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Sample records for induction chemotherapy implications

  1. Prediction of distant metastasis in head neck cancer patients: implications for induction chemotherapy and pre-treatment staging?

    International Nuclear Information System (INIS)

    Studer, G.; Glanzmann, C.; Seifert, B.

    2008-01-01

    Background and purpose: intensity modulated radiation therapy (IMRT) combined treatment approaches, surgical and radiodiagnostic advances, respectively, lead to improved local-regional control in head neck cancer (HNC). With increasing local-regional control, distant metastases (DM) become more meaningful. In some trials without concomitant chemotherapy, induction chemotherapy (IC) resulted in an absolute reduction of DM by ∝10-15%. In order to define a more efficient selection of patients at risk for DM with respect to IC and M-staging, we analysed our patients treated by contemporary standards. Patients and methods: between 1/2002 to 12/2007, 409 HNC patients were treated with IMRT; 303/409 (74%) underwent definitive, 106 (26%) postoperative IMRT. The mean/median follow-up was 23/20 months (3-72). 70% tolerated 4-7, 9% 1-3 cycles of simultaneous cisplatin. Treatment followed a prospectively designed protocol. In a previous study with 172 HNC IMRT patients, gross tumor volume (GTV) was found the strongest predictor for local-regional control. In the current study, this criterion has been prospectively tested for DM. Numbers needed to treat were calculated for IC. Results: DM developed in 28/399 (7%) patients; 10 presented initially with DM (total 38/409). In 13/28 (46%), DM remained the only manifestation of disease. GTV was the strongest predictor for DM (p 70 cc; only 6 of them (6/73, 8%) developed isolated DM. Conclusion: GTV was the most significant predictor for DM, that could guide selective pre-treatment M-staging. The subgroup with isolated DM in the high risk group, that could benefit from IC, is small. (orig.)

  2. Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma

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    Saito, Yuki; Ando, Mizuo; Omura, Go; Yasuhara, Kazuo; Yoshida, Masafumi; Takahashi, Wataru; Yamasoba, Tatsuya

    2016-01-01

    Objectives/Hypothesis We aimed to determine the effectiveness of induction chemotherapy for treating p16?positive oropharyngeal cancer in our department. Study Design This was a retrospective case series to assess treatment effectiveness. Methods We administered induction chemotherapy to patients with stage III to IV oropharyngeal p16?positive squamous cell carcinoma between 2008 and 2013. Induction chemotherapy was administered using combinations of docetaxel, cisplatin, and 5?fluorouracil. ...

  3. Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions.

    Science.gov (United States)

    Upadhyay, Vivek A; Fathi, Amir T

    2018-03-01

    This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations. Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.

  4. Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma.

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    Saito, Yuki; Ando, Mizuo; Omura, Go; Yasuhara, Kazuo; Yoshida, Masafumi; Takahashi, Wataru; Yamasoba, Tatsuya

    2016-04-01

    We aimed to determine the effectiveness of induction chemotherapy for treating p16-positive oropharyngeal cancer in our department. This was a retrospective case series to assess treatment effectiveness. We administered induction chemotherapy to patients with stage III to IV oropharyngeal p16-positive squamous cell carcinoma between 2008 and 2013. Induction chemotherapy was administered using combinations of docetaxel, cisplatin, and 5-fluorouracil. We measured the survival rates using the Kaplan-Meier method and log-rank test. We reviewed 23 patients (18 men and 5 women; age, 42-79 years). Induction chemotherapy resulted in partial or complete remission (20 patients) and in stable (2 patients) or progressive (1 patient) disease. In partial or complete remission, subsequent radiotherapy was performed in 16 patients, chemoradiotherapy in two, and transoral resection in two. In stable or progressive disease, subsequent open surgery was performed. Overall, one patient died of cervical lymph node metastasis, one died of kidney cancer, and one died of myocardial infarction. Event-free, distant-metastasis-free survival was present for 20 patients. The 3-year disease-specific survival was 95%; the overall survival was 87%. Two patients required gastrostomies during chemoradiotherapy and three required tracheotomies, but these were closed in all patients. The therapeutic response to induction chemotherapy for p16-positive oropharyngeal cancer was good. Partial or complete remission was achieved in almost 90% patients, and control of local and distant metastases was possible when it was followed by radiotherapy alone or with transoral resection of the primary tumor. A multicenter study is required to confirm these findings. 4.

  5. Induction chemotherapy followed by concurrent radiotherapy and chemotherapy in stage III non-small cell lung cancer

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    Bouillet, T.; MOrere, J.F.; Piperno-Neuman, S.; Boaziz, C.; Breau, J.L.; Mazeron, J.J.; Haddad, E.

    1997-01-01

    The purpose was to determine the efficacy and safety of induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of stage III non-small cell lung cancer and whether the response to induction chemotherapy can predict the response to subsequent chemoradiotherapy and survival. In conclusion, there is a statistically significant relationship not only between the response to ICT and the response to CCrt, but also between the response to ICT and the local outcome and survival. (authors)

  6. Economic implications of labor induction.

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    Garcia-Simon, Raquel; Montañes, Antonio; Clemente, Jesús; Del Pino, María D; Romero, Manuel A; Fabre, Ernesto; Oros, Daniel

    2016-04-01

    To assess health service costs associated with labor induction according to different clinical situations in a tertiary-level hospital. In a prospective study, individual patient cost data were assessed for women admitted for induction of labor at a tertiary hospital in Spain between November 1, 2012, and August 31, 2013. The costs of labor induction were estimated according to maternal and neonatal outcomes, method of delivery, cervical condition at admission, and obstetric indication. Direct costs including professional fees, epidural, maternal stay, consumables, and drugs were calculated. Overall, 412 women were included in the final cost analysis. The mean total cost of labor induction was €3589.87 (95% confidence interval [CI] 3475.13-3704.61). Cesarean delivery after labor induction (€4830.45, 95% CI 4623.13-5037.58) was significantly more expensive than spontaneous delivery (€3037.45, 95% CI 2966.91-3179.99) and instrumental vaginal delivery (€3344.31, 95%CI 3151.69-3536.93). The total cost for patients with a very unfavorable cervix (Bishop score Labor induction for hypertensive disorders of pregnancy was the most expensive obstetric indication for induction of labor (€4347.32, 95% CI 3890.45-4804.18). Following the induction of labor, a number of patient- and treatment-related factors influence costs associated with delivery. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  7. [Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

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    Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

    2004-06-01

    To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

  8. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Lan, Xiao-Wen; Zou, Xue-Bin; Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

    The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic

  9. Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

    International Nuclear Information System (INIS)

    Takita, H.; Pitoniak, R.F.

    2000-01-01

    Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

  10. Hyperfractionated Radiotherapy Following Induction Chemotherapy for Stage III Non-Small Cell Lung Cancer-Random iced for Adjuvant Chemotherapy vs. Observation

    International Nuclear Information System (INIS)

    Choi, Eun Kyung; Chang, Hye Sook; Ahn, Seung Do

    1993-01-01

    Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer(NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hypefractionated radiotherapy (120 cGy/fx BID, 0480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 mg/m2, Vinblastin B mg/ m2, Cisplatin 60 Mg/ m2) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient refusal, 39 completed planned therapy. Twenty-three(58%) patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy, 1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hypefractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 35 patients who completed induction chemotherapy and radiotherapy, 25 patients(64%) including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radiotherapy. Nine patients were allocated to adjuvant chemotherapy group and 4/9 shewed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant

  11. Accelerated proliferation of non-small cell lung cancer cells after induction chemotherapy

    International Nuclear Information System (INIS)

    El Sharouni, S.Y.; Kal, H.B.

    2003-01-01

    Induction chemotherapy of non-small cell lung cancer (NSCLC) stage IIIB with gemcitabine and cisplatin for downstaging the tumour with the aim for further treatment with ionising radiation, is one of the treatments for lung cancer employed. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, i.e. the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth. Interval times between end of chemotherapy and day of diagnostic CT, planning CT and first day of radiotherapy were determined. Increase in tumour volume was measured for 23 patients with NSCLC by measuring the primary tumour dimensions on the diagnostic CT made after induction chemotherapy and on the CT used for radiotherapy planning. Volume doubling times were calculated from the time interval between the two CTs and ratio of the volumes on CT planning and CT diagnostic. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, till CT planning 66 days and till first day of radiotherapy 76 (29 - 108) days. Tumour doubling times ranged from 9 to 153 days with a mean of 47 days. This is far less than the mean doubling time of NSCL in untreated patients. This study shows that time interval between chemo- and start of radiotherapy varies between 29 to 108 days. The consequence is fast tumour progression as result of accelerated proliferation: mean tumour-doubling times are decreased by a factor of 2 to 4. The gain obtained with induction chemotherapy with regard to volume reduction was practically lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo- and radiotherapy to as short as possible

  12. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

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    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  13. Response assessment after induction chemotherapy for head and neck squamous cell carcinoma : From physical examination to modern imaging techniques and beyond

    NARCIS (Netherlands)

    de Bree, Remco; Wolf, Gregory T; de Keizer, Bart; Nixon, Iain J; Hartl, Dana M; Forastiere, Arlene A; Haigentz, Missak; Rinaldo, Alessandra; Rodrigo, Juan P.; Saba, Nabil F; Suárez, Carlos; Vermorken, Jan B; Ferlito, Alfio

