) genotypes using pcr-based dna markers

International Nuclear Information System (INIS)

Rahman, S.U.; Younis, M.; Iqbal, M.Z.; Nawaz, M.

2014-01-01

The most effective and environmental friendly approach for the control of wheat rust disease is the use of resistant genotypes. The present study was conducted to explore rust resistance potential of 85 elite wheat genotypes (36 varieties and 49 advanced lines) using various types of DNA markers like STS, SCAR and SSR. DNA markers linked with different genes conferring resistance to rusts (Leaf rust=Lr, Yellow rust=Yr and Stem rust=Sr) were employed in this study. A total of 18 genes, consisting of eleven Lr (lr1, lr10, lr19, lr21, lr28, lr34, lr39, lr46, lr47, lr51 and lr52), four Yr (yr5, yr18, yr26 and yr29) and three Sr genes (sr2, sr29, and sr36) were studied through linked DNA markers. Maximum number of Lr genes was found in 17 advanced lines and 9 varieties, Yr genes in 26 advanced lines and 20 wheat varieties, and Sr genes in 43 advanced lines and 27 varieties. Minimum number of Lr genes was found in advanced line D-97 and variety Kohinoor-83, Yr genes in wheat variety Bwp-97 and Sr genes in 6 advanced lines and 8 varieties. Molecular data revealed that genotypes having same origin, from a specified area showed resistance for similar type of genes. In this study, an average similarity of 84% was recorded among wheat genotypes. Out of 18 loci, 15 were found to be polymorphic. (author)

Tokamaks with high-performance resistive magnets: advanced test reactors and prospects for commercial applications

International Nuclear Information System (INIS)

Bromberg, L.; Cohn, D.R.; Williams, J.E.C.; Becker, H.; Leclaire, R.; Yang, T.

1981-10-01

Scoping studies have been made of tokamak reactors with high performance resistive magnets which maximize advantages gained from high field operation and reduced shielding requirements, and minimize resistive power requirements. High field operation can provide very high values of fusion power density and n tau/sub e/ while the resistive power losses can be kept relatively small. Relatively high values of Q' = Fusion Power/Magnet Resistive Power can be obtained. The use of high field also facilitates operation in the DD-DT advanced fuel mode. The general engineering and operational features of machines with high performance magnets are discussed. Illustrative parameters are given for advanced test reactors and for possible commercial reactors. Commercial applications that are discussed are the production of fissile fuel, electricity generation with and without fissioning blankets and synthetic fuel production

High temperature creep strength of Advanced Radiation Resistant Oxide Dispersion Strengthened Steels

Energy Technology Data Exchange (ETDEWEB)

Noh, Sanghoon; Kim, Tae Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

Austenitic stainless steel may be one of the candidates because of good strength and corrosion resistance at the high temperatures, however irradiation swelling well occurred to 120dpa at high temperatures and this leads the decrease of the mechanical properties and dimensional stability. Compared to this, ferritic/martensitic steel is a good solution because of excellent thermal conductivity and good swelling resistance. Unfortunately, the available temperature range of ferritic/martensitic steel is limited up to 650 .deg. C. ODS steel is the most promising structural material because of excellent creep and irradiation resistance by uniformly distributed nano-oxide particles with a high density which is extremely stable at the high temperature in ferritic/martensitic matrix. In this study, high temperature strength of advanced radiation resistance ODS steel was investigated for the core structural material of next generation nuclear systems. ODS martensitic steel was designed to have high homogeneity, productivity and reproducibility. Mechanical alloying, hot isostactic pressing and hot rolling processes were employed to fabricate the ODS steels, and creep rupture test as well as tensile test were examined to investigate the behavior at high temperatures. ODS steels were fabricated by a mechanical alloying and hot consolidation processes. Mechanical properties at high temperatures were investigated. The creep resistance of advanced radiation resistant ODS steels was more superior than those of ferritic/ martensitic steel, austenitic stainless steel and even a conventional ODS steel.

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

International Nuclear Information System (INIS)

Harima, Yoko; Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko; Tanigawa, Noboru

2013-01-01

Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Harima, Yoko, E-mail: harima@takii.kmu.ac.jp [Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka (Japan); Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko [Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka (Japan); Tanigawa, Noboru [Department of Radiology, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka (Japan)

2013-12-01

Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

Aspiration rate following chemoradiation for head and neck cancer: An underreported occurrence

International Nuclear Information System (INIS)

Nguyen, Nam P.; Frank, Cheryl; Moltz, Candace C.; Vos, Paul; Smith, Herbert J.; Bhamidipati, Prabhakar V.; Karlsson, Ulf; Nguyen, Phuc D.; Alfieri, Alan; Nguyen, Ly M.; Lemanski, Claire; Chan, Wayne; Rose, Sue; Sallah, Sabah

2006-01-01

Background and purpose: We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. Patients and methods: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1-7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6-7) or continued weight loss. Patients with abnormal swallow (grade 3-7) received swallowing therapy following MBS. Results: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1-10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). Conclusions: Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

International Nuclear Information System (INIS)

Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won; Kim, Young-Woo; Bae, Jae-Moon; Lee, Jun Ho; Choi, Il Ju; Kim, Yeon-Joo; Kim, Dae Yong

2012-01-01

Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

Impact of concomitant chemoradiation on survival for patients with T1-2N1 head and neck cancer.

Science.gov (United States)

Zumsteg, Zachary S; Kim, Sungjin; David, John M; Yoshida, Emi J; Tighiouart, Mourad; Shiao, Stephen L; Scher, Kevin; Mita, Alain; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

2017-05-01

Single-modality radiotherapy is considered a standard-of-care option for certain stage III, T1-2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population. This study analyzed patients in the National Cancer Data Base with cT1-2N1M0 invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx who were diagnosed between 2004 and 2012 and were undergoing definitive radiation. Patients who were undergoing surgery before radiation with unknown follow-up or for whom either the receipt or timing of chemotherapy was unknown were excluded. In all, 5030 patients with T1-2N1 oropharyngeal, laryngeal, or hypopharyngeal cancer were included. The median follow-up was 56.8 months (95% confidence interval [CI], 55.7-58.6 months). Overall, 68% of the patients received concomitant chemoradiation (CCRT). The use of CCRT significantly increased during the time period of this study from 53% in 2004 to 78% in 2012 (P cancer (HR, 0.74; 95% CI, 0.65-0.85; P Cancer 2017;123:1555-1565. © 2017 American Cancer Society. © 2016 American Cancer Society.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

Science.gov (United States)

Schernberg, Antoine; Huguet, Florence; Moureau-Zabotto, Laurence; Chargari, Cyrus; Rivin Del Campo, Eleonor; Schlienger, Michel; Escande, Alexandre; Touboul, Emmanuel; Deutsch, Eric

2017-07-01

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of phosphoenolpyruvate carboxykinase linked to chemoradiation susceptibility of human colon cancer cells

International Nuclear Information System (INIS)

Park, Ji-Won; Yang, Se Young; Kim, Dae Yong; Oh, Jae Hwan; Cho, Jae Youl; Yoo, Byong Chul; Kim, Seung Cheol; Kim, Won Ki; Hong, Jun Pyu; Kim, Kyung-Hee; Yeo, Hyun Yang; Lee, Jae Yong; Kim, M Sun; Kim, Jong Heon

2014-01-01

Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative. To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization–time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response. We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of

Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors.

Science.gov (United States)

Bagrodia, Aditya; Lee, Byron H; Lee, William; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Pietzak, Eugene J; Gao, Sizhi Paul; Zabor, Emily C; Ostrovnaya, Irina; Kaffenberger, Samuel D; Syed, Aijazuddin; Arcila, Maria E; Chaganti, Raju S; Kundra, Ritika; Eng, Jana; Hreiki, Joseph; Vacic, Vladimir; Arora, Kanika; Oschwald, Dayna M; Berger, Michael F; Bajorin, Dean F; Bains, Manjit S; Schultz, Nikolaus; Reuter, Victor E; Sheinfeld, Joel; Bosl, George J; Al-Ahmadie, Hikmat A; Solit, David B; Feldman, Darren R

2016-11-20

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture-based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic

Gene expression profiles in cervical cancer with radiation therapy alone and chemo-radiation therapy

International Nuclear Information System (INIS)

Lee, Kyu Chan; Kim, Joo Young; Hwang, You Jin; Kim, Meyoung Kon; Choi, Myung Sun; Kim, Chul Young

2003-01-01

To analyze the gene expression profiles of uterine cervical cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a cDNA microarray. Sixteen patients, 8 with squamous cell carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated with concurrent chemo-radiation, were included in the study. Before the starting of the treatment, tumor biopsies were carried out, and the second time biopsies were performed after a radiation dose of 16.2-27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were performed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during chemoradiation therapy. The 33P-labeled cDNAs were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the cDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel. The data were normalized by the Z transformation, and the comparisons were performed on the Z-ratio values calculated. The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved in cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, including G protein coupled receptor kinase 6, were decreased with the Z-ratio values of below -2.0. After the radiation therapy, most of the genes, with a previously increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were

The comparison between effect of chemoradiation with weekly cisplatin with or without celecoxib in treatment of nasopharyngeal carcinoma: A phase III clinical trial

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Mohamad Mohammadianpanah

2009-07-01

Full Text Available Introduction: Concurrent cisplatin-based chemoradiation is currently considered the treatment of choice for locoregional nasopharyngeal carcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2 inhibitor which can potentially enhance the effect of radiotherapy. The aim of this study was to determine the efficacy and safety of celecoxib in nasopharyngeal carcinoma. Materials and Methods: Patients with newly diagnosed locoregional nasopharyngeal carcinoma were included in this clinical trial study. The patients were assigned to receive 7 weeks concurrent chemoradiation with weekly cisplatin and either celecoxib 100 mg twice daily or placebo. After completion of chemoradiation, all patients received combined chemotherapy with cisplatin plus 5-Fu every 3 weeks for 3 cycles. Clinical response rates and treatment-related toxicity were the primary and secondary end-point of the study. Results: Total of 50 eligible patients with the median age of 43 years were enrolled in the trial. Overall (complete and partial clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in study group and 44% and 56% in control group respectively (P>0.25. There was no difference in terms of treatment-related toxicity rates between two groups. Conclusions: This clinical trial showed that addition of celecoxib 100 mg twice daily to concurrent chemoradiation does not increase the response rates and treatment-related toxicities in patients with locoregional nasopharyngeal carcinoma.

Analysis of Clinical and Dosimetric Factors Associated With Change in Renal Function in Patients With Gastrointestinal Malignancies After Chemoradiation to the Abdomen

International Nuclear Information System (INIS)

May, Kilian Salerno; Khushalani, Nikhil I.; Chandrasekhar, Rameela; Wilding, Gregory E.; Iyer, Renuka V.; Ma, Wen W.; Flaherty, Leayn; Russo, Richard C. C.; Fakih, Marwan; Kuvshinoff, Boris W.; Gibbs, John F.; Javle, Milind M.; Yang, Gary Y.

2010-01-01

Purpose: To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. Methods and Materials: A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema. Results: Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p 10 ), and mean kidney dose were significantly associated with development of Grade ≥2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). Conclusions: We observed correlation between pre-RT CrCl, V 10 , and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

Analysis of clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen.

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May, Kilian Salerno; Khushalani, Nikhil I; Chandrasekhar, Rameela; Wilding, Gregory E; Iyer, Renuka V; Ma, Wen W; Flaherty, Leayn; Russo, Richard C; Fakih, Marwan; Kuvshinoff, Boris W; Gibbs, John F; Javle, Milind M; Yang, Gary Y

2010-03-15

To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema. Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p kidney dose were significantly associated with development of Grade > or =2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). We observed correlation between pre-RT CrCl, V(10), and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications. Published by Elsevier Inc.

Diffusion barrier coatings for high temperature corrosion resistance of advanced carbon/carbon composites

International Nuclear Information System (INIS)

Singh Raman, K.S.

2000-01-01

Carbon possesses an excellent combination of mechanical and thermal properties, viz., excellent creep resistance at temperatures up to 2400 deg C in non-oxidizing environment and a low thermal expansion coefficient. These properties make carbon a potential material for very high temperature applications. However, the use of carbon materials at high temperatures is considerably restricted due to their extremely poor oxidation resistance at temperatures above 400 deg C. The obvious choice for improving high temperature oxidation resistance of such materials is a suitable diffusion barrier coating. This paper presents an overview of recent developments in advanced diffusion- and thermal-barrier coatings for ceramic composites, with particular reference to C/C composites. The paper discusses the development of multiphase and multi-component ceramic coatings, and recent investigations on the oxidation resistance of the coated C/C composites. The paper also discusses the cases of innovative engineering solutions for traditional problems with the ceramic coatings, and the scope of intelligent processing in developing coatings for the C/C composites. Copyright (2000) AD-TECH - International Foundation for the Advancement of Technology Ltd

Resistance of Advanced Soybean Lines to Pod Borrer (Etiella zinckenella

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Heru Kuswantoro

2017-07-01

Full Text Available The increasing and stabilizing of soybean product in Indonesia face many limitations. One of the limiting factors is pod borrer (Etiella zinckenella Treitschke infestation that is able to cause yield loss up to 80%. Objective of the research was to find out some advanced soybean lines that resistant to pod borrer. Design was randomized complete block with three replications. Soybean lines were grown gradualy to ensure the simultanously flowering. The plants were caged at 35 days after planting (DAT and infested with the imago of E. zinckenella at 56 DAT. Results showed that different soybean lines affected imago population, eggs population, larvae population, infected pods and infected seeds. Some genotypes were consistantly resistant to E. zinckenella. The resistance of those genotypes were non preference resistance based on eggs population, larvae population, infected pod and infected seeds. This study discovered nine soybean lines that is resistant to E. zinckenella, so that it can be beneficial for improving soybean resistance to this pest through releasing as a new resistant pod borer variety after tested further in potential yield and genetic x environment interaction trials. In addition, there were three varieties and two germplasm accessions that can be used as gene sources for improving the resistance of the varieties. The three varieties are able to be cultivated directly in field to decrease the E. zinckenella occurrence. 

29-34 Yellow Rust Resistance in Advanced Lines and Commercial ...

African Journals Online (AJOL)

rust pathogen. The objective of this study was to characterize seedling yellow rust resistance in 21 advanced bread wheat lines and 20 cultivars from Ethiopia. Yellow rust infection types (ITs) produced on test wheat lines and cultivars from nine yellow rust races were compared with ITs produced on standard differential lines ...

Advanced fire-resistant forms of activated carbon and methods of adsorbing and separating gases using same

Science.gov (United States)

Xiong, Yongliang; Wang, Yifeng

2015-02-03

Advanced, fire-resistant activated carbon compositions useful in adsorbing gases; and having vastly improved fire resistance are provided, and methods for synthesizing the compositions are also provided. The advanced compositions have high gas adsorption capacities and rapid adsorption kinetics (comparable to commercially-available activated carbon), without having any intrinsic fire hazard. They also have superior performance to Mordenites in both adsorption capacities and kinetics. In addition, the advanced compositions do not pose the fibrous inhalation hazard that exists with use of Mordenites. The fire-resistant compositions combine activated carbon mixed with one or more hydrated and/or carbonate-containing minerals that release H.sub.2O and/or CO.sub.2 when heated. This effect raises the spontaneous ignition temperature to over 500.degree. C. in most examples, and over 800.degree. C. in some examples. Also provided are methods for removing and/or separating target gases, such as Krypton or Argon, from a gas stream by using such advanced activated carbons.

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

International Nuclear Information System (INIS)

Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

2009-01-01

Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

Multidisciplinary Service Utilization Pattern by Advanced Head and Neck Cancer Patients: A Single Institution Study

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Jacqueline C. Junn

2012-01-01

Full Text Available Purpose. To analyze the patterns and associations of adjunctive service visits by head and neck cancer patients receiving primary, concurrent chemoradiation therapy. Methods. Retrospective chart review of patients receiving adjunctive support during a uniform chemoradiation regimen for stages III-IV head and neck squamous cell carcinoma. Univariate and multivariate models for each outcome were obtained from simple and multivariate linear regression analyses. Results. Fifty-two consecutive patients were assessed. Female gender, single marital status, and nonprivate insurance were factors associated with an increased number of social work visits. In a multivariate analysis, female gender and marital status were related to increased social work services. Female gender and stage IV disease were significant for increased nursing visits. In a multivariate analysis for nursing visits, living greater than 20 miles between home and hospital was a negative predictive factor. Conclusion. Treatment of advanced stage head and neck cancer with concurrent chemoradiation warrants a multidisciplinary approach. Female gender, single marital status, and stage IV disease were correlated with increased utilization of social work and nursing services. Distance over 20 miles from the center was a negative factor. This information may help guide the treatment team to allocate resources for the comprehensive care of patients.

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

International Nuclear Information System (INIS)

Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

2013-01-01

The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

Relationship between XRCC1 polymorphism and acute complication of chemoradiation therapy in the patients with colorectal cancer

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Kim, Woo Chul; Choi, Sun Keun [Inha University College of Medicine, Incheon (Korea, Republic of); Hong, Yun Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

2006-03-15

It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of 30.6 {approx} 59.4 Gy (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorphisms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorphisms also affected the decrease of the WBC and platelet count during radiation therapy. Although the present sample size was too small

Relationship between XRCC1 polymorphism and acute complication of chemoradiation therapy in the patients with colorectal cancer

International Nuclear Information System (INIS)

Kim, Woo Chul; Choi, Sun Keun; Hong, Yun Chul

2006-01-01

It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of 30.6 ∼ 59.4 Gy (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorphisms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorphisms also affected the decrease of the WBC and platelet count during radiation therapy. Although the present sample size was too small for

The impact of meticillin-resistant Staphylococcus aureus on patients with advanced cancer and their family members: A qualitative study.

Science.gov (United States)

Gleeson, Aoife; Larkin, Philip; O'Sullivan, Niamh

2016-04-01

Little is known about the impact of meticillin-resistant Staphylococcus aureus on patients with advanced cancer, such as its impact on the quality of life of this vulnerable group. To date, research on meticillin-resistant Staphylococcus aureus in the palliative care setting has had a quantitative focus. The purpose of this study was to explore the impact of a meticillin-resistant Staphylococcus aureus diagnosis on patients and their carers. This article reports upon a qualitative interview study of nine patients with advanced cancer and meticillin-resistant Staphylococcus aureus and nine family members (n = 18). Framework analysis was used to analyse the data. Patients and family members of patients with advanced cancer either admitted to the specialist palliative care unit or receiving palliative care in the hospital setting, who had a laboratory confirmed diagnosis of meticillin-resistant Staphylococcus aureus colonisation, were considered for inclusion in the study. Four themes were identified using framework analysis: reactions to receiving a meticillin-resistant Staphylococcus aureus diagnosis, the need for effective communication of the meticillin-resistant Staphylococcus aureus diagnosis, the enigmatic nature of meticillin-resistant Staphylococcus aureus, and lessons to guide the future care of meticillin-resistant Staphylococcus aureus patients. This article indicates that meticillin-resistant Staphylococcus aureus can have a significant impact on advanced cancer patients and their families. This impact may be underestimated, but early and careful face-to-face explanation about meticillin-resistant Staphylococcus aureus and its implications can help patients and their families to cope better with it. These findings should be considered when developing policy relating to meticillin-resistant Staphylococcus aureus management and infection control in specialist palliative care settings. © The Author(s) 2015.

Concurrent chemoradiation for oesophageal cancer: factor influencing myelotoxicity

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MacKean, J.; Denham, J.W. [Newcastle Mater Misericordiae Hospital, NSW (Australia). Radiation Oncology Department; Burmeister, B.H. [Queensland Radium Inst., Herston, QLD (Australia); Lamb, D.S. [Wellington Hospital, Wellington (New Zealand). Wellington Regional Oncology Unit

1996-11-01

Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer can cause life-threatening myelosuppression. This non-randomized study examines 95 patients from three Australasian centres treated on the TransTasman Radiation Oncology `definitive` chemoradiation study. Duration of fluorouracil infusion and patient age were independently predictive of myelotoxicity after the first cycle of CT/RT. Overall rates of grade 111 and IV neutropaenic were 23% and of thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic septic episodes followed the first cycle and six the second. All five patients recovered after the first cycle but there were four treatment-related deaths occurring after the second cycle of CT/RT. Recommendations are made concerning initial dosing, dose reductions and delays to minimize adverse patient outcomes from myelosuppression. 8 refs., 4 tabs., 3 figs.

The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer.

Science.gov (United States)

Soekmadji, Carolina; Nelson, Colleen C

2015-01-01

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

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Trog, D.; Bank, P.; Wendt, T.G. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Radiation Oncology; Koscielny, S.; Beleites, E. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Ear Nose Throat Diseases

1999-09-01

Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p<0.05) except 60 Gy and over (p>0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [German] Hintergrund: Bei Patienten mit lokoregionaer fortgeschrittenen Karzinomen im Kopf-Hals-Bereich fuehrt die alleinige konventionell fraktionierte Radiotherapie zu unuenstigen lokoregionaeren Tumorkontrollraten und Ueberlebensraten. Die Therapieintensivierung durch simultane Radiochemotherapie fuehrt zu gesteigerter Akutmorbiditaet. Die chemische

Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

International Nuclear Information System (INIS)

Zuur, Charlotte L.; Simis, Yvonne J.W.; Verkaik, Roxanna S.; Schornagel, Jan H.; Balm, Alfons J.M.; Dreschler, Wouter A.; Rasch, Coen R.N.

2008-01-01

Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m 2 , daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

Anorectal Function and Quality of Life in Patients With Early Stage Rectal Cancer Treated With Chemoradiation and Local Excision.

Science.gov (United States)

Lynn, Patricio B; Renfro, Lindsay A; Carrero, Xiomara W; Shi, Qian; Strombom, Paul L; Chow, Oliver; Garcia-Aguilar, Julio

2017-05-01

Little is known about anorectal function and quality of life after chemoradiation followed by local excision, which is an alternative to total mesorectal excision for selected patients with early rectal cancer. The purpose of this study was to prospectively assess anorectal function and health-related quality of life of patients with T2N0 rectal cancer who were treated with an alternative approach. This was a prospective, phase II trial. The study was multicentric (American College of Surgeons Oncology Group trial Z6041). Patients with stage cT2N0 rectal adenocarcinomas were treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by local excision. Anorectal function and quality of life were assessed at enrollment and 1 year postoperatively with the Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment of Cancer Therapy-Colorectal Questionnaire. Results were compared, and multivariable analysis was performed to identify predictors of outcome. Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year. Compared with baseline, no significant differences were found on Fecal Incontinence Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were significantly worse in the lifestyle (p Cancer Therapy overall score, but the physical well-being subscale was significantly worse and emotional well-being was improved after surgery. Treatment with the original chemoradiation regimen predicted worse depression/self-perception and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex was predictive of worse scores in the Functional Assessment of Cancer Therapy overall score and trial outcome index. Small sample size, relatively short follow-up, and absence of information before cancer diagnosis were study limitations. Chemoradiation followed by local excision had minimal impact on anorectal function 1 year after surgery. Overall quality of

Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

International Nuclear Information System (INIS)

Choi, Chel Hun; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Woo Young; Nam, Hee Rim; Kim, Byoung-Gie; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo

2007-01-01

Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m 2 (Day 1) and 5-fluorouracil 1000 mg/m 2 (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile

Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

2002-01-01

Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

Science.gov (United States)

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

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Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Massachusetts General Hospital, Boston, Massachusetts (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Garofalo, Michael C. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Bendell, Johanna [Sarah Cannon Research Institute, Nashville, Tennessee (United States); Berger, Adam C. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Oldenburg, Nicklas B.E. [North Main Radiation Oncology, Providence, Rhode Island (United States); Anne, Pramila Rani [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Perera, Francisco [London Regional Cancer Program/Western Ontario, London, Ontario (Canada); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Jabbour, Salma K. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Nowlan, Adam [Piedmont Hospital, Atlanta, Georgia (United States); DeNittis, Albert [Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania (United States); Crane, Christopher [University of Texas-MD Anderson Cancer Center, Houston, Texas (United States)

2015-09-01

Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

Optimal time interval between capecitabine intake and radiotherapy in preoperative chemoradiation for locally advanced rectal cancer

International Nuclear Information System (INIS)

Yu, Chang Sik; Kim, Tae Won; Kim, Jong Hoon; Choi, Won Sik; Kim, Hee Cheol; Chang, Heung Moon; Ryu, Min Hee; Jang, Se Jin; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Choi, Eun Kyung; Kim, Jin Cheon

2007-01-01

Purpose: Capecitabine and its metabolites reach peak plasma concentrations 1 to 2 hours after a single oral administration, and concentrations rapidly decrease thereafter. We performed a retrospective analysis to find the optimal time interval between capecitabine administration and radiotherapy for rectal cancer. Methods and Materials: The time interval between capecitabine intake and radiotherapy was measured in patients who were treated with preoperative radiotherapy and concurrent capecitabine for rectal cancer. Patients were classified into the following groups. Group A1 included patients who took capecitabine 1 hour before radiotherapy, and Group B1 included all other patients. Group B1 was then subdivided into Group A2 (patients who took capecitabine 2 hours before radiotherapy) and Group B2. Group B2 was further divided into Group A3 and Group B3 with the same method. Total mesorectal excision was performed 6 weeks after completion of chemoradiation and the pathologic response was evaluated. Results: A total of 200 patients were enrolled in this study. Pathologic examination showed that Group A1 had higher rates of complete regression of primary tumors in the rectum (23.5% vs. 9.6%, p = 0.01), good response (44.7% vs. 25.2%, p = 0.006), and lower T stages (p = 0.021) compared with Group B1; however, Groups A2 and A3 did not show any improvement compared with Groups B2 and B3. Multivariate analysis showed that increases in primary tumors in the rectum and good response were only significant when capecitabine was administered 1 hour before radiotherapy. Conclusion: In preoperative chemoradiotherapy for rectal cancer, the pathologic response could be improved by administering capecitabine 1 hour before radiotherapy

Locally advanced unresectable pancreatic cancer: Induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone: Definitive results of the 2000-2001 FFCD/SFRO phase III trial; Cancer du pancreas localement evolue non resecable: chimioradiotherapie d'induction suivie de chimiotherapie par gemcitabine contre chimiotherapie exclusive par gemcitabine: resultats definitifs de l'etude de phase III 2000-2001de la FFCD et de la SFRO

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Barhoumi, M.; Mornex, F. [EA 3738, departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, 165, chemin du Grand-Revoyet, 69310 Pierre-Benite (France); Bonnetain, F. [EA 4184, unite de biostatistiques et d' epidemiologie, centre Georges-Francois-Leclerc, 21034 Dijon cedex (France); Inserm UMR 866, faculte de medecine, 21078 Dijon cedex (France); Universite de Bourgogne, BP 27877, 21078 Dijon cedex (France); Rougier, P. [Service d' hepato-gastro-enterologie oncologie digestive, centre hospitalier Ambroise-Pare, 9, avenue Charles-de-Gaulle, 92100 Boulogne-Billancourt (France); Mariette, C. [Service de chirurgie digestive et generale, rez-de-jardin-aile-ouest, hopital Claude-Huriez, 59037 Lille cedex (France); Bouche, O. [CHU, 51092 Reims cedex (France); Bosset, J.F. [Service de radiotherapie, CHU de Besancon, 25030 Besancon cedex (France); Aparicio, T. [Service de gastroenterologie, hopital Avicenne, AP-HP, 93000 Bobigny (France); Mineur, L. [Service de radiotherapie oncologie digestive, institut Sainte-Catherine, 84082 Avignon cedex 2 (France); Azzedine, A. [Centre hospitalier Henri-Duffaut, 84902 Avignon (France); Hammel, P. [Service de gastroenterologie pancreatologie, hopital Beaujon, 92110 Clichy (France); Butel, J. [Hopital d' Abbeville, 80142 Abbeville (France); Stremsdoerfer, N. [Service d' hepatogastroenterologie, centre hospitalier Pierre-Oudot, 38317 Bourgoin-Jallieu (France); Maingon, P. [Departement de radiotherapie, centre Georges-Francois-Leclerc, 21079 Dijon cedex (France); Bedenne, L. [Inserm UMR 866, faculte de medecine, 21078 Dijon cedex (France); Universite de Bourgogne, 21078 Dijon cedex (France); Service d' hepatogastroenterologie, CHU Le-Bocage, 21034 Dijon cedex (France); Chauffert, B. [Inserm UMR 866, faculte de medecine, 21078 Dijon cedex (France); Universite de Bourgogne, 21078 Dijon cedex (France); Departement d' oncologie medicale, centre Georges-Francois-Leclerc, 21079 Dijon cedex (France)

2011-06-15

Purpose. - To compare chemo-radiation with systemic chemotherapy to chemotherapy alone in locally advanced pancreatic cancer. Patients and methods. - One hundred and nineteen patients with locally advanced pancreatic cancer, with World Health Organization performance status of zero to two were randomly assigned to either the induction chemo-radiation group (60 Gy, 2 Gy/fraction; concomitant 5-fluoro-uracil infusion, 300 mg/m{sup 2} per day, days 1-5 for 6 weeks; cisplatin, 20 mg/m{sup 2} per day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m{sup 2} weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m{sup 2} weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. Results. - Overall survival was shorter in the chemo-radiation than in the gemcitabine arm (median survival 8.6 [99% confidence interval 7.1-11.4] and 13 months [8,9,9-18], p = 0.03). One-year survival was, respectively, 32 and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the chemo-radiation arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). Conclusion. - This intensive induction schedule of chemo-radiation was more toxic and less effective than gemcitabine alone. (authors)

Screening of ten advanced chickpea lines for blight and wilt resistance

International Nuclear Information System (INIS)

Jamil, F.F.; Haq, I.; Sarwar, N.; Alam, S.S.; Khan, J.A.; Hanif, M.; Khan, I.A.; Sarwar, M.; Haq, M.A.