    2017-01-01

    Significant correlations between the response to induction chemotherapy and success of subsequent radiotherapy have been reported and suggest that the response to induction chemotherapy is able to predict a response to radiotherapy. Therefore, induction chemotherapy may be used to tailor the

  14. Assessment of the nutritional status of adult patients with acute myeloid leukemia during induction chemotherapy.

    Science.gov (United States)

    Deluche, Elise; Girault, Stephane; Jesus, Pierre; Monzat, Sophie; Turlure, Pascal; Leobon, Sophie; Abraham, Julie; Daly, Nathalie; Dauriac, Olivia; Bordessoule, Dominique

    2017-09-01

    To the best of our knowledge, few studies have evaluated the nutritional status in patients with acute myeloid leukemia (AML) during induction treatment. The aim of this retrospective study was to describe nutritional status of newly diagnosed adult patients with AML at admission and during induction chemotherapy. We included consecutive newly diagnosed adult patients with AML who were admitted to the Department of Hematology (Limoges University Hospital) from April 2010 to January 2014. Nutritional assessment included body mass index (BMI) and weight loss to diagnose undernutrition. Weekly laboratory tests were collected and total energy expenditure was calculated to adapt food intake. Of 95 patients, 14 (15%) presented with undernutrition at admission: low BMI values (P 5% for 9.5% patients. After chemotherapy induction, 17 patients (18%) were undernutrition (P = 0.05). Patients without undernutrition had a significantly lower median weight, BMI, and serum albumin level at discharge compared with their admission values (P nutritional status undergoing induction chemotherapy have shorter hospital stays and longer survival. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer

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    Broemme, J.O.; Schmuecking, M.; Leiser, D.; Geretschlaeger, A.; Ghadjar, P.; Aebersold, D.M. [Bern Univ. Hospital and Bern Univ. (Switzerland). Dept. of Radiation Oncology; Arnold, A.; Giger, R. [Bern Univ. (Switzerland). Head and Neck Surgery; Rauch, D. [Bern Univ. (Switzerland). Medical Oncology; Plasswilm, L. [Kantonsspital, St. Gallen (Switzerland). Radiation Oncology

    2013-08-15

    Background: Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. Materials and methods: The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. Results: The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. Conclusion: Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired. (orig.)

  16. Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

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    Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Bohr, C. [University Hospital Erlangen, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen (Germany)

    2014-02-15

    To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D{sub mean}, D{sub max} and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D{sub mean} to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target

  17. Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

    International Nuclear Information System (INIS)

    Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R.; Bohr, C.

    2014-01-01

    To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D mean , D max and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D mean to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target volume

  18. Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes.

    Science.gov (United States)

    McNamara, Michael J; Adelstein, David J; Allende, Daniela S; Bodmann, Joanna W; Ives, Denise I; Murthy, Sudish C; Raymond, Daniel; Raja, Siva; Rodriguez, Cristina P; Sohal, Davendra; Stephans, Kevin L; Videtic, Gregory M M; Rybicki, Lisa A

    2017-06-01

    Preoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted. Between 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50 mg/m 2 d1, oxaliplatin 130 mg/m 2 d1, and fluorouracil 200 mg/m 2 /day continuous infusion for 3 weeks, was given every 21 days for 3 cycles and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy @ 1.8-2.0 Gy/day and 2 cycles of cisplatin (20 mg/m 2 /day) and fluorouracil (1000 mg/m 2 /day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. Persistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43-8.43), p = 0.006], recurrence free survival [HR 3.04 (1.34-6.92), p = 0.008], and overall survival [HR 3.31 (1.43-7.66), p = 0.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (p = 0.048) and N descriptor (pN) (p = 0.002), a greater median number of involved lymph nodes (3 v 1, p = 0.003), and greater residual tumor viability (p = 0.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease. Persistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.

  19. 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.

  20. Type III radical hysterectomy after induction chemotherapy for patients with locally advanced cervical carcinoma.

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    Lopez-Graniel, C; Reyes, M; Chanona, G; Gonzalez, A; Robles, E; Mohar, A; Lopez-Basave, H; De La Garza, J G; Dueñas-Gonzalez, A

    2001-01-01

    Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally

  1. Routine interim disease assessment in patients undergoing induction chemotherapy for acute myeloid leukemia: Can we do better?

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    Campuzano-Zuluaga, Germán; Deutsch, Yehuda; Salzberg, Matthew; Gomez, Alexandra; Vargas, Fernando; Elias, Roy; Kwon, Deukwoo; Goodman, Mark; Ikpatt, Offiong F; Chapman, Jennifer R; Watts, Justin; Vega, Francisco; Swords, Ronan

    2016-03-01

    The presence of >5% blasts at "day 14" (D14), in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) is problematic. It is unclear if a second course of chemotherapy for early persistent disease will alter outcome in these patients. We conducted a retrospective study of AML patients undergoing induction chemotherapy where diagnostic, interim (around day 14), and recovery (days 21-42) bone marrow (BM) evaluations were available for review. Of the 113 patients included in the final analysis, 99 (87.6%) achieved CR at hematologic recovery. At D14, 90 patients (79.6%) had 5% blasts). Of these, 11 (47.8%) received a second course of chemotherapy (double induction [DI]) and 12 (52.2%) were observed until count recovery (single induction [SI]). No significant difference in CR rates was observed between these two groups (58.3% DI group vs. 45.5% SI group, P value = 0.684). In our analysis, D14 BM evaluation did not uniformly identify patients with primary induction failure. To unequivocally determine the value of a D14 marrow assessment in AML, prospective studies in the context of large cooperative group trials are required. Considering our findings and similar reports from others, we propose that D14 marrow assessment should be individualized, and that other factors, such as cytogenetics and early peripheral blood blast clearance should be considered, to identify patients most likely to benefit from interim disease assessment during AML induction therapy. © 2015 Wiley Periodicals, Inc.

  2. Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

    Science.gov (United States)

    Nedved, Adrienne N; DeFrates, Sean R; Hladnik, Lindsay M; Stockerl-Goldstein, Keith E

    2016-10-01

    Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. Single-center, retrospective, observational, cohort study. Large, tertiary care academic medical center. A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; plinezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia. © 2016 Pharmacotherapy Publications, Inc.

  3. Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer. A pilot study

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    Jereczek-Fossa, B.; Medical Univ. Gdansk; De Braud, F.; Gasparetto, M.; De Pas, T.; Tradati, N.; Leonardi, M.C.; Marsiglia, H.R.; Orecchia, R.; Milan Univ.

    1998-01-01

    Purpose: To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer. Methods: A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m 2 , day 1) and 5-fluorouracil (1000 mg/m 2 in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m 2 ). Results: Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed. Conclusions: High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer. (orig.) [de

  4. [The effect of sodium phenylbutyrate to agents used in induction chemotherapy on laryngeal carcinoma cells Hep-2 in vitro].

    Science.gov (United States)

    Gao, Jing; Ruan, Xinyong; Pan, Xinliang; Xu, Fenglei; Lei, Dapeng; Liu, Dayu

    2005-08-01

    To study the effect of sodium phenylbutyrate when it combined with agents used in induction chemotherapy on laryngeal carcinoma cells Hep-2 in vitro. MTT were used to examine the growth inhibition of Hep-2 cells treated by the combination of PB with 5-FU or CDDP in vitro. When 5-FU or CDDP combined with PB respectively, there was significantly difference between every two dose groups of the two agents or every dose group and control group ( P < 0.05). When the dosage of 5-FU or CDDP was definition,there was significantly difference between every two dose groups of PB ( P < 0.05). PB could enhance the cytotoxic effects of agents used in induction chemotherapy on laryngeal carcinoma cells Hep-2 in vitro, which showed the possibility in reinforcement the treatment effect and reduction the occurrence of the complication and toxic reaction of induction chemotherapy on laryngeal carcinoma.

  5. RETROPERITONEAL LYMPH NODE DISSECTION AFTER INDUCTION CHEMOTHERAPY IN METASTATIC TESTICULAR NON-SEMINOMA

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    V. B. Matveev

    2014-07-01

    Full Text Available Objective: to evaluate the outcome of retroperitoneal lymph node dissection (RLND in disseminated testicular non-seminoma patients with residual metastases after induction chemotherapy. Material and methods. The RLND performed in 1983 to 2007 were analyzed in 367 testicular non-seminoma patients with residual retroperitoneal masses after ineffective induction chemotherapy. The median age was 26.06.9 years. Orchidectomy was performed in all patients. Category N1 was regarded in 12 (3.3% patients, N2 in 79 (21.5%, N3 in 238 (64.9%, Nx in 38 (10.4%. Distant metastases were present in 133 (36.2% cases. The baseline tumor marker level was elevated in 328 (89.4% patients (S1 in 169 (46.0%, S2 in 108 (29.4%, S3 in 51 (13.9%, Sx in 39 (10.6%. According to the IGCCCG prognostic model, 149 (40.6% patients were classified as good prognostic group, 100 (27.2% as moderate, 77 (21.0% as poor ones; the prognostic group was not defined in 41 (11.2% cases who had started treatment at another facility due to data unavailability. After orchifuniculectomy, all patients received induction cisplatin-based chemotherapy which resulted in tumor shrinkage <50% in 70 (19.1%, 51-90% in 166 (45.2%, and >90% - in 29 (7.9% cases. The response was not properly assessed in 102 (27.8% cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all patients (<2 cm - 52 (14.2%, 2-5 cm - 166 (45.2%, >5 cm - 149 (40.6%. The tumor markers level remained elevated following chemotherapy in 70 (19.1% cases. All patients underwent RLND (complete in 295 (80.4% cases. Radical RLND demanded resection of adjacent organs in 22 (5.9% cases. Extraretroperitoneal metastases were removed simultaneously with retroperitoneal tumor in 22 (5.9% patients. Postoperative chemotherapy was administered in 100 (27.2% cases. The median followup was 82.1 (3-188 months. Results. Complications developed in 31 (8.5% of the 367 of patients. Mortality rate was 0.6% (2/367 cases. Resection of

  6. Chemotherapy

    Science.gov (United States)

    ... nurse can help you balance the risks of chemotherapy against the potential benefits. It is important to note that the information provided here is basic and does not take the place of professional advice. If you have any questions ... Publication Quimioterapia (Chemotherapy) Una publicación de ...

  7. Study on delineation of tumor volume of primary locally advanced nasopharyngeal carcinoma after induction chemotherapy

    International Nuclear Information System (INIS)

    Long Jinhua; Dong Shi; Jin Feng; Wu Weili; Gan Jiaying; Chen Haixia; Li Yuanyuan; Gong Xiuyun

    2012-01-01

    Objective: To investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better. Methods: Between Mar 2010 to Jan 2011, 11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy, target volumes were delineated based on fused CT imaging before and after IC following project determination. Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTV nx in order to ensure radical doses for the imaging tumor volume before IC, the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test. Results: Before and after IC, the average volumes of GTV nx were respectively 44.72 cm 3 and 28.87 (t=3.89, P=0.003), the average volumes of GTV nd were respectively 32.76 cm 3 and 19.82 cm 3 (t=2.47, P=0.033), the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased (t=2.93-4.59, all P<0.05). Conclusions: LANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy shows significant shrinkage of tumor volume. The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC. (authors)

  8. Severe oral infection due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia.

    Science.gov (United States)

    Ishihara, Yuko; Kanda, Junya; Tanaka, Kaori; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kako, Shinichi; Nishida, Junji; Watanabe, Kunitomo; Kanda, Yoshinobu

    2014-12-01

    We report a case of severe oral infection with a high fever due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia. The patient did not improve on treatment with meropenem, clindamycin, or vancomycin until neutrophil recovery. Since L. rhamnosus GG is used in dairy products, and the patient ingested dairy products daily before starting chemotherapy, we suspected an association between the ingestion of dairy products and the development of infection. Pulsed-field gel electrophoresis using two different restriction enzymes showed that the strain isolated from the patient was identical to the L. rhamnosus GG strain isolated from dairy products and ATCC #53103. This was confirmed by a PCR assay with species-specific L. rhamnosus GG primers. Since Lactobacillus infection, particularly L. rhamnosus infection, can be fatal in immunocompromised hosts, we should consider Lactobacillus as a causative organism when Gram-positive rods are detected during treatment with broad-spectrum antibiotics and vancomycin. The causal association between the ingestion of dairy products containing Lactobacillus and Lactobacillus infection in immunocompromised hosts warrants further study.

  9. Induction chemotherapy combined with three-dimensional conformal radiation therapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zheng Aiqing; Yu Jinming; Zhao Xianguang; Wang Xuetao; Wei Guangsheng

    2005-01-01

    Objective: To evaluate the effect and complication of induction chemotherapy combined with three-dimensional conformal radiation therapy (3DCRT) for locally advanced non small cell lung cancer (NSCLC). Methods: Ninety-two such patients were randomized into radiation therapy alone group(RT-, 50 patients) and induction chemotherapy combined radiotherapy group (CMT-, 42 patients). The induction chemotherapy consisted of 2-4 cycles of platinum-based regimen. Results: The overall median survival time was 15 months with 12 months in the RT group and 18 months in the CMT group (P=0.014) respectively. The 1-year overall survival rates were 48.6% and 71.2% in RT and CMT group, respectively (P=0.004). The 2-year survival rates were 20.8% and 37.6% in RT and CMT group, respectively (P=0.041). Treatment was well tolerated and the toxicities were similar in either group. Conclusion: The addition of induction chemotherapy to 3DCRT takes a survival advantage over 3DCRT alone for Stage III NSCLC without increasing toxicities. (authors)

  10. [Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

    Science.gov (United States)

    Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

    2015-09-01

    To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in

  11. Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

    Science.gov (United States)

    Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

    2012-09-01

    We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

  12. Induction Cisplatin and Fluorouracil-Based Chemotherapy Followed by Concurrent Chemoradiation for Muscle-Invasive Bladder Cancer

    International Nuclear Information System (INIS)

    Lin, C.-C.; Hsu, C.-H.; Cheng, Jason C.; Huang, C.-Y.; Tsai, Y.-C.; Hsu, F.-M.; Huang, K.-H.; Cheng, A.-L.; Pu, Y.-S.

    2009-01-01

    Purpose: To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. Methods and Materials: Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age ≥70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS ≥80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. Results: Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. Conclusions: Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

  13. A pilot study of daunorubicin-augmented hyper-CVAD induction chemotherapy for adults with acute lymphoblastic leukemia.

    Science.gov (United States)

    Kim, Sung-Yong; Park, Ji Hyun; Yoon, So Young; Cho, Yo-Han; Lee, Mark Hong

    2018-02-01

    Induction of complete remission (CR) is imperative for long-term survival in adult acute lymphoblastic leukemia (ALL) patients regardless of transplantation eligibility. Hyper-CVAD chemotherapy is a widely-used frontline remission induction regimen for these patients. We conducted a pilot trial of frontline remission induction using daunorubicin-augmented hyper-CVAD regimen (hyper-CVDD) in adult ALL patients (n = 15). The CR rate after this modified regimen was 100% (n = 15). Twelve patients were able to proceed to allogeneic hematopoietic cell transplantation, two patients died before transplantation due to infection, and the remaining one who was ineligible for transplant due to her age received an additional five courses of consolidation chemotherapy. Overall survival (OS) and event-free survival (EFS) of the study patients was 61.0 and 47.5% at 3 years. OS and relapse-free survival of transplanted patients was 66.8 and 55.0% at 3 years. This pilot trial demonstrates the favorable efficacy of the hyper-CVDD chemotherapy as a frontline remission induction regimen. Further clinical trials using this regimen are warranted.

  14. 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

    International Nuclear Information System (INIS)

    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

  15. Comparison of induction chemotherapy before radiotherapy with radiotherapy only in patients with locally advanced squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Brodin, O.; Nou, E.; Mercke, C.

    1996-01-01

    The aim of this randomised trial was to investigate the effect of induction chemotherapy before radiotherapy on survival in 302 patients with non-resectable squamous cell carcinoma of the lung. Radiotherapy, 56 Gy to the chest, was given to 154 patients and combined treatment, with chemotherapy preceding the radiotherapy, to 148 patients. Chemotherapy consisted of three courses of cisplatin (120 mg/m 2 ) and etoposide (100 mg/m 2 i.v. for 3 days) administered every fourth week. Median survival was 10.5 months in the radiotherapy arm and 11 months in the combined treatment arm. The 2-year survival rate was 17% in the radiotherapy arm and 21% in the combined treatment arm. Addition of chemotherapy seemed to significantly improve survival, according to the Cox multivariate analysis (P = 0.04), but as only a trend according to life-table analysis (P = 0.11). Chemotherapy also accomplished a trend towards improved local control (P 0.08) and towards decreased metastatic disease (P = 0.10). 2 patients in the combined treatment arm, but none in the radiotherapy ar, died from toxicity. The conclusion was that the value of the chemotherapy used in this study was very modest, but the results strongly support further research for more efficient drugs and combinations. (author)

  16. Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

    Directory of Open Access Journals (Sweden)

    Louis Chesler

    2008-11-01

    Full Text Available Chemoresistance in neuroblastoma is a significant issue complicating treatment of this common pediatric solid tumor. MYCN-amplified neuroblastomas are infrequently mutated at p53 and are chemosensitive at diagnosis but acquire p53 mutations and chemoresistance with relapse. Paradoxically, Myc-driven transformation is thought to require apoptotic blockade. We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy. Tumors formed with high penetrance and low latency in p53-haploinsufficient TH-MYCN mice. Cyclophosphamide (CPM induced a complete remission in p53 wild type TH-MYCN tumors, mirroring the sensitivity of childhood neuroblastoma to this agent. Treated tumors showed a prominent proliferation block, induction of p53 protein, and massive apoptosis proceeding through induction of the Bcl-2 homology domain-3-only proteins PUMA and Bim, leading to the activation of Bax and cleavage of caspase-3 and -9. Apoptosis induced by CPM was reduced in p53-haploinsufficient tumors. Treatment of MYCN-expressing human neuroblastoma cell lines with CPM induced apoptosis that was suppressible by siRNA to p53. Taken together, the results indicate that the p53 pathway plays a significant role in opposing MYCN-driven oncogenesis in a mouse model of neuroblastoma and that basal inactivation of the pathway is achieved in progressing tumors. This, in part, explains the striking sensitivity of such tumors to chemotoxic agents that induce p53-dependent apoptosis and is consistent with clinical observations that therapy-associated mutations in p53 are a likely contributor to the biology of tumors at relapse and secondarily mediate resistance to therapy.