2002-01-01

Ten advanced chickpea lines developed at NIAB were screened for resistance to Ascochyta blight and Fusarium wilt diseases in different sets of experiments conducted under controlled environment. Inoculation of plants by spore suspension of virulent strains of Ascochyta rabiei revealed that one line (97313) was resistant tolerant, two lines (97305, 97392) were tolerant, six lines (97306, 97310, 97311, 97303, 97302, 97393) were tolerant/susceptible and one line (97301) was susceptible. Screening of the same lines against Fusarium wilt by water culture method showed that two lines (97301, 97313) were moderately resistant, four lines (97302, 97303, 97306, 97393) were tolerant and the remaining four lines were susceptible. Screening through phytotoxic culture filtrates revealed that two lines (97302, 97313) were less sensitive to culture filtrates of Ascochyta rabiei and Fusarium oxysporum than the resistant check (CM88). These lines were also analyzed spectrophotometrically for peroxidase enzyme activity. Maximum enzyme activity was detected after 48 hours of inoculation with A. rabiei in three lines (97305, 97311, 97313) and resistant check (CM88) while enzyme activity in the remaining lines reached its maximum after 72 hours of inoculation which was comparable to the susceptible check (Pb-1). These studies lead to the conclusion that one line (97313) exhibited resistance against both the diseases and can be used as a source of resistance for further improvement of chickpea germplasm. (author)

Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

Directory of Open Access Journals (Sweden)

Sayan Paul

2014-01-01

Full Text Available Aims: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9 enzyme with head and neck squamous cell carcinoma (HNSCC and response in patients receiving cisplatin-based radical chemoradiation (CT-RT. Materials and Methods: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs by polymerase chain reaction (PCR-based restriction fragment length polymorphism (RFLP. Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO criteria. Results and Analysis: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.8% and CYP2C9FNx013 (25% were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (n = 436 carrying variant alleles of CYP2C9FNx012 (69.6% or CYP2C9FNx013 (65.2% were found to respond poorly to cisplatin-based radical CT-RT. Conclusion: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.

Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

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Pang, Qingsong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Wei, Qingyi [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Yuan, Xianglin [Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan (China); Lopez Guerra, Jose Luis [Department of Medicine, Universitat Autònoma de Barcelona (Spain); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Zhuang, Yan [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Wang, Li-E. [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States)

2013-04-01

Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

Science.gov (United States)

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

International Nuclear Information System (INIS)

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-01-01

Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment

Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency

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Cook, B. A.; Harringa, J. L.; Russel, A. M.

2012-12-01

This report summarizes the work performed by an Ames-led project team under a 4-year DOE-ITP sponsored project titled, 'Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency.' The Report serves as the project deliverable for the CPS agreement number 15015. The purpose of this project was to develop and commercialize a family of lightweight, bulk composite materials that are highly resistant to degradation by erosive and abrasive wear. These materials, based on AlMgB{sub 14}, are projected to save over 30 TBtu of energy per year when fully implemented in industrial applications, with the associated environmental benefits of eliminating the burning of 1.5 M tons/yr of coal and averting the release of 4.2 M tons/yr of CO{sub 2} into the air. This program targeted applications in the mining, drilling, machining, and dry erosion applications as key platforms for initial commercialization, which includes some of the most severe wear conditions in industry. Production-scale manufacturing of this technology has begun through a start-up company, NewTech Ceramics (NTC). This project included providing technical support to NTC in order to facilitate cost-effective mass production of the wear-resistant boride components. Resolution of issues related to processing scale-up, reduction in energy intensity during processing, and improving the quality and performance of the composites, without adding to the cost of processing were among the primary technical focus areas of this program. Compositional refinements were also investigated in order to achieve the maximum wear resistance. In addition, synthesis of large-scale, single-phase AlMgB{sub 14} powder was conducted for use as PVD sputtering targets for nanocoating applications.

Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of advanced squamous cell carcinoma of the head and neck. A phase II trial

International Nuclear Information System (INIS)

Merlano, Marco; Russi, Elvio G.; Numico, Gianmauro; Colantonio, Ida; Garrone, Ornella; Pelissero, Antonio; Granetto, Cristina; Gasco, Milena; Di Costanzo, Gianna; Heouaine, Abdelhamid; Vigna Taglianti, Riccardo; Cipolat, Marco

2005-01-01

Aim of the present study was to test, activity and toxicity of a rapidly alternating chemoradiation (paclitaxel based) in 31 patients with unresectable, locally advanced or recurrent after surgery, head and neck cancer. Three-year overall survival and progression-free survival were 61.4 and 73.7%, respectively. Main side effects remain a major problem

TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)

International Nuclear Information System (INIS)

Leong, Trevor; Smithers, B Mark; Michael, Michael; Gebski, Val; Boussioutas, Alex; Miller, Danielle; Simes, John; Zalcberg, John; Haustermans, Karin; Lordick, Florian; Schuhmacher, Christoph; Swallow, Carol; Darling, Gail; Wong, Rebecca

2015-01-01

The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy. Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of

Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

International Nuclear Information System (INIS)

Takahashi, Hidenori; Ohigashi, Hiroaki; Goto, Kunihito; Marubashi, Shigeru; Yano, Masahiko; Ishikawa, Osamu

2013-01-01

During the period from 2002 to 2011, a total of 240 consecutive patients with resectable pancreatic cancer received preoperative chemoradiation therapy (CRT). Among 240 patients, 201 patients underwent the subsequent pancreatectomy (resection rate: 84%). The 5-year overall survival of resected cases was 56% and the median survival of 39 unresected cases was 11 months. The 5-year locoregional recurrence rate of resected cases was 15%. The 5-year overall survival of the entire cohort (n=240) was 47%. The preoperative CRT and subsequent pancreatectomy provided a favorable surgical result, which was contributed by several characteristics of preoperative CRT: the prominent locoregional treatment effect with lower incidence of locoregional recurrence, and the discrimination between patients who are likely to benefit from subsequent surgery and those who are not. (author)

The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer

International Nuclear Information System (INIS)

Mak, Daisy; Joon, Daryl Lim; Chao, Michael; Wada, Morikatsu; Joon, Michael Lim; See, Andrew; Feigen, Malcolm; Jenkins, Patricia; Mercuri, Angelina; McNamara, Joanne; Poon, Aurora; Khoo, Vincent

2010-01-01

Purpose: To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. Methods and materials: Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed. Results: Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease. Conclusions: PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.

Investigation of Hafnium oxide/Copper resistive memory for advanced encryption applications

Science.gov (United States)

Briggs, Benjamin D.

The Advanced Encryption Standard (AES) is a widely used encryption algorithm to protect data and communications in today's digital age. Modern AES CMOS implementations require large amounts of dedicated logic and must be tuned for either performance or power consumption. A high throughput, low power, and low die area AES implementation is required in the growing mobile sector. An emerging non-volatile memory device known as resistive memory (ReRAM) is a simple metal-insulator-metal capacitor device structure with the ability to switch between two stable resistance states. Currently, ReRAM is targeted as a non-volatile memory replacement technology to eventually replace flash. Its advantages over flash include ease of fabrication, speed, and lower power consumption. In addition to memory, ReRAM can also be used in advanced logic implementations given its purely resistive behavior. The combination of a new non-volatile memory element ReRAM along with high performance, low power CMOS opens new avenues for logic implementations. This dissertation will cover the design and process implementation of a ReRAM-CMOS hybrid circuit, built using IBM's 10LPe process, for the improvement of hardware AES implementations. Further the device characteristics of ReRAM, specifically the HfO2/Cu memory system, and mechanisms for operation are not fully correlated. Of particular interest to this work is the role of material properties such as the stoichiometry, crystallinity, and doping of the HfO2 layer and their effect on the switching characteristics of resistive memory. Material properties were varied by a combination of atomic layer deposition and reactive sputtering of the HfO2 layer. Several studies will be discussed on how the above mentioned material properties influence switching parameters, and change the underlying physics of device operation.

Superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Evaluation of preservation of organ function

International Nuclear Information System (INIS)

Akisada, Takeshi; Harada, Tamotsu; Imai, Shigeki; Gyoten, Masayuki; Hiraoka, Takashi

2008-01-01

The objective of this study was to evaluate preservation of organ function in the treatment of superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Among 96 patients receiving concomitant radiation and intra-arterial docetaxel, systemic cisplatin and 5-fluorouracil (FU) chemotherapy, we identified laryngeal preservation rate, studied tracheostomy cases and gastrostomy cases, and evaluated videofluoroscopic examination and videoendoscopy. Laryngeal preservation rate of hypopharyngeal cancer is very high at 96.2%, and that of laryngeal cancer is high at 71.4%. Videofluoroscopic examination revealed improved swallowing function in 2 of 12, no change in 3, slightly worse in 5, and worse in 2 patients. Following treatment, the incidence of aspiration increased to 4 patients. Videoendoscopy revealed residual vallecula in a few cases. Only 7 patients (7.3%) required a tracheostomy and 4 patients (4.2%) required a gastrostomy. Most of the patients are able to swallow after chemoradiation. Our new chemoradiation protocol is as good as other treatment modalities for maintaining organ preservation and function. (author)

Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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Warner, Andrew [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Dahele, Max [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Hu, Bo; Palma, David A. [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology, MAASTRO Clinic, Maastricht (Netherlands); Tsujino, Kayoko [Department of Radiation Oncology, Hyogo Cancer Center, Akashi (Japan); Moreno-Jimenez, Marta [Department of Oncology, Clínica Universidad, Universidad de Navarra, Pamplona (Spain); Kim, Tae Hyun [Department of Radiation Oncology, National Cancer Center, Goyang-si, Gyeonggi (Korea, Republic of); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina (United States); Rengan, Ramesh [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); De Petris, Luigi [Department of Oncology and Pathology, Karolinska University Hospital, Stockholm (Sweden); Ramella, Sara [Department of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); De Dios, Núria Rodriguez [Department of Radiation Oncology, Hospital de la Esperanza, Parc de Salut Mar, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Rodrigues, George, E-mail: George.Rodrigues@lhsc.on.ca [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada)

2016-03-01

Purpose: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Methods and Materials: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. Results: Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm{sup 3}: 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV{sub 1}], defined as the ratio of FEV{sub 1} to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm{sup 3} or GTV ≥100 cm{sup 3} and FEV{sub 1} ≥80%) and high-risk (GTV ≥100 cm{sup 3} and FEV{sub 1} <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV{sub 1}, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R{sup 2} = 0

Practice insights on patient care-management overview for chemoradiation toxic mucositis-guidelines, guideline-supported therapies and high potency polymerized cross-linked sucralfate (ProThelial).

Science.gov (United States)

McCullough, Ricky W

2018-01-01

Aim To offer a practice insight for the management of chemoradiation toxic mucositis. Method Review chemoradiation toxic mucositis, its pathobiology and breadth of symptom presentation. Review mucositis guidelines and guideline-supported anti-mucositis therapies. Offer guidance on guidelines and an abbreviated review of high potency cross-linked sucralfate for management of chemoradiation toxic mucositis. Result There are six major mucositis guidelines but only one that is current and regularly updated. Guidelines from the Multinational Association Supportive Cancer Care suggest 14 interventions gleaned from controlled trials, 12 of which are off-label uses of therapies that offer statistically significant but incrementally beneficial outcomes. Several evidence-based limitations of guidelines are discussed. Data on high potency polymerized cross-linked sucralfate confirming complete prevention and rapid (2-3 days) elimination, sustained throughout cancer treatment is verified as high quality evidence in accordance to standards adopted by Agency for Healthcare Research and Quality. A 96-97% reduction in mucositis duration qualifies as a positive Glasziou treatment effect, which is discussed as an additional measure of evidence-based medicine. Conclusion Statistically significant but fractional treatment effects of guideline-supported interventions are not likely to substantially alter the course of mucositis when it occurs nor completely prevent its onset. Complete prevention and rapid sustained elimination should be the goal, therefore high potency polymerized cross-linked sucralfate may be useful. Where guidelines fail, institution-based protocols led by oncology pharmacists could succeed. In an effort to eliminate toxic mucositis, enhance compliance to chemoradiation regimens, and improve survival, such protocols for practice may verify pharmacoeconomic benefits, if any, in using high potency polymerized cross-linked sucralfate to manage toxic mucositis.

Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

Science.gov (United States)

Werner, C. R.; Humphreys, B. T.; Mulugeta, L.

2014-01-01

The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

Advanced Corrosion-Resistant Zr Alloys for High Burnup and Generation IV Application

International Nuclear Information System (INIS)

Jeong, Y. H.; Park, S. Y.; Lee, M. H.; Choi, B. K.; Baek, J. H.; Park, J. Y.; Kim, J. H.; Kim, H. G.; Jung, Y. H.; Bang, B. G.

2006-08-01

The systematic study was performed to develop the advanced corrosion-resistant Zr alloys for high burnup and Gen IV application. The corrosion behavior was significantly changed with the alloy composition and the corrosion environment. In general, the model alloys with a higher alloying elements showed a higher corrosion resistance. Among the model alloys tested in this study, Zr-10Cr-0.2Fe showed the best corrosion resistance regardless of the corrosion condition. The oxide on the higher corrosion-resistant alloy such as Zr-1.0Cr-0.2Fe consisted of mainly columnar grains, and it have a higher tetragonal phase stability. In comparison with other alloys being considered for the SCWR, the Zr alloys showed a lower corrosion rate than ferritic-martensitic steels. The results of this study imply that, at least from a corrosion standpoint, Zr alloys deserve consideration as potential cladding or structural materials in supercritical water cooled reactors

Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

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Kim, Kyubo [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu, E-mail: ekchie93@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University (Korea, Republic of)

2012-09-01

Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size {>=}2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.

Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Wang, Chia-Chun; Cheng, Jason Chia-Hsien; Tsai, Chiao-Ling; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Hsieh, Min-Shu; Chang, Yih-Leong; Hsu, Feng-Ming

2015-01-01

Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

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Kumar Smriti

2011-09-01

Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

Cervical cancer stem cells and correlation with radiation response in locally advanced cervical cancer

International Nuclear Information System (INIS)

Chopra, Supriya; Goda, Jayant Sastri; Deodhar, Kedar

2016-01-01

While tumour-initiating cells (TIC) have been reported across solid tumours, there is dearth of data regarding TICs and radiation response in cervical cancer. From October, 2013- July, 2015 patients with locally advanced cervical cancer were included. Pretreatment biopsy was obtained. IHC was performed for SOX-2,OCT-4, Nanog (ESC), CD44 and Podoplanin (TIC). Semiquantitative scoring was used for IHC. All patients received uniform concurrent chemoradiation and brachytherapy. On follow up, local control and distant relapse was recorded

Enteral Feeding Tubes in Patients Undergoing Definitive Chemoradiation Therapy for Head-and-Neck Cancer: A Critical Review

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Koyfman, Shlomo A., E-mail: koyfmas@ccf.org [Departments of Radiation and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Adelstein, David J. [Departments of Radiation and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

2012-11-01

Definitive chemoradiation therapy has evolved as the preferred organ preservation strategy in the treatment of locally advanced head-and-neck cancer (LA-HNC). Dry mouth and dysphagia are among the most common and most debilitating treatment-related toxicities that frequently necessitate the placement of enteral feeding tubes (FT) in these patients to help them meet their nutritional requirements. The use of either a percutaneous endoscopic gastrostomy tube or a nasogastric tube, the choice of using a prophylactic vs a reactive approach, and the effects of FTs on weight loss, hospitalization, quality of life, and long-term functional outcomes are areas of continued controversy. Considerable variations in practice patterns exist in the United States and abroad. This critical review synthesizes the current data for the use of enteral FTs in this patient population and clarifies the relative advantages of different types of FTs and the timing of their use. Recent developments in the biologic understanding and treatment approaches for LA-HNC appear to be favorably impacting the frequency and severity of treatment-related dysphagia and may reduce the need for enteral tube feeding in the future.

Cost-effectiveness of response evaluation after chemoradiation in patients with advanced oropharyngeal cancer using 18F-FDG-PET-CT and/or diffusion-weighted MRI.

Science.gov (United States)

Greuter, Marjolein Je; Schouten, Charlotte S; Castelijns, Jonas A; de Graaf, Pim; Comans, Emile Fi; Hoekstra, Otto S; de Bree, Remco; Coupé, Veerle Mh

2017-04-11

Considerable variation exists in diagnostic tests used for local response evaluation after chemoradiation in patients with advanced oropharyngeal cancer. The yield of invasive examination under general anesthesia (EUA) with biopsies in all patients is low and it may induce substantial morbidity. We explored four response evaluation strategies to detect local residual disease in terms of diagnostic accuracy and cost-effectiveness. We built a decision-analytic model using trial data of forty-six patients and scientific literature. We estimated for four strategies the proportion of correct diagnoses, costs concerning diagnostic instruments and the proportion of unnecessary EUA indications. Besides a reference strategy, i.e. EUA for all patients, we considered three imaging strategies consisting of 18 FDG-PET-CT, diffusion-weighted MRI (DW-MRI), or both 18 FDG-PET-CT and DW-MRI followed by EUA after a positive test. The impact of uncertainty was assessed in sensitivity analyses. The EUA strategy led to 96% correct diagnoses. Expected costs were €468 per patient whereas 89% of EUA indications were unnecessary. The DW-MRI strategy was the least costly strategy, but also led to the lowest proportion of correct diagnoses, i.e. 93%. The PET-CT strategy and combined imaging strategy were dominated by the EUA strategy due to respectively a smaller or equal proportion of correct diagnoses, at higher costs. However, the combination of PET-CT and DW-MRI had the highest sensitivity. All imaging strategies considerably reduced (unnecessary) EUA indications and its associated burden compared to the EUA strategy. Because the combined PET-CT and DW-MRI strategy costs only an additional €927 per patient, it is preferred over immediate EUA since it reaches the same diagnostic accuracy in detecting local residual disease while leading to substantially less unnecessary EUA indications. However, if healthcare resources are limited, DW-MRI is the strategy of choice because of lower

Effect of radiation and combined chemoradiation therapy on cardiac activity in patients with esophagus cancer. [Combined effects of /sup 60/Co. gamma. rays and methylglyoxal-bis(guanylhydrazone) an antineoplastic drug

Energy Technology Data Exchange (ETDEWEB)

Neklyudova, V I; Shkhvatsabaya, L V; Ivanova, E M

1978-12-01

The results of a comparative study of the effect of radiation and combined chemoradiation therapy with methyl-GAG in 51 patients with cancer of the chest region of the esophagus indicate an adverse effect of these methods of treatment on cardiac activity. Against the background of chemoradiation therapy, these changes were more marked due perhaps to some cardiotoxic effect of methyl-GAG. However, the changes induced did not lead to considerable disorders of hemodynamics during treatment.

Organ Preservation With Concurrent Chemoradiation for Advanced Laryngeal Cancer: Are We Succeeding?

International Nuclear Information System (INIS)

Lambert, Louise; Fortin, Bernard; Soulieres, Denis; Guertin, Louis; Coulombe, Genevieve; Charpentier, Danielle; Tabet, Jean-Claude; Belair, Manon; Khaouam, Nader; Nguyen-Tan, Phuc Felix

2010-01-01

Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

Science.gov (United States)

Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Design and Performance Optimizations of Advanced Erosion-Resistant Low Conductivity Thermal Barrier Coatings for Rotorcraft Engines

Science.gov (United States)

Zhu, Dongming; Miller, Robert A.; Kuczmarski, Maria A.

2012-01-01

Thermal barrier coatings will be more aggressively designed to protect gas turbine engine hot-section components in order to meet future rotorcraft engine higher fuel efficiency and lower emission goals. For thermal barrier coatings designed for rotorcraft turbine airfoil applications, further improved erosion and impact resistance are crucial for engine performance and durability, because the rotorcraft are often operated in the most severe sand erosive environments. Advanced low thermal conductivity and erosion-resistant thermal barrier coatings are being developed, with the current emphasis being placed on thermal barrier coating toughness improvements using multicomponent alloying and processing optimization approaches. The performance of the advanced thermal barrier coatings has been evaluated in a high temperature erosion burner rig and a laser heat-flux rig to simulate engine erosion and thermal gradient environments. The results have shown that the coating composition and architecture optimizations can effectively improve the erosion and impact resistance of the coating systems, while maintaining low thermal conductivity and cyclic oxidation durability

Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

International Nuclear Information System (INIS)

Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

2016-01-01

Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

Structural Component Fabrication and Characterization of Advanced Radiation Resistant ODS Steel for Next Generation Nuclear Systems

International Nuclear Information System (INIS)

Noh, Sang Hoon; Kim, Young Chun; Jin, Hyun Ju; Choi, Byoung Kwon; Kang, Suk Hoon; Kim, Tae Kyu

2016-01-01

In a sodium-cooled fast reactor (SFR), the coolant outlet temperature and peak temperature of the fuel cladding tube will be about 545 .deg. C and 700 .deg. C with 250 dpa of a very high neutron dose rate. To realize this system, it is necessary to develop an advanced structural material having high creep and irradiation resistance at high temperatures. Austenitic stainless steel may be one of the candidates because of good strength and corrosion resistance at the high temperatures, however irradiation swelling severely occurred to 120dpa at high temperatures and this eventually leads to a decrease of the mechanical properties and dimensional stability. Advanced radiation resistant ODS steel (ARROS) has been newly developed for the in-core structural components in SFR, which has very attractive microstructures to achieve both superior creep and radiation resistances at high temperatures [4]. Nevertheless, the use of ARROS as a structural material essentially requires the fabrication technology development for component parts such as sheet, plate and tube. In this study, plates and tubes were tentatively fabricated with a newly developed alloy, ARROS. Microstructures as well as mechanical properties were also investigated to determine the optimized condition of the fabrication processes.

Determining the fracture resistance of advanced SiC fiber reinforced SiC matrix composites

International Nuclear Information System (INIS)

Nozawa, T.; Katoh, Y.; Kishimoto, H.

2007-01-01

Full text of publication follows: One of the perceived advantages for highly-crystalline and stoichiometric silicon carbide (SiC) and SiC composites, e.g., advanced SiC fiber reinforced chemically-vapor-infiltrated (CVI) SiC matrix composites, is the retention of fast fracture properties after neutron irradiation at high-temperatures (∼1000 deg. C) to intermediate-doses (∼15 dpa). Accordingly, it has been clarified that the maximum allowable stress (or strain) limit seems unaffected in certain irradiation conditions. Meanwhile, understanding the mechanism of crack propagation from flaws, as potential weakest link to cause composite failure, is somehow lacking, despite that determining the strength criterion based on the fracture mechanics will eventually become important considering the nature of composites' fracture. This study aims to evaluate crack propagation behaviors of advanced SiC/SiC and to provide fundamentals on fracture resistance of the composites to define the strength limit for the practical component design. For those purposes, the effects of irreversible energies related to interfacial de-bonding, fiber bridging, and microcrack forming on the fracture resistance were evaluated. Two-dimensional SiC/SiC composites were fabricated by CVI or nano-infiltration and transient-eutectic-phase (NITE ) methods. Hi-Nicalon TM Type-S or Tyranno TM -SA fibers were used as reinforcements. In-plane mode-I fracture resistance was evaluated by the single edge notched bend technique. The key finding is the continuous Load increase with the crack growth for any types of advanced composites, while many studies specified the gradual load decrease for the conventional composites once the crack initiates. This high quasi-ductility appeared due primarily to high friction (>100 MPa) at the fiber/matrix interface using rough SiC fibers. The preliminary analysis based on the linear elastic fracture mechanics, which does not consider the effects of irreversible energy

Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

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Higuchi, Katsuhiko, E-mail: k.higu@kitasato-u.ac.jp [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Komori, Shouko [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Tanabe, Satoshi [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Azuma, Mizutomo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Ishiyama, Hiromichi [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Sasaki, Tohru; Ishido, Kenji [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Natsuya [Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Hayakawa, Kazushige [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Koizumi, Wasaburo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan)

2014-07-15

Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Yoo EJ

2013-06-01

Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management

International Nuclear Information System (INIS)

Smith, J. Joshua; Chow, Oliver S.; Gollub, Marc J.; Nash, Garrett M.; Temple, Larissa K.; Weiser, Martin R.; Guillem, José G.; Paty, Philip B.; Avila, Karin; Garcia-Aguilar, Julio

2015-01-01

Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or—in patients treated with NOM—the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment

Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

Science.gov (United States)

Smith, J Joshua; Chow, Oliver S; Gollub, Marc J; Nash, Garrett M; Temple, Larissa K; Weiser, Martin R; Guillem, José G; Paty, Philip B; Avila, Karin; Garcia-Aguilar, Julio

2015-10-23

Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance

Concomitant pelvic irradiation and chemotherapy in locally advanced cervical carcinoma. A retrospective study of 92 patients treated at the Curie Institute

International Nuclear Information System (INIS)

Nguyen, D.; Rochefordiere, A. de la; Chauveinc, L.; Cosset, J.M.; Clough, K.B.; Mouret-Fourme, E.; Guyonnet, M.

2002-01-01

The prognosis of locally advanced cervix cancers is poor with metastatic and local recurrence risks. Recent publications reported that concurrent chemotherapy and pelvic radiation increased local control compared to radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We report 92 cases of patients with locally advanced cervix cancer treated between 1986 and 1998 at the Institut Curie. Patients and methods. - Concurrent chemo-radiation was exclusive in 51 cases and added to surgery in 41 cases. Chemotherapy with 5FU -Cisplatin-Mitomycin C-Vindesin (protocol A) was performed for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B). Results. -Median follow-up was 64 months (6-149 months). Five-year disease-free survival rate was 47% and local control rate was 70%. Disease-free survival was correlated with therapeutic response. After exclusive chemo-radiation, the good responsive patients had a better DFS (54% vs 26%, p=0.018). In the surgery group, those patients with sterilized lymph nodes and tumours had also a higher DFS (76% vs 47%, p=0.036). Toxicity was higher with protocol A. Conclusion. - From our study, it appears that local control of advanced cervix cancers is better with combined chemoradiotherapy but disease-free survival stays low according to the metastatic evolution. Metastasis without local recurrence remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with radiotherapy. (author)

Head and neck cancer. Usefulness of concurrent chemoradiation therapy with TPF

International Nuclear Information System (INIS)

Yoshida, Tomoyuki

2010-01-01

History of chemotherapy and radiotherapy for head and neck cancer (HNC) leading to the present regimen concurrent chemoradiation therapy (CCRT) with docetaxel, cisplatin, fluorouracil (5-FU), taxotere (docetaxel)+cisplatin+5-FU (TRF), is described together with authors' experience of its trials. History of the CCRT explains results of clinical trials of radio- and chemo-therapies conducted globally and in Japan with various regimens like neo-adjuvant, adjuvant, concurrent and alternating one. During the process, CCRT has been established as a standard therapy of nasopharyngeal cancer. Trials of CCRT further added with molecular targeting anticancer (cetuximab) are now in consideration and practice in HNC field. A phase I CCRT study conducted by authors with TPF at lower doses of the 3 agents than those reported abroad having resulted in outcomes with satisfactory tolerance, based on which phase II trials with 2 Gy/day for 5 days/week (total, 60 Gy) have been performed. The therapy is to be once discontinued for 2 weeks when the cumulative dose attains 40 Gy. Currently available results in 48 HNC patients (44 males, 4 females, middle-/hypo-pharynx and larynx cancers, age 48-72 y, stage III-N2b or more advanced) within 8-60 (mean 45.1) mo follow-up are: chemotherapy completion in 87.5%, total dose 60-70 Gy in all patients; adverse events grade 3-4, 14.9-54.2% (hematological), 50.0% (mucositis), 18.8% (nausea), and 6.3% (liver function); response rate of 87.5% including 77.1% complete response (CR); and 57 mo-survival and progression-free survival rates of 75.9 and 57.8%, respectively. The results suggest usefulness of CCRT with TPF for the disease. Similar clinical trials are now in progress globally. (T.T.)

Advanced Corrosion-Resistant Zr Alloys for High Burnup and Generation IV Applications

International Nuclear Information System (INIS)

Arthur Motta; Yong Hwan Jeong; R.J. Comstock; G.S. Was; Y.S. Kim

2006-01-01

The objective of this collaboration between four institutions in the US and Korea is to demonstrate a technical basis for the improvement of the corrosion resistance of zirconium-based alloys in more extreme operating environments (such as those present in severe fuel duty, cycles high burnup, boiling, aggressive chemistry) and to investigate the feasibility (from the point of view of corrosion rate) of using advanced zirconium-based alloys in a supercritical water environment

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

Science.gov (United States)

Barney, Christian L; Walston, Steve; Zamora, Pedro; Healy, Erin H; Nolan, Nicole; Diavolitsis, Virginia M; Neki, Anterpreet; Rupert, Robert; Savvides, Panos; Agrawal, Amit; Old, Matthew; Ozer, Enver; Carrau, Ricardo; Kang, Stephen; Rocco, James; Teknos, Theodoros; Grecula, John C; Wobb, Jessica; Mitchell, Darrion; Blakaj, Dukagjin; Bhatt, Aashish D

2018-04-01

Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome

International Nuclear Information System (INIS)

Lee, Ching-Chih; Huang, Tze-Ta; Lee, Moon-Sing; Hsiao, Shih-Hsuan; Lin, Hon-Yi; Su, Yu-Chieh; Hsu, Feng-Chun; Hung, Shih-Kai

2010-01-01

Current staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC. A retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome. GTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (≧13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn ≧ 13 ml, overall survival was better after ≧4 cycles of chemotherapy than after less than 4 cycles. The incorporation of GTVprn can provide more information to adjust treatment strategy

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

Energy Technology Data Exchange (ETDEWEB)

Chen, X; Song, Y; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other daily CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.

Postoperative versus definitive chemoradiation in early-stage anal cancer. Results of a matched-pair analysis

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Berger, B.; Menzel, M.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Breucha, G. [Kreiskrankenhaus Hechingen, Tuebingen Univ. (Germany). Dept. of Surgery

2012-07-15

Background and purpose: The goal of the present study was to comparatively assess the results of definitive chemoradiation (CRT) with or without previous macroscopically complete resection in patients with early-stage node-negative (T1-2 N0) anal carcinoma. Patients and methods: A total of 20 patients with T1-2 N0 anal carcinoma who received radiotherapy (RT) with or without chemotherapy following incidental R0/1 tumor resection (S/CRT group) were selected. These were matched to 20 comparable patients who underwent definitive chemoradiation without previous surgery (CRT group). Major objectives of this analysis were treatment outcomes in terms of locoregional tumor control (LRC), overall survival (OS), colostomy-free survival, and toxicity. Results: Patients treated postoperatively received significantly lower RT doses (median 54.0 Gy vs. 59.7 Gy; p < 0.001) and less frequently concomitant chemotherapy than those treated definitely. The 5-year LRC and 5-year OS rates were 97.5% and 90.0%, respectively, without significant differences between the S/CRT and the CRT groups. The distribution of acute and late toxicities was comparable, and the 5-year colostomy-free survival was 95% in both groups. Conclusion: This matched-pair comparison of incidental R0/1 resection plus dose-reduced CRT with standard definitive CRT of early-stage anal cancer shows similar treatment results. Thus, dose-reduced RT with or without chemotherapy may be considered in R0/1 resected patients with T1-2 N0 anal carcinoma. (orig.)

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial.

Science.gov (United States)

Hegde, John V; Shaverdian, Narek; Felix, Carol; Wang, Pin-Chieh; Veruttipong, Darlene; Hsu, Sophia; Riess, Jonathan W; Rao, Shyam D; Daly, Megan E; Chen, Allen M

2018-03-01

To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer. Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m 2 , and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m 2 , every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale. Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m 2 ) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m 2 vs 22.3 kg/m 2 ; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up. De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC

DEFF Research Database (Denmark)

Hansen, Olfred; Schytte, Tine; Nielsen, Morten

2015-01-01

. Material and methods. Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups ... specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups ..., the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy...

EORTC 24051: Unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma

International Nuclear Information System (INIS)

Lalami, Yassine; Specenier, Pol M.; Awada, Ahmad; Lacombe, Denis; Liberatoscioli, Cecilia; Fortpied, Catherine; El-Hariry, Iman; Bogaerts, Jan; Andry, Guy; Langendijk, J.A.; Vermorken, Jan B.

2012-01-01

Background: In this phase I/II study, the addition of lapatinib (LAP) was investigated in combination with the sequential use of both approaches TPF induction chemotherapy (ICT) followed by chemoradiation (CRT) in locally advanced larynx or hypopharynx squamous cell carcinoma. Patients and methods: Objectives were to assess maximum tolerated dose, dose-limiting toxicity (DLT) and to recommend a safe dose of LAP when administered with 4 cycles of TPF followed by CRT. Results: Seven male patients were included. Three patients were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF). Renal toxicity was observed among these three patients (grade 3 [n = 1], grade 2 [n = 1] and grade 1 [n = 1]), with 1 DLT, leading to treatment interruption in this group. Nephrotoxicity was reversible after stopping LAP and hydration of the patients. In a second cohort of four patients administering docetaxel from the second cycle, 3 more DLTs were observed (grade 2 renal toxicity and grade 3 diarrhea, grade 3 anorexia and grade 3 stomatitis, and grade 4 neutropenia). Based on the occurrence of 4 DLTs at the first dose level of LAP, patient recruitment was closed. Conclusion: These data indicate that LAP cannot be combined safely with full dose TPF.

Comprehensive clinical study of concurrent chemotherapy breathing IMRT middle part of locally advanced esophageal cancer

International Nuclear Information System (INIS)

Jung, Jae Hong; Moon, Seong Kwon; Kim, Seung Chul

2015-01-01

The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity- modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC)

Retiform hemangioendothelioma over forehead: A rare tumor treated with chemoradiation and a review of literature

Directory of Open Access Journals (Sweden)

Anup Sunil Tamhankar

2015-01-01

Full Text Available Retiform hemangioendothelioma (RH is low grade tumor of skin and subcutaneous tissue. It needs to be differentiated from angiosarcoma as RH has excellent prognosis. It is usually seen in young adults on extremities. Sometimes it may mimic benign conditions and can delay treatment. Surgery has been mainstay of its treatment with or without adjuvant radiation. We present first case of RH on face. This is only second case being treated with definitive chemoradiation. So it′s important to distinguish RH from angiosarcoma due to treatment implications as well.

Study on the Hot Extrusion Process of Advanced Radiation Resistant Oxide Dispersion Strengthened Steel Tubes

Energy Technology Data Exchange (ETDEWEB)

Choi, Byoungkwon; Noh, Sanghoon; Kim, Kibaik; Kang, Suk Hoon; Chun, Youngbum; Kim, Tae Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

Ferritic/martensitic steel has a better thermal conductivity and swelling resistance than austenitic stainless steel. Unfortunately, the available temperature range of ferritic/martensitic steel is limited at up to 650 .deg. C. Oxide dispersion strengthened (ODS) steels have been developed as the most prospective core structural materials for next generation nuclear systems because of their excellent high strength and irradiation resistance. The material performances of this new alloy are attributed to the existence of uniformly distributed nano-oxide particles with a high density, which is extremely stable at high temperature in a ferritic/martensitic matrix. This microstructure can be very attractive in achieving superior mechanical properties at high temperatures, and thus, these favorable microstructures should be obtained through the controls of the fabrication process parameters during the mechanical alloying and hot consolidation procedures. In this study, a hot extrusion process for advanced radiation resistant ODS steel tube was investigated. ODS martensitic steel was designed to have high homogeneity, productivity, and reproducibility. Mechanical alloying and hot consolidation processes were employed to fabricate the ODS steels. A microstructure observation and creep rupture test were examined to investigate the effects of the optimized fabrication conditions. Advanced radiation resistant ODS steel has been designed to have homogeneity, productivity, and reproducibility. For these characteristics, modified mechanical alloying and hot consolidation processes were developed. Microstructure observation revealed that the ODS steel has uniformly distributed fine-grain nano-oxide particles. The fabrication process for the tubing is also being propelled in earnest.

Study on the Hot Extrusion Process of Advanced Radiation Resistant Oxide Dispersion Strengthened Steel Tubes

International Nuclear Information System (INIS)

Choi, Byoungkwon; Noh, Sanghoon; Kim, Kibaik; Kang, Suk Hoon; Chun, Youngbum; Kim, Tae Kyu

2014-01-01

Ferritic/martensitic steel has a better thermal conductivity and swelling resistance than austenitic stainless steel. Unfortunately, the available temperature range of ferritic/martensitic steel is limited at up to 650 .deg. C. Oxide dispersion strengthened (ODS) steels have been developed as the most prospective core structural materials for next generation nuclear systems because of their excellent high strength and irradiation resistance. The material performances of this new alloy are attributed to the existence of uniformly distributed nano-oxide particles with a high density, which is extremely stable at high temperature in a ferritic/martensitic matrix. This microstructure can be very attractive in achieving superior mechanical properties at high temperatures, and thus, these favorable microstructures should be obtained through the controls of the fabrication process parameters during the mechanical alloying and hot consolidation procedures. In this study, a hot extrusion process for advanced radiation resistant ODS steel tube was investigated. ODS martensitic steel was designed to have high homogeneity, productivity, and reproducibility. Mechanical alloying and hot consolidation processes were employed to fabricate the ODS steels. A microstructure observation and creep rupture test were examined to investigate the effects of the optimized fabrication conditions. Advanced radiation resistant ODS steel has been designed to have homogeneity, productivity, and reproducibility. For these characteristics, modified mechanical alloying and hot consolidation processes were developed. Microstructure observation revealed that the ODS steel has uniformly distributed fine-grain nano-oxide particles. The fabrication process for the tubing is also being propelled in earnest

A Matched-Case Comparison to Explore the Role of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer

Energy Technology Data Exchange (ETDEWEB)

Choi, Chel Hun; Lee, Yoo-Young; Kim, Min Kyu; Kim, Tae-Joong; Lee, Jeong-Won [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Nam, Hee Rim; Huh, Seung Jae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Je-Ho; Bae, Duk-Soo [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Byoung-Gie, E-mail: bksong.kim@samsung.com [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2011-12-01

Purpose: The aim of this study was to compare the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone in patients with locally advanced cervical carcinoma. Methods and Materials: Using medical records from January 2001 to December 2007, 39 patients treated with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three additional cycles of chemotherapy with cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1,000 mg/m{sup 2} per day (Days 1-5) given every 3 weeks. The primary endpoint was overall survival. Results: During a median follow-up period of 35 months (range, 8-96 months), 10 (25.6%) and 16 (41.0%) patients showed disease progression in Groups 1 and 2, respectively. Distant recurrence with or without locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in Group 1 (23.1% vs. 7.7%, p = 0.06). By contreast, there was no difference in locoregional or lymphogenous recurrence between the two groups. The rate of overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%, p = 0.042), whereas the difference in progression-free survival between the groups was not statistically significant (70.1% vs. 55.1%, p = 0.079). Although the difference was not statistically significant, neutropenia was more common in Group 1 than in Group 2 (10.9% vs. 4.7%, p = 0.07). Conclusions: Consolidation chemotherapy after CCRT may improve survival and reduce distant recurrence without additional toxicity compared to CCRT alone in patients with locally advanced cervical carcinoma.

SU-F-J-222: Using PET Imaging to Evaluate Proliferation and Blood Flow in Irradiated and Non-Irradiated Bone Marrow 1 Year After Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

McGuire, S; Ponto, L; Menda, Y [University Of Iowa, Iowa City, IA (United States)

2016-06-15

Purpose: To compare proliferation and blood flow in pelvic and thoracic bone marrow 1 year after pelvic chemoradiation. Methods: Sixteen pelvic cancer patients were enrolled in an IRB-approved protocol to acquire FLT PET images during radiation therapy simulation (baseline) and 1 year after chemoradiation therapy. Three subjects also had optional O-15 water PET images acquired 1 year after chemoradiation therapy. Baseline FLT PET images were used to create IMRT plans to spare pelvic bone marrow identified as regions with FLT SUV ≥ 2 without compromising PTV coverage or OAR sparing. Marrow VOIs were defined using a 50% maximum pixel value threshold on baseline FLT PET images (VIEW, PMOD version 3.5) in the sacrum and thoracic spine representing irradiated and non-irradiated regions, respectively. FLT PET and O-15 water PET images acquired 1 year after therapy were co-registered to baseline images (FUSION PMOD) and the same VOIs were used to measure proliferation (FLT SUV) and blood flow (O-15 water uptake). Separate image-based input functions were used for blood flow quantitation in each VOI. Results: Mean 1 year FLT SUV in sacral and thoracic VOIs for were 1.1 ± 0.4 and 6.5 ± 1.7, respectively for N = 16 subjects and were 1.2 ± 0.2 and 5.6 ± 1.6, respectively for N = 3 subjects who also underwent O-15 water imaging. Blood flow measures in equivalent sacral and thoracic marrow regions (N = 3) were 21.3 ± 8.7 and 18.3 ± 4.9 mL/min/100mL respectively. Conclusion: Decreased bone marrow proliferation measured by FLT SUV does not appear to correspond to decreased blood flow as measured by O-15 water PET imaging. Based on this small sample at a single time point, reduced blood supply does not explain reductions in bone marrow proliferative activity 1 year after chemoradiation therapy.

Using [18F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

International Nuclear Information System (INIS)

McGuire, Sarah M.; Bhatia, Sudershan K.; Sun, Wenqing; Jacobson, Geraldine M.; Menda, Yusuf; Ponto, Laura L.; Smith, Brian J.; Gross, Brandie A.; Bayouth, John E.; Sunderland, John J.; Graham, Michael M.; Buatti, John M.

2016-01-01

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [ 18 F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4

Histologic assessment of treatment effect of preoperative chemo-radiation in patients presenting with resectable pancreatic adenocarcinoma; Chimioradiotherapie preoperatoire des adenocarcinomes du pancreas: evaluation anatomopathologique de l'efficacite therapeutique

Energy Technology Data Exchange (ETDEWEB)

Le Scodan, R. [Departement de radiotherapie, centre Rene-Huguenin, 35, rue Dailly, 92210 Saint-Cloud (France); Mornex, F. [Departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Benite cedex (France); Partensky, C. [Service de chirurgie digestive, hopital edouard-Herriot, 5, place Arsonval, 69003 Lyon (France); Mercier, C. [Departement de statistiques medicales, centre hospitalier Lyon-Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Benite cedex (France); Valette, P.J. [Service de radiologie digestive, hopital edouard-Herriot, 5, place Arsonval, 69003 Lyon (France); Ychou, M. [Departement d' oncologie medicale, centre Val-d' Aurelle-Paul-Lamarque, 208, rue des Apothicaires, 34298 Montpellier cedex 5 (France); Bibeau, F. [Departement de pathologie, centre Val-d' Aurelle-Paul-Lamarque, 208, rue des Apothicaires, 34298 Montpellier cedex 5 (France); Scoazec, J.Y. [Laboratoire d' anatomie et de cytologie pathologiques, hopital edouard-Herriot, 5, place Arsonval, 69003 Lyon (France)

2011-04-15

Purpose. - Several phase II studies have shown the feasibility of neo-adjuvant chemo-radiation regimens for resectable localized pancreatic adenocarcinoma. However, there is to date no completed phase III study to validate this approach and treatment effects evaluation still remains an active area of investigation. From the mature results of the SFRO-FFCD 9704 trial, we explored the anti-tumoral effect of a 5-fluoro-uracil and cisplatin-based preoperative chemo-radiation regimen, with a special highlight on the histopathological response and performed a literature review. Patients and methods. - Treatment consisted of concurrent radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300 mg/m{sup 2}/day, five days/week, weeks 1-5) and cisplatin (20 mg/m{sup 2}/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumour in patients without progression. Results. - In all, 41 patients were enrolled, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (=80% of severely degenerative cancer cells), with one complete pathologic response. The local recurrence and two-year survival rates were 4 and 32%, respectively, for the 26 operated patients. Conclusion. - Our results suggest that preoperative chemo-radiation provides anti-tumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neo-adjuvant chemo-radiation may serve as a surrogate marker for treatment efficacy and further research is needed to determine new prognostic and predictive factors of treatment response. (authors)

Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

DEFF Research Database (Denmark)

Ramlov, Anne; Pedersen, Erik Morre; Røhl, Lisbeth

2017-01-01

and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition......PURPOSE: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin...

Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

Science.gov (United States)

Boysen, Anders Kindberg; Wettergren, Yvonne; Sorensen, Boe Sandahl; Taflin, Helena; Gustavson, Bengt; Spindler, Karen-Lise Garm

2017-11-01

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

Using [{sup 18}F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

McGuire, Sarah M., E-mail: sarah-mcguire@uiowa.edu [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bhatia, Sudershan K.; Sun, Wenqing [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Jacobson, Geraldine M. [Department of Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); Menda, Yusuf; Ponto, Laura L. [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Smith, Brian J. [Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa (United States); Gross, Brandie A. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bayouth, John E. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Sunderland, John J.; Graham, Michael M. [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Buatti, John M. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States)

2016-09-01

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [{sup 18}F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity

Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease.

Science.gov (United States)

Wardell, Suzanne E; Nelson, Erik R; Chao, Christina A; McDonnell, Donald P

2013-05-01

There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer. A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed. The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy. Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. ©2013 AACR.

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

Science.gov (United States)

Berlin, Jordan D; Feng, Yang; Catalano, Paul; Abbruzzese, James L; Philip, Philip A; McWilliams, Robert R; Lowy, Andrew M; Benson, Al B; Blackstock, A William

2018-01-01

Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated. © 2017 S. Karger AG, Basel.

Pelvic Lymph Node Status Assessed by 18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Low-Risk Group for Distant Recurrence in Locally Advanced Cervical Cancer: A Prospective Study

International Nuclear Information System (INIS)

Kang, Sokbom; Park, Jung-Yeol; Lim, Myung-Chul; Song, Yong-Joong; Park, Se-Hyun; Kim, Seok-Ki; Chung, Dae-Chul; Seo, Sang-Soo; Kim, Joo-Young; Park, Sang-Yoon

2011-01-01

Purpose: To develop a prediction model to identify a low-risk group for distant recurrence in patients with locally advanced cervical cancer treated by concurrent chemoradiation. Methods and Materials: Prospectively, 62 patients with locally advanced cervical cancer were recruited as a training cohort. Clinical variables and parameters obtained from positron emission tomography (PET) and magnetic resonance imaging were analyzed by logistic regression. For the test set, 54 patients were recruited independently. To identify the low-risk group, negative likelihood ratio (LR) less than 0.2 was set to be a cutoff. Results: Among the training cohort, multivariate logistic analysis revealed that advanced International Federation of Gynecology and Obstetrics (FIGO) stage and a high serum squamous cancer cell (SCC) antigen level were significant risk factors (p = 0.015 and 0.025, respectively). Using the two parameters, criteria to determine a low-risk subset for distant recurrence were postulated: (1) FIGO Stage IIB or less and (2) pretreatment SCC < 2.4 (Model A). Positive pelvic node on PET completely predicted all cases with distant recurrence and thus was considered as another prediction model (Model B). In the test cohort, although Model A did not showed diagnostic performance, Model B completely predicted all cases with distant recurrence and showed a sensitivity of 100% with negative LR of 0. Across the training and test cohort (n = 116), the false negative rate was 0 (95% confidence interval 0%-7.6%). Conclusions: Positive pelvic node on PET is a useful marker in prediction of distant recurrence in patients with locally advanced cervical cancer who are treated with concurrent chemoradiation.

Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI.

Science.gov (United States)

Rinkel, Rico N; Verdonck-de Leeuw, Irma M; Doornaert, Patricia; Buter, Jan; de Bree, Remco; Langendijk, Johannes A; Aaronson, Neil K; Leemans, C René

2016-07-01

The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs.

Diuretics Combined With Compression in Resistant Limb Edema of Advanced Disease-A Case Series Report.

Science.gov (United States)

Gradalski, Tomasz

2018-04-01

The extremity edema of advanced disease is a common, multifactorial feature, which impairs patients' activities and quality of life. The most frequently chosen management is based on combined decongestive physiotherapy or pharmacotherapy (with diuretics or steroids). Subcutaneous lymphatic drainage in refractory edema may decrease the swelling, prevent spontaneous lymphorrhea, but also increase the risk of infection. Safe and effective conservative management in diuretics-resistant edemas is lacking. The objective of this prospective, observational study was to assess the effectiveness and tolerability of combined physiotherapeutic and diuretic therapy in edemas refractory to parenteral diuretics. A group of 19 patients with advanced disease and severe bilateral leg edema resistant to parenteral diuretic therapy were treated for three days with a combination of multilayer short-stretch compression bandaging and furosemide in hypersaline intravenous infusion. A clinically meaningful decrease in mean limb volume (of 1.52 L; 20.6%; P performance status in any patient. Stable levels of blood pressure, laboratory kidney profile (potassium, sodium, creatinine clearance), and serum albumin were observed. Maintenance of the achieved results with a good compliance was seen during an informal follow-up at the hospice. The combination of compression therapy with hypersaline diuretics could be considered as a valuable option for refractory cases of limb edema in advanced disease. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Khalifa, J. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Tensaouti, F. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Chaltiel, L. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Biostatistics, Toulouse (France); Lotterie, J.A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Catalaa, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Radiology, Toulouse (France); Sunyach, M.P. [Centre Leon Berard, Department of Radiation Oncology, Lyon (France); Ibarrola, D. [CERMEP - Imagerie du Vivant, Lyon (France); Noel, G. [EA 3430, University of Strasbourg, Department of Radiation Oncology, Centre Paul Strauss, Strasbourg (France); Truc, G. [Centre Georges-Francois Leclerc, Department of Radiation Oncology, Dijon (France); Walker, P. [University of Burgundy, Laboratory of Electronics, Computer Science and Imaging (Le2I), UMR 6306 CNRS, Dijon (France); Magne, N. [Institut de cancerologie Lucien-Neuwirth, Department of Radiation Oncology, Saint-Priest-en-Jarez (France); Charissoux, M. [Department of Radiation Oncology, Institut du Cancer de Montpellier, Montpellier (France); Ken, S. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Medical Physics, Toulouse (France); Peran, P. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Berry, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Moyal, E.C. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Universite Toulouse III Paul Sabatier, Toulouse (France); INSERM U1037, Centre de Recherches contre le Cancer de Toulouse, Toulouse (FR); Laprie, A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (FR); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (FR); Universite Toulouse III Paul Sabatier, Toulouse (FR)

2016-11-15

To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t{sub end}; MR acquisitions performed at t{sub end-2M}, t{sub end-4M} and t{sub end-6M} (respectively 2, 4 and 6 months before t{sub end}) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∇B from t{sub end-4M} to t{sub end-2M} and ∇B from t{sub end-6M} to t{sub end-4M}. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F{sub h}P{sub g}) was a relevant biomarker. A ratio R(F{sub h}P{sub g}) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F{sub h}Pg) (≥0.61) was associated with more relapse at t{sub end} compared to low R(F{sub h}Pg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F{sub h}P{sub g} from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. (orig.)

Oncofertility in the setting of advanced cervical cancer - A case report

Directory of Open Access Journals (Sweden)

Catherine Gordon

2018-05-01

Full Text Available Objective: To consider fertility options in women with advanced cervical cancer. Design: Case report. Setting: Large tertiary care center. Patient: A 30-year-old nulligravida woman diagnosed with FIGO Stage IBI squamous cell carcinoma of the cervix that had metastasized to a pelvic lymph node. Interventions: Robotic radical trachelectomy with pelvic lymphadenectomy and cerclage placement, followed by ovarian stimulation with oocyte retrieval and in vitro fertilization. Subsequent therapy included adjuvant chemoradiation and embryo transfer to a surrogate mother. Main outcome measures: Cervical cancer remission, live birth from surrogate pregnancy. Results: 33-year-old woman in her third year of remission from advanced cervical cancer with healthy twin girls. Conclusions: Fertility options may exist for patients even in the setting of metastatic cervical cancer. Early involvement of a reproductive endocrinologist is imperative. This case emphasizes the importance of cross-specialty communication. Keywords: Cervical cancer, Oncofertility, Radical trachelectomy, In vitro fertilization

Removal of total and antibiotic resistant bacteria in advanced wastewater treatment by ozonation in combination with different filtering techniques.

Science.gov (United States)

Lüddeke, Frauke; Heß, Stefanie; Gallert, Claudia; Winter, Josef; Güde, Hans; Löffler, Herbert

2015-02-01

Elimination of bacteria by ozonation in combination with charcoal or slow sand filtration for advanced sewage treatment to improve the quality of treated sewage and to reduce the potential risk for human health of receiving surface waters was investigated in pilot scale at the sewage treatment plant Eriskirch, Baden-Wuerttemberg/Germany. To determine the elimination of sewage bacteria, inflowing and leaving wastewater of different treatment processes was analysed in a culture-based approach for its content of Escherichia coli, enterococci and staphylococci and their resistance against selected antibiotics over a period of 17 month. For enterococci, single species and their antibiotic resistances were identified. In comparison to the established flocculation filtration at Eriskirch, ozonation plus charcoal or sand filtration (pilot-scale) reduced the concentrations of total and antibiotic resistant E. coli, enterococci and staphylococci. However, antibiotic resistant E. coli and staphylococci apparently survived ozone treatment better than antibiotic sensitive strains. Neither vancomycin resistant enterococci nor methicillin resistant Staphylococcus aureus (MRSA) were detected. The decreased percentage of antibiotic resistant enterococci after ozonation may be explained by a different ozone sensitivity of species: Enterococcus faecium and Enterococcus faecalis, which determined the resistance-level, seemed to be more sensitive for ozone than other Enterococcus-species. Overall, ozonation followed by charcoal or sand filtration led to 0.8-1.1 log-units less total and antibiotic resistant E. coli, enterococci and staphylococci, as compared to the respective concentrations in treated sewage by only flocculation filtration. Thus, advanced wastewater treatment by ozonation plus charcoal or sand filtration after common sewage treatment is an effective tool for further elimination of microorganisms from sewage before discharge in surface waters. Copyright © 2014 Elsevier

Control of the Resistive Wall Mode in Advanced Tokamak Plasmas on DIII-D

International Nuclear Information System (INIS)

Garofalo, A.M.; Strait, E.J.; Bialek, J.; Frederickson, E.; Gryaznevich, M.; Jensen, T.H.; Johnson, L.C.; La Haye, R.J.; Navratil, G.A.; Lazarus, E.A.; Luce, T.C.; Makowski, M.; Okabayashi, M.; Rice, B.W.; Scoville, J.T.; Turnbull, A.D.; Walker, M.L.

1999-01-01

Resistive wall mode (RWM) instabilities are found to be a limiting factor in advanced tokamak (AT) regimes with low internal inductance. Even small amplitude modes can affect the rotation profile and the performance of these ELMing H-mode discharges. Although complete stabilization of the RWM by plasma rotation has not yet been observed, several discharges with increased beam momentum and power injection sustained good steady-state performance for record time extents. The first investigation of active feedback control of the RWM has shown promising results: the leakage of the radial magnetic flux through the resistive wall can be successfully controlled, and the duration of the high beta phase can be prolonged. The results provide a comparative test of several approaches to active feedback control, and are being used to benchmark the analysis and computational models of active control

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

Science.gov (United States)

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

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Kirchheiner, Kathrin, E-mail: kathrin.kirchheiner@meduniwien.ac.at [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital of Vienna, Vienna (Austria); Pötter, Richard [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Tanderup, Kari; Lindegaard, Jacob C. [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Haie-Meder, Christine [Department of Radiotherapy, Gustave-Roussy, Villejuif (France); Petrič, Primož [Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana (Slovenia); Department of Radiation Oncology, National Center for Cancer Care and Research, Doha (Qatar); Mahantshetty, Umesh [Department of Radiation Oncology, Tata Memorial Hospital, Mumbai (India); Jürgenliemk-Schulz, Ina M. [Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht (Netherlands); Rai, Bhavana [Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Cooper, Rachel [Leeds Cancer Centre, St James' s University Hospital, Leeds (United Kingdom); Dörr, Wolfgang [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Nout, Remi A. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Lindegaard, Jacob; Tanderup, Kari; Fokdal, Lars; Van Der Steen Banasik, Elzbieta; Haie-Meder, Christine; Dumas, Isabelle; and others

2016-04-01

Purpose: This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials: In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population. Results: General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea). Conclusions: This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to

Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

International Nuclear Information System (INIS)

Kirchheiner, Kathrin; Pötter, Richard; Tanderup, Kari; Lindegaard, Jacob C.; Haie-Meder, Christine; Petrič, Primož; Mahantshetty, Umesh; Jürgenliemk-Schulz, Ina M.; Rai, Bhavana; Cooper, Rachel; Dörr, Wolfgang; Nout, Remi A.; Lindegaard, Jacob; Tanderup, Kari; Fokdal, Lars; Van Der Steen Banasik, Elzbieta; Haie-Meder, Christine; Dumas, Isabelle

2016-01-01

Purpose: This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials: In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population. Results: General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea). Conclusions: This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of

Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.

Science.gov (United States)

Zeng, H Z; Qu, Y Q; Liang, A B; Deng, A M; Zhang, W J; Xiu, B; Wang, H; Wang, H

2011-01-01

CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.

Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

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Markovina, Stephanie [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Duan, Fenghai [Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Snyder, Bradley S. [Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Siegel, Barry A. [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Machtay, Mitchell [Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (United States); Bradley, Jeffrey D., E-mail: jbradley@radonc.wustl.edu [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States)

2015-11-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local

Regional Lymph Node Uptake of ["1"8F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

International Nuclear Information System (INIS)

Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.; Siegel, Barry A.; Machtay, Mitchell; Bradley, Jeffrey D.

2015-01-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment ["1"8F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.

Role of concurrent chemoradiation in inoperable carcinoma esophagus: A prospective study

Directory of Open Access Journals (Sweden)

Virendra Bhandari

2014-01-01

Full Text Available Introduction: The treatment of choice in cancer esophagus is controversial. Radiation therapy oncology group, Eastern cooperative oncology group and Cochrane studies have shown superiority of concurrent chemoradiation in inoperable carcinoma esophagus. In these studies full dose cisplatin was given every 3 weeks along with radiotherapy and hence had some toxicity. So, we started treating inoperable carcinoma esophagus patients with low dose weekly cisplatin given concurrently with radiotherapy aiming at low toxicity and similar results. Materials and Methods: A total of 31 cases of inoperable cases of carcinoma esophagus were treated with once weekly cisplatin 30 mg/m 2 along with radiotherapy 60 Gy in 30 fractions in 6 weeks on Telecobalt/Linear accelerator. Results : w0 e could achieve lower toxicity with 80%, 35% and 19% with 1, 2, and 3 year′s survival with a median survival of 18 months. So, we conclude that this regimen is better than 3 weekly chemotherapy regimen as is better tolerated with less toxicity and similar outcome.

Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

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Siew, Edward D; Ikizler, Talat Alp

2010-01-01

Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of "uremic toxins" are believed to contribute to the etiology of IR and acquired defects in the insulin-receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end-stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin-proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin-free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

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Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Conradi, Lena [Department of General Surgery, University Medical Center of Göttingen (Germany); Weiss, Christian [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sprenger, Thilo [Department of General Surgery, University Medical Center of Göttingen (Germany); Middel, Peter [Institute for Pathology, University Medical Center, Göttingen (Germany); Rau, Tillman [Institute of Pathology, University Hospital Erlangen, Erlangen (Germany); Dellas, Kathrin [Department of Radiotherapy, Lübeck University (Germany); Kitz, Julia [Institute for Pathology, University Medical Center, Göttingen (Germany); Rödel, Franz [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sauer, Rolf [Department of Radiation Oncology, University of Erlangen (Germany); Rüschoff, Josef [Targos Molecular Pathology, Kassel (Germany); Beissbarth, Tim [Department of Medical Statistics, University Medical Center of Göttingen (Germany); Arnold, Dirk [Tumor Biology Center Freiburg, University of Freiburg (Germany); Ghadimi, B. Michael [Department of General Surgery, University Medical Center of Göttingen (Germany); Rödel, Claus [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Liersch, Torsten [Department of General Surgery, University Medical Center of Göttingen (Germany)

2013-12-01

Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

International Nuclear Information System (INIS)

Fokas, Emmanouil; Conradi, Lena; Weiss, Christian; Sprenger, Thilo; Middel, Peter; Rau, Tillman; Dellas, Kathrin; Kitz, Julia; Rödel, Franz; Sauer, Rolf; Rüschoff, Josef; Beissbarth, Tim; Arnold, Dirk; Ghadimi, B. Michael; Rödel, Claus; Liersch, Torsten

2013-01-01

Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

[A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

Science.gov (United States)

Iwama, Mitsuru; Kimura, Yutaka; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

2017-11-01

Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

Concurrent chemoradiation for vaginal cancer.

Directory of Open Access Journals (Sweden)

David T Miyamoto

Full Text Available BACKGROUND: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT or concurrent chemoradiation therapy (CRT. METHODS: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS and disease-free survival (DFS rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. RESULTS: The median age at diagnosis was 61 years (range, 18-92 years and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011. Twenty-three patients (45% in the RT group had a relapse at any site compared to 3 (15% in the CRT group (p = 0.027. With regard to the sites of first relapse, 10 patients (14% had local only, 4 (6% had local and regional, 9 (13% had regional only, 1 (1% had regional and distant, and 2 (3% had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04. CONCLUSIONS: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

Definitive chemoradiation for locoregional recurrences of esophageal cancer after primary curative treatment.