  17. Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

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    Ladra, Matthew M. [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Mandeville, Henry C. [The Royal Marsden Hospital, London (United Kingdom); Niemierko, Andrzej; Padera, Timothy P.; Friedmann, Alison M.; MacDonald, Shannon M.; Ebb, David; Chen, Yen-Lin; Tarbell, Nancy J. [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Yock, Torunn I., E-mail: tyock@partners.org [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2015-06-01

    Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results: With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.

  18. A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

    International Nuclear Information System (INIS)

    Graf, Reinhold; Hildebrandt, Bert; Tilly, Wolfgang; Riess, Hanno; Felix, Roland; Budach, Volker; Wust, Peter

    2006-01-01

    The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival

  19. A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

    Directory of Open Access Journals (Sweden)

    Felix Roland

    2006-02-01

    Full Text Available Abstract Background The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Methods Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck cancer by two different protocols. The sequential protocol (SEQ; 1987–1992 started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i. of folinic acid [FA] and 5-fluorouracil [5-FU], followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993 combined two courses of FA/5-FU c.i. plus mitomycin (MMC concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Results Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.. Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00, response rates (67 vs. 90 % for primary, p = 0.02, and local control (LC; 17.6% vs. 41%, p = 0.03, were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08 and overall (14.7% vs. 23.7%, p = 0.11 survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%. Late toxicity was similar in both groups. Conclusion Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.

  20. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy.

    Science.gov (United States)

    Alibhai, Shabbir M H; O'Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M; Timilshina, Narhari; Tomlinson, George A; Klepin, Heidi D; Culos-Reed, S Nicole

    2012-10-01

    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. p53/Surviving Ratio as a Parameter for Chemotherapy Induction Response in Children with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Rinaldi Lenggana

    2016-11-01

    Full Text Available Acute myeloid leukemia (AML is a malignancy that is often found in children. Many studies into the failure of apoptosis function, or programmed cell death, is one of the most important regulatory mechanisms of cellular hemostasis which is closely linked to the development of cancer, are important. Also, regulation of the apoptotic (p53 and anti-apoptotic (surviving proteins influence treatment outcome. One role of p53 is to monitor cellular stress necessary to induce apoptosis. Surviving (BIRC5 is a group of proteins in the apoptosis inhibitor which works by inhibiting caspase-3. The role of surviving is considered very important in oncogenesis proliferation and cell growth regulation. Chemotherapy in childhood AML can inhibit cell growth and induce slowing as well as stopping the cell cycle. Thus, the aim of this study was to compare p53 and surviving before and after receiving induction chemotherapy in children with AML and also to determine the p53/surviving ratio. Peripheral blood mononuclear cells were collected from AML children before treatment and three months after starting their induction therapy. p53 and surviving were measured by flowcytometry using monoclonal antibodies. Data were analyzed by t-test for comparison between groups and Spearman’s test to find out the correlation between variables with a significant value of p < 0.05. A total of 8 children were evaluated. The intensity of p53 expression was not significantly increased after induction phase chemotherapy (p = 0.224, but surviving expression and the ratio of p53/surviving were significantly increased in the treatment group compared with the levels prior to chemotherapy (p = 0.002, p = 0.034, and there was a strong negative correlation between p53 and surviving after chemotherapy (r = −0.63, p = 0.049.

  2. Results of the Tremplin trial proposing an induction chemotherapy followed by concomitant radiotherapy with cisplatin ou cetuximab in order to protect the larynx

    International Nuclear Information System (INIS)

    Pointreau, Y.; Calais, G.; Pointreau, Y.; Calais, G.; Pointreau, Y.; Rolland, F.; Bardet, E.; Alfonsi, M.; Baudoux, A.; Sire, G.; De Raucourt, D.; Tuchais, C.; Lefebvre, J.L.

    2010-01-01

    The authors report a randomized phase II trial which aimed at comparing over three months the laryngeal protection after a TPF-based induction chemotherapy followed by radiotherapy in combination with cisplatin or cetuximab. Over two years, 153 patients have been concerned. The TPF-based induction chemotherapy followed by radiotherapy with cetuximab seems to be the less toxic. A longer monitoring is needed to get better information in terms of laryngeal protection rate, life quality, and laryngeal functionality. Short communication

  3. Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy.

    Science.gov (United States)

    Tan, S Y; Poh, B K; Nadrah, M H; Jannah, N A; Rahman, J; Ismail, M N

    2013-07-01

    The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia. This cross-sectional study included 53 paediatric patients aged 3-12 years old, who were diagnosed with either acute lymphoblastic leukaemia or acute myelogenous leukaemia and were undergoing chemotherapy treatments (induction or consolidation phase). Patients were matched for sex, age (±6 months) and ethnicity with healthy children as controls. Weight, height, body mass index, waist circumference, mid-upper arm circumference, triceps skinfold thickness, mid-upper arm muscle area and fat area were determined. Dietary intake was assessed using 3-day food records. Anthropometric variables were generally higher among patients compared to controls, although the differences were not statistically significant (P > 0.05). The prevalence of overnutrition among patients according to body mass index-for-age, waist circumference-for-age, mid-upper arm circumference-for-age and triceps skinfold-for-age were 24.5%, 29.1%, 17.0% and 30.2%, respectively. Mean energy [5732 ± 1958 kJ (1370 ± 468 kcal) versus 6945 ± 1970 kJ (1660 ± 471 kcal), P children with acute leukaemia was higher despite lower energy intake compared to controls. Studies assessing physical activity, the complex interaction and the effects of treatment drugs are warranted to better manage malnutrition among paediatric patients. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  4. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zheng Jijun; Wang Ge; Yang, G.Y.

    2010-01-01

    This Phase II study was conducted to evaluate the activity and feasibility of a regimen of nedaplatin and 5-fluorouracil as induction chemotherapy, followed by intensity-modulated radiotherapy concurrent with chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Patients received neoadjuvant chemotherapy comprised two cycles of 5-fluorouracil at 700 mg/m 2 /day administered on days 1-4 as continuous intravenous infusion and nedaplatin (100 mg/m 2 administered intravenous (i.v.) over 2 h) given after the administration of 5-fluorouracil on day 1, repeated every 3 weeks, followed by intensity-modulated radiotherapy concurrent with nedaplatin. During intensity-modulated radiotherapy, nedaplatin was administered at a dose of 100 mg/m 2 intravenous infusion on days 1, 22 and 43, given -60 min before radiation. Fifty-nine (95.8%) of the 60 patients were assessable for response. Thirty-eight cases of complete response and 14 cases of partial response were confirmed after completion of chemoradiation, with the objective response rate of 86.7% (95% confidence interval (CI), 78.1-95.3%). The median follow-up period was 48 months (range, 30-62 months). The 3-year progression-free survival and overall survival were 75.0% (95% CI, 63.0-87.0%) and 85.5% (95% CI, 75.9-95.1%). No patient showed Grade 3 or higher renal dysfunction. The most commonly observed late effect was xerostomia, but the severity diminished over time, and the detectable xerostomia at 24 months was 10.2%. There were no treatment-related deaths during this study. Neoadjuvant chemotherapy with nedaplatin and 5-fluorouracil followed by concomitant nedaplatin and intensity-modulated radiotherapy is an effective and safe treatment for Southern China patients affected by locoregionally advanced nasopharyngeal carcinoma. (author)

  5. [A Case of Advanced Rectal Cancer Resected Successfully after Induction Chemotherapy with Modified FOLFOX6 plus Panitumumab].

    Science.gov (United States)

    Yukawa, Yoshimi; Uchima, Yasutake; Kawamura, Minori; Takeda, Osami; Hanno, Hajime; Takayanagi, Shigenori; Hirooka, Tomoomi; Dozaiku, Toshio; Hirooka, Takashi; Aomatsu, Naoki; Hirakawa, Toshiki; Iwauchi, Takehiko; Nishii, Takafumi; Morimoto, Junya; Nakazawa, Kazunori; Takeuchi, Kazuhiro

    2016-05-01

    We report a case of advanced colon cancer that was effectively treated with mFOLFOX6 plus panitumumab combination chemotherapy. The patient was a 54-year-old man who had type 2 colon cancer of the rectum. An abdominal CT scan demonstrated rectal cancer with bulky lymph node metastasis and 1 hepatic node (rectal cancer SI [bladder retroperitoneum], N2M0H1P0, cStage IV). He was treated with mFOLFOX6 plus panitumumab as neoadjuvant chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and regional metastatic lymph nodes had reduced in size (rectal cancer A, N1H1P0M0, cStage IV). Anterior rectal resection with D3 nodal dissection and left lateral segmentectomy of the liver was performed. The histological diagnosis was tubular adenocarcinoma (tub2-1), int, INF a, pMP, ly0, v0, pDM0, pPM0, R0. He was treated with 4 courses of mFOLFOX6 after surgery. The patient has been in good health without a recurrence for 2 years and 5 months after surgery. This case suggests that induction chemotherapy with mFOLFOX6 plus panitumumab is a potentially effective regimen for advanced colon cancer.