Science.gov (United States)

Jeene, P M; Versteijne, E; van Berge Henegouwen, M I; Bergmann, J J G H M; Geijsen, E D; Muller, K; van Laarhoven, H W M; Hulshof, M C C M

2017-02-01

The aim of this study was to determine the outcome of salvage definitive chemoradiation (dCRT) for a locoregional recurrence after any prior curative treatment outside previously irradiated areas. Thirty-nine patients treated between January 2005 and December 2014 were reviewed for locoregional recurrent esophageal cancer outside previously irradiated areas. All patients received salvage treatment with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel and carboplatin. The median follow-up period was 15 months (range 1.7-120). The median overall survival (OS) for all patients after salvage dCRT was 22 months (95% CI 6.2-37.6). The 1-, 3-, and 5-year OS was 72%, 31%, and 28%, respectively. Median survival after salvage dCRT for a regional lymph node recurrence was 33 months (95% CI 5.8-60.3) versus 14 months (95% CI 6.8-21.6) for a recurrence at the anastomosis (P = 0.022, logrank). Median OS was 35 months for the squamous cell carcinoma group and 19 months for the adenocarcinoma group (P = 0.67). Sixteen of 39 patients developed a locoregional recurrence after salvaged dCRT. The median locoregional recurrence-free survival (LRFS) was 24 months. The 1-, 3-, and 5-year LRFS was 79%, 36%, and 36%, respectively. Median disease-free survival (DFS) was 15 months. The 1-, 3-, and 5-year DFS was 66%, 27%, and 27%, respectively. Of 16 patients, 8 (50%) with a primary failure at the site of the anastomosis developed a local recurrence after salvaged dCRT compared to 7 of 22 patients (32%) with a primary recurrence in a lymph node. Definitive chemoradiation is a feasible and effective treatment for locoregional recurrent esophageal cancer outside a previously irradiated area, and should be given with a curative intent. This holds true for recurrence of both squamous cell carcinoma and adenocarcinoma. Lymph node recurrences have a markedly better prognosis than recurrences at the site of the anastomosis. © 2016

Advanced core concepts with enhanced proliferation resistance by transmutation of minor actinides

International Nuclear Information System (INIS)

Saito, Masaki

2005-01-01

''Protected Plutonium Production (P 3 )'' has been proposed to establish high burn-up cores and to produce protected with high proliferation resistance due to high decay heat and large number of spontaneous fission neutron of 238 Pu by the transmutation of Minor Actinides (MAs) which is presently treated as high-level waste. The burn-up calculations have shown that the advanced fuel with UO 2 (11-13% enrichment of 235 U) by doping 237 Np to produce 238 Pu in the commercialized large LWRs burn up to 100 GWd/t with 238 Pu to Pu ratio of about 20% which means the fuel is highly protected from proliferation. It was also predicted that medium or small size LWR cores with 15-17% enrichment, liquid metal cooled cores, and gas cooled cores added by 1-2% Np could achieve 100 GWd/t burning with bearing high proliferation resistance. The 237 Np mass balance calculations have revealed that more than 20 nuclear P 3 plants of 300 MWe could be supplied with enough 237 Np from the Japanese commercial plants in equilibrium fuel cycles. From the present studies, it is confirmed that MAs are treated as burnable and fertile materials not only to extend the core life but also to improve plutonium proliferation resistance of the future nuclear energy systems instead of their geological disposal or just their burning through fission. (author)

Dose–Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

International Nuclear Information System (INIS)

Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

2012-01-01

Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose–volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)–based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women’s Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman’s correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU–based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

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Amini, Arya; Xiao Lianchun; Allen, Pamela K.; Suzuki, Akihiro; Hayashi, Yuki; Liao, Zhongxing; Hofstetter, Wayne; Crane, Christopher; Komaki, Ritsuko; Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A.; Welsh, James

2012-01-01

Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1–56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic

Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

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Amini, Arya [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); UC Irvine School of Medicine, Irvine, California (United States); Xiao Lianchun [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suzuki, Akihiro; Hayashi, Yuki [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hofstetter, Wayne [Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2012-06-01

Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment

Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.

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Yang, Cheng-Chieh; Tu, Hsi-Feng; Wu, Cheng-Hsien; Chang, Hsiu-Chuan; Chiang, Wei-Fan; Shih, Nai-Chia; Lee, Yong-Syu; Kao, Shou-Yen; Chang, Kuo-Wei

2016-05-01

When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute toxicity of chemoradiation for rectal cancer; Akuttoxizitaet der simultanen Radiochemotherapie des Rektumkarzinoms

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Roedel, C. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Fietkau, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Keilholz, L. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Grabenbauer, G.G. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Kessler, H. [Erlangen-Nuernberg Univ., Erlangen (Germany). Chirurgische Klinik; Martus, P. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizinische Statistik und Dokumentation; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik

1997-08-01

Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) {+-} 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m{sup 2}/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [Deutsch] Von 1987 bis 1995 wurde bei 120 Patienten mit Rektumkarzinom (73 Primaertumoren, 47 Rezidivtumoren) eine simultane Radiochemotherapie durchgefuehrt. 56 Patienten wurden praeoperativ, 64 Patienten postoperativ behandelt. Die Bestrahlung erfolgte ueber eine Vier-Felder-Technik mit 6- bis 10-MV-Photonen. Die Einzeldosis betrug 1,8 Gy im Referenzpunkt (Isozentrum, ICRU 50

Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non–Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

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Machtay, Mitchell; Bae, Kyounghwa; Movsas, Benjamin; Paulus, Rebecca; Gore, Elizabeth M.; Komaki, Ritsuko; Albain, Kathy; Sause, William T.; Curran, Walter J.

2012-01-01

Purpose: Patients treated with chemoradiotherapy for locally advanced non–small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray’s proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

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Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

2018-05-01

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: A prospective, hypothesis driven study on patients with locally advanced rectal cancer

International Nuclear Information System (INIS)

Buijsen, Jeroen; Stiphout, Ruud G. van; Menheere, Paul P.C.A.; Lammering, Guido; Lambin, Philippe

2014-01-01

Purpose/objective: Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer. Material/methods: 295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol ( (NCT01067872)). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages). Results: 276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response. Conclusion: CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Al-Amro, Abdullah; Al-Rajhi, Nasser; Khafaga, Yasser; Memon, Mohammad; Al-Hebshi, Adnan; El-Enbabi, Ashraf; El-Husseiny, Gamal; Radawi, Amer; Belal, Abdulaziz; Allam, Ayman; El-Sebaie, Medhat

2005-01-01

Purpose: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Methods and Materials: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m 2 and epirubicin 70 mg/m 2 on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m 2 for 4 days on Days 42, 63, and 84. Results: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient

Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

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Isohashi, Fumiaki; Yoshioka, Yasuo; Mabuchi, Seiji; Konishi, Koji; Koizumi, Masahiko; Takahashi, Yutaka; Ogata, Toshiyuki; Maruoka, Shintaroh; Kimura, Tadashi; Ogawa, Kazuhiko

2013-01-01

Purpose: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. Methods and Materials: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors and the incidence of grade 2 or higher chronic GI complications were evaluated. Results: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. Conclusions: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative

[A case of a geriatric patient with stage IV anal canal cancer showing complete response to chemoradiation therapy].

Science.gov (United States)

Kuroda, Masatoshi; Hirai, Ryuji; Ikeda, Eiji; Tsuji, Hisashi; Takagi, Shoji; Yamano, Toshihisa; Yoshitomi, Seiji

2012-11-01

We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

Science.gov (United States)

Balacescu, Ovidiu; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica

2014-04-08

Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

International Nuclear Information System (INIS)

Balacescu, Ovidiu; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura

2014-01-01

Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. ‘DNA Replication, Recombination and Repair’ represented one of the most important mechanisms activated in non-responsive cervical tumors, and the ‘Role of BRCA1 in DNA Damage Response’ was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information

Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

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Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2014-03-01

Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: a single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care.

Science.gov (United States)

Lambrecht, Maarten; Mercier, Carole; Geussens, Yasmyne; Nuyts, Sandra

2013-10-01

Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation. A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care (n = 31) and a study group receiving standard of care + daily CP mouth rinses (n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale. No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5). In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice.

Recurrence of paraneoplastic membranous glomerulonephritis following chemoradiation in a man with non-small-cell lung carcinoma

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Kara Leonard

2013-04-01

Full Text Available Membranous glomerulonephritis can occur as a rare paraneoplastic complication of human cancers. In this case report, we describe a patient who presented acutely with symptoms of the nephrotic syndrome including heavy proteinuria and anasarca. He was subsequently diagnosed with membranous glomerulonephritis, and soon afterwards was found to have stage IIIB non-small cell lung cancer. Following chemoradiation therapy, both the patient’s cancer and membranous glomerulonephritis dramatically improved. However, approximately 14 months following his initial presentation, the patient was found to have a recurrence of his nephrotic-range proteinuria which corresponded temporally with recurrence of his cancer. We present details of the case and a review of the relevant scientific literature.

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

Science.gov (United States)

Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

2012-02-01

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

Science.gov (United States)

Zecha, Judith A. E. M.; Raber-Durlacher, Judith E.; Nair, Raj G.; Epstein, Joel B.; Sonis, Stephen T.; Elad, Sharon; Hamblin, Michael R.; Barasch, Andrei; Migliorati, Cesar A.; Milstein, Dan M. J.; Genot, Marie-Thérèse; Lansaat, Liset; van der Brink, Ron; Arnabat-Dominguez, Josep; van der Molen, Lisette; Jacobi, Irene; van Diessen, Judi; de Lange, Jan; Smeele, Ludi E.; Schubert, Mark M.

2016-01-01

Purpose There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods This study is a narrative non-systematic review. Results We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck

Chemoradiation Therapy for Potentially Resectable Gastric Cancer: Clinical Outcomes Among Patients Who Do Not Undergo Planned Surgery

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Kim, Michelle M.; Mansfield, Paul F.; Das, Prajnan; Janjan, Nora A.; Badgwell, Brian D.; Phan, Alexandria T.; Delclos, Marc E.; Maru, Dipen; Ajani, Jaffer A.; Crane, Christopher H.; Krishnan, Sunil

2008-01-01

Purpose: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. Methods and Materials: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Results: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. Conclusions: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

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Chitapanarux, Imjai; Tungkasamit, Tharatorn; Petsuksiri, Janjira; Kannarunimit, Danita; Katanyoo, Kanyarat; Chakkabat, Chakkapong; Setakornnukul, Jiraporn; Wongsrita, Somying; Jirawatwarakul, Naruemon; Lertbusayanukul, Chawalit; Sripan, Patumrat; Traisathit, Patrinee

2018-03-01

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

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Jotte, Robert M; Spigel, David R

2015-01-01

Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

Dynamic contrast-enhanced MRI, diffusion-weighted MRI and {sup 18}F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation

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Ng, Shu-Hang [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Liao, Chun-Ta [Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Chien-Yu; Chang, Joseph Tung-Chieh; Fan, Kang-Hsing [Chang Gung University, Department of Radiation Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chan, Sheng-Chieh; Yen, Tzu-Chen [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Yu-Chun [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Ko, Sheung-Fat [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Hung-Ming [Chang Gung University, Department of Medical Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Yang, Lan-Yan [Chang Gung University, Biostatistics and Informatics Unit, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Jiun-Jie [Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung Memorial Hospital, Neuroscience Research Center, Taoyuan (China); Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Keelung (China); Chang Gung University / Chang Gung Memorial Hospital, Linkou, Medical Imaging Research Center, Institute for Radiological Research, Taoyuan (China)

2016-11-15

We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation. Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and {sup 18}F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates. Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K{sub ep})-tumour < 3.79 min{sup -1} (P = 0.001), relative volume of extracellular extravascular space (V{sub e})-node < 0.23 (P = 0.004) and SUV{sub max}-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001). K{sub ep}-tumour, V{sub e}-node and SUV{sub max}-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification. (orig.)

Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

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Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Kyubo, E-mail: kyubokim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Jin Ho [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

2013-11-01

Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

International Nuclear Information System (INIS)

Chon, Young Eun; Seong, Jinsil; Kim, Beom Kyung; Cha, Jihye; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Shin, Sung Kwan; Kim, Do Young

2011-01-01

Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

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Chon, Young Eun [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Beom Kyung [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Jihye [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of); Shin, Sung Kwan, E-mail: kaarma@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Do Young, E-mail: dyk1025@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of)

2011-12-01

Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Numerical Study of Equilibrium, Stability, and Advanced Resistive Wall Mode Feedback Algorithms on KSTAR

Science.gov (United States)

Katsuro-Hopkins, Oksana; Sabbagh, S. A.; Bialek, J. M.; Park, H. K.; Kim, J. Y.; You, K.-I.; Glasser, A. H.; Lao, L. L.

2007-11-01

Stability to ideal MHD kink/ballooning modes and the resistive wall mode (RWM) is investigated for the KSTAR tokamak. Free-boundary equilibria that comply with magnetic field coil current constraints are computed for monotonic and reversed shear safety factor profiles and H-mode tokamak pressure profiles. Advanced tokamak operation at moderate to low plasma internal inductance shows that a factor of two improvement in the plasma beta limit over the no-wall beta limit is possible for toroidal mode number of unity. The KSTAR conducting structure, passive stabilizers, and in-vessel control coils are modeled by the VALEN-3D code and the active RWM stabilization performance of the device is evaluated using both standard and advanced feedback algorithms. Steady-state power and voltage requirements for the system are estimated based on the expected noise on the RWM sensor signals. Using NSTX experimental RWM sensors noise data as input, a reduced VALEN state-space LQG controller is designed to realistically assess KSTAR stabilization system performance.

Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

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Lee, Taek Sang [Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Soon Beom, E-mail: tslee70@gmail.com [Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Young Tak [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Park, Byung Joo [Department of Preventive Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Man [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Min [Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Young Tae [Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Hoon [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Tai [Department of Obstetrics and Gynecology, Hanyang University Medical Center, Seoul (Korea, Republic of)

2013-06-01

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

International Nuclear Information System (INIS)

Pijls-Johannesma, Madelon; Houben, Ruud; Boersma, Liesbeth; Grutters, Janneke; Seghers, Katarina; Lambin, Philippe; Wanders, Rinus; De Ruysscher, Dirk

2009-01-01

Background and purpose: Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer leads to a high incidence of severe, mostly esophageal, toxicity. The purpose of this study was to investigate the evolution of quality of life (QoL) in patients with lung cancer, selected for curative radiotherapy (RT) or chemo-RT. Methods: Seventy-five lung cancer patients completed a longitudinal the EORTC QLQ-C30 and LC13. Linear mixed regression models were fitted to investigate the impact of different factors on overall QoL. Results: Overall QoL decreased shortly after the end of RT (4 points, p = 0.19), but increased back to baseline within 3 months. Mean scores of role functioning (p = 0.018), cognitive functioning (p = 0.002), dyspnoea (EORTC QLQ-LC13; p = 0.043), dysphagia (p = 0.005) and hoarseness (p = 0.029), showed a significant worsening over time. Emotional functioning (p = 0.033) improved significantly over time. Severe esophagitis (≥grade 2) was reported in only 12% of the patients. Next to maximal esophageal toxicity ≥grade 2 (p = .0.010), also tumor stage IIIA (p < 0.001), tumor stage IIIB (p = 0.003), gender (p = 0.042) and fatigue (p < 0.001) appeared to be significant predictors of QoL. Conclusion: High-dose radiotherapy or concurrent chemo-radiation in the treatment of lung cancer seems to be a well-tolerated treatment option with preservation of QoL.

Diffusion-weighted MRI - a new parameter for advanced rectal carcinoma?

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Hein, P.A.; Lukas, P.; DeVries, A.F.; Pfeiffer, K.-P.

2003-01-01

Purpose: To evaluate the predictive value of apparent diffusion coefficient (ADC) on therapy outcome of combined chemoradiation in patients with primary carcinoma of the rectum. Materials and Method: Prior to standardized, combined, neoadjuvant chemoradiation, 16 patients with primary carcinoma of the rectum (cT3) were examined with magnetic resonance imaging (MRI). Diffusion weighted spin echo echo-planar images (SE-EPI) and contrast-enhanced T 1 -weighted spin echo (SE) images at 1.5 Tesla were obtained. The mean ADC of the tumor region was calculated and correlated with the therapy outcome substantiated by postsurgical histopathologic staging. Results: Tumor downstaging (pT0-2) occurred in 9 patients (therapy responders) and no down-staging (pT3) in 7 patients (therapy non-responders). The mean ADC measured 0.476±0.114 x 10 -3 mm 2 /s in the responder group and 0.703±0.085 x 10 -3 mm 2 /s in the non-responder group. Comparison of the mean ADC between the groups reached statistical significance (p=0.001). Conclusion: The mean ADC might be a new quantitative parameter to predict therapy outcome of combined preoperative chemoradiation in patients with primary carcinoma of the rectum. (orig.) [de

Two cases of pathological complete response to neoadjuvant chemoradiation therapy in pancreatic cancer

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Fujii-Nishimura, Yoko; Nishiyama, Ryo; Kitago, Minoru

2015-01-01

Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years. (author)

Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

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Olugbenga T. Okusanya

2015-01-01

Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

Treatment results of incomplete chemoradiotherapy in locally advanced cervical cancer

Directory of Open Access Journals (Sweden)

Gao Y

2013-04-01

Full Text Available Ying Gao,1,* Fei Gao,2,* Zi Liu,1 Li-ping Song1 1Department of Radiotherapy Oncology, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Objective: Regimens that combine chemotherapy and radiotherapy increase toxicity and compromise a patient’s ability to adhere to the treatment plan. We evaluated the efficacy and safety of a partially completed chemoradiation regimen prescribed for locally advanced carcinoma of the cervix. Methods: Medical records of 156 patients with locally advanced cervical cancer stage IIB–IVA who received chemoradiation with cisplatin (40 mg/m2 and 5-fluorouracil (500 mg/m2 from October 2006 to October 2008 were collected. The treatment protocol called for two cycles of chemotherapy. External beam radiation therapy was administered using a 10-MeV electron beam. Local control, disease free survival, overall survival, and toxicities were evaluated. Results: With a median follow-up of 37.5 months, 89 patients (57% completed the planned protocol. Sixty seven patients (43% completed fewer than two cycles. The 3-year local control rate was significantly better in the patient group that completed the prescribed plan (92.1% compared to 80.6%; P = 0.033. No statistical significance was observed between the groups that completed or did not complete the two cycle protocol with regard to disease free survival (80.9% and 73.2%, respectively; P = 0.250, overall survival (84.3% and 79.1%; P = 0.405, and progression survival (3.4% and 3.0%; P = 0.892. Differences in acute hematologic toxicity and subcutaneous toxicity were observed between the two groups. Conclusions: Completion of two cycles of 5-fluorouracil and cisplatin with radiotherapy was effective, safe, and responsible for better local control

Chemoradiation therapy and resection for carcinoma of the esophagus: short-term results

International Nuclear Information System (INIS)

Parker, E.F.; Marks, R.D. Jr.; Kratz, J.M.; Chaikhouni, A.; Warren, E.T.; Bartles, D.M.

1985-01-01

The purpose of this report is to record the results of a treatment protocol for patients with carcinoma of the esophagus. In May, 1980, the authors initiated a program of chemoradiation therapy preliminary to resection in patients in whom the protocol was applicable. The chemotherapy consisted of mitomycin-C, 10 mg as a bolus intravenous injection on day 1, and 5-fluorouracil, 1,000 mg per square meter of body surface area given intravenously on each of days 1 through 4. The radiation therapy consisted of 3,000 rads in three weeks using cobalt 60 or 6 MeV or greater, with ports to cover the tumor and mediastinum. Among the patients treated according to the protocol, the operability rate was increased. The resectability rate remained about the same as in our previous experience. The operative mortality was lessened appreciably. The percentage of resected specimens of the esophagus showing residual tumor decreased. However, the absence of any residual tumor in the surgical specimen has not conferred any improved chance of long-term survival to date

Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Ha, Ye J. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Chan W. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Park, Jong L.; Kim, Seon Y. [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun K. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

2015-03-01

Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

International Nuclear Information System (INIS)

Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Cho, Dong H.; Park, Jong L.; Kim, Seon Y.; Kim, Jong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.

2015-01-01

Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types

Acute toxicity after a diverting stoma and spacer prior to chemoradiation in locally advanced rectal cancer

NARCIS (Netherlands)

Van Der Voort Van Zyp, Jochem R N; Ceha, Heleen M.; Niehe, Valerie; Marinelli, Andreas W K S; Putter, Hein; Marijnen, Corrie A M

2015-01-01

Abstract Background and purpose Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ≥3 acute diarrhea there is a relationship between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined

Advances and Challenges in Genomic Selection for Disease Resistance.

Science.gov (United States)

Poland, Jesse; Rutkoski, Jessica

2016-08-04

Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

Chromium-modified a-C films with advanced structural, mechanical and corrosive-resistant characteristics

Energy Technology Data Exchange (ETDEWEB)

Ming, Miao Yi [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Jiang, Xiaohong, E-mail: jxh0668@sina.com [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Piliptsou, D.G., E-mail: pdg_@mail.ru [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Zhuang, Yuzhao; Rogachev, A.V.; Rudenkov, A.S. [International Chinese-Belarusian scientific laboratory on vacuum-plasma technology, Nanjing University of Science and Technology, Nanjing 210094 (China); Francisk Skorina Gomel State University, Gomel 246019 (Belarus); Balmakou, A. [Faculty of Material Science and Technology, Slovak University of Technology, Trnava 91724 (Slovakia)

2016-08-30

Highlights: • Influence of the chromium interlayer on the structure and mechanical properties of a-C:Cr films. • Residual stress and wear of a-C:Cr and Cr/a-C varies due to their phase and surface morphology. • Chromium-modified a-C films with advanced structural, mechanical and corrosive-resistant characteristics. - Abstract: To improve structural, mechanical and chemical properties of diamond-like carbon films, we developed amorphous carbon chromium-modified composite films fabricated by means of cathode magnetic filtered arc deposition. The properties were analyzed by Raman spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy for the purpose of the structure characterization, elemental analysis and topology examination. Moreover, we also assessed residual stress, the coefficient of friction, hardness, the elastic modulus and corrosion parameters through X-ray double-crystal surface profilometry, tribo-testing, nanoindenter-testing, as well as contact angle measurements and potentiodynamic polarization analysis. As a result of a comparative analysis, we revealed a substantial improvement in the characteristics of developed composite films in comparison with amorphous carbon films. For example, Cr-modification is resulted, in greater integrated performance, toughness and corrosion resistance; the residual stress was reduced substantially.

N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

Directory of Open Access Journals (Sweden)

Karolline S. da Silva

2017-09-01

Full Text Available Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin in healthy rats, associated or not with N-acetylcysteine (NAC treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML and pyrraline (PYR were determined by LC/mass spectrometry (LC-MS/MS and ELISA.Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups.Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE

The ESTRO Breur Lecture 2010: Toward a tailored patient approach in rectal cancer

International Nuclear Information System (INIS)

Haustermans, Karin; Debucquoy, Annelies; Lambrecht, Maarten

2011-01-01

The last decades have been characterized by tremendous improvements in the treatment of rectal cancer. Based on the evidence gathered in these years, the standard treatment of patients with locally advanced rectal cancer has now become preoperative chemoradiation (CRT) followed by total mesorectal excision. Although the locoregional control with this treatment regimen is quite favorable for the majority of the patients, there is still room for further improvement. For those patients with a good response to preoperative chemoradiation (CRT), extensive surgery could be avoided and replaced by minimal invasive surgery or no surgery at all. To date however, the only way to ascertain a complete remission is pathologic examination of the resection specimen. Early response prediction of the tumor to preoperative CRT is essential for further selection of patients who could be spared invasive surgery. This could be achieved by assessing molecular markers present in the tumor tissue and blood of the patients or by non invasive functional imaging before and during preoperative treatment. For those patients with a less favorable response, treatment intensification might be the way to go. This could be accomplished by dose painting on resistant tumor regions or by the addition of molecular targeted agents to the standard treatment. In this article, we review the current standard of care and the remaining challenges in the treatment of patients with locally advanced rectal cancer.

Clinical evaluation of chemoradiotherapy for advanced cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Kaneyasu, Yuko; Okawa, Tomohiko [Tokyo Women`s Medical Coll. (Japan); Okawa-Kita, Midori

1997-11-01

Locally advanced cervical cancer has a poor prognosis, poor survival rate, and high local failure rate. A number of questions regarding the optimal agents and schedule of concurrent chemoradiation remain unanswered. To improve the cure rate for advanced or recurrent cervix cancer, we studied intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. We analyzed 52 cases of advanced or recurrent cervical cancer treated by IAIC with or without radiotherapy. IAIC regimen was separated into two groups: group I consisted of 5-FU+MMC{+-}ADM (30 cases) and group II of CDDP+MMC{+-}5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR+PR) was 71%, 87% in patients receiving radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in group I and 38% in group II by chemotherapy regimen. Severe (more than grade III) hematological acute side effects were found in 48% of all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region which need narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervical cancer. But we should check blood flow distribution periodically, and control the concentration of drugs. To improve the survival rate for advanced or recurrent cervical cancer, we should discuss neoadjuvant chemotherapy followed by chemoradiotherapy and maintenance systemic chemotherapy. (author)

Clinical evaluation of chemoradiotherapy for advanced cervical cancer

International Nuclear Information System (INIS)

Kaneyasu, Yuko; Okawa, Tomohiko; Okawa-Kita, Midori.

1997-01-01

Locally advanced cervical cancer has a poor prognosis, poor survival rate, and high local failure rate. A number of questions regarding the optimal agents and schedule of concurrent chemoradiation remain unanswered. To improve the cure rate for advanced or recurrent cervix cancer, we studied intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. We analyzed 52 cases of advanced or recurrent cervical cancer treated by IAIC with or without radiotherapy. IAIC regimen was separated into two groups: group I consisted of 5-FU+MMC±ADM (30 cases) and group II of CDDP+MMC±5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR+PR) was 71%, 87% in patients receiving radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in group I and 38% in group II by chemotherapy regimen. Severe (more than grade III) hematological acute side effects were found in 48% of all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region which need narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervical cancer. But we should check blood flow distribution periodically, and control the concentration of drugs. To improve the survival rate for advanced or recurrent cervical cancer, we should discuss neoadjuvant chemotherapy followed by chemoradiotherapy and maintenance systemic chemotherapy. (author)

Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

International Nuclear Information System (INIS)

Banerjee, Robyn; Chakraborty, Santam; Nygren, Ian; Sinha, Richie

2013-01-01

Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3 small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

2014-01-01

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2014-06-15

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

International Nuclear Information System (INIS)

Janjan, Nora A.; Crane, Christopher N.; Feig, Barry W.; Cleary, Karen; Dubrow, Ronelle; Curley, Steven A.; Ellis, Lee M.; Vauthey, Jean-Nicolas; Lenzi, Renato; Lynch, Patrick; Wolff, Robert; Brown, Thomas; Pazdur, Richard; Abbruzzese, James; Hoff, Paulo M.; Allen, Pamela; Brown, Barry; Skibber, John

2000-01-01

Rationale: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. Methods and Materials: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m 2 ) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). Results: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per

Tensile and toughness assessment of the procured advanced alloys

Energy Technology Data Exchange (ETDEWEB)

Tan, Lizhen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sokolov, Mikhail A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hoelzer, David T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Busby, Jeremy T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2015-09-11

Life extension of the existing nuclear reactors imposes irradiation of high fluences to structural materials, resulting in significant challenges to the traditional reactor materials such as type 304 and 316 stainless steels. Advanced alloys with superior radiation resistance will increase safety margins, design flexibility, and economics for not only the life extension of the existing fleet but also new builds with advanced reactor designs. The Electric Power Research Institute (EPRI) teamed up with Department of Energy (DOE) to initiate the Advanced Radiation Resistant Materials (ARRM) program, aiming to develop and test degradation resistant alloys from current commercial alloy specifications by 2021 to a new advanced alloy with superior degradation resistance by 2024 in light water reactor (LWR)-relevant environments

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

Science.gov (United States)

Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

2016-04-01

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

2016-04-01

Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Neutrophilia in locally advanced cervical cancer: A novel biomarker for image-guided adaptive brachytherapy?

Science.gov (United States)

Escande, Alexandre; Haie-Meder, Christine; Maroun, Pierre; Gouy, Sébastien; Mazeron, Renaud; Leroy, Thomas; Bentivegna, Enrica; Morice, Philippe; Deutsch, Eric; Chargari, Cyrus

2016-01-01

Objective To study the prognostic value of leucocyte disorders in a prospective cohort of cervical cancer patients receiving definitive chemoradiation plus image—guided adaptive brachytherapy (IGABT). Results 113 patients were identified. All patients received a pelvic irradiation concomitant with chemotherapy, extended to the para-aortic area in 13 patients with IVB disease. Neutrophilia and leukocytosis were significant univariate prognostic factors for poorer local failure-free survival (p = 0.000 and p = 0.002, respectively), associated with tumor size, high-risk clinical target volume (HR-CTV) and anemia. No effect was shown for distant metastases but leukocytosis and neutrophila were both poor prognostic factors for in-field relapses (p = 0.003 and p 7,500/μl (p = 0.018) were independent factors for poorer survival without local failure, with hazard ratio (HR) of 3.1. Materials and methods We examined patients treated in our Institution between April 2009 and July 2015 by concurrent chemoradiation (45 Gy in 25 fractions +/− lymph node boosts) followed by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate brachytherapy (15 Gy to the intermediate-risk clinical target volume). The prognostic value of pretreatment leucocyte disorders was examined. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10,000 and 7,500/μl, respectively. Conclusions Neutrophilia is a significant prognostic factor for local relapse in locally advanced cervical cancer treated with MRI-based IGABT. This biomarker could help identifying patients with higher risk of local relapse and requiring dose escalation. PMID:27713124

TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Dalah, E; Tai, A; Oshima, K; Hall, W; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2015-06-15

Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment

Reliability of Strength Testing using the Advanced Resistive Exercise Device and Free Weights

Science.gov (United States)

English, Kirk L.; Loehr, James A.; Laughlin, Mitzi A.; Lee, Stuart M. C.; Hagan, R. Donald

2008-01-01

The Advanced Resistive Exercise Device (ARED) was developed for use on the International Space Station as a countermeasure against muscle atrophy and decreased strength. This investigation examined the reliability of one-repetition maximum (1RM) strength testing using ARED and traditional free weight (FW) exercise. Methods: Six males (180.8 +/- 4.3 cm, 83.6 +/- 6.4 kg, 36 +/- 8 y, mean +/- SD) who had not engaged in resistive exercise for at least six months volunteered to participate in this project. Subjects completed four 1RM testing sessions each for FW and ARED (eight total sessions) using a balanced, randomized, crossover design. All testing using one device was completed before progressing to the other. During each session, 1RM was measured for the squat, heel raise, and deadlift exercises. Generalizability (G) and intraclass correlation coefficients (ICC) were calculated for each exercise on each device and were used to predict the number of sessions needed to obtain a reliable 1RM measurement (G . 0.90). Interclass reliability coefficients and Pearson's correlation coefficients (R) also were calculated for the highest 1RM value (1RM9sub peak)) obtained for each exercise on each device to quantify 1RM relationships between devices.

Chemotherapy resistance mechanisms in advanced skin cancer

Directory of Open Access Journals (Sweden)

Bhuvanesh Sukhlal Kalal

2017-03-01

Full Text Available Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma.

Impact of primary para-aortic lymphadenectomy on distant failure in locally advanced cervical cancer patients treated in the era of image-guided adaptive brachytherapy.

Science.gov (United States)

Chargari, Cyrus; Mazeron, Renaud; Dunant, Ariane; Gouy, Sébastien; Petit, Claire; Maroun, Pierre; Uzan, Catherine; Annede, Pierre; Bentivegna, Enrica; Balleyguier, Corinne; Genestie, Catherine; Pautier, Patricia; Leary, Alexandra; Lhomme, Catherine; Deutsch, Eric; Morice, Philippe; Haie-Meder, Christine

2016-12-01

To investigate the impact of a primary para-aortic lymphadenectomy (PAL) in locally advanced cervical cancer patients receiving definitive chemoradiation, we reviewed the clinical records of consecutive patients treated in our Institution and receiving an external beam irradiation followed with an image-guided adaptive brachytherapy for a locally advanced cervical cancer. We examined the impact of performing a primary PAL as part of primary staging for guiding irradiation fields in patients without extra-pelvic PET uptake. The outcome of patients presenting para-aortic lymph node uptake (PALNU) was also examined. 186 patients were identified. Median follow-up was 44.4 months. Patients receiving a primary PAL (PAL group) and those who received upfront pelvic chemoradiation (no-PAL group) did not significantly differ for loco-regional failures. Survival without distant failure (DFFS), including para-aortic relapses, was at 3 years 87 % (95 % CI 84-90 %) in PAL group, 67 % (95 % CI 59-85 %) in the no-PAL group and 44 % (95 % CI 32-66 %) in the PALNU group (p = 0.04 for comparison between PAL and no-PAL groups). In a multivariate model including para-aortic lymphadenectomy, pelvic nodal uptake and high-risk clinical target volume as adjustment variables, a para-aortic lymphadenectomy was significant for DFS (HR = 0.47, 95 % CI 0.26-0.84, p = 0.01). Although confounding factors could account for these retrospective results, a primary PAL with tailored irradiation fields based on para-aortic histological findings seems to be associated with a better control for distant metastases. A randomized trial is testing the benefit of this strategy.

Combined chemo-radiation therapy to adult patients with B-cell lymphoma in stage I and II

International Nuclear Information System (INIS)

Shimoyama, Masanori

1988-01-01

155 adult patients with B-lymphoma in stage I and II who were treated in National Cancer Center Hospital between 1975 and 1986 were analyzed for treatment outcome. 5-year survival rates were about 66 % in these patients and almost equal in the patients treated with radiation alone, doxorubicin-containing combination chemotherapy alone, or combined chemoradiation therapy. However, when analysis was limited to patients in stage I, patients treated with chemotherapy alone seemed to have better survival rate than those treated with radiation alone. In the patients who were in stage III or more and had bulky mass more than 10 cm in diameter, small residual tumor was sometimes detected by restaging procedure after achieving apparent remission by multi-drug chemotherapy. In these patients, additional radiation therapy was quite usefull to eradicate residual tumor cell to cure. (author)

SU-F-R-50: Radiation-Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

International Nuclear Information System (INIS)

Chen, X; Schott, D; Song, Y; Li, D; Hall, W; Erickson, B; Li, X

2016-01-01

Purpose: In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogram including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two-tailed t-test and the correlations were analyzed using Spearman rank correlation tests. Results: In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P<0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response. Conclusion: Significant changes in HU histogram and the histogram-based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.

SU-F-R-50: Radiation-Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, X; Schott, D; Song, Y; Li, D; Hall, W; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogram including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two-tailed t-test and the correlations were analyzed using Spearman rank correlation tests. Results: In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P<0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response. Conclusion: Significant changes in HU histogram and the histogram-based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.

Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

Science.gov (United States)

Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

2016-01-01

Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

Advances in pharmacovigilance initiatives surrounding antimicrobial resistance-Indian perspective.

Science.gov (United States)

Bairy, Laxminarayana Kurady; Nayak, Veena; A, Avinash; Kunder, Sushil Kiran

2016-08-01

In recent years the development of antimicrobial resistance has been accelerating, the discovery of new antimicrobial agents has slowed substantially in past decades. This review mainly focuses on the problem of antimicrobial resistance(AMR); the various contributor mechanisms, consequences and future of AMR. The review also highlights the irrational use of antimicrobials, improving their usage and problems associated with pharmacovigilance of antimicrobial resistance. Pharmacovigilance in the form of surveillance of antibiotic use is being done in 90% of the countries worldwide through the WHONET program developed by WHO. However, the data comes from a limited area of the globe. Data from every part of the world is required, so that there is geographical representation of every region. A major hurdle in quantifying the extent of antimicrobial resistance is the fact that there are several known microbes, that may turn out to be resistant to one or more of the several known antimicrobial agents. The global action plan initiated by WHO, if implemented successfully will definitely reduce AMR and will help in evaluating treatment interventions.

Recent advances in the management of resistant hypertension

OpenAIRE

Manolis, Athanasios J.; Kallistratos, Manolis S.; Doumas, Michalis; Pagoni, Stamatina; Poulimenos, Leonidas

2015-01-01

And suddenly, following the preliminary results of renal denervation and carotid baroreceptor stimulation, a big interest in resistant hypertension rose, and all interventionists, many of them with no previous experience with hypertension, fell in love with hypertension and especially resistant hypertension. In the European Society of Hypertension/International Society of Hypertension (ESH/ISH) 2014 Joint Hypertension meeting in Athens, there were no more than four to five sessions related to...

Effect of hydronephrosis on survival in advanced stage cervical cancer.

Science.gov (United States)

Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

2015-01-01

Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (phydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (pHydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be stratified into subgroups according to presence or absence of hydronephrosis.

Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

International Nuclear Information System (INIS)

Morganti, Alessio G.; Mignogna, Samantha; Deodato, Francesco; Massaccesi, Mariangela; Cilla, Savino; Calista, Franco; Serafini, Giovanni; Digesu, Cinzia; Macchia, Gabriella; Picardi, Vincenzo; Caravatta, Luciana; Di Lullo, Liberato; Giglio, Gianfranco; Sallustio, Giuseppina; Piermattei, Angelo

2011-01-01

Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m 2 plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

Concurrent chemoradiotherapy for advanced hypopharyngeal or cervical esophageal cancer

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Endo, Sohei; Hamada, Norihisa; Shigihara, Shuntaro

2001-01-01

Chemotherapy has been shown to be most effective when delivered concurrently with radiation for patients with untreated advanced-stage tumors. We conducted a concurrent chemoradiation protocol using systemic infusion of Cisplatin (CDDP) and 5-Fluorouracil (FU), followed by radical surgery. Thirty-six patients with advanced hypopharyngeal (n=28) or cervical esophageal cancer (n=8) received intravenous administration of CDDP (100 mg/m 2 ), followed by a 120-hour continuous infusion of 5-FU (1000 mg/m 2 /day), and concomitant radiotherapy (200 cGy/day x 20-35 fractions). One patient died of aspiration pneumonia. The rate of grade 3-4 hematological chemotoxicity was 27.8% (10/36). Pharyngo-laryngo-cervical esophagectomies were performed in 23 patients, one received partial resection of the hypopharynx, and one received radical neck dissection. Ten remaining patients refused radical surgery. In the resected specimens, 11 out of 24 (46%) were confirmed as complete response (CR). The median length of follow-up was 74.5 weeks. The projected 5-year survival was 39.7%. When the patients who had refused radical surgery for residual tumor were excluded, the 5-year survival rate rose up to 70.0% in the patients with hypopharyngeal cancer. Concurrent chemoradiotherapy can be safely and effectively applied. Preliminary pathological results indicate the possibility in improving the rate of organ preservation. (author)

Histologic response after neoadjuvant chemoradiotherapy in locally ...

African Journals Online (AJOL)

Background: Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically. This study aimed to assess pathological response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching ...

Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

International Nuclear Information System (INIS)

Cho, Kwan Ho

2004-01-01

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

Concurrent chemoradiotherapy in locally advanced carcinoma of the uterine cervix: a phase I/II prospective study

International Nuclear Information System (INIS)

Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hye Sook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

1998-01-01

Prospective, single arm. Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The international Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4, 140-5, 040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m 2 /day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m 2 /dy intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of 1 of RT. The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and II+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a

Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

International Nuclear Information System (INIS)

Dewas, Claire Vautravers; Créhange, Gilles; Maingon, Philippe; Dalban, Cécile; Petitfils, Aurélie; Peignaux, Karine; Truc, Gilles; Martin, Etienne; Khoury, Cédric; Dewas, Sylvain

2012-01-01

Chemoradiation is the standard treatment for anal cancer. 3D conformal radiotherapy (3D-CRT) is usually split in 2 sequences with a therapeutic break (gap) in between. Intensity-modulated radiation therapy (IMRT) makes it possible to reduce treatment time by abandoning this gap. The purpose of this study was to compare outcomes and toxicities in patients treated with either IMRT or 3D-CRT. Between 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6]. There was no difference between the two groups for response to treatment (p= 0.46). Two-year overall survival, locoregional relapse-free survival and colostomy-free survival rates were 88.5%, 63% and 60.3%, respectively for the IMRT group and 81%, 76.5% and 81.1% for the 3D-CRT group (all NS). Ten patients (37%) in 3D-CRT and 11 patients (45.8%) in IMRT (p= 0.524) had grade 3 acute toxicity. No grade 4 toxicity occurred. Our study suggests that further investigations concerning the use of IMRT to treat cancer of the anus are warranted. IMRT makes it possible to remove the gap, but with no impact on the prognosis. Nonetheless, a longer follow-up is essential to determine whether or not IMRT has an impact on late toxicity, local control and survival compared with conventional 3D-CRT

Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

Directory of Open Access Journals (Sweden)

Upasana Baruah

2014-01-01

Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

Assessment of peri- and postoperative complications and Karnofsky-performance status in head and neck cancer patients after radiation or chemoradiation that underwent surgery with regional or free-flap reconstruction for salvage, palliation, or to improve function

Directory of Open Access Journals (Sweden)

Sertel Serkan

2011-09-01

Full Text Available Abstract Background Surgery after (chemoradiation (RCTX/RTX is felt to be plagued with a high incidence of wound healing complications reported to be as high as 70%. The additional use of vascularized flaps may help to decrease this high rate of complications. Therefore, we examined within a retrospective single-institutional study the peri--and postoperative complications in patients who underwent surgery for salvage, palliation or functional rehabilitation after (chemoradiation with regional and free flaps. As a second study end point the Karnofsky performance status (KPS was determined preoperatively and 3 months postoperatively to assess the impact of such extensive procedures on the overall performance status of this heavily pretreated patient population. Findings 21 patients were treated between 2005 and 2010 in a single institution (17 male, 4 female for salvage (10/21, palliation (4/21, or functional rehabilitation (7/21. Overall 23 flaps were performed of which 8 were free flaps. Major recipient site complications were observed in only 4 pts. (19% (1 postoperative haemorrhage, 1 partial flap loss, 2 fistulas and major donor site complications in 1 pt (wound dehiscence. Also 2 minor donor site complications were observed. The overall complication rate was 33%. There was no free flap loss. Assessment of pre- and postoperative KPS revealed improvement in 13 out of 21 patients (62%. A decline of KPS was noted in only one patient. Conclusions We conclude that within this (chemoradiated patient population surgical interventions for salvage, palliation or improve function can be safely performed once vascularised grafts are used.

Molecular mechanisms of cisplatin resistance in cervical cancer.

Science.gov (United States)

Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

2016-01-01

Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

Molecular mechanisms of cisplatin resistance in cervical cancer

Directory of Open Access Journals (Sweden)

Zhu H

2016-06-01

Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

Radiation-resistant requirements analysis of device and control component for advanced spent fuel management process

Energy Technology Data Exchange (ETDEWEB)

Song, Tai Gil; Park, G. Y.; Kim, S. Y.; Lee, J. Y.; Kim, S. H.; Yoon, J. S. [Korea Atomic Energy Research Institute, Taejeon (Korea)

2002-02-01

It is known that high levels of radiation can cause significant damage by altering the properties of materials. A practical understanding of the effects of radiation - how radiation affects various types of materials and components - is required to design equipment to operate reliably in a gamma radiation environment. When designing equipment to operate in a high gamma radiation environment, such as will be present in a nuclear spent fuel handling facility, several important steps should be followed. In order to active test of the advanced spent fuel management process, the radiation-resistant analysis of the device and control component for active test which is concerned about the radiation environment is conducted. Also the system design process is analysis and reviewed. In the foreign literature, 'threshold' values are generally reported. the threshold values are normally the dose required to begin degradation in a particular material property. The radiation effect analysis for the device of vol-oxidation and metalization, which are main device for the advanced spent fuel management process, is performed by the SCALE 4.4 code. 5 refs., 4 figs., 13 tabs. (Author)

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

International Nuclear Information System (INIS)

Leong, Trevor; Joon, Daryl Lim; Willis, David; Jayamoham, Jayasingham; Spry, Nigel; Harvey, Jennifer; Di Iulio, Juliana; Milner, Alvin; Mann, G. Bruce; Michael, Michael

2011-01-01

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.

Extreme ultraviolet resist materials for sub-7 nm patterning.

Science.gov (United States)

Li, Li; Liu, Xuan; Pal, Shyam; Wang, Shulan; Ober, Christopher K; Giannelis, Emmanuel P

2017-08-14

Continuous ongoing development of dense integrated circuits requires significant advancements in nanoscale patterning technology. As a key process in semiconductor high volume manufacturing (HVM), high resolution lithography is crucial in keeping with Moore's law. Currently, lithography technology for the sub-7 nm node and beyond has been actively investigated approaching atomic level patterning. EUV technology is now considered to be a potential alternative to HVM for replacing in some cases ArF immersion technology combined with multi-patterning. Development of innovative resist materials will be required to improve advanced fabrication strategies. In this article, advancements in novel resist materials are reviewed to identify design criteria for establishment of a next generation resist platform. Development strategies and the challenges in next generation resist materials are summarized and discussed.

Extreme ultraviolet resist materials for sub-7 nm patterning

KAUST Repository

Li, Li; Liu, Xuan; Pal, Shyam; Wang, Shulan; Ober, Christopher K.; Giannelis, Emmanuel P.

2017-01-01

Continuous ongoing development of dense integrated circuits requires significant advancements in nanoscale patterning technology. As a key process in semiconductor high volume manufacturing (HVM), high resolution lithography is crucial in keeping with Moore's law. Currently, lithography technology for the sub-7 nm node and beyond has been actively investigated approaching atomic level patterning. EUV technology is now considered to be a potential alternative to HVM for replacing in some cases ArF immersion technology combined with multi-patterning. Development of innovative resist materials will be required to improve advanced fabrication strategies. In this article, advancements in novel resist materials are reviewed to identify design criteria for establishment of a next generation resist platform. Development strategies and the challenges in next generation resist materials are summarized and discussed.

Auxinic herbicides, mechanisms of action, and weed resistance: A look into recent plant science advances

Directory of Open Access Journals (Sweden)

Pedro Jacob Christoffoleti

2015-08-01

Full Text Available Auxin governs dynamic cellular processes involved at several stages of plant growth and development. In this review, we discuss the mechanisms employed by auxin in light of recent scientific advances, with a focus on synthetic auxins as herbicides and synthetic auxin resistance mechanisms. Two auxin receptors were reported. The plasma membrane receptor ABP1 (Auxin Binding Protein 1 alters the structure and arrangement of actin filaments and microtubules, leading to plant epinasty and reducing peroxisomes and mitochondria mobility in the cell environment. The second auxin receptor is the gene transcription pathway regulated by the SCFTir/AFB ubiquitination complex, which destroys transcription repressor proteins that interrupt Auxin Response Factor (ARF activation. As a result mRNA related with Abscisic Acid (ABA and ethylene are transcribed, producing high quantities of theses hormones. Their associated action leads to high production of Reactive Oxygen Species (ROS, leading to tissue and plant death. Recently, another ubiquitination pathway which is described as a new auxin signaling route is the F-box protein S-Phase Kinase-Associated Protein 2A (SKP2A. It is active in cell division regulation and there is evidence that auxin herbicides can deregulate the SKP2A pathway, which leads to severe defects in plant development. In this discussion, we propose that SFCSKP2A auxin binding site alteration could be a new auxinic herbicide resistance mechanism, a concept which may contribute to the current progress in plant biology in its quest to clarify the many questions that still surround auxin herbicide mechanisms of action and the mechanisms of weed resistance.

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

Science.gov (United States)

Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

2014-01-01

BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

International Nuclear Information System (INIS)

Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

2015-01-01

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

Energy Technology Data Exchange (ETDEWEB)

Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

2015-06-01

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

Advanced surveillance of Resistance Temperature Detectors in Nuclear Power Plants

International Nuclear Information System (INIS)

Montalvo, C.; García-Berrocal, A.; Bermejo, J.A.; Queral, C.

2014-01-01

Highlights: • A two time constant transfer function is proposed to describe the Resistance Temperature Detector dynamics. • One constant is only related to the inner dynamics whereas the other one is related to the process and to the inner dynamics. • The two time constants have been found in several RTDs from a Nuclear Power Plant. • A Monte Carlo simulation is used to properly adjust the sampling time to find both constants. - Abstract: The dynamic response of several RTDs located at the cold leg of a PWR has been studied. A theoretical model for the heat transfer between the RTDs and the surrounding fluid is derived. It proposes a two real poles transfer function. By means of noise analysis techniques in the time domain (autoregressive models) and the Dynamic Data System methodology, the two time constants of the system can be found. A Monte Carlo simulation is performed in order to choose the proper sampling time to obtain both constants. The two poles are found and they permit an advance in situ surveillance of the sensor response time and the sensor dynamics performance. One of the poles is related to the inner dynamics whereas the other one is linked to the process and the inner dynamics. So surveillance on the process and on the inner dynamics can be distinguished

Extreme ultraviolet resist materials for sub-7 nm patterning

KAUST Repository

Li, Li

2017-06-26

Continuous ongoing development of dense integrated circuits requires significant advancements in nanoscale patterning technology. As a key process in semiconductor high volume manufacturing (HVM), high resolution lithography is crucial in keeping with Moore\\'s law. Currently, lithography technology for the sub-7 nm node and beyond has been actively investigated approaching atomic level patterning. EUV technology is now considered to be a potential alternative to HVM for replacing in some cases ArF immersion technology combined with multi-patterning. Development of innovative resist materials will be required to improve advanced fabrication strategies. In this article, advancements in novel resist materials are reviewed to identify design criteria for establishment of a next generation resist platform. Development strategies and the challenges in next generation resist materials are summarized and discussed.

Profiling Prostate Cancer Therapeutic Resistance

OpenAIRE

Cameron A. Wade; Natasha Kyprianou

2018-01-01

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

Generation of advanced fire blight-resistant apple (Malus × domestica) selections of the fifth generation within 7 years of applying the early flowering approach.

Science.gov (United States)

Schlathölter, Ina; Jänsch, Melanie; Flachowsky, Henryk; Broggini, Giovanni Antonio Lodovico; Hanke, Magda-Viola; Patocchi, Andrea

2018-03-14

The approach presented here can be applied to reduce the time needed to introduce traits from wild apples into null segregant advanced selections by one-fourth. Interesting traits like resistances to pathogens are often found within the wild apple gene pool. However, the long juvenile phase of apple seedlings hampers the rapid introduction of these traits into new cultivars. The rapid crop cycle breeding approach used in this paper is based on the overexpression of the birch (Betula pendula) MADS4 transcription factor in apple. Using the early flowering line T1190 and 'Evereste' as source of the fire blight resistance (Fb_E locus), we successfully established 18 advanced selections of the fifth generation in the greenhouse within 7 years. Fifteen individuals showed the habitus expected of a regular apple seedling, while three showed very short internodes. The null segregants possessing a regular habitus maintained the high level of fire blight resistance typical for 'Evereste'. Using SSR markers, we estimated the percentage of genetic drag from 'Evereste' still associated with Fb_E on linkage group 12 (LG12). Eight out of the 18 selections had only 4% of 'Evereste' genome left. Since genotypes carrying the apple scab resistance gene Rvi6 and the fire blight resistance QTL Fb_F7 were used as parents in the course of the experiments, these resistances were also identified in some of the null segregants. One seedling is particularly interesting as, beside Fb_E, it also carries Fb_F7 heterozygously and Rvi6 homozygously. If null segregants obtained using this method will be considered as not genetically modified in Europe, as is already the case in the USA, this genotype could be a very promising parent for breeding new fire blight and scab-resistant apple cultivars in European apple breeding programs.

High-Performance Corrosion-Resistant Materials: Iron-Based Amorphous-Metal Thermal-Spray Coatings: SAM HPCRM Program ? FY04 Annual Report ? Rev. 0 - DARPA DSO & DOE OCRWM Co-Sponsored Advanced Materials Program

Energy Technology Data Exchange (ETDEWEB)

Farmer, J; Haslam, J; Wong, F; Ji, S; Day, S; Branagan, D; Marshall, M; Meacham, B; Buffa, E; Blue, C; Rivard, J; Beardsley, M; Buffa, E; Blue, C; Rivard, J; Beardsley, M; Weaver, D; Aprigliano, L; Kohler, L; Bayles, R; Lemieux, E; Wolejsza, T; Martin, F; Yang, N; Lucadamo, G; Perepezko, J; Hildal, K; Kaufman, L; Heuer, A; Ernst, F; Michal, G; Kahn, H; Lavernia, E

2007-09-19

The multi-institutional High Performance Corrosion Resistant Materials (HPCRM) Team is cosponsored by the Defense Advanced Projects Agency (DARPA) Defense Science Office (DSO) and the Department of Energy (DOE) Office of Civilian Radioactive Waste Management (OCRWM), and has developed new corrosion-resistant, iron-based amorphous metals that can be applied as coatings with advanced thermal spray technology. Two compositions have corrosion resistance superior to wrought nickel-based Alloy C-22 (UNS No. N06022) in very aggressive environments, including concentrated calcium-chloride brines at elevated temperature. Corrosion costs the Department of Defense billions of dollars every year, with an immense quantity of material in various structures undergoing corrosion. For example, in addition to fluid and seawater piping, ballast tanks, and propulsions systems, approximately 345 million square feet of structure aboard naval ships and crafts require costly corrosion control measures. The use of advanced corrosion-resistant materials to prevent the continuous degradation of this massive surface area would be extremely beneficial. The Fe-based corrosion-resistant, amorphous-metal coatings under development may prove of importance for applications on ships. Such coatings could be used as an 'integral drip shield' on spent fuel containers, as well as protective coatings that could be applied over welds, thereby preventing exposure to environments that might cause stress corrosion cracking. In the future, such new high-performance iron-based materials could be substituted for more-expensive nickel-based alloys, thereby enabling a reduction in the $58-billion life cycle cost for the long-term storage of the Nation's spent nuclear fuel by tens of percent.

18F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

International Nuclear Information System (INIS)

Siva, Shankar; Hicks, Rodney J.; Callahan, Jason; Deb, Siddhartha; Young, Richard J.; Bressel, Mathias; Mileshkin, Linda; Rischin, Danny; Bernshaw, David; Narayan, Kailash

2015-01-01

To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed. Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status. In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but

Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

International Nuclear Information System (INIS)

Gradishar, William J

2016-01-01

Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

New Generation of Resistant Sugar Beet Varieties for Advanced Integrated Management of Cercospora Leaf Spot in Central Europe.

Science.gov (United States)

Vogel, Johannes; Kenter, Christine; Holst, Carsten; Märländer, Bernward

2018-01-01

Cercospora leaf spot (CLS) epidemics in sugar beet have been increasing in recent years causing higher use of fungicides. Concomitantly, the availability of effective fungicides is at risk because of resistance development in the fungus, the lack of new active ingredients as well as restrictive approval practices. A key option for an integrated management of CLS is cultivation of resistant varieties. Because of the yield penalty in resistant varieties, acceptance in commercial practice so far has been low. The aim of our study was to characterize recent sugar beet varieties registered in Germany in terms of resistance and tolerance to CLS and their value for integrated pest management. The genetic basis of CLS resistance in varieties is protected by intellectual property rights even after variety registration and not open to the public due to economic competition. To gain reliable data for cultivation, varieties have to be tested for their resistance traits under field conditions at varying levels of infection with Cercospora beticola . In collaboration with variety related stakeholders, 15 sugar beet varieties were tested in 49 field trials in Germany from 2014 to 2016 for their yield response to CLS. The trials were set up in a split-plot design with and without infection (i.e., with and without fungicide). The classification of varietal reaction to CLS is based on symptomatic leaf area (susceptibility) and the resulting relative yield loss (tolerance). Since the relation between both parameters varied among varieties, it was used as an additional parameter to describe tolerance. On this basis, three groups of varieties were identified. They can be characterized as a susceptible, a resistant and a presumably tolerant cluster. A comparison of the data with an older dataset originating from 2009 to 2011 revealed that yield performance of recent varieties with resistance to C. beticola caught up with susceptible varieties due to breeding progress. They showed no

Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparoscopic lymphadenectomy

Energy Technology Data Exchange (ETDEWEB)

Marnitz, Simone; Schram, Johanna; Budach, Volker [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Sackerer, Irina [Technische Universitaet Muenchen, Department of Radiation Oncology, Muenchen (Germany); Vercellino, Giuseppe Filiberto [University Medicine Berlin, Department of Gynecology, Campus Benjamin Franklin, Berlin (Germany); Sehouli, Jalid [University Medicine Berlin, Department of Gynecology, Campus Benjamin Franklin and Virchow, Berlin (Germany); Koehler, Christhardt [ASKLEPIOS Clinic Hamburg-Harburg, Department of Specialized Surgical and Oncologic Gynecology, Hamburg (Germany)

2015-05-01

The purpose of this work was to evaluate the use of extended-field chemoradiation (EFRT) with concomitant chemotherapy in patients with histologically confirmed para-aortic metastases after laparoscopic para-aortic and pelvic lymphadenectomy (LAE) with regard to oncologic results and treatment-related toxicity. A total of 44 women with squamous cell carcinoma (82 %) and adenocarcinoma (18 %) of the cervix in FIGO stages IIA (n = 3), IIB (n = 29); IIIB (n = 9), and IVA (n = 3) and histologically proven para-aortic metastases underwent EFRT and chemotherapy. Laparoscopic LAE was performed in 40 patients. Patients underwent chemoradiation with conventional fractionation of 1.8-50.4 Gy to the para-aortic and pelvic region. In addition, MRI-guided brachytherapy was performed to the cervix with 5-6 single doses of 5 Gy for a total dose of 25-30 Gy. The mean number of harvested lymph nodes was 17 in the pelvic as well as para-aortic regions, respectively. Laparoscopic intervention did not delay chemoradiation. Follow-up was 6-76 months (mean 25.1 months). There was no grade 4 or 5 acute radiation toxicity. In all, 8, 4, and 11 % grade 1, 2, and 3 gastrointestinal late toxicities and 7, 11, and 19 % grade 1, 2 and 3 genitourinary late toxicities were recorded. Despite the excellent locoregional (pelvic) control rates of 89.1 and 82.8 % after 2 and 5 years, respectively, the overall survival rates were 68.4 and 54.1 % after 2 and 5 years, respectively. Of the 44 patients, 43 remained tumor free in the para-aortic region. In patients with proven para-aortic disease, excellent pelvic and para-aortic control could be achieved by laparoscopic LAE followed by EFRT. More than half of the patients were long-term survivors. The high risk of distant metastases should be addressed by further improving systemic treatment. (orig.) [German] Ziel dieser Arbeit war es,die onkologischen Ergebnisse und die Toxizitaet der ''Extended-field''-Radiochemotherapie (EFRT) im

The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

Science.gov (United States)

Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

2013-09-01

Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

Re-irradiation with 36 Gy (1.5 Gy Twice Daily) Plus Paclitaxel for Advanced Recurrent and Previously Irradiated SCCHN is Feasible.

Science.gov (United States)

Rades, Dirk; Bartscht, Tobias; Idel, Christian; Hakim, Samer G

2018-01-01

Many patients developing a loco-regional recurrence of squamous cell carcinoma of head and neck (SCCHN) have a poor prognosis. Often, recurrences are unresectable, and patients require a second course of radiotherapy or chemoradiation. We present an approach of chemoradiation including mainly 30 Gy of radiotherapy (1.5 Gy twice daily) plus concurrent paclitaxel. To further improve the prognoses of these patients, we increased the radiation dose from 30 to 36 Gy. In four patients with recurrent and previously irradiated SCCHN (60-70 Gy) chemoradiation was carried out using 36 Gy (1.5 Gy twice daily) and concurrent paclitaxel (4-5 times 20-25 mg/m 2 ). One-year loco-regional control rates were 75% inside and 67% outside re-irradiated regions. One-year survival was 50%, and median survival time 11 months. Toxicities were mild (grade 0-2). Re-irradiation with 36 Gy (1.5 Gy twice daily) plus paclitaxel appears feasible and may lead to promising outcomes. This study is preceding a phase I trial. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

RTOG 0417: Efficacy of Bevacizumab in Combination With Definitive Radiation Therapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma

International Nuclear Information System (INIS)

Schefter, Tracey; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian Patrick; Small, William; Sause, William; Gaffney, David

2014-01-01

Purpose: Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS). Methods and Materials: Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m 2 ) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method. Results: 49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively. Conclusion: In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical cancer

National Antimicrobial Resistance Monitoring System: Two Decades of Advancing Public Health Through Integrated Surveillance of Antimicrobial Resistance.