  6. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

    International Nuclear Information System (INIS)

    Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

    2007-01-01

    Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

  7. Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade.

    Science.gov (United States)

    Zhu, Dong-wang; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping

    2013-06-21

    The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, benefited from TPF induction chemotherapy as measured by distant metastasis-free survival (P=0.048, HR=0.373) as well as overall survival (P=0.078, HR=0.410). Annexin A1 can be used as a prognostic biomarker for OSCC. Patients with moderate/poorly differentiated OSCC and low Annexin A1 expression can benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression can potentially be used as a predictive biomarker to select OSCC patients with moderate/poorly differentiated tumor who may benefit from TPF induction chemotherapy.

  8. Impact of chemotherapy and definitive radiotherapy for laryngeal preservation. A comparative study of concurrent chemoradiotherapy and induction chemotherapy followed by radiation therapy

    International Nuclear Information System (INIS)

    Hiraga, Yukihiro; Kou, Junichi

    2013-01-01

    During the past 23 years, from June 1989 to December 2012, our treatment paradigm for head and neck squamous cell carcinoma (HNSCC) had involved comprehensive use of chemotherapy and radiation therapy followed by surgery. Between 1989 and 2005, chemotherapy using fluorouracil and carboplatin had been administered via intravenous drip infusion as induction chemotherapy (ICT), and more recently between 2006 and 2012 as concurrent chemoradiotherapy (CCRT). In the present study, we examined the superiority of definitive CCRT (dCCRT) over the ICT followed by definitive radiotherapy (ICT-dRT) as to the impact on the treatment of HNSCC with the stage-categories of T2-T4a, retrospectively analyzing survival rates and laryngeal preservation rates at the 3-year point between the two groups. The number of patients assigned for this study was 76, all of whom were previously untreated, and of whom 51 suffered from laryngeal carcinoma and 25 from hypopharyngeal carcinoma: 21 with Stage II, 25 with Stage III, 23 with Stage IV A, 7 with Stage IV C. The three-year overall survival rate and cause-specific survival rate were 54.5%, 73.5% in the ICT-dRT group and 69.2%, 80.5% in the dCCRT group, respectively, both of which statistically had no difference. But the dCCRT was found to contribute to obtaining a higher rate of laryngeal preservation than that of the ICT-dRT in T2 and T3 but not in T4a. In conclusion, dCCRT showed more significant efficacy for organ preservation on T2 and T3 HNSCC than ICT-dRT. (author)

  9. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12...... and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  10. 18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

    International Nuclear Information System (INIS)

    Piccardo, Arnoldo; Lopci, Egesta; Foppiani, Luca; Morana, Giovanni; Conte, Massimo

    2014-01-01

    Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. 123 I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established. 18 F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with 123 I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of 18 F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of 123 I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

  11. {sup 18}F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Lopci, Egesta [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine and Endocrinology, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Conte, Massimo [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy)

    2014-03-15

    Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. {sup 123}I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.{sup 18}F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with {sup 123}I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of {sup 18}F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of {sup 123}I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

  12. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel

    2016-01-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose...

  13. Erythrocyte abnormalities induced by chemotherapy and radiotherapy: Induction of preleukaemic states

    International Nuclear Information System (INIS)

    Renoux, M.; Bernard, J.-F.; Boivin, P.; Schlegel, N.; Amar, M.; Torres, M.; Lopez, M.

    1978-01-01

    Increased incidence of acute leukaemia (AL) following exposure to ionizing radiation is well documented. AL has also been reported with increased frequency after chemotherapy for nonmalignant diseases. The effect of chemotherapy and/or radiotherapy on the following erythrocyte parameters: pyruvate-kinase (PK) activity, phospho-fructo-kinase (PFK) activity, HbF level, red cell antigens production and bone marrow sideroblasts, has been studied in 31 patients with myelomatosis and in 33 patients with nonhaematological malignancies. We have demonstrated the apperance after chemotherapy or radiotherapy of some abnormalities usually associated with leukaemia or preleukaemic states. In patients treated for myelomatosis, a PK deficiency has been detected in 58 % of the cases, an increased HbF level in 47 %, a modification of blood groups antigens in 68 % and abnormal sideroblasts in 30 %. No PFK deficiency was found. In patients treated for solid tumors, a PK deficiency in 50 % of the cases, a PFK deficiency in 20 %, an increased HbF level in 10 %, a modification of blood group antigens in 40 % has been detected. Chemotherapy administered over a period of 3 months has been shown to induce these abnormalities. Localized radiotherapy may have a similar effect. The combination of these two factors seems to cause an increase in the frequency and intensity of these abnormalities. (author)

  14. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, M

    1998-01-01

    .0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two......The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S......-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10...

  15. CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer

    International Nuclear Information System (INIS)

    Melchardt, Thomas; Hufnagl, Clemens; Magnes, Teresa; Weiss, Lukas; Hutarew, Georg; Neureiter, Daniel; Schlattau, Alexander; Moser, Gerhard; Gaggl, Alexander; Tränkenschuh, Wolfgang; Greil, Richard; Egle, Alexander

    2015-01-01

    Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment. A cohort of 78 patients with advanced head and neck cancer treated with induction chemotherapy was assessed for clinical outcome and toxicity during treatment with curative intention. Genetic polymorphisms primary associated with treatment efficacy (ERCC2-rs13181, rs1799793, ERCC1-rs3212986, rs11615, XRCC1-rs25487) or with docetaxel caused toxicity (CYP39A1-rs7761731, SLCO1B3-rs11045585) were evaluated in all patients. The results of these analyses were correlated with the clinical outcome of the patients (loco regional control, progression free survival, overall survival) and treatment related toxicity during induction chemotherapy. Median progression free survival and overall survival was 20 and 31 months in an intention to treat analysis, respectively. Overall response rate to induction chemotherapy was high with 78.1 % of all patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. Genotype A of the CYP39A1 rs7761731 polymorphism was associated with a higher incidence of leucopenia and infections or death during induction chemotherapy. Intensive induction chemotherapy results in a high response rate in the majority of patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. The CYP39A1 polymorphism rs7761731 may help to identify patients at high risk for treatment related toxicity

  16. Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

    International Nuclear Information System (INIS)

    Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur

    2011-01-01

    Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics

  17. Gemtuzumab Ozogamicin (GO Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Cathy C Zhang

    2018-01-01

    Full Text Available Gemtuzumab ozogamicin (GO is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML. Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs. Herein, we use cell line and patient-derived xenograft (PDX AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34. In vivo, the two chemoresistant subpopulations (CLL1+/CD117− and CD34+/CD38+ showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved...

  20. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Jih-Luh Tang

    Full Text Available Invasive fungal infections (IFIs is an important complication for acute myeloid leukemia (AML patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6% patients, and 66.8% of patients achieved complete remission (CR or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs. Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106. Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100-2.141, p value = 0.012. Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.

  1. Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade

    International Nuclear Information System (INIS)

    Zhu, Dong-wang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang

    2013-01-01

    The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, <50% and ≥50% of stained cells, respectively) to Annexin A1 cellular membrane and cytoplasm staining. There was a significant correlation between Annexin A1 expression and pathologic differentiation grade (P=0.015) in OSCC patients. The proportion of patients with low Annexin A1 expression was significantly higher amongst those with moderate/poorly differentiated tumor (78/167) compared to those with well differentiated tumor (18/65). Multivariate Cox model analysis showed clinical stage (P=0.001) and Annexin A1 expression (P=0.038) as independent prognostic risk factors. Furthermore, a low Annexin A1 expression level was predictive of longer disease-free survival (P=0.036, HR=0.620) and locoregional recurrence-free survival (P=0.031, HR=0.607) compared to high Annexin A1 expression. Patients with moderate/poorly differentiated tumor and low Annexin A1 expression benefited from TPF induction chemotherapy as measured by distant metastasis

  2. Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11 leukemia with lineage switch and extreme leukocytosis

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    Čolović Nataša

    2015-01-01

    Full Text Available Introduction. In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. Case Outline. In April of 2012 a 37-year-old male presented with bilateral deep leg vein thrombosis and malaise. Laboratory data were as follows: Hb 118 g/L, WBC 354x109/L (with 91% blasts in differential leukocyte count, platelets 60Ч109/L. Bone marrow aspirate and immunophenotype revealed the presence of acute lymphoblastic leukemia. Cytogenetic analysis was as follows: 46,XY,t(4;11(q21:q23 [2]/62-82,XY,t(4;11[18]. Molecular analysis showed MLL-AF4 rearrangement. The patient was on low molecular weight heparin and combined chemotherapy according to protocol HyperCVAD. On day 10 after chemotherapy he got chest pain. Three days later AMI was diagnosed (creatine kinase 66 U/L, CK-MB 13U/L, troponin 1.19 μg/L. Electrocardiogram showed the ST elevation in leads D1, D2, aVL, V5 and V6 and “micro q” in D1. On echocardiography, hypokinesia of the left ventricle and ejection fraction of 39% was found. After recovering from AMI and restoring left ventricle ejection fraction to 59%, second course of HyperCVAD was given. The control bone marrow aspirate showed 88% of blasts but with monoblastic appearance. Flow cytometry confirmed a lineage switch from lymphoblasts to monoblasts. In further course of the disease he was treated with a variety of chemotherapeutic combinations without achieving remission. Eventually, palliative chemotherapy was administered to reduce the bulk of blasts. He died five months after the initial diagnosis. Conclusion. AMI in young adults with acute leukemia is a very rare complication

  3. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

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    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  4. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

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    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-01-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  5. Prognostic value and clinical impact of 18FDG-PET in the management of children with Burkitt lymphoma after induction chemotherapy.