Science.gov (United States)

Karp, Beth E; Tate, Heather; Plumblee, Jodie R; Dessai, Uday; Whichard, Jean M; Thacker, Eileen L; Hale, Kis Robertson; Wilson, Wanda; Friedman, Cindy R; Griffin, Patricia M; McDermott, Patrick F

2017-10-01

Drug-resistant bacterial infections pose a serious and growing public health threat globally. In this review, we describe the role of the National Antimicrobial Resistance Monitoring System (NARMS) in providing data that help address the resistance problem and show how such a program can have broad positive impacts on public health. NARMS was formed two decades ago to help assess the consequences to human health arising from the use of antimicrobial drugs in food animal production in the United States. A collaboration among the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Department of Agriculture, and state and local health departments, NARMS uses an integrated "One Health" approach to monitor antimicrobial resistance in enteric bacteria from humans, retail meat, and food animals. NARMS has adapted to changing needs and threats by expanding surveillance catchment areas, examining new isolate sources, adding bacteria, adjusting sampling schemes, and modifying antimicrobial agents tested. NARMS data are not only essential for ensuring that antimicrobial drugs approved for food animals are used in ways that are safe for human health but they also help address broader food safety priorities. NARMS surveillance, applied research studies, and outbreak isolate testing provide data on the emergence of drug-resistant enteric bacteria; genetic mechanisms underlying resistance; movement of bacterial populations among humans, food, and food animals; and sources and outcomes of resistant and susceptible infections. These data can be used to guide and evaluate the impact of science-based policies, regulatory actions, antimicrobial stewardship initiatives, and other public health efforts aimed at preserving drug effectiveness, improving patient outcomes, and preventing infections. Many improvements have been made to NARMS over time and the program will continue to adapt to address emerging resistance threats, changes in

High-Performance Corrosion-Resistant Materials: Iron-Based Amorphous-Metal Thermal-Spray Coatings: SAM HPCRM Program ? FY04 Annual Report ? Rev. 0 - DARPA DSO and DOE OCRWM Co-Sponsored Advanced Materials Program

International Nuclear Information System (INIS)

Farmer, J; Haslam, J; Wong, F; Ji, S; Day, S; Branagan, D; Marshall, M; Meacham, B; Buffa, E; Blue, C; Rivard, J; Beardsley, M; Buffa, E; Blue, C; Rivard, J; Beardsley, M; Weaver, D; Aprigliano, L; Kohler, L; Bayles, R; Lemieux, E; Wolejsza, T; Martin, F; Yang, N; Lucadamo, G; Perepezko, J; Hildal, K; Kaufman, L; Heuer, A; Ernst, F; Michal, G; Kahn, H; Lavernia, E

2007-01-01

The multi-institutional High Performance Corrosion Resistant Materials (HPCRM) Team is cosponsored by the Defense Advanced Projects Agency (DARPA) Defense Science Office (DSO) and the Department of Energy (DOE) Office of Civilian Radioactive Waste Management (OCRWM), and has developed new corrosion-resistant, iron-based amorphous metals that can be applied as coatings with advanced thermal spray technology. Two compositions have corrosion resistance superior to wrought nickel-based Alloy C-22 (UNS No. N06022) in very aggressive environments, including concentrated calcium-chloride brines at elevated temperature. Corrosion costs the Department of Defense billions of dollars every year, with an immense quantity of material in various structures undergoing corrosion. For example, in addition to fluid and seawater piping, ballast tanks, and propulsions systems, approximately 345 million square feet of structure aboard naval ships and crafts require costly corrosion control measures. The use of advanced corrosion-resistant materials to prevent the continuous degradation of this massive surface area would be extremely beneficial. The Fe-based corrosion-resistant, amorphous-metal coatings under development may prove of importance for applications on ships. Such coatings could be used as an 'integral drip shield' on spent fuel containers, as well as protective coatings that could be applied over welds, thereby preventing exposure to environments that might cause stress corrosion cracking. In the future, such new high-performance iron-based materials could be substituted for more-expensive nickel-based alloys, thereby enabling a reduction in the $58-billion life cycle cost for the long-term storage of the Nation's spent nuclear fuel by tens of percent

Wear Resistance Analysis of A359/SiC/20p Advanced Composite Joints Welded by Friction Stir Welding

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O. Cuevas Mata

Full Text Available Abstract Advancement in automotive part development demands new cost-effective materials with higher mechanical properties and improved wear resistance as compared to existing materials. For instance, Aluminum Matrix Composites (AMC shows improved mechanical properties as wear and abrasion resistance, high strength, chemical and dimensional stability. Automotive industry has focused in AMC for a variety of applications in automotive parts in order to improve the fuel economy, minimize vehicle emissions, improve design options, and increase the performance. Wear resistance is one of the most important factors in useful life of the automotive components, overall in those components submitted to mechanical systems like automotive brakes and suspensions. Friction Stir Welding (FSW rises as the most capable process to joining AMC, principally for the capacity to weld without compromising their ceramic reinforcement. The aim of this study is focused on the analysis of wear characteristics of the friction-stir welded joint of aluminum matrix reinforced with 20 percent in weight silicon carbide composite (A359/SiC/20p. The experimental procedure consisted in cut samples into small plates and perform three welds on these with a FSW machine using a tool with 20 mm shoulder diameter and 8 mm pin diameter. The wear features of the three welded joints and parent metal were analyzed at constant load applying 5 N and a rotational speed of 100 rpm employing a Pin-on - Disk wear testing apparatus, using a sapphire steel ball with 6 mm diameter. The experimental results indicate that the three welded joints had low friction coefficient compared with the parent metal. The results determine that the FSW process parameters affect the wear resistance of the welded joints owing to different microstructural modifications during welding that causes a low wear resistance on the welded zone.

Improvement of electrical resistivity tomography for leachate injection monitoring

International Nuclear Information System (INIS)

Clement, R.; Descloitres, M.; Guenther, T.; Oxarango, L.; Morra, C.; Laurent, J.-P.; Gourc, J.-P.

2010-01-01

Leachate recirculation is a key process in the scope of operating municipal waste landfills as bioreactors, which aims to increase the moisture content to optimize the biodegradation in landfills. Given that liquid flows exhibit a complex behaviour in very heterogeneous porous media, in situ monitoring methods are required. Surface time-lapse electrical resistivity tomography (ERT) is usually proposed. Using numerical modelling with typical 2D and 3D injection plume patterns and 2D and 3D inversion codes, we show that wrong changes of resistivity can be calculated at depth if standard parameters are used for time-lapse ERT inversion. Major artefacts typically exhibit significant increases of resistivity (more than +30%) which can be misinterpreted as gas migration within the waste. In order to eliminate these artefacts, we tested an advanced time-lapse ERT procedure that includes (i) two advanced inversion tools and (ii) two alternative array geometries. The first advanced tool uses invariant regions in the model. The second advanced tool uses an inversion with a 'minimum length' constraint. The alternative arrays focus on (i) a pole-dipole array (2D case), and (ii) a star array (3D case). The results show that these two advanced inversion tools and the two alternative arrays remove almost completely the artefacts within +/-5% both for 2D and 3D situations. As a field application, time-lapse ERT is applied using the star array during a 3D leachate injection in a non-hazardous municipal waste landfill. To evaluate the robustness of the two advanced tools, a synthetic model including both true decrease and increase of resistivity is built. The advanced time-lapse ERT procedure eliminates unwanted artefacts, while keeping a satisfactory image of true resistivity variations. This study demonstrates that significant and robust improvements can be obtained for time-lapse ERT monitoring of leachate recirculation in waste landfills.

{sup 18}F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

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Siva, Shankar; Hicks, Rodney J.; Callahan, Jason [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia); University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Deb, Siddhartha [Peter MacCallum Cancer Centre, Department of Pathology, East Melbourne (Australia); Young, Richard J. [Peter MacCallum Cancer Centre, Molecular Therapeutics and Biomarkers Laboratory, East Melbourne (Australia); Bressel, Mathias [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, East Melbourne (Australia); Mileshkin, Linda [Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Rischin, Danny [University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Bernshaw, David; Narayan, Kailash [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia)

2015-11-15

To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed. Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status. In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis

International Nuclear Information System (INIS)

Koëter, M.; Kathiravetpillai, N.; Gooszen, J.A.; Berge Henegouwen, M.I. van; Gisbertz, S.S.; Sangen, M.J.C. van der; Luyer, M.D.P.; Nieuwenhuijzen, G.A.P.; Hulshof, M.C.C.M.

2017-01-01

Purpose: To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Methods and Materials: Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. Results: Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. Conclusion: With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis.

Science.gov (United States)

Koëter, M; Kathiravetpillai, N; Gooszen, J A; van Berge Henegouwen, M I; Gisbertz, S S; van der Sangen, M J C; Luyer, M D P; Nieuwenhuijzen, G A P; Hulshof, M C C M

2017-03-15

To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis

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Koëter, M.; Kathiravetpillai, N. [Department of Surgery, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Gooszen, J.A.; Berge Henegouwen, M.I. van; Gisbertz, S.S. [Department of Surgery, Academic Medical Centre Amsterdam, Amsterdam (Netherlands); Sangen, M.J.C. van der [Department of Radiation Oncology, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Luyer, M.D.P. [Department of Surgery, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Nieuwenhuijzen, G.A.P., E-mail: grard.nieuwenhuijzen@catharinaziekenhuis.nl [Department of Surgery, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Hulshof, M.C.C.M. [Department of Radiation Oncology, Academic Medical Centre Amsterdam, Amsterdam (Netherlands)

2017-03-15

Purpose: To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Methods and Materials: Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. Results: Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. Conclusion: With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.

Induction concurrent chemoradiation therapy for invading apical non-small cell lung cancer

International Nuclear Information System (INIS)

Miyoshi, Shinichiro; Nakamura, Kenji

2004-01-01

Although non-small cell lung cancer (NSCLC) involving the superior sulcus has been generally treated with radiation therapy (RT) followed by surgery, local recurrence is still a big problem to be solved. We investigated a role of induction therapy, especially induction concurrent chemoradiation therapy (CRT), on the surgical results of this type of NSCLC. We retrospectively reviewed 30 patients with NSCLC invading the apex of the chest wall who underwent surgery from 1987 to 1996. Ten patients (57±8 years) received surgery alone, 9 (55±13 years) received RT (42±7 Gy) followed by surgery and 11 (51±9 years) received cisplatin based chemotherapy and RT (47±5 Gy) as an induction therapy. Two and 4-year survival rates were 30% and 20% in patients with surgery alone, 22% and 11% in patients with induction RT, and 73% and 53% in patients with induction CRT, respectively. The survival was significantly better in patients with induction CRT than those with induction RT or surgery alone. Univariate analysis demonstrated that curability (yes versus no: p=0.027) and induction therapy (surgery alone and RT versus CRT: p=0.0173) were significant prognostic factors. Multivariate analysis revealed that only induction therapy (p=0.0238) was a significant prognostic factor. Induction CRT seems to improve the survival in patients with NSCLC invading the apex of the chest wall compared with induction RT or surgery alone. (author)

Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

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Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

2013-07-15

Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

NARCIS (Netherlands)

Gillessen, S.; Omlin, A.; Attard, G.; Bono, J.S. de; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P.S.; Sartor, O.; Smith, M.R.; Soule, H.R.; Akaza, H.; Beer, T.M.; Beltran, H.; Chinnaiyan, A.M.; Daugaard, G.; Davis, I.D.; Santis, M. de; Drake, C.G.; Eeles, R.A.; Fanti, S.; Gleave, M.E.; Heidenreich, A.; Hussain, M.; James, N.D.; Lecouvet, F.E.; Logothetis, C.J.; Mastris, K.; Nilsson, S.; Oh, W.K.; Olmos, D.; Padhani, A.R.; Parker, C.; Rubin, M.A.; Schalken, J.A.; Scher, H.I.; Sella, A.; Shore, N.D.; Small, E.J.; Sternberg, C.N.; Suzuki, H; Sweeney, C.J.; Tannock, I.F.; Tombal, B.

2015-01-01

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant

Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

International Nuclear Information System (INIS)

Tomaszewski, Jonathan M.; Link, Emma; Leong, Trevor; Heriot, Alexander; Vazquez, Melisa; Chander, Sarat; Chu, Julie; Foo, Marcus; Lee, Mark T.; Lynch, Craig A.; Mackay, John; Michael, Michael; Tran, Phillip; Ngan, Samuel Y.

2012-01-01

Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78–88), 92% (95% CI, 89–96), 73% (95% CI, 68–79), and 82% (95% CI, 77–87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.

Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

Energy Technology Data Exchange (ETDEWEB)

Tomaszewski, Jonathan M., E-mail: jonathan.tomaszewski@petermac.org [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Link, Emma [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Leong, Trevor [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia); Heriot, Alexander [University of Melbourne, Parkville, Victoria (Australia); Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Vazquez, Melisa [Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Chander, Sarat; Chu, Julie; Foo, Marcus; Lee, Mark T. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Lynch, Craig A. [Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Mackay, John [University of Melbourne, Parkville, Victoria (Australia); Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Michael, Michael [University of Melbourne, Parkville, Victoria (Australia); Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Tran, Phillip [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Ngan, Samuel Y. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia)

2012-06-01

Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.

Advanced accumulator for PWR

International Nuclear Information System (INIS)

Ichimura, Taiki; Chikahata, Hideyuki

1997-01-01

Advanced accumulators have been incorporated into the APWR design in order to simplify the safety system configuration and to improve reliability. The advanced accumulators refill the reactor vessel with a large discharge flow rate in a large LOCA, then switch to a small flow rate to continue safety injection for core reflooding. The functions of the conventional accumulator and the low head safety injection pump are integrated into this advanced accumulator. Injection performance tests simulating LOCA conditions and visualization tests for new designs have been carried out. This paper describes the APWR ECCS configuration, the advanced accumulator design and some of the injection performance and visualization test results. It was verified that the flow resistance of the advanced accumulator is independent of the model scale. The similarity law and performance data of the advanced accumulator for applying APWR was established. (author)

FIGO IVB (Para-aortic lymph adenopathy) squamous cell carcinoma of uterine cervix associated with a left pelvic kidney: a therapeutic challenge

International Nuclear Information System (INIS)

Ali, N.; Karsan, F.; Abbasi, A.N.; Khan, Z.R.

2012-01-01

The standard of care for locally advanced carcinoma of uterine cervix is concurrent chemoradiation therapy followed by intracavitary brachytherapy, when there is para-aortic lymphadenopathy, radiation field needs to be extended to para-aortic region. In the latter case dose limiting organs are spinal cord, kidneys and small intestine. We present a challenging case of FIGO IVB squamous cell carcinoma of cervix and a pelvic kidney. This patient received chemoradiation to pelvis and para-aortic field, brachytherapy was not performed as patient already had undergone attempted hysterectomy. Treatment, outcome and challenges encountered in this case are presented and literature is reviewed. (author)

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

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Deek, Matthew P.; Benenati, Brian [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Kim, Sinae [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Biometrics Division, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting; Ahmed, Inaya; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

2016-01-01

Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

Patterns of Care for Elderly Patients With Locally Advanced Head and Neck Cancer.

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Juarez, Jesus E; Choi, Jehee; St John, Maie; Abemayor, Elliot; TenNapel, Mindi; Chen, Allen M

2017-07-15

To compare patterns of care for elderly patients aged ≥70 years with locally advanced head and neck cancer versus those of younger patients treated for the same disease. The medical records of 421 consecutive patients over the age of 50 years treated at a single institution between April 2011 and June 2016 for stage III/IV squamous cell carcinoma of the head and neck were reviewed. The primary treatment approach was compared using a t test statistic among 3 age cohorts: 50 to 59 years (118 patients); 60 to 69 years (152 patients); and 70 years and older (151 patients). Logistical regression was used to determine variables that influenced the likelihood of receiving surgery versus nonsurgical treatment, as well as radiation alone versus chemoradiation. There was no difference in sex, T stage, N stage, Karnofsky performance status, or the number of chronic comorbid conditions among the 3 age cohorts (P>.05 for all). A greater proportion of elderly patients aged ≥70 years were treated by radiation alone compared with those aged 50 to 59 and 60 to 69 years (44% vs 16% and 24%, P=.01). Increasing age was associated with a greater likelihood of receiving primary nonsurgical versus surgical treatment (odds ratio 1.023, 95% confidence interval 1.004-1.042) and radiation alone compared with chemoradiation (odds ratio 1.054; 95% confidence interval 1.034-1.075). Ten chemotherapy regimens were used concurrently with radiation for patients aged ≥70 years, including carboplatin/paclitaxel (19%), carboplatin/cetuximab (19%), cisplatin (17%), and cetuximab (17%). Despite similar performance status and comorbidity burden compared with their younger counterparts, patients aged ≥70 years were more commonly treated with less-aggressive strategies, including radiation alone. The variability of concurrent chemotherapy regimens used further suggests that the standard of care remains to be defined for this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Resistance patterns among multidrug-resistant tuberculosis patients in greater metropolitan Mumbai: trends over time.

Science.gov (United States)

Dalal, Alpa; Pawaskar, Akshay; Das, Mrinalini; Desai, Ranjan; Prabhudesai, Pralhad; Chhajed, Prashant; Rajan, Sujeet; Reddy, Deepesh; Babu, Sajit; Jayalakshmi, T K; Saranchuk, Peter; Rodrigues, Camilla; Isaakidis, Petros

2015-01-01

While the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India. This was a retrospective, observational study of drug susceptibility testing (DST) results among MDR-TB patients from eight health care facilities in greater Mumbai between 2005 and 2013. We classified resistance patterns into four categories: MDR-TB, pre-XDR-TB, XDR-TB and XXDR-TB. A total of 340 MDR-TB patients were included in the study. Pre-XDR-TB was the most common form of drug-resistant TB observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB. The proportion of patients with MDR-TB was 39.4% in the period 2005-2007 and 27.8% in 2011-2013, while the proportion of those with XDR-TB and XXDR-TB was changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time period. During the same periods, the proportions of patients with ofloxacin, moxifloxacin and ethionamide resistance significantly increased from 57.6% to 75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (pMumbai highlight the need for individualized drug regimens, designed on the basis of DST results involving first- and second-line anti-TB drugs and treatment history of the patient. A drug-resistant TB case-finding strategy based on molecular techniques that identify only rifampicin resistance will lead to initiation of suboptimal treatment regimens for a significant number of patients, which may in turn contribute to amplification of resistance and transmission of strains with increasingly advanced resistance within the community.

Irradiation of FDG-PET–Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation

International Nuclear Information System (INIS)

Rose, Brent S.; Jee, Kyung-Wook; Niemierko, Andrzej; Murphy, Janet E.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Lee, Leslie K.; Wang, Yingbing; Drapek, Lorraine C.; Hong, Theodore S.; Wo, Jennifer Y.

2016-01-01

Purpose: Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT. Methods and Materials: The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM_5_0 and IBM_5_0, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC. Results: Mean ± SD ANC nadir was 0.77 × 10"9/L (±0.66 × 10"9/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM_5_0 and IBM_5_0 were all significantly associated with ANC nadir. However, model performance for ABM_5_0 was not superior to that of the TBM and IBM_5_0 models. Conclusions: Irradiation of pelvic BM was associated with HT. However, FDG-PET–defined ABM models failed to improve model performance compared to the TBM model.

Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

Science.gov (United States)

2016-01-01

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod

Directory of Open Access Journals (Sweden)

Taku Fujimura

2018-01-01

Full Text Available Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

Effects of advanced treatment systems on the removal of antibiotic resistance genes in wastewater treatment plants from Hangzhou, China.

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Chen, Hong; Zhang, Mingmei

2013-08-06

This study aimed at quantifying the concentration and removal of antibiotic resistance genes (ARGs) in three municipal wastewater treatment plants (WWTPs) employing different advanced treatment systems [biological aerated filter, constructed wetland, and ultraviolet (UV) disinfection]. The concentrations of tetM, tetO, tetQ, tetW, sulI, sulII, intI1, and 16S rDNA genes were examined in wastewater and biosolid samples. In municipal WWTPs, ARG reductions of 1-3 orders of magnitude were observed, and no difference was found among the three municipal WWTPs with different treatment processes (p > 0.05). In advanced treatment systems, 1-3 orders of magnitude of reductions in ARGs were observed in constructed wetlands, 0.6-1.2 orders of magnitude of reductions in ARGs were observed in the biological aerated filter, but no apparent decrease by UV disinfection was observed. A significant difference was found between constructed wetlands and biological filter (p removal of ARGs and 16S rDNA genes (R(2) = 0.391-0.866; p removal values with WWTP (p > 0.05) but also have the advantage in ARG relative abundance removal, and it should be given priority to be an advanced treatment system for further ARG attenuation from WWTP.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

Science.gov (United States)

Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

2012-11-01

Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Relationship Between Low Hemoglobin Levels and Outcomes After Treatment With Radiation or Chemoradiation in Patients With Cervical Cancer: Has the Impact of Anemia Been Overstated?

International Nuclear Information System (INIS)

Bishop, Andrew J.; Allen, Pamela K.; Klopp, Ann H.; Meyer, Larissa A.; Eifel, Patricia J.

2015-01-01

Purpose: Previous reports have suggested that anemia increases rates of recurrence after radiation therapy for cervical cancer. However, these studies may not have fully corrected for confounding risk factors. Using a well-characterized cohort of cervical cancer patients, we examined the association between anemia and outcomes before and after the introduction of chemoradiation as standard of care. Methods and Materials: We reviewed the records of 2454 patients who underwent definitive radiation therapy from 1980 through 2011. Minimum hemoglobin level (Hgb min ) was recorded for 2359 patients (96%). Endpoints included freedom from central recurrence (FFCR), freedom from distant metastasis (FFDM), and disease-specific survival (DSS). Results: For the entire cohort, hemoglobin concentrations of 9, 10, and 12 g/dL before and during radiation were all significantly associated with FFCR, FFDM, and DSS (all P<.001) on univariate analysis. However, on multivariate analysis, only Hgb min less than 10 g/dL during RT (RT-Hgb <10 ) remained significant, and it was correlated with lower DSS (P=.02, hazard ratio [HR] = 1.28) and FFDM (P=.03, HR = 1.33) but not with FFCR. In a subset analysis of patients receiving chemoradiation (n=678), RT-Hgb <10 was associated only with DSS (P=.008, HR = 1.49), not with FFCR or FFDM. In this subgroup, despite an association between RT-Hgb <10 and DSS, the use of transfusion was not correlated with benefit. Conclusions: No evidence was found supporting anemia as an independent predictor of central recurrence in patients treated with definitive radiation therapy with or without chemotherapy. Less emphasis on correcting anemia in cervical cancer patients may be warranted

Relationship Between Low Hemoglobin Levels and Outcomes After Treatment With Radiation or Chemoradiation in Patients With Cervical Cancer: Has the Impact of Anemia Been Overstated?

Energy Technology Data Exchange (ETDEWEB)

Bishop, Andrew J.; Allen, Pamela K.; Klopp, Ann H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Meyer, Larissa A. [Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eifel, Patricia J., E-mail: peifel@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-01-01

Purpose: Previous reports have suggested that anemia increases rates of recurrence after radiation therapy for cervical cancer. However, these studies may not have fully corrected for confounding risk factors. Using a well-characterized cohort of cervical cancer patients, we examined the association between anemia and outcomes before and after the introduction of chemoradiation as standard of care. Methods and Materials: We reviewed the records of 2454 patients who underwent definitive radiation therapy from 1980 through 2011. Minimum hemoglobin level (Hgb{sub min}) was recorded for 2359 patients (96%). Endpoints included freedom from central recurrence (FFCR), freedom from distant metastasis (FFDM), and disease-specific survival (DSS). Results: For the entire cohort, hemoglobin concentrations of 9, 10, and 12 g/dL before and during radiation were all significantly associated with FFCR, FFDM, and DSS (all P<.001) on univariate analysis. However, on multivariate analysis, only Hgb{sub min} less than 10 g/dL during RT (RT-Hgb{sub <10}) remained significant, and it was correlated with lower DSS (P=.02, hazard ratio [HR] = 1.28) and FFDM (P=.03, HR = 1.33) but not with FFCR. In a subset analysis of patients receiving chemoradiation (n=678), RT-Hgb{sub <10} was associated only with DSS (P=.008, HR = 1.49), not with FFCR or FFDM. In this subgroup, despite an association between RT-Hgb{sub <10} and DSS, the use of transfusion was not correlated with benefit. Conclusions: No evidence was found supporting anemia as an independent predictor of central recurrence in patients treated with definitive radiation therapy with or without chemotherapy. Less emphasis on correcting anemia in cervical cancer patients may be warranted.

Improvement of electrical resistivity tomography for leachate injection monitoring.

Science.gov (United States)

Clément, R; Descloitres, M; Günther, T; Oxarango, L; Morra, C; Laurent, J-P; Gourc, J-P

2010-03-01

Leachate recirculation is a key process in the scope of operating municipal waste landfills as bioreactors, which aims to increase the moisture content to optimize the biodegradation in landfills. Given that liquid flows exhibit a complex behaviour in very heterogeneous porous media, in situ monitoring methods are required. Surface time-lapse electrical resistivity tomography (ERT) is usually proposed. Using numerical modelling with typical 2D and 3D injection plume patterns and 2D and 3D inversion codes, we show that wrong changes of resistivity can be calculated at depth if standard parameters are used for time-lapse ERT inversion. Major artefacts typically exhibit significant increases of resistivity (more than +30%) which can be misinterpreted as gas migration within the waste. In order to eliminate these artefacts, we tested an advanced time-lapse ERT procedure that includes (i) two advanced inversion tools and (ii) two alternative array geometries. The first advanced tool uses invariant regions in the model. The second advanced tool uses an inversion with a "minimum length" constraint. The alternative arrays focus on (i) a pole-dipole array (2D case), and (ii) a star array (3D case). The results show that these two advanced inversion tools and the two alternative arrays remove almost completely the artefacts within +/-5% both for 2D and 3D situations. As a field application, time-lapse ERT is applied using the star array during a 3D leachate injection in a non-hazardous municipal waste landfill. To evaluate the robustness of the two advanced tools, a synthetic model including both true decrease and increase of resistivity is built. The advanced time-lapse ERT procedure eliminates unwanted artefacts, while keeping a satisfactory image of true resistivity variations. This study demonstrates that significant and robust improvements can be obtained for time-lapse ERT monitoring of leachate recirculation in waste landfills. Copyright 2009 Elsevier Ltd. All rights

The role of postoperative radiation and chemoradiation in Merkel Cell Carcinoma: A systematic review of the literature

Directory of Open Access Journals (Sweden)

Shaakir eHasan

2013-11-01

Full Text Available Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC. Methods: A PubMed, MEDLINE search was conducted between 1995-2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion. Results: Thirty-four studies (n = 4475 were included. The median age was 73 years, median follow-up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%. Three-year LC was 20% [median 10%] in the observation cohort, compared to 65% [62%] with postoperative RT and 67% [75%] with postoperative chemoRT; these findings were statistically significant (P

Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

International Nuclear Information System (INIS)

Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

2015-01-01

In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

Postoperative Chemoradiation Therapy in High-Risk Cervical Cancer: Re-evaluating the Findings of Gynecologic Oncology Group Study 109 in a Large, Population-Based Cohort

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Trifiletti, Daniel M. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Swisher-McClure, Samuel [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Hegarty, Sarah E. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grover, Surbhi, E-mail: Surbhi.grover@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2015-12-01

Purpose: To review the National Cancer Database (NCDB) to evaluate postoperative high-risk cervical cancer patients for factors associated with a benefit from chemoradiation therapy (CRT) over external beam radiation therapy alone (EBRT). Methods and Materials: The National Cancer Database was queried for women with cervical cancer treated with hysterectomy and adjuvant EBRT from 2002 to 2012. Only patients with pathologic lymph node involvement (LN+), positive surgical margins, and/or parametrial invasion were included in our analysis (on the basis of Peter's criteria). Univariable and multivariable analyses (MVA) were performed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate for factors associated with of CRT utilization and overall survival (OS). Results: A total of 3053 patients met inclusion criteria, and 2479 received adjuvant CRT (81%), whereas 574 (19%) received EBRT alone. Factors associated with increased CRT utilization on MVA included age <69 years, year of diagnosis ≥2008, non-adenocarcinoma histology, and LN+. Use of CRT improved OS among the entire cohort on MVA (HR 0.76, CI 0.601-0.962; P=.022). On MVA, CRT improved OS in patients with LN+ as their sole Peter's criteria (HR 0.58, CI 0.413-0.814; P=.002). Chemoradiation therapy did not improve OS in patients with only positive margins (P=.73), only parametrial invasion (P=.95), or any combination of these 2 factors without LN+ (P=.63). Conclusions: The use of adjuvant CRT after hysterectomy improves OS in patients with high-risk cervical cancer compared with EBRT alone, but this benefit seems to be restricted to patients with LN+. The benefits of adjuvant CRT over EBRT alone in patients with parametrial invasion and/or positive margins (without nodal involvement) are unknown.

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard; Johnstone, David W.; Watson, Thomas; Smudzin, Therese; Keng, Peter C.

2008-01-01

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m 2 , 20 mg/m 2 , and 25 mg/m 2 were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m 2 ), II (20 mg/m 2 ), and III (25 mg/m 2 ), the mean peak plasma level was 0.23 ± 0.06 μmol/l, 0.32 ± 0.05 μmol/l, and 0.52 ± 0.14 μmol/l, respectively; AUC was 0.44 ± 0.09 μmol/l, 0.61 ± 0.1 μmol/l, and 0.96 ± 0.23 μmol/l, respectively; and duration of drug concentration >0.05 μmol/l (t > 0.05 μmol/l) was 1.6 ± 0.3 h, 1.9 ± 0.2 h, and 3.0 ± 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 μmol/l for a minimum of 1.6 h was sufficient for effective radiosensitization

Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost

DEFF Research Database (Denmark)

Appelt, Ane L; Vogelius, Ivan R; Pløen, John

2014-01-01

PURPOSE/OBJECTIVE(S): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS: Between March 2005 and November 2008, 248...... patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic...... on stratification for tumor regression grade and resection margin status indicated the presence of response migration. CONCLUSIONS: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical...

The advance in the therapy of therapy-resistant keloids

International Nuclear Information System (INIS)

Yao Hongxia; Zhang Jinshan

2009-01-01

Keloids are huamn benign dermal tumors, excessive fibroproliferative disorders that enlarge and extend beyond the margins of the origin wounds. Some keloids have proven to be very resistant to treatment, for example, several treatment modalities including surgical excision in combination with radiotherapy in the form of roentgen radiation (X-ray), pharmaceuticals, intralesional corticosteroids or calcium ions blocking agents, silicone gel sheets, physical therapy such as pressuretherapy, lasertherapy, cryotherpay might be less efficacious, and sometimes they cannot be performed because of limited conditions. Some keloids have higher recurrence rates. It is difficult to treat some keloids with complications of infection. 32 P-phosphours combination with vittamin E may be iuseful to treat therapy-resistant keloids. (authors)

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

Science.gov (United States)

Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Electrical Resistivity Measurements: a Review

Science.gov (United States)

Singh, Yadunath

World-wide interest on the use of ceramic materials for aerospace and other advanced engineering applications, has led to the need for inspection techniques capable of detecting unusually electrical and thermal anomalies in these compounds. Modern ceramic materials offer many attractive physical, electrical and mechanical properties for a wide and rapidly growing range of industrial applications; moreover specific use may be made of their electrical resistance, chemical resistance, and thermal barrier properties. In this review, we report the development and various techniques for the resistivity measurement of solid kind of samples.

Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

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Palma, David A., E-mail: david.palma@uwo.ca [Department of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Dios, Núria Rodríguez de [Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Universidad Pompeu Fabra, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barriger, R. Bryan [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moreno-Jiménez, Marta [Department of Oncology, Radiation Oncology Division, Clínica Universidad de Navarra, University of Navarra, Pamplona (Spain); Kim, Tae Hyun [Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of); Ramella, Sara [Division of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Everitt, Sarah [Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Australia and Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University (Australia); Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); and others

2013-11-15

Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors

Resistance gene management: concepts and practice

Science.gov (United States)

Christopher C. Mundt

2012-01-01

There is now a very long history of genetics/breeding for disease resistance in annual crops. These efforts have resulted in conceptual advances and frustrations, as well as practical successes and failures. This talk will review this history and its relevance to the genetics of resistance in forest species. All plant breeders and pathologists are familiar with boom-...

Advanced Fuels Campaign FY 2015 Accomplishments Report

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Braase, Lori Ann [Idaho National Lab. (INL), Idaho Falls, ID (United States); Carmack, William Jonathan [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-10-29

The mission of the Advanced Fuels Campaign (AFC) is to perform research, development, and demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors; enhance proliferation resistance of nuclear fuel; effectively utilize nuclear energy resources; and address the longer-term waste management challenges. This report is a compilation of technical accomplishment summaries for FY-15. Emphasis is on advanced accident-tolerant LWR fuel systems, advanced transmutation fuels technologies, and capability development.

Fatal bleeding in a nasopharyngeal carcinoma patient after concurrent chemoradiation plus cetuximab: a case report

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Zheng LY

2013-06-01

Full Text Available LingYan Zheng,1 SenXiang Yan,1 Danfang Yan,1 JingSong Yang,1 YiXiang Wang2 1Department of Radiation Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China; 2Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong KongAbstract: Carotid blowout syndrome (CBS refers to the clinical signs and symptoms related to rupture of the carotid artery (CA and its branches, which mainly results from malignant invasion of the CA by head and neck cancers. Here, we present a 46-year-old male patient who suffered from nasopharyngeal carcinoma and was treated with a combination of chemoradiation and cetuximab. The patient was stage IVb (T4N2M0 clinically, with encasement of the left internal carotid artery, as shown on pretreatment magnetic resonance imaging. Three months after completion of radiotherapy, the patient died of sudden massive epistaxis. CBS is a lethal complication of nasopharyngeal carcinoma, so the risk of CBS should be carefully assessed in patients with imaging showing CA encasement. Till now, the precise prediction and prevention of CBS remain to be explored. Keywords: nasopharyngeal carcinoma, carotid blowout syndrome, diagnosis, cetuximab, prevention

Clinical results for salvage surgery in head and neck carcinoma after chemoradiation or radiation

International Nuclear Information System (INIS)

Ishida, Katsuhiro; Makino, Yohjiroh; Nagaoka, Masato; Seino, Youichi; Hama, Takanori; Aoki, Kensuke; Uchida, Mitsuru; Kato, Takakuni

2013-01-01

The objective of this study was to examine the post-operative complications of surgical procedures in oral or pharyngeal carcinoma by analyzing and comparing between patients who underwent salvage surgery after chemoradiation and radiation. A retrospective review was performed of 18 patients who underwent salvage surgery and reconstruction after concurrent chemoradiotherapy (CCRT group), and another 41 patients who underwent salvage surgery and reconstruction after radiation therapy (RT group). No perioperative deaths or life threatening systemic complications occurred, and all flaps survived completely in both groups. Surgical site infection (SSI) occurred in five patients (12.2%) in the RT group and seven patients (38%) in the CCRT group. SSI other than donor site infection occurred in four patients (9%) in the RT group and four patients (22%) in the CCRT group. The rate of SSI excluding donor site infection did not differ significantly between patients who underwent salvage surgery after CCRT and RT. The rate of donor site infection was higher in the CCRT group than in the RT group (p=0.04). This study showed that salvage surgery after CCRT or RT can be performed safely, without significant morbidity or mortality. However, patients who received CCRT are at risk for major complications caused by minor troubles, and thus reconstruction after salvage surgery should be performed with sufficient care. (author)

Early diffusion weighted magnetic resonance imaging can predict survival in women with locally advanced cancer of the cervix treated with combined chemo-radiation

International Nuclear Information System (INIS)

Somoye, Gbolahan; Parkin, David; Harry, Vanessa; Semple, Scott; Plataniotis, George; Scott, Neil; Gilbert, Fiona J.

2012-01-01

To assess the predictive value of diffusion weighted imaging (DWI) for survival in women treated for advanced cancer of the cervix with concurrent chemo-radiotherapy. Twenty women treated for advanced cancer of the cervix were recruited and followed up for a median of 26 (range -3 /mm 2 /s), respectively, P = 0.02. The median change in ADC 14 days after treatment commencement was significantly higher in the alive group compared to non-survivors, 0.28 and 0.14 (x 10 -3 /mm 2 /s), respectively, P = 0.02. There was no evidence of a difference between survivors and non-survivors for pretreatment baseline or post-therapy ADC values. Functional DWI early in the treatment of advanced cancer of the cervix may provide useful information in predicting survival. (orig.)

Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation

International Nuclear Information System (INIS)

Marconi, Daniel Grossi; Fregnani, Jose Humberto Tavares Guerreiro; Rossini, Rodrigo Ribeiro; Netto, Ana Karina Borges Junqueira; Lucchesi, Fabiano Rubião; Tsunoda, Audrey Tieko; Kamrava, Mitchell

2016-01-01

Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation. This was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10 −3 mm 2 /s) were extracted for each ROI: Minimum - ADC min , Maximum - ADC max , Mean - ADC mean , and Standard Deviation of the ADC - ADC dev . Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume – GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-value < 0.05 was considered significant. Women median age was 52 years (range 23–90). 67 % had FIGO stage I-II disease while 33 % had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2 Gy (range 74–84). Women with disease staged III-IV (FIGO) had significantly higher mean ADC max values compared with those

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

International Nuclear Information System (INIS)

Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

2011-01-01

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer.

Science.gov (United States)

Shaib, Walid L; Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B; Maithel, Shishir K; Kooby, David; Landry, Jerome; El-Rayes, Bassel F

2016-02-01

Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. ©AlphaMed Press.

Outwitting the series resistance in scanning spreading resistance microscopy

International Nuclear Information System (INIS)

Schulze, A.; Cao, R.; Eyben, P.; Hantschel, T.; Vandervorst, W.

2016-01-01

The performance of nanoelectronics devices critically depends on the distribution of active dopants inside these structures. For this reason, dopant profiling has been defined as one of the major metrology challenges by the international technology roadmap of semiconductors. Scanning spreading resistance microscopy (SSRM) has evolved as one of the most viable approaches over the last decade due to its excellent spatial resolution, sensitivity and quantification accuracy. However, in case of advanced device architectures like fins and nanowires a proper measurement of the spreading resistance is often hampered by the increasing impact of parasitic series resistances (e.g. bulk series resistance) arising from the confined nature of the aforementioned structures. In order to overcome this limitation we report in this paper the development and implementation of a novel SSRM mode (fast Fourier transform-SSRM: FFT-SSRM) which essentially decouples the spreading resistance from parasitic series resistance components. We show that this can be achieved by a force modulation (leading to a modulated spreading resistance signal) in combination with a lock-in deconvolution concept. In this paper we first introduce the principle of operation of the technique. We discuss in detail the underlying physical mechanisms as well as the technical implementation on a state-of-the-art atomic force microscope (AFM). We demonstrate the performance of FFT-SSRM and its ability to remove substantial series resistance components in practice. Eventually, the possibility of decoupling the spreading resistance from the intrinsic probe resistance will be demonstrated and discussed. - Highlights: • A novel electrical AFM mode for carrier profiling in confined volumes is presented. • Thereby the force and hence the contact area between AFM probe and sample is modulated. • Information on the spreading resistance is derived using a lock-in approach. • Bulk series resistance components are

Patterns of failure after use of 18F-FDG PET/CT in integration of extended-field chemo-IMRT and 3D-brachytherapy plannings for advanced cervical cancers with extensive lymph node metastases

International Nuclear Information System (INIS)

Chung, Yih-Lin; Horng, Cheng-Fang; Lee, Pei-Ing; Chen, Fong-Lin

2016-01-01

The study is to evaluate the patterns of failure, toxicities and long-term outcomes of aggressive treatment using 18 F-FDG PET/CT-guided chemoradiation plannings for advanced cervical cancer with extensive nodal extent that has been regarded as a systemic disease. We retrospectively reviewed 72 consecutive patients with 18 F-FDG PET/CT-detected widespread pelvic, para-aortic and/or supraclavicular lymph nodes treated with curative-intent PET-guided cisplatin-based extended-field dose-escalating intensity-modulated radiotherapy (IMRT) and adaptive high-dose-rate intracavitary 3D-brachytherapy between 2002 and 2010. The failure sites were specifically localized by comparing recurrences on fusion of post-therapy recurrent 18 F-FDG PET/CT scans to the initial PET-guided radiation plannings for IMRT and brachytherapy. The median follow-up time for the 72 patients was 66 months (range, 3–142 months). The 5-year disease-free survival rate calculated by the Kaplan-Meier method for the patients with extensive N1 disease with the uppermost PET-positive pelvic-only nodes (26 patients), and the patients with M1 disease with the uppermost PET-positive para-aortic (31 patients) or supraclavicular (15 patients) nodes was 78.5 %, and 41.8–50 %, respectively (N1 vs. M1, p = 0.0465). Eight (11.1 %), 18 (25.0 %), and 3 (4.2 %) of the patients developed in-field recurrence, out-of-field and/or distant metastasis, and combined failure, respectively. The 6 (8.3 %) local failures around the uterine cervix were all at the junction between IMRT and brachytherapy in the parametrium. The rate of late grade 3/4 bladder and bowel toxicities was 4.2 and 9.7 %, respectively. When compared to conventional pelvic chemoradiation/2D-brachytherapy during 1990–2001, the adoption of 18 F-FDG PET-guided extended-field dose-escalating chemoradiation plannings in IMRT and 3D-brachytherapy after 2002 appeared to provide higher disease-free and overall survival rates with acceptable toxicities in

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

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Martens, Milou H., E-mail: mh.martens@hotmail.com [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Heeswijk, Miriam M. van [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Broek, Joris J. van den [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Rao, Sheng-Xiang [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Radiology, Fudan University, Shanghai (China); Vandecaveye, Vincent [Department of Radiology, University Hospital Leuven, Leuven (Belgium); Vliegen, Roy A. [Department of Radiology, Atrium Medical Center, Heerlen (Netherlands); Schreurs, Wilhelmina H. [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Beets, Geerard L. [Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Lambregts, Doenja M.J. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Beets-Tan, Regina G.H. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3 different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypTchemoradiation therapy) and a volume reduction of Δ80% to 86.6%. Accuracies for whole-volume measurements to assess tumor regression grade 1 to 2 were 52% to 61%, and for T-downstaging 51% to 57%. Overall accuracies for tumor length ranged between 48% and 53% and for 3D size measurement between 52% and 56%. Conclusions: Magnetic resonance volumetry using whole-tumor volume measurements can be helpful in rectal cancer response assessment with selected cut-off values. Measurements of tumor length or 3-dimensional tumor size are not helpful. Magnetic resonance volumetry is mainly accurate to assess a complete tumor response (ypT0) after chemoradiation therapy (accuracies up to 80%).

Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

International Nuclear Information System (INIS)

Uyterlinde, Wilma; Chen, Chun; Nijkamp, Jasper; Obbink, Marieke Groot; Sonke, Jan-Jakob; Belderbos, Jose; Heuvel, Michel van den

2014-01-01

Purpose: To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m 2 cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared. Results: Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ⩾2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH). Conclusion: Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

International Nuclear Information System (INIS)

Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy

2014-01-01

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

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Morganti, Alessio G. [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso (Italy); Falconi, Massimo [Department of Surgery, University of Verona, Verona (Italy); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht (Netherlands); Mattiucci, Gian-Carlo, E-mail: gcmattiucci@rm.unicatt.it [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Alfieri, Sergio [Department of Surgery, Università Cattolica S. Cuore, Rome (Italy); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid (Spain); Dubois, Jean-Bernard [Département de Radiothérapie, CRLC, Montpellier Cedex (France); Fastner, Gerd [Department of Radiotherapy, PMU, Salzburg (Austria); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Maidment, Bert W. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Reni, Michele [Department of Oncology, S. Raffaele Scientific Institute, Milan (Italy); Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Ippolito, Edy [Department of Radiation Oncology, University Campus Biomedico, Roma (Italy); and others

2014-11-15

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

Emerging Therapies for Stage III Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy and Immunotherapy

Directory of Open Access Journals (Sweden)

Sameera S. Kumar

2017-09-01

Full Text Available The current standard of care for locally advanced non-small cell lung cancer (NSCLC includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an “abscopal effect” although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This “quadmodality” approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.

Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

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Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2015-06-15

The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun

2015-01-01

The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited

E-cadherin and Vimentin as Predictors of Resistance to Preoperative Systemic Therapy in Patients with Advanced Breast Cancer

Directory of Open Access Journals (Sweden)

Sonar. S. Panigoro

2017-01-01

Full Text Available Loss of E-cadherin and increased vimentin expression are associated with epithelial-mesenchymal transition andcancer stemness which are responsible for treatment resistance. The study aims to evaluate the role of E-cadherin andvimentin as predictors of resistance to preoperative systemic therapy in patients with advanced breast cancer. This wasa cross-sectional analytical study in patients with stage III-IV breast cancer in Dharmais Cancer Hospital and dr. CiptoMangunkusumo National Hospital from July 2015 to April 2016. Patients had biopsy specimens embedded in paraffinblocks. Expressions of E-cadherin and vimentin proteins were done immunohistochemically. Treatment response wasevaluated histopathologically using Miller-Payne criteria on mastectomy specimens. A total of 65 patients were enrolled.Five patients with invasive lobular carcinoma were excluded. Thirty one had chemotherapy and 29 had hormonaltherapy. After treatment, 46 patients were eligible for mastectomy. E-cadherin and vimentin were positive in 28 (60.9%and 11 (20.3% of specimens. Twenty-three (50% patients showed no response. Treatment resistance were associatedwith type of therapy (OR=4.4; 95% CI=1.27-15.41; p=0.017 and vimentin expression (OR=6.75; 95% CI=1.27-30.02;p=0.016. Hormonal therapy (ORadj=6.26; 95%CI=1.59-24.6; p=0.009 and positive vimentin (ORadj=8.75; 95%CI=1.43-57.4; p=0.019 were independent predictors of treatment resistance. In conclusion, E-cadherin and vimentin can beused as predictors of resistance to preoperative systemic therapy in patients with advanced breast cancer. Keywords: breast cancer, cancer stemness, E-cadherin, preoperative therapy, vimentin.   Peran E-cadherin dan Vimentin sebagai Prediktor Resistensi Terapi Sistemik Preoperatif pada Pasien Kanker Payudara Stadium Lanjut Abstrak Hilangnya ekspresi E-cadherin dan meningkatnya ekspresi vimentin dihubungkan dengan epithelial-mesenchymaltransition dan cancer stemness yang bertanggungjawab terhadap

Down-selection of candidate alloys for further testing of advanced replacement materials for LWR core internals

Energy Technology Data Exchange (ETDEWEB)

Was, Gary [Univ. of Michigan, Ann Arbor, MI (United States). Applied Physics Program; Leonard, Keith J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tan, Lizhen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-09-01

Life extension of the existing nuclear reactors imposes irradiation of high fluences to structural materials, resulting in significant challenges to the traditional reactor materials such as type 304 and 316 stainless steels. Advanced alloys with superior radiation resistance will increase safety margins, design flexibility, and economics for not only the life extension of the existing fleet but also new builds with advanced reactor designs. The Electric Power Research Institute (EPRI) teamed up with Department of Energy (DOE) Light Water Reactor Sustainability Program to initiate the Advanced Radiation Resistant Materials (ARRM) program, aiming to identify and develop advanced alloys with superior degradation resistance in light water reactor (LWR)-relevant environments by 2024.

Calcium-Magnesium-Alumino-Silicates (CMAS) Reaction Mechanisms and Resistance of Advanced Turbine Environmental Barrier Coatings for SiC/SiC Ceramic Matrix Composites

Science.gov (United States)

Zhu, Dongming; Costa, Gustavo; Harder, Bryan J.; Wiesner, Valerie L.; Hurst, Janet B.; Puleo, Bernadette J.

2017-01-01

Environmental barrier coatings (EBCs) and SiC/SiC ceramic matrix composites (CMCs) systems will play a crucial role in future turbine engines for hot-section component applications because of their ability to significantly increase engine operating temperatures, reduce engine weight and cooling requirements. The development of prime-reliant environmental barrier coatings is an essential requirement to enable the applications of the 2700-3000 F EBC - CMC systems. This presentation primarily focuses on the reaction mechanisms of advanced NASA environmental barrier coating systems, when in contact with Calcium-Magnesium Alumino-Silicates (CMAS) at high temperatures. Advanced oxide-silicate defect cluster environmental barrier coatings are being designed for ultimate balanced controls of the EBC temperature capability and CMAS reactivity, thus improving the CMAS resistance. Further CMAS mitigation strategies are also discussed.

Sphincter saving and abdomino-perineal resections following neoadjuvant chemoradiation in locally advanced low rectal cancer

International Nuclear Information System (INIS)

Gawad, W.; Fakhr, I.; Lotayef, M.; Mansour, O.; Mokhtar, N.

2015-01-01

Background: The improvement in surgical techniques alongside neoadjuvant chemo radiation enabled more patients with low rectal cancer to have sphincter preservation. Study aim: To compare the oncologic and functional outcome in patients with locally advanced low rectal cancer treated by neoadjuvant chemo radiation followed by sphincter saving resection (SSR) against those who underwent abdomino-perineal resection (APR). Patients and methods: A total of 111 patients with low rectal cancer were included in the study. Sixty-one consented patients who prospectively underwent SSR, from Jan 2008 to Jan 2013, and a retrospective group, formed of 50 patients, selected from cases seen at NCI, with comparable demographic, clinical and pathologic criteria, who underwent APR from Jan 2003 to Jan 2008. All lesions were <5 cm from anal verge. All 111 patients received preoperative chemo radiation and total mesorectal excision. Results: All tumors were located at a median of 3.6 cm (range 2.5-4.5 cm) for the SSR group, and 3.5 cm (range 2.5-4.6 cm) for the APR group, from the anal verge. The median follow-up was 34 months (range 1-60 months) for both groups. The difference in disease recurrence and OS between the APR and SSR groups were both statistically insignificant. Conclusion: In low rectal cancer, the sphincter preservation appears to have nearly the same oncologic outcome compared to APR, this might be attributed to the small sample size and short follow up period. However, patients with sphincter preservation have certainly demonstrated an indisputable better functional outcome, in terms of stoma avoidance and adequate continence.

Cervical necrosis after chemoradiation for cervical cancer: case series and literature review

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Fawaz, Ziad Simon; Barkati, Maroie; Beauchemin, Marie-Claude; Sauthier, Philippe; Gauthier, Philippe; Nguyen, Thu Van

2013-01-01

The aim of this study was to assess the management of cervical necrosis (CN) following radiotherapy (RT) and the impact of smoking status. This rare complication mimics a neoplastic recurrence, and causes concern among attending physicians. Between July 2008 and March 2013, 5 women on 285 with localized cervical cancer had a CN following RT. Patients were treated with concomitant chemoradiation. The medical records were reviewed to abstract demographic and clinical information until March 2013. 1.75% (95% confidence interval: 0.23 to 3.28%) developed CN. All patients were smokers with a mean of 19.5 pack-years (range: 7.5-45 pack-years). All patients were treated with weekly Cisplatin chemotherapy and external beam radiation to the pelvis, 45 Gy in 25 fractions. Four patients received an extra boost with a median dose of 7.2 Gy (range: 5.4-10 Gy). All patients had intracavitary brachytherapy (range: 27.9 to 30 Gy). Clinical presentation was similar for all the cases: vaginal discharge associated with pain. Mean time for time post-radiation therapy to necrosis was 9.3 months (range: 2.2-20.5 months). Standard workup was done to exclude cancer recurrence: biopsies and radiologic imaging. Conservative treatment was performed with excellent results. Resolution of the necrosis was complete after a few months (range: 1 to 4 months). Median follow-up until March 2013 was 19 months. All the patients were alive with no clinical evidence of disease. This study, the largest to date, shows that conservative management of CN after RT is effective, and should be attempted. This complication is more common in smokers, and counseling intervention should result in fewer complications of CN

The new criteria of clinical response for the primary tumor based on the findings of histological response after chemoradiation therapy in esophageal cancer

International Nuclear Information System (INIS)

Okumura, Hiroshi; Natsugoe, Shoji; Yokomakura, Naoya; Matsumoto, Masataka; Aikou, Takashi

2005-01-01

The incidence of chemoradiation therapy (CRT) increased in order to improve the surgical resectabilty and clinical outcome. It is important to accurately assess the effect of CRT for selecting further treatment and predicting prognosis. We tried to make the new criteria for imaging diagnosis after we reevaluated the discrepancy between clinical and histological effect of CRT. Subjects were 36 patients with advanced esophageal cancer who underwent esophagectomy with lymphadenectomy after CRT that consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The clinical and histological response was firstly evaluated based on esophageal disease guidelines for clinical and pathologic studies on carcinoma of the esophagus by the Japanese Society of Clinical response in imaging was reassessed based on the histological response. The number of tumors judged as clinical complete response/partial response/no change (CR/PR/NC) was 0/26/10, and the histological grading 1/2/3 was 17/11/8, respectively. Imaging for Grade 1 tumors showed the existence of viable cancer cells in biopsy specimen. Of 16 patients with such finding, 14 (88%) were histologically judged as Grade 1. Imaging characteristics for grade 3 tumors was more than a 75% reduction in esophagography, and the existence of scar formation by esophagoscopy. All five (100%) patients with these findings were histologically judged as Grade 3. The findings of grade 1 and 3 based on new criteria were independent predictive factors for CRT effect. According to new criteria, it was possible to predict the histological effect by the combination of esophagography and endoscopy in more than 80% of patients after CRT. Our new criteria may offer important information on the selection of further treatment or the prediction of prognosis after CRT in patients with esophageal cancer. (author)

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

Science.gov (United States)

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

Novel minimally invasive chemoradiation therapy combined with biliary stenting for multidisciplinary approach to unresectable bile duct carcinoma

International Nuclear Information System (INIS)

Suzuki, Masanori; Sato, Takeaki; Umino, Noriaki

2001-01-01

Multidisciplinary treatment is a useful approach to unresectable non-metastatic bile duct carcinoma with invasion of the hepatic artery and portal vein. The authors developed a multidisciplinary treatment consisting of chemoradiation therapy combined with intraluminal bile duct irradiation plus external irradiation and systemic or local chemotherapy. The aim of this regimen was to improve the ability to locally control bile duct carcinoma by intraluminal irradiation and to shorten the treatment period compared to external irradiation therapy alone. According to the treatment schedule whole-body irradiation is performed first and followed by systemic administration of 5-fluorouracil (5-FU, 600 mg/m 2 /day) and cisplatin (CDDP, 10 mg/m 2 /day) after biliary stenting plus simultaneously intraluminal irradiation (8 Gy/week x 3, total 24 Gy) administered with 192 Ir-RALS (Remote After Loading System). Two novel types of applicators specifically designed by the authors for intraluminal radiation of the bile duct were improved. The authors have used this multidisciplinary approach to treat 3 patients with bile duct carcinoma. Its application has shortened the course of multidisciplinary therapy to about 6 weeks, and the patients have surviveed more than 6-8 months without recurrence. (K.H.)

A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer

International Nuclear Information System (INIS)

Hatae, Masayuki; Takahashi, Takeshi; Kodama, Shoji

2005-01-01

Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m 2 as Level 1 or at 90 mg/m 2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6 patients receiving 80 mg/m 2 of CDGP and in all 2 patients receiving 90 mg/m 2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was partial response (PR) or better in all patients. The complete response (CR) rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration CDGP at 80 mg/m 2 on Days 1 and 29 is safe and effective. (author)

Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer

International Nuclear Information System (INIS)

Haj Mohammad, Nadia; Kamphuis, Martijn; Hulshof, Maarten C.C.M.; Lutkenhaus, Lotte J.; Gisbertz, Suzanne S.; Bergman, Jacques J.G.H.M.; Bruin-Bon, H.A.C.M. Rianne de; Geijsen, Elisabeth D.; Bel, Arjan; Boekholdt, S. Mathijs; Laarhoven, Hanneke W.M. van

2015-01-01

Background and purpose: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy. Methods: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. Results: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7–73.8 ml, p < 0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11–26 mmHg, p < 0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2–14 mmHg, p = 0.008) and an increase in heart rate with 6 beats/min (95% CI 1–11 beats/min, p = 0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. Conclusion: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated

Wafer plane inspection with soft resist thresholding

Science.gov (United States)

Hess, Carl; Shi, Rui-fang; Wihl, Mark; Xiong, Yalin; Pang, Song

2008-10-01

Wafer Plane Inspection (WPI) is an inspection mode on the KLA-Tencor TeraScaTM platform that uses the high signalto- noise ratio images from the high numerical aperture microscope, and then models the entire lithographic process to enable defect detection on the wafer plane[1]. This technology meets the needs of some advanced mask manufacturers to identify the lithographically-significant defects while ignoring the other non-lithographically-significant defects. WPI accomplishes this goal by performing defect detection based on a modeled image of how the mask features would actually print in the photoresist. There are several advantages to this approach: (1) the high fidelity of the images provide a sensitivity advantage over competing approaches; (2) the ability to perform defect detection on the wafer plane allows one to only see those defects that have a printing impact on the wafer; (3) the use of modeling on the lithographic portion of the flow enables unprecedented flexibility to support arbitrary illumination profiles, process-window inspection in unit time, and combination modes to find both printing and non-printing defects. WPI is proving to be a valuable addition to the KLA-Tencor detection algorithm suite. The modeling portion of WPI uses a single resist threshold as the final step in the processing. This has been shown to be adequate on several advanced customer layers, but is not ideal for all layers. Actual resist chemistry has complicated processes including acid and base-diffusion and quench that are not consistently well-modeled with a single resist threshold. We have considered the use of an advanced resist model for WPI, but rejected it because the burdensome requirements for the calibration of the model were not practical for reticle inspection. This paper describes an alternative approach that allows for a "soft" resist threshold to be applied that provides a more robust solution for the most challenging processes. This approach is just

Acute toxicity after a diverting stoma and spacer prior to chemoradiation in locally advanced rectal cancer

International Nuclear Information System (INIS)

Voort van Zyp, Jochem R.N. van der; Ceha, Heleen M.; Niehe, Valerie; Marinelli, Andreas W.K.S.; Putter, Hein; Marijnen, Corrie A.M.

2015-01-01

Background and purpose: Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ⩾3 acute diarrhea there is a relationship between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined placement of a diverting stoma and sigmoid spacer (DSSS) led to reduced irradiated small bowel volume and less grade ⩾3 acute diarrhea in the treatment of LARC. Materials/methods: Between 2003 and 2010, 54 of 189 LARC patients treated with CRT in two institutions had a DSSS prior to CRT. Data on patient and treatment characteristics and outcomes were collected retrospectively. Delineation of small bowel was performed with planning CT-scans. CTCAE version 4.0 was used for acute toxicity. Results: Patients with a DSSS had significantly less small bowel volume irradiated up to doses of 20 Gy. This difference was not observed for the higher dose levels. CRT induced grade ⩾3 acute diarrhea was not different between the two groups (8.3% vs. 12.8%; p = 0.41). Conclusion: DSSS is not clearly beneficial to reduce grade ⩾3 acute diarrhea, and it must be considered whether placement of a DSSS is justified for this purpose

Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

International Nuclear Information System (INIS)

Park, Shin Hyung; Kim, Jae Chul

2016-01-01

The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer

Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

Energy Technology Data Exchange (ETDEWEB)

Park, Shin Hyung; Kim, Jae Chul [Dept. of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

2016-06-15

The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

Corrosion-resistant coating development

Energy Technology Data Exchange (ETDEWEB)

Stinton, D.P.; Kupp, D.M.; Martin, R.L. [Oak Ridge National Lab., TN (United States)

1997-12-01

SiC-based heat exchangers have been identified as the prime candidate material for use as heat exchangers in advanced combined cycle power plants. Unfortunately, hot corrosion of the SiC-based materials created by alkali metal salts present in the combustion gases dictates the need for corrosion-resistant coatings. The well-documented corrosion resistance of CS-50 combined with its low (and tailorable) coefficient of thermal expansion and low modulus makes CS-50 an ideal candidate for this application. Coatings produced by gelcasting and traditional particulate processing have been evaluated.

Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

Science.gov (United States)

Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

2016-07-04

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

Directory of Open Access Journals (Sweden)

Lopez-Saura Pedro

2009-07-01

Full Text Available Abstract Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC or squamous cell skin carcinomas (SCSC. Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination, 40% PR (>30% tumor reduction, and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052.

Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

International Nuclear Information System (INIS)

Anasagasti-Angulo, Lorenzo; Garcia-Vega, Yanelda; Barcelona-Perez, Silvia; Lopez-Saura, Pedro; Bello-Rivero, Iraldo

2009-01-01

Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Current Controlled Trials RPCEC00000052

Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

Directory of Open Access Journals (Sweden)

Mariël Brinkhuis

2002-01-01

Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

Association analysis of resistance to cereal cyst nematodes (Heterodera avenae) and root lesion nematodes (Pratylenchus neglectus and P. thornei) in CIMMYT advanced spring wheat lines for semi-arid conditions.

Science.gov (United States)

Dababat, Abdelfattah A; Ferney, Gomez-Becerra Hugo; Erginbas-Orakci, Gul; Dreisigacker, Susanne; Imren, Mustafa; Toktay, Halil; Elekcioglu, Halil I; Mekete, Tesfamariam; Nicol, Julie M; Ansari, Omid; Ogbonnaya, Francis

2016-12-01

To identify loci linked to nematode resistance genes, a total of 126 of CIMMYT advanced spring wheat lines adapted to semi-arid conditions were screened for resistance to Heterodera avenae , Pratylenchus neglectus , and P. thornei , of which 107 lines were genotyped with 1,310 DArT. Association of DArT markers with nematode response was analyzed using the general linear model. Results showed that 11 markers were associated with resistance to H. avenae (pathotype Ha21), 25 markers with resistance to P. neglectus , and 9 significant markers were identified to be linked with resistance to P. thornei . In this work we confirmed that chromosome 4A (~90-105 cM) can be a source of resistance to P. thornei as has been recently reported. Other significant markers were also identified on chromosomal regions where no resistant genes have been reported for both nematodes species. These novel QTL were mapped to chromosomes 5A, 6A, and 7A for H. avenae ; on chromosomes 1A, 1B, 3A, 3B, 6B, 7AS, and 7D for P. neglectus ; and on chromosomes 1D, 2A, and 5B for P. thornei and represent potentially new loci linked to resistance that may be useful for selecting parents and deploying resistance into elite germplasm adapted to regions where nematodes are causing problem.

Development of advanced austenitic stainless steels resistant to void swelling under irradiation

International Nuclear Information System (INIS)

Rouxel, Baptiste

2016-01-01

In the framework of studies about Sodium Fast Reactors (SFR) of generation IV, the CEA is developing new austenitic steel grades for the fuel cladding. These steels demonstrate very good mechanical properties but their use is limited because of the void swelling under irradiation. Beyond a high irradiation dose, cavities appear in the alloys and weaken the material. The reference material in France is a 15Cr/15Ni steel, named AIM1, stabilized with titanium. This study try to understand the role played by various chemical elements and microstructural parameters on the formation of the cavities under irradiation, and contribute to the development of a new grade AIM2 more resistant to swelling. In an analytical approach, model materials were elaborated with various chemical compositions and microstructures. Ten grades were cast with chemical variations in Ti, Nb, Ni and P. Four specific microstructures for each alloy highlighted the effect of dislocations, solutes or nano-precipitates on the void swelling. These materials were characterized using TEM and SANS, before irradiation with Fe"2"+ (2 MeV) ions in the order to simulate the damages caused by neutrons. Comparing the irradiated microstructures, it is demonstrated that the solutes have a dominating effect on the formation of cavities. Specifically titanium in solid solution reduces the swelling whereas niobium does not show this effect. Finally, a matrix enriched by 15% to 25% of nickel is still favorable to limit swelling in these advanced austenitic stainless steels. (author) [fr

Advanced servomanipulator development

International Nuclear Information System (INIS)

Kuban, D.P.

1985-01-01

The Advanced Servomanipulator (ASM) System consists of three major components: the ASM slave, the dual arm master controller (DAMC) or master, and the control system. The ASM is remotely maintainable force-reflecting servomanipulator developed at the Oak Ridge National Laboratory (ORNL) as part of the Consolidated Fuel Reprocessing Program. This new manipulator addresses requirements of advanced nuclear fuel reprocessing with emphasis on force reflection, remote maintainability, reliability, radiation tolerance, and corrosion resistance. The advanced servomanipulator is uniquely subdivided into remotely replaceable modules which will permit in situ manipulator repair by spare module replacement. Manipulator modularization and increased reliability are accomplished through a force transmission system that uses gears and torque tubes. Digital control algorithms and mechanical precision are used to offset the increased backlash, friction, and inertia resulting from the gear drives. This results in the first remotely maintainable force-reflecting servomanipulator in the world

Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

Directory of Open Access Journals (Sweden)

Masayoshi Hashimoto

2016-10-01

Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

Molecular Genetic Changes Associated With Colorectal Carcinogenesis Are Not Prognostic for Tumor Regression Following Preoperative Chemoradiation of Rectal Carcinoma

International Nuclear Information System (INIS)

Zauber, N. Peter; Marotta, Steven P.; Berman, Errol; Grann, Alison; Rao, Maithili; Komati, Naga; Ribiero, Kezia; Bishop, D. Timothy

2009-01-01

Purpose: Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis. Methods and Materials: Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen. Results: Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression. Conclusions: Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.

Advances in titanium alloys

International Nuclear Information System (INIS)

Seagle, S.R.; Wood, J.R.

1993-01-01

As described above, new developments in the aerospace market are focusing on higher temperature alloys for jet engine components and higher strength/toughness alloys for airframe applications. Conventional alloys for engines have reached their maximum useful temperature of about 1000 F (540 C) because of oxidation resistance requirements. IMI 834 and Ti-1100 advanced alloys show some improvement, however, the major improvement appears to be in gamma titanium aluminides which could extend the maximum usage temperature to about 1500 F (815 C). This puts titanium alloys in a competitive position to replace nickel-base superalloys. Advanced airframe alloys such as Ti-6-22-22S, Beta C TM , Ti-15-333 and Ti-10-2-3 with higher strength than conventional Ti-6-4 are being utilized in significantly greater quantities, both in military and commercial applications. These alloys offer improved strength with little or no sacrifice in toughness and improved formability, in some cases. Advanced industrial alloys are being developed for improved corrosion resistance in more reducing and higher temperature environments such as those encountered in sour gas wells. Efforts are focused on small precious metal additions to optimize corrosion performance for specific applications at a modest increase in cost. As these applications develop, the usage of titanium alloys for industrial markets should steadily increase to approach that for aerospace applications. (orig.)

Insect-resistance and high-yield transgenic tobacco obtained by ...

African Journals Online (AJOL)

hope&shola

2010-10-04

Oct 4, 2010 ... had great significance for agricultural sustained develop- ment. Significant advances have been made in insect- resistant gene cry engineering (Cui and Guo, 1998; Ni et al., 1998; Yan, 2003). Insect-resistant trangenic cotton, harbouring the modified, synthesized gene cry, has already been commercialized ...

The imunocytochemical advances in prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma

International Nuclear Information System (INIS)

Zelyins'ka, G.V.

2015-01-01

The topical issues is the problem of prognosis of metastasis radioiodine resistant metastasis. We offered the methods of prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma with the help of immunocytochemical detection of the cytokeratin 17 and thyroid peroxidase. With the purpose of prognosis of metastasis radioiodine resistibility the cytokeratin 17 is taped in punctates of primary papillary carcinomas. This approach allows predict response of metastases on radioiodine therapy to choose proper therapeutic approach

Pretreatment organ function in patients with advanced head and neck cancer: clinical outcome measures and patients' views

Directory of Open Access Journals (Sweden)

Rasch Coen RN

2009-11-01

Full Text Available Abstract Background Aim of this study is to thoroughly assess pretreatment organ function in advanced head and neck cancer through various clinical outcome measures and patients' views. Methods A comprehensive, multidimensional assessment was used, that included quality of life, swallowing, mouth opening, and weight changes. Fifty-five patients with stage III-IV disease were entered in this study prior to organ preserving (chemoradiation treatment. Results All patients showed pretreatment abnormalities or problems, identified by one or more of the outcome measures. Most frequent problems concerned swallowing, pain, and weight loss. Interestingly, clinical outcome measures and patients' perception did no always concur. E.g. videofluoroscopy identified aspiration and laryngeal penetration in 18% of the patients, whereas only 7 patients (13% perceived this as problematic; only 2 out of 7 patients with objective trismus actually perceived trismus. Conclusion The assessment identified several problems already pre-treatment, in this patient population. A thorough assessment of both clinical measures and patients' views appears to be necessary to gain insight in all (perceived pre-existing functional and quality of life problems.

Effects of neoadyuvancy on the resectability of locally advanced rectal cancer in the HSJD period 2008-2011

International Nuclear Information System (INIS)

Delgado Rodriguez, Karla

2014-01-01

Rectal cancer has been remains an important medical and social problem; comprises about 30% of colorectal cancers. It is the most commonly diagnosed cancer and has been the third leading cause of cancer death in men and women in the United States. The diagnosis of this disease is based on a rectal examination and a rigid rectosigmoidoscopy that allows to establish the distance between the anal margin and the lesion, as well as to take biopsy for histopathological analysis. Determining the surgical resectability of locally advanced rectal cancer after receiving neoadjuvant chemoradiation treatment at Hospital San Juan de Dios. Records of 86 patients were reviewed, diagnosed with rectal cancer who had received radiotherapy between January 2008 and December 2011. The neoadjuvant treatment has verified the achieve of a high percentage of resectability without correspondence to the findings obtained in the imaging studies. Most of staging was done only with CT. This has demonstrated the importance of obtaining other images with magnetic resonance and USTR as pillars for the design and follow-up of patients with rectal cancer [es

MEHODOLOGY FOR PROLIFERATION RESISTANCE FOR ADVANCE NUCLEAR ENERGY SYSTEMS

International Nuclear Information System (INIS)

YUE, M.; CHANG, L.Y.; BARI, R.

2006-01-01

The Technology Goals for Generation IV nuclear energy systems highlight Proliferation Resistance and Physical Protection (PRandPP) as one of the four goal areas for Generation 1V nuclear technology. Accordingly, an evaluation methodology is being developed by a PRandPP Experts Group. This paper presents a possible approach, which is based on Markov modeling, to the evaluation methodology for Generation IV nuclear energy systems being developed for PRandPP. Using the Markov model, a variety of proliferation scenarios can be constructed and the proliferation resistance measures can be quantified, particularly the probability of detection. To model the system with increased fidelity, the Markov model is further developed to incorporate multiple safeguards approaches in this paper. The approach to the determination of the associated parameters is presented. Evaluations of diversion scenarios for an example sodium fast reactor (ESFR) energy system are used to illustrate the methodology. The Markov model is particularly useful because it can provide the probability density function of the time it takes for the effort to be detected at a specific stage of the proliferation effort

Study to develop improved fire resistant aircraft passenger seat materials

Science.gov (United States)

Duskin, F. E.; Schutter, K. J.; Sieth, H. H.; Trabold, E. L.

1980-01-01

The Phase 3 study of the NASA 'Improved Fire Resistant Aircraft Seat Materials' involved fire tests of improved materials in multilayered combinations representative of cushion configurations. Tests were conducted to determine their thermal, smoke, and fire resistance characteristics. Additionally, a 'Design Guideline' for Fire Resistant Passenger Seats was written outlining general seat design considerations. Finally, a three-abreast 'Tourist Class' passenger seat assembly fabricated from the most advanced fire-resistant materials was delivered.

Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

NARCIS (Netherlands)

Kroon, Jan; Puhr, Martin; Buijs, Jeroen T.; Van Der Horst, Geertje; Lemhemmer, Daniël; Marijt, Koen A.; Hwang, Ming S.; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Meijer, Onno C.; Culig, Zoran; Van Der Pluijm, Gabri

2016-01-01

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCA). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

NARCIS (Netherlands)

Kroon, Jan; Kroon, Jan; Puhr, M.; Buijs, J.T.; van der Horst, G.; Hemmer, D.M.; Marijt, K.A.; Hwang, M.S.; Masood, M.; Grimm, S.; Storm, Gerrit; Metselaar, Josbert Maarten; Meijer, O.C.; Culig, Z.; van der Pluijm, M.

2016-01-01

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

Candida Species Biofilms’ Antifungal Resistance

Science.gov (United States)

Silva, Sónia; Rodrigues, Célia F.; Araújo, Daniela; Rodrigues, Maria Elisa; Henriques, Mariana

2017-01-01

Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. PMID:29371527

Precision medicine for advanced prostate cancer.

Science.gov (United States)

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

High dose rate afterloading intraluminal brachytherapy for advanced inoperable rectal carcinoma

International Nuclear Information System (INIS)

Hoskin, Peter J.; Canha, Sandra M. de; Bownes, Peter; Bryant, Linda; Jones, Rob Glynne

2004-01-01

Background and purpose: High dose rate intraluminal brachytherapy for tumours of the rectal and anal canal which were inoperable either because of the age and frailty of the patient or because of advanced disease has been evaluated. Patients and methods: In a retrospective review of 50 consecutive patients the two main indications for brachytherapy were as part of a radical radiation programme in those unfit for major surgery (26 patients) or as palliation for advanced or metastatic disease (22 patients). Radical treatment was either sole treatment delivering 6 Gy fraction 2 to 3 times weekly up to 36 Gy or as a boost of 12 Gy after 45 Gy in 25 fractions external beam chemoradiation. Palliative treatments were given predominantly as a single dose of 10 Gy. Results: This was predominantly a group of frail elderly patients with a median age of 82 years (range 35-91). Local tumour response was seen in 21/25 assessable patients with 14 complete responses. Median survival for the entire population was 6 months (range 1-54 months); in patients treated with 'radical' intent this was 25 months (range 1.5-54) and in the palliative group 7.2 months (range 1-37). The most common presenting symptom was bleeding per rectum for which a 64% response rate was obtained with 57% complete responses. Mucous discharge responded in 64% with 28% complete responses. The median duration of response was 7 months. Conclusion: Intraluminal HDR brachytherapy is an effective local treatment for patients otherwise unfit for radical surgery both as a component of radical treatment, or as a simple single palliative procedure

Biological basis of chemo-radiation

International Nuclear Information System (INIS)

Mornex, F.; Van Houtte, P.; Cosset, J.M.

1997-01-01

Radiation therapy has been for years treatment of choice of locally advanced non small cell lung cancer. Improvement due to the combination of radiation and chemotherapy has been shown recently through several randomized trials and a recent meta-analysis. These results may be explained by biological mechanisms, yet un-completely explored, which are detailed in this review and applied to lung cancer. The optimal combination scheme is not yet defined, even trough the concurrent approach is promising, at the expense of an increased toxicity which is the limiting factor of treatment escalation doses. Biological findings and future results of randomized trials will hopefully open new avenues in the therapeutic strategy of this poor prognosis disease. (authors)

Resistência de plantas daninhas aos herbicidas Weed resistance to herbicides

Directory of Open Access Journals (Sweden)

Pedro J. Christoffoleti

1994-01-01

Full Text Available A resistência de plantas daninhas aos herbicidas ocorre em função de um processo evolutivo. O desenvolvimento de biótipos de plantas daninhas resistentes é imposto pela agricultura moderna, através da pressão de seleção causada pelo uso intensivo dos herbicidas. O conhecimento dos mecanismos e fatores que favorecem o aparecimento de biótipos de plantas daninhas resistentes é fundamental para que técnicas de manejo sejam utilizadas no sentido de evitar ou retardar o aparecimento de plantas resistentes em uma área. São poucos os relatos ou citações de literatura no Brasil. Sendo assim, este trabalho de revisão procura relatar os principais avanços e descobertas na área de plantas daninhas resistentes aos herbicidas.Weed herbicide resistance has evolved from weed evolution. The modern agriculture is responsible for this evolution because of the intensive use of herbicides. The knowledge of mechanisms and factors that influence the weed herbicide resistance play an important role in the weed manegement techniques used to avoid or delay herbicide resistance appearence. There are not many report or scientific papers about herbi cide resistance in Brasil. Therefore, this literature review aims to provide information about the main advances and discoveries in the field of weed herbicide resistance.

Serum Transforming Growth Factor-β1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy

Energy Technology Data Exchange (ETDEWEB)

Lu, Shao-Lun; Hsu, Feng-Ming; Tsai, Chiao-Ling; Wu, Jian-Kuan [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Koong, Albert C.; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China)

2015-12-01

Purpose: Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy. Methods and Materials: We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically. Results: Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-β1 (TGF-β1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-β1 concentration (−11,310 vs −5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-β1 concentration (−37.4% vs −25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-β1 >7040 pg/mL (P=.014) were independent factors associated with PPCs. Conclusions: Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.

Colonial Taxation, Corruption and Resistance in Igbominaland ...

African Journals Online (AJOL)

Colonial Taxation, Corruption and Resistance in Igbominaland. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES ... While taxation definitely stimulated economic activities in Igbominaland at ...

a stable simple sequence repeat marker for resistance to white ...

African Journals Online (AJOL)

ACSS

between resistant and susceptible materials in parental and advanced generations. ... efforts de sélection de variétés de tabac résistantes à la moisissure blanche. A cet effet, deux ... dominant monogenic type of resistance is being used in ...

New possibilities and view for treatment of castration resistant prostate cancer

International Nuclear Information System (INIS)

Barilla, R.; Andrasina, I.

2012-01-01

Prostate cancer is currently known as the most common cancer and the second leading cause of death from cancer in men in Western population. Advanced prostate cancer is initially sensitive to androgen-deprivation therapy (ADT) but later on progresses to castration resistant state. Understanding the mechanisms that transform prostate cancer (PCA) into a castration-resistant state enables investigators to explore suppression of extraresticular andronegs and other critical pathways to suggest appropriate and rational therapeutic design. Docetaxel based chemotherapy is established as the standard first line chemotherapy in patients with metastatic castration-resistant advanced prostate cancer with improved survival. However, prognosis remains poor and median survival is usually not longer than 2 years. Several Phase III studies have been completed recently, e.g. with new antiandrogens, new taxanes, immunotherapy and therapeutic antibodies. Multidisciplinary management and optimization of their role and and the most appropriate timing is the most important task in the treatment of advanced prostate cancer. (author)

Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

2015-07-01

Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

International Nuclear Information System (INIS)

Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

2015-01-01

Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

High Velocity Oxidation and Hot Corrosion Resistance of Some ODS Alloys

Science.gov (United States)

Lowell, C. E.; Deadmore, D. L.

1977-01-01

Several oxide dispersion strengthened (ODS) alloys were tested for cyclic, high velocity, oxidation, and hot corrosion resistance. These results were compared to the resistance of an advanced, NiCrAl coated superalloy. An ODS FeCrAl were identified as having sufficient oxidation and hot corrosion resistance to allow potential use in an aircraft gas turbine without coating.

Enhancing VVER annular proliferation resistance fuel with minor actinides

International Nuclear Information System (INIS)

Chang, G. S.

2007-01-01

Key aspects of the Global Nuclear Energy Partnership (GNEP) are to significantly advance the science and technology of nuclear energy systems and the Advanced Fuel Cycle (AFC) program. It consists of both innovative nuclear reactors and innovative research in separation and transmutation. To accomplish these goals, international cooperation is very important and public acceptance is crucial. The merits of nuclear energy are high-density energy, with low environmental impacts (i.e. almost zero greenhouse gas emission). Planned efforts involve near term and intermediate-term improvements in fuel utilization and recycling in current light water reactors (LWRs) as well as the longer-term development of new nuclear energy systems that offer much improved fuel utilization and proliferation resistance, along with continued advances in operational safety. The challenges are solving the energy needs of the world, protection against nuclear proliferation, the problem of nuclear waste, and the global environmental problem. To reduce spent fuel for storage and enhance the proliferation resistance for the intermediate-term, there are two major approaches (a) increase the discharged spent fuel burnup in the advanced LWR (Gen-III Plus), which not only can reduce the spent fuel for storage, but also increase the 2 38Pu and 2 40Pu isotopes ratio to enhance the proliferation resistance, and (b) use of transuranic nuclides ( 2 37Np and 2 41Am) in the high burnup fuel, which can drastically increase the proliferation resistance isotope ratio of 2 38Pu /Pu. For future advanced nuclear systems, the minor actinides (MA) are viewed more as a resource to be recycled, or transmuted to less hazardous and possibly more useful forms, rather than simply as a waste stream to be disposed of in expensive repository facilities. As a result, MAs play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors

SU-D-207B-07: Development of a CT-Radiomics Based Early Response Prediction Model During Delivery of Chemoradiation Therapy for Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Klawikowski, S; Christian, J; Schott, D; Zhang, M; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: Pilot study developing a CT-texture based model for early assessment of treatment response during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily CT data acquired for 24 pancreatic head cancer patients using CT-on-rails, during the routine CT-guided CRT delivery with a radiation dose of 50.4 Gy in 28 fractions, were analyzed. The pancreas head was contoured on each daily CT. Texture analysis was performed within the pancreas head contour using a research tool (IBEX). Over 1300 texture metrics including: grey level co-occurrence, run-length, histogram, neighborhood intensity difference, and geometrical shape features were calculated for each daily CT. Metric-trend information was established by finding the best fit of either a linear, quadratic, or exponential function for each metric value verses accumulated dose. Thus all the daily CT texture information was consolidated into a best-fit trend type for a given patient and texture metric. Linear correlation was performed between the patient histological response vector (good, medium, poor) and all combinations of 23 patient subgroups (statistical jackknife) determining which metrics were most correlated to response and repeatedly reliable across most patients. Control correlations against CT scanner, reconstruction kernel, and gated/nongated CT images were also calculated. Euclidean distance measure was used to group/sort patient vectors based on the data of these trend-response metrics. Results: We found four specific trend-metrics (Gray Level Coocurence Matrix311-1InverseDiffMomentNorm, Gray Level Coocurence Matrix311-1InverseDiffNorm, Gray Level Coocurence Matrix311-1 Homogeneity2, and Intensity Direct Local StdMean) that were highly correlated with patient response and repeatedly reliable. Our four trend-metric model successfully ordered our pilot response dataset (p=0.00070). We found no significant correlation to our control parameters: gating (p=0.7717), scanner (p

Characterizations of Soil Profiles Through Electric Resistivity Ratio

Directory of Open Access Journals (Sweden)

Chik Z

2015-04-01

Full Text Available This paper presents how near surface soil characteristics are obtained through soil electric resistivity ratio from soil apparent resistivity profile. In recent advances of electrical sensors, soil apparent resistivity is implemented as nondestructive method for obtaining near surface soil profile. Although geo-electric techniques offer an improvement to traditional soil sampling methods, the resulting data are still often misinterpreted for obtaining soil characteristics through apparent electrical resistivity in the field. Because, soil resistivity as before rain and after rain are changeable due to the presence of more moisture contents in field investigations. In this study, the parameter of soil electric resistivity ratio is incorporated to obtain reliable near surface soil profiles from apparent resistivity of adjacent two layers in soil. The variations of potential differences are taken into account for using four probes method to get the soil apparent resistivity profile. The research is significant for simpler and faster soil characterizations using resistivity ratio of apparent resistivity in soil investigations.

Finite-element semi-discretization of linearized compressible and resistive MHD

International Nuclear Information System (INIS)

Kerner, W.; Jakoby, A.; Lerbinger, K.

1985-08-01

The full resistive MHD equations are linearized around an equilibrium with cylindrical symmetry and solved numerically as an initial-value problem. The semi-discretization using cubic and quadratic finite elements for the spatial discretization and a fully implicit time advance yields very accurate results even for small values of the resistivity. In the application different phenomena such as waves, resistive instabilities and overstable modes are addressed. (orig.)

Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer

International Nuclear Information System (INIS)

Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

2016-01-01

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. The online version of this article (doi:10.1186/s12885-016-2452-5) contains supplementary material, which is available to authorized users

Salvage lymphadenectomy of the right recurrent nerve node with tracheal involvement after definitive chemoradiation therapy for esophageal squamous cell carcinoma. Report of two cases

International Nuclear Information System (INIS)

Doki, Yuichiro; Yasuda, Takushi; Miyata, Hiroshi

2007-01-01

Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma. (author)

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

International Nuclear Information System (INIS)

Hsieh, Chen-Hsi; Shueng, Pei-Wei; Wei, Ming-Chow; Lee, Hsing-Yi; Hsiao, Sheng-Mou; Chen, Chien-An; Wang, Li-Ying; Hsieh, Yen-Ping; Tsai, Tung-Hu; Chen, Yu-Jen

2009-01-01

To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m 2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted

Elemental segregation during resistance spot welding of boron containing advanced high strength steels

NARCIS (Netherlands)

Amirthalingam, M.; Van der Aa, E.M.; Kwakernaak, C.; Hermans, M.J.M.; Richardson, I.M.

2015-01-01

The partitioning behaviour of carbon, phosphorous and boron during the solidification of a resistance spot weld pool was studied using experimental simulations and a phase field model. Steels with varying carbon, phosphorous and boron contents were designed and subjected to a range of resistant spot

Management of unresectable, locally advanced pancreatic adenocarcinoma.

Science.gov (United States)

Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

2018-02-01

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

Advances in induced resistance by natural compounds: towards new options for woody crop protection

Directory of Open Access Journals (Sweden)

Eugenio Llorens

Full Text Available ABSTRACT: The activation of defensive responses of plants is a promising tool for controlling pests in conventional agriculture. Over the last few years, several compounds have been studied to protect crops from pests, without displaying direct toxicity for pathogenic organisms. These compounds have the ability to induce a priming state on the plants that results in resistance (or tolerance against subsequent infection by a pathogen. In terms of molecular response, induced plant defense involves a broad number of physical and biochemical changes such as callose deposition or phenolic compounds, activation of salicylic and/or jasmonic acid pathways or synthesis of defense-related enzymes. Despite the large number of studies performed to ascertain the physiological and biochemical basis of induced resistance, only a few resistance-activating compounds have been studied as a real alternative to classic means of control and the studies geared towards incorporating induced resistance into disease management programs are relatively rare. The incorporation of natural resistance inducer in pest management programs of woody crops, alone or in combination with classical methods, could be a reliable method for reducing the amount of chemical residues in the environment. In this review, we discuss the current knowledge of induced resistance in woody crops, focusing on the mode of action of compounds authorized for conventional agriculture. We conclude by discussing the environmental and economic advantages of applying resistance inducers to conventional agriculture with special emphasis on natural compounds.

A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea.

Science.gov (United States)

Houshyari, Mohammad; Hajalikhani, Farzaneh; Rakhsha, Afshin; Hajian, Parastoo

2015-03-25

In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan-Meier method and the log -rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients' age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P=0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P<0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P=0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17.6 and 16 months, respectively (P=0

Preoperative Chemoradiation With Irinotecan and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: Long-Term Results of a Phase II Study

International Nuclear Information System (INIS)

Hong, Yong Sang; Kim, Dae Yong; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Jeong, Jun Yong; Sohn, Dae Kyung; Kim, Dae-Hyun; Chang, Hee Jin; Park, Jae-Gahb; Jung, Kyung Hae

2011-01-01

Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m 2 of irinotecan per week for 5 consecutive weeks and 1,650 mg/m 2 of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.

Analysis of nuclear proliferation resistance reprocessing and recycling technologies

International Nuclear Information System (INIS)

Paviet-Hartmann, Patricia; Cerefice, Gary; Stacey, Marcela; Bakhtiar, Steven

2011-01-01

The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate - and should not be equated - with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R and D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

Analysis of nuclear proliferation resistance reprocessing and recycling technologies

Energy Technology Data Exchange (ETDEWEB)

Patricia Paviet-Hartmann; Gary Cerefice; Marcela Stacey; Steven Bakhtiar

2011-05-01

The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate – and should not be equated -with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. . Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R&D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

Directory of Open Access Journals (Sweden)

Chien Chih-Yen

2011-03-01

Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

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Showalter, Timothy N. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group, RTOG Statistical Center, Philadelphia, PA (United States); Berger, Adam C., E-mail: adam.berger@jefferson.edu [Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Safran, Howard [Department of Medicine, Miriam Hospital, Brown University Oncology Group, Providence, RI (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Benson, Al B. [Division of Hematology-Oncology, Northwestern University, Chicago, IL (United States); MacDonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

Analytical chemistry requirements for advanced reactors

International Nuclear Information System (INIS)

Jayashree, S.; Velmurugan, S.

2015-01-01

The nuclear power industry has been developing and improving reactor technology for more than five decades. Newer advanced reactors now being built have simpler designs which reduce capital cost. The greatest departure from most designs now in operation is that many incorporate passive or inherent safety features which require no active controls or operational intervention to avoid accidents in the event of malfunction, and may rely on gravity, natural convection or resistance to high temperatures. India is developing the Advanced Heavy Water Reactor (AHWR) in its plan to utilise thorium in nuclear power program

Muscle Volume Increases Following 16 Weeks of Resistive Exercise Training with the Advanced Resistive Exercise Device (ARED) and Free Weights

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Nash, R. E.; Loehr, J. A.; Lee, S. M. C.; English, K. L.; Evans, H.; Smith, S. A.; Hagan, R. D.

2009-01-01

Space flight-induced muscle atrophy, particularly in the postural and locomotorymuscles, may impair task performance during long-duration space missions and planetary exploration. High intensity free weight (FW) resistive exercise training has been shown to prevent atrophy during bed rest, a space flight analog. NASA developed the Advanced Resistive Exercise Device (ARED) to simulate the characteristics of FW exercise (i.e. constant mass, inertial force) and to be used as a countermeasure during International Space Station (ISS) missions. PURPOSE: To compare the efficacy of ARED and FW training to induce hypertrophy in specific muscle groups in ambulatory subjects prior to deploying ARED on the ISS. METHODS: Twenty untrained subjects were assigned to either the ARED (8 males, 3 females) or FW (6 males, 3 females) group and participated in a periodizedtraining protocol consisting of squat (SQ), heel raise (HR), and deadlift(DL) exercises 3 d wk-1 for 16 wks. SQ, HR, and DL muscle strength (1RM) was measured before, after 8 wks, and after 16 wks of training to prescribe exercise and measure strength changes. Muscle volume of the vastigroup (V), hamstring group (H), hip adductor group (ADD), medial gastrocnemius(MG), lateral gastrocnemius(LG), and deep posterior muscles including soleus(DP) was measured using MRI pre-and post-training. Consecutive cross-sectional images (8 mm slices with a 2 mm gap) were analyzed and summed. Anatomical references insured that the same muscle sections were analyzed pre-and post-training. Two-way repeated measures ANOVAs (ptraining devices. RESULTS: SQ, HR, and DL 1RM increased in both FW (SQ: 49+/-6%, HR: 12+/-2%, DL: 23+/-4%) and ARED (SQ: 31+/-4%, HR: 18+/-2%, DL: 23+/-3%) groups. Both groups increased muscle volume in the V (FW: 13+/-2%, ARED: 10+/-2%), H (FW: 3+/-1%, ARED: 3+/-1 %), ADD (FW: 15=/-2%, ARED: 10+/-1%), LG (FW: 7+/-2%, ARED: 4+/-1%), MG (FW: 7+/-2%, ARED: 5+/-2%), and DP (FW: 2+/-1%; ARED: 2+/-1%) after training. There

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

Science.gov (United States)

Choi, Il Jung; Park, Eunku Seul; Han, Myung Seok; Choi, Youngmin; Je, Goo Hwa; Kim, Hyun Ho

2008-01-01

Objective To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m2/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated. PMID:19471554

Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.

Science.gov (United States)

Papadimitrakopoulou, Vasiliki A; Frank, Steven J; Cohen, Ezra W; Hirsch, Fred R; Myers, Jeffrey N; Heymach, John V; Lin, Heather; Tran, Hai T; Chen, Changhu R; Jimeno, Antonio; Nedzi, Lucien; Vasselli, Joseph R; Lowe, Elizabeth S; Raben, David

2016-03-01

Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs. Vandetanib with CRT was feasible. © 2015 Wiley Periodicals, Inc.

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

Science.gov (United States)

Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

2017-11-24

To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.