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    clement eBailly

    2014-12-01

    Full Text Available Objective: Burkitt Lymphoma (BL is a rare and aggressive form of B cell lymphoma that is curable using intensive chemotherapy. Obtaining a complete response (CR at the end of induction chemotherapy is a major prognostic factor. This study retrospectively evaluates the potential impact of 18FDG-PET in the management of children with BL after induction chemotherapy, and the prognostic performance of the Deauville criteria.Methods: 19 children with BL treated according to the French LMB2001 protocol between 2005 and 2012 were included. 18FDG-PET and conventional imaging (CI were performed after induction chemotherapy to confirm CR. 18FDG-PET was interpreted according to Deauville criteria with follow up and/or histology as the gold standard.Results: 18FDG-PET was negative in 15 cases, in agreement with CI in 9/15 cases. The six discordant cases confirmed to be negative by histology, were considered as true negative for 18FDG-PET. Negative predictive value (NPV of CI and 18FDG-PET were 73 and 93% respectively. The five-year PFS was significantly higher in patients with negative 18FDG-PET than those with positive 18FDG-PET (p=0.011. Conclusion: 18FDG-PET interpreted using Deauville criteria can help confirm CR at the end of induction chemotherapy, with a prognostic impact on five-year PFS. Its high NPV could limit the use of residual mass biopsy. Given the small size of our population, these results need to be confirmed by future prospective studies on a larger population.

  6. Correlation of FDG-PET measurements with morphometric tumor response after induction chemotherapy and adjuvant radiotherapy in stage III non-small cell lung cancer (NSCLC)

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    Baum, R.P.; Niesen, A.; Griesinger, F.

    2002-01-01

    Full text: Docetaxel (D) and carboplatin (C) combination chemotherapy (DC) has shown high response rates in advanced NSCLC. Histologic tumor response after chemotherapy or combined modality induction is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction chemotherapy with etoposide, ifosfamide and cisplatin (VIP) has been shown to be predictive of outcome in NSCLC. Finally, erythropoietin (EPO) may prevent the decrease in hemoglobin levels that was seen in a previous study of DC (median drop 2.7 g/dl) and thus may enhance treatment efficacy. The aim of the present study was to correlate FDG-PET studies with histomorphometric findings after DC induction chemotherapy plus Epo. 33 patients (pts) with NSCLC stage IIIA (7 pts) or IIIB (24 pts) were enrolled and received treatment with D 100 mg/m 2 dl and C AUC 7.5 d2 q21 days for 4 cycles. Epo was given at 10,000 IU s.c. three times a week. All pts received adjuvant radiotherapy. Of 33 enrolled patients, 22 were evaluable for response by CT imaging. 14/22 pts (64 %) achieved PR. Of the 22 responders, 20 were evaluable for repeated FDG-PET studies. 13/20 pts had a decrease of standardized uptake values (SUV) and of the metabolic tumor index (MTI) by >50 %, 9/20 had SUV <2.5 (CR). Seven of these 9 pts underwent tumor resection, and specimens were subjected to morphometric analysis. In 7/7 cases, no vital tumor cells were detected in the specimens. In contrast to our previous study, hemoglobin levels increased by a median of 0.3 g/dl. Morphometric tumor response after induction chemotherapy correlates strongly with metabolic remission by FDG-PET. FDG-PET appears to be a useful non-invasive diagnostic tool to predict pathologic response and potentially long-term outcome in stage III NSCLC. (author)

  7. Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

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    Ponzanelli, Anna; Vigo, Viviana; Marcenaro, Michela; Bacigalupo, Almalina; Gatteschi, Beatrice; Ravetti, Jean-Luis; Corvò, Renzo; Benasso, Marco

    2008-08-01

    Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

  8. Randomized Study of Concurrent Carboplatin, Paclitaxel, and Radiotherapy with or Without Prior Induction Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

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    Gouda, Y.S.; Eldeeb, N.A.; Omar, A.M.; Kohail, H.M.; El-Geneidy, M.M.; Elkerm, Y.M.

    2006-01-01

    Background: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. Materials and Methods: In this trial 50 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6) on day I and 28 th followed by concomitant paclitaxel (45 mg/m 2 ) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. Results: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagi tis was significantly higher in group A and B than in group C (ρ=0.023). Hematological toxicities was also significantly higher in group A and B than in group C (ρ=0.003). The response rate was significantly higher in group A and B than in group C (75%,79%, and 40% respectively) (ρ =0.020). The time to in-field progresion was significantly

  9. Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

    International Nuclear Information System (INIS)

    Chua, Daniel T.T.; Sham, Jonathan S.T.; Choy, Damon; Kwong, Dora L.W.; Au, Gordon K.H.; Kwong, Philip W.K.; Yau, C.-C.; Cheng, Ashley C.K.; Wan, K.Y.

    2001-01-01

    Purpose: Our center contributed 183 patients to the Asian-Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available. Methods and Materials: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho's T3 disease, N2-N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (≤3 cm, >3-6 cm, > 6 cm). Patients were randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m 2 and epirubicin 110 mg/m 2 D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan-Meier method and significance of survival curve differences calculated using log-rank test. Analysis was performed based on the intent-to-treat. Results: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease

  10. Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

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    Gagel, B.; Piroth, M.; Pinkawa, M.; Fischedik, K.; Asadpour, B.; Schmachtenberg, A.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany); Reinartz, P.; Zimny, M.; Buell, U. [Dept. of Nuclear Medicine, RWTH Aachen (Germany); Stanzel, S. [Inst. for Medical Statistics, RWTH Aachen (Germany); Breuer, C.; Skobel, E. [Dept. of Internal Medicine I, RWTH Aachen (Germany)

    2006-05-15

    Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m{sup 2}) and vinorelbine (30 mg/m{sup 2}) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [{sup 18}F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m{sup 2}. The dose of gemcitabine was increased by 100 mg/m{sup 2} until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m{sup 2}, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m{sup 2} every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

  11. Correlation of pre-and post-induction chemotherapy 18-FDG PET findings with histopathology in patients with locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Chan, Andrea M.; Berlangieri, Sam; Ngai, Michael W.

    2009-01-01

    Full text: Objective: To correlate 18F-FDG PET metabolic response to therapy with histopathology and survival, in patients with locally advanced (stage IIl) non-small cell lung carcinoma (NSCLC) receiving induction chemotherapy. Methods: A retrospective review of all patients with stage III NSCLC planned for induction chemotherapy and surgical resection, in whom pre- and post-chemotherapy FDG-PET at Austin Health between 2004 and 2007 was performed. The staging and positive nodal stations as determined by PET was compared to histopathological findings after resection. The tumour response on serial FDG PET was also compared to overall outcome. Results: 9 patients were included. There was a 100 % correlation between pre- or post- chemotherapy nodal staging and final histopathological nodal stage. Ninety percent of all positive nodal stations (9/10) seen on histopathology were correctly localised by pre- or post-chemotherapy FDG PET. Only one patient with a metastatic lymph node at nodal station 9 R could not be localised by prior PET studies. Of the patients in whom a down-staging in tumour status was observed on the postchemotherapy FDG-PET, 83% (5/6) of patients were still alive (follow-up range of 8 to 40 months) as compared with 33% (1/3 ) (follow-up range of 9-13 months) for non-responders. Conclusion: There is good correlation between pre- and/or post- chemotherapy FDG PET and final histopathology for the nodal staging of stage III NSCLC. There is an overall trend for those patients in whom PET resulted in a down-staging of tumour to have a longer survival.

  12. Using low-dose radiation to potentiate the effect of induction chemotherapy in head and neck cancer: Results of a prospective phase 2 trial

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    Susanne M. Arnold, MD

    2016-10-01

    Conclusion: Chemopotentiating LDFRT combined with paclitaxel and carboplatin is effective in SCCHN and provided an excellent median overall survival of 107.2 months, with median PFS not yet reached in this locally advanced SCCHN cohort. This compares favorably to prior investigations and caused fewer grade 3 and 4 toxicities than more intensive, 3-drug induction regimens. This trial demonstrates the innovative use of LDFRT as a potentiator of chemotherapy.

  13. [Disappearance of residual disease confirmed by RT-PCR following induction chemotherapy in two hypoplastic leukemia patients with t(8;21)].

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    Sawada, M; Tsurumi, H; Yamada, T; Hara, T; Oyama, M; Moriwaki, H

    1999-04-01

    Reverse transcriptase-polymerase chain reaction (RT-PCR) methods often detect the AML1/MTG8 fusion transcript even in acute myelogenous leukemia (AML) patients with t(8;21) who have been in long-term remission. We encountered 2 hypoplastic leukemia patients with t(8;21) who achieved cytogenetic remission with short-term conventional chemotherapy. Patient 1 was a 42-year-old woman. Chromosomal analysis detected t(8;21) (q22;q22) and PCR analysis (35 cycles PCR amplification; detection limit 1 x 10(-5) cells) detected the AML1/MTG8 fusion transcript. Complete remission was obtained with 1 course of chemotherapy consisting of low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days). After 2 courses of consolidation chemotherapy consisting of conventional-dose cytarabine and mitoxantrone, the RT-PCR findings were negative for the AML1/MTG8 fusion transcript. Patient 2 was a 67-year-old man. Cytogenetic analysis detected t(8;21) (q22;q22), and was positive for the AML1/MTG8 fusion transcript. After 2 courses of induction chemotherapy comprising low-dose cytarabine (20 mg x 14 days) and etoposide (50 mg x 14 days), and 3 courses of conventional consolidation chemotherapy, RT-PCR analysis confirmed the disappearance of the AML1/MTG8 fusion transcript.

  14. Radiation dose reduction for patients with extranodal NK/T-cell lymphoma with complete response after initial induction chemotherapy

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    Wang L

    2016-09-01

    Full Text Available Liang Wang,1,2,* Xi-wen Bi,1,3,* Zhong-jun Xia,1,2 Hui-qiang Huang,1,3 Wen-qi Jiang,1,3 Yu-jing Zhang1,4 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Hematologic Oncology, 3Department of Medical Oncology, 4Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Previous studies have found that radiotherapy (RT dose less than 50 Gy resulted in inferior outcomes for early stage extranodal NK/T-cell lymphoma (ENKTL. Nowadays, induction chemotherapy (CT followed by RT consolidation is often used. For patients who get complete response (CR after CT, whether RT dose can be safely reduced or not remains unknown. This retrospective study compared the survival outcomes between patients who received higher dose (>50 Gy and lower dose (≤50 Gy RT after CR was attained by CT. One hundred and forty four patients of early stage ENKTL got CR after induction CT and received RT consolidation. Thirty-one patients received lower dose RT (median 46 Gy, range, 36–50 Gy, and 113 patients received higher dose RT (median 56 Gy, range, 52–66 Gy. In univariate survival analysis, age >60, local tumor invasion, and non-asparaginase-based CT were associated with inferior progression-free survival (PFS and overall survival (OS. However, there were no differences in PFS and OS between patients treated with higher and lower dose RT, which was confirmed in the multivariate survival analysis. Furthermore, reduced dose RT did not affect local control rate. Most common RT-related side effects were grade 1/2 mucositis and dermatitis, and the incidence rate of grade 3 mucositis or dermatitis was lower in patients treated with reduced dose RT (9.7% vs 15.0% for mucositis, and 6.5% vs 17.7% for dermatitis. In conclusion, this study found that RT dose could be safely reduced without

  15. Cost implications in the management of induction of labour.

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    Taylor, S J; Armour, C L

    1997-11-01

    For many years the standard treatment of induction of labour has been amniotomy followed by intravenous oxytocin. More recently prostaglandin E2 (PGE2; dinoprostone), in various preparations, has been used to both ripen the cervix before amniotomy and administration of oxytocin, and to induce labour on its own. Since the acquisition cost of PGE2 is approximately 15 times that of oxytocin, it is important to justify the use of PGE2. In this paper, literature from 1970 to 1996 has been reviewed and outcomes following the use of PGE2, plus amniotomy and oxytocin if necessary, have been compared with outcomes following the use of amniotomy plus oxytocin alone. No significant differences in the mode of delivery and no serious adverse effects in mothers or babies were detected. Three economic analyses of these approaches to induction of labour have been reviewed. While under certain conditions there may be some cost savings associated with the use of PGE2, neither of the studies reviewed showed substantial, reliable cost savings. Further research is required to identify the patients who would gain most benefit from the use of PGE2.

  16. Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

    International Nuclear Information System (INIS)

    Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Roh, Jong-Lyel; Lee, Sang-wook; Song, Si Yeol; Lee, Jeong Hyun; Kim, Jae Seung; Cho, Kyung-Ja; Kim, Sung-Bae

    2011-01-01

    Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

  17. Non-response to sad mood induction: implications for emotion research.

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    Rottenberg, Jonathan; Kovacs, Maria; Yaroslavsky, Ilya

    2018-05-01

    Experimental induction of sad mood states is a mainstay of laboratory research on affect and cognition, mood regulation, and mood disorders. Typically, the success of such mood manipulations is reported as a statistically significant pre- to post-induction change in the self-rated intensity of the target affect. The present commentary was motivated by an unexpected finding in one of our studies concerning the response rate to a well-validated sad mood induction. Using the customary statistical approach, we found a significant mean increase in self-rated sadness intensity with a moderate effect size, verifying the "success" of the mood induction. However, that "success" masked that, between one-fifth and about one-third of our samples (adolescents who had histories of childhood-onset major depressive disorder and healthy controls) reported absolutely no sadness in response to the mood induction procedure. We consider implications of our experience for emotion research by (1) commenting upon the typically overlooked phenomenon of nonresponse, (2) suggesting changes in reporting practices regarding mood induction success, and (3) outlining future directions to help scientists determine why some subjects do not respond to experimental mood induction.

  18. The value of {sup 18}F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

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    Rossum, Peter S.N. van [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States); University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Fried, David V.; Zhang, Lifei; Court, Laurence E. [The University of Texas MD Anderson Cancer Center, Department of Radiation Physics, Houston, TX (United States); Hofstetter, Wayne L. [The University of Texas MD Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery, Houston, TX (United States); Ho, Linus [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Meijer, Gert J. [University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Carter, Brett W. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lin, Steven H. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2017-01-15

    The purpose of our study was to determine the value of {sup 18}F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, {sup 18}F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV{sub max}, SUV{sub mean}, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). {sup 18}F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early {sup 18}F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  19. Betel nut chewing history is an independent prognosticator for smoking patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil.

    Science.gov (United States)

    Su, Yan-Ye; Chien, Chih-Yen; Luo, Sheng-Dean; Huang, Tai-Lin; Lin, Wei-Che; Fang, Fu-Min; Chiu, Tai-Jan; Chen, Yen-Hao; Lai, Chi-Chih; Hsu, Cheng-Ming; Li, Shau-Hsuan

    2016-03-22

    Smoking and betel nut chewing are well-known risk factors for head and neck squamous cell carcinoma (HNSCC). Smoking is also a strong prognosticator for patients with locally advanced HNSCC receiving induction chemotherapy. Smoking with or without betel nut chewing is a common practice in Asia. However, little is known regarding whether betel nut chewing can serve as a prognostic factor for smoking patients with locally advanced HNSCC receiving induction chemotherapy. The aim of this study was to evaluate the prognostic impact of betel nut chewing in such patients receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF). From January 2010 to December 2012, we retrospectively analyzed 162 smoking patients with locally advanced HNSCC who received induction chemotherapy with TPF at our institution. Background characteristics, including a history of betel nut chewing, were analyzed as potential prognostic factors. Among the 162 smoking patients, 131 patients (81%) were betel nut chewers, while 31 (19%) were non-betel nut chewers. One hundred fifty-six (96%) were men, and 6 (4%) were women. The median age was 53 years. The overall response rates to induction chemotherapy were 57 and 77% in patients with and without betel nut chewing history, respectively (P = 0.038). The 2-year progression survival rates were 37 and 67% in patients with and without betel nut chewing history, respectively (P = 0.004). The 2-year overall survival rates were 47 and 71% in patients with and without betel nut chewing history, respectively (P = 0.017). Betel nut chewing history was independently associated with a poor response to induction chemotherapy, an inferior progression-free survival rate, and a poor overall survival rate. Our results indicate that betel nut chewing history is independently associated with poor prognosis in smoking patients with locally advanced HNSCC receiving induction chemotherapy with TPF. Further investigation is warranted to

  20. The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Rossum, Peter S.N. van; Fried, David V.; Zhang, Lifei; Court, Laurence E.; Hofstetter, Wayne L.; Ho, Linus; Meijer, Gert J.; Carter, Brett W.; Lin, Steven H.

    2017-01-01

    The purpose of our study was to determine the value of 18 F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18 F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV max , SUV mean , metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). 18 F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18 F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  1. 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.

  2. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

    Science.gov (United States)

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple

  3. Results of the Tremplin trial proposing an induction chemotherapy followed by concomitant radiotherapy with cisplatin ou cetuximab in order to protect the larynx; Resultats de l'essai Tremplin proposant une chimiotherapie d'induction suivie d'une radiotherapie concomitante avec cisplatine ou cetuximab dans le but de preserver le larynx

    Energy Technology Data Exchange (ETDEWEB)

    Pointreau, Y.; Calais, G. [Service de radiotherapie, Centre regional universitaire de cancerologie Henry-S.-Kaplan, Hopital Bretonneau, CHU de Tours, 37 (France); Pointreau, Y.; Calais, G. [Universite Francois-Rabelais de Tours, 37 (France); Pointreau, Y. [CNRS, UMR 6239 - Genetique, immunotherapie, chimie et cancer - et Laboratoire de pharmacologie-toxicologie, CHRU de Tours, 37 (France); Rolland, F.; Bardet, E. [Centre Rene-Gauducheau, 44 - Nantes (France); Alfonsi, M. [Clinique Sainte-Catherine, 84 - Avignon (France); Baudoux, A. [Clinique Sainte-Elisabeth, Namur (Belgium); Sire, G. [Centre hospitalier de Lorient, 56 (France); De Raucourt, D. [Centre Francois-Baclesse, 14 - Caen (France); Tuchais, C. [Centre Paul-Papin, 49 - Angers (France); Lefebvre, J.L. [Centre Oscar-Lambret, 59 - Lille (France)

    2010-10-15

    The authors report a randomized phase II trial which aimed at comparing over three months the laryngeal protection after a TPF-based induction chemotherapy followed by radiotherapy in combination with cisplatin or cetuximab. Over two years, 153 patients have been concerned. The TPF-based induction chemotherapy followed by radiotherapy with cetuximab seems to be the less toxic. A longer monitoring is needed to get better information in terms of laryngeal protection rate, life quality, and laryngeal functionality. Short communication

  4. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial.

    Science.gov (United States)

    Pearson, Andrew D J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Ellershaw, Caroline; Machin, David

    2008-03-01

    The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1.8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2.95 years (range 1.03-20.97), were randomly assigned-132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109

  5. Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Sim, Sang; Rosenzweig, Kenneth E.; Schindelheim, Rachel; Ng, Kenneth K.; Leibel, Steven A.

    2001-01-01

    Purpose: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. Results: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p=0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p=0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. Conclusion: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher

  6. A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hiraga, Yukihiro; Kou, Junichi

    2012-01-01

    Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

  7. Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Xia, Bing; Wang, Jia-Zhou; Liu, Qi; Cheng, Jing-Yi; Zhu, Zheng-Fei; Fu, Xiao-Long

    2013-01-01

    The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

  8. Augmented therapy of extensive Hodgkin's disease: radiation to bulk disease or prolongation of induction chemotherapy did not improve survival

    International Nuclear Information System (INIS)

    Rafla, S.; Coleman, M.; Propert, K.; Glicksman, A.; Peterson, B.; Nissen, N.; Brunner, K.; Kaufmann, T.; Holland, J.; Anderson, J.; Gottlieb, A.

    1996-01-01

    Purpose: This prospective, randomized trial in extensive, untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to 'bulk' disease) compared to standard, six months chemotherapy. Materials and Methods: Two-hundred fifty-eight patients, mostly stage IV, were randomized to four treatment regimens consisting of 6 cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; 6 cycles of CVPP followed by 25 Gray (Gy) radiotherapy; or 3 cycles CVPP, 25 Gy radiotherapy, and 3 cycles CVPP. Results: Complete remissions were achieved in 65% of all patients. A 58% overall 5 year survival was obtained. Relapses in irradiated areas of bulk disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease free survival or overall survival amongst the four regimens. Elderly patients responded less frequently. Conclusion: While radiotherapy provided control of local (bulk) disease, no impact on overall survival was apparent. Likewise doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit when compared to the standard six months of treatment

  9. Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with nodal Stage N2-3.

    Science.gov (United States)

    Kawahira, Masahiro; Yokota, Tomoya; Hamauchi, Satoshi; Onozawa, Yusuke; Ogawa, Hirofumi; Onoe, Tsuyoshi; Kamijo, Tomoyuki; Iida, Yoshiyuki; Nishimura, Tetsuo; Onitsuka, Tetsuro; Yasui, Hirofumi

    2017-08-01

    Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) has been established as the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC). The survival benefit of induction chemotherapy (ICT) for LA-NPC remains controversial. We analyzed the efficacy and feasibility of docetaxel, cisplatin and 5-fluorouracil (TPF) ICT followed by CCRT for LA-NPC with nodal Stage N2-3. We performed a retrospective analysis of 28 LA-NPC patients with nodal Stage N2-3 receiving induction TPF followed by CCRT (TPF group; n = 12) or CCRT-AC (CCRT group; n = 16) between October 2006 and May 2016. The median follow-up periods were 36.4 (range 6.7-55.2) and 40.1 months (range 4.3-99.0) for the TPF and CCRT groups, respectively. One- and three-year overall survival for the TPF group vs. the CCRT group were 100% and 100% vs. 94% and 75%, respectively (P = 0.21). The cumulative one- and three-year incidences of locoregional recurrence or progression for the TPF group vs. the CCRT group were 10% and 21% vs. 16% and 32% (P = 0.49), and those of distant metastasis were 0% and 0% vs. 26% and 26%, respectively (P = 0.08). The common Grade 3-4 acute toxicities were neutropenia, anorexia, febrile neutropenia, and stomatitis in the TPF group. The Grade 3-4 late toxicities did not differ significantly between the two groups. This study suggests that induction TPF followed by CCRT might reduce distant metastasis, so this combination may be feasible for the treatment of LA-NPC with nodal Stage N2-3. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  10. Recovery of sperm production following radiation therapy for Hodgkin's disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP)

    International Nuclear Information System (INIS)

    Dubey, Praveen; Wilson, Gene; Mathur, Kevin K.; Hagemeister, Frederick B.; Fuller, Lillian M.; Ha, Chul S.; Cox, James D.; Meistrich, Marvin L.

    2000-01-01

    Purpose: The effect on human male fertility of radiotherapy following chemotherapy for the treatment of Hodgkin's disease (HD) is unknown. The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study. Patients: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy. The most inferior radiation portals for patients were: mantle, 1 patient; paraaortic-spleen, 3 patients; upper abdomen, 24 patients; abdominal spade, 4 patients; and pelvic, 2 patients. Testicular radiation dose measurements were available for 20 of these patients. Results: Before the start of radiation, 90% of patients were normospermic. The magnitude of the decline in sperm counts was related to the measured testicular dose and/or radiation fields employed. The minimum postradiotherapy counts, expressed as a fraction of pretreatment counts, for the various treatment groups are as follows: paraaortic-spleen, 20%; upper abdomen, testicular dose < 30 cGy, 4%; upper abdomen, testicular dose 30-39 cGy, 0.9%; abdominal spade, 0.02%; and pelvis, 0%. The time to nadir of sperm counts averaged 4.5 months. Recovery to normospermic levels occurred in 96% of patients, with most recovering to that level within 18 months. Conclusion: The effect of radiation following NOVP chemotherapy on sperm counts was no greater than would be expected with radiation therapy alone. In most patients, sperm counts recovered to levels compatible with normal fertility

  11. Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy

    International Nuclear Information System (INIS)

    Schneider, José; Gonzalez-Roces, Severino; Pollán, Marina; Lucas, Raul; Tejerina, Armando; Martin, Miguel; Alba, Alfonso

    2001-01-01

    Axillary node status after induction chemotherapy for locally advanced breast cancer has been shown on multivariate analysis to be an independent predictor of relapse. However, it has been postulated that responders to induction chemotherapy with a clinically negative axilla could be spared the burden of lymphadenectomy, because most of them will not show histological nodal invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally been identified as a significant predictor of patient survival. We studied the expression of the genes encoding multidrug resistance associated protein (MDR1) and lung cancer associated resistance protein (LRP) in formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for locally advanced breast cancer by means of induction chemotherapy followed by rescue mastectomy. P-glycoprotein expression was assessed by means of immunohistochemistry before treatment in 23 cases, and by means of reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46 (6 failed). LRP expression was detected by means of immunohistochemistry, with the LRP-56 monoclonal antibody, in 31 cases before treatment. Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67, estrogen receptor and progesterone receptor are routinely performed in our laboratory in every case, and the results obtained were included in the study. All patients had received between two and six cycles of standard 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one patient received four cycles of a docetaxel-adriamycin combination, and the other four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF) polychemotherapy]. Response was assessed in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a complete clinical response, 37 a partial response, and the remaining 13 showed stable disease. This makes a

  12. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  13. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

    Science.gov (United States)

    2013-01-01

    Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using

  14. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.

    Directory of Open Access Journals (Sweden)

    Brian D Lehmann

    Full Text Available Triple-negative breast cancer (TNBC is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype, with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM and mesenchymal stem-like (MSL subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype into four (TNBCtype-4 tumor-specific subtypes (BL1, BL2, M and LAR and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50 or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively. Collectively, we provide pre-clinical data that could inform

  15. Clinical evaluation of bone marrow transplantation using total body irradiation and induction chemotherapy. Treatment results during twelve years at our hospital and some problems on the therapy

    International Nuclear Information System (INIS)

    Kawamura, Toshiki; Koga, Sukehiko; Kikukawa, Kaoru; Okamoto, Masataka; Miyazaki, Hitoshi; Kojima, Hiroshi; Esaki, Kohji

    2000-01-01

    We performed sixty patients with hematological malignancies the total body irradiation prior to bone marrow transplantation (TBI-BMT) from 1988 to 2000. We delivered our each patient hyperfractionated TBI consisting of 2 fractions of 3 Gy per day for 2 consecutive days following induction chemotherapy. It proved that TBI-BMT was a valuable treatment method for hematological malignancies which have poor prognosis. About the cumulative survival rate, patients of first remission were better outcome than patients beyond second remission. However, the therapy remained some problems which were the prophylaxis of GVHD for HLA-matched unrelated recipients. And we have to consider a new maintenance procedure to prevent relapse from transplanted donor cell. (author)

  16. Folate deficiency in north Indian children undergoing maintenance chemotherapy for acute lymphoblastic leukemia-Implications and outcome.

    Science.gov (United States)

    Roy Moulik, Nirmalya; Kumar, Archana; Agrawal, Suraksha; Mahdi, Abbas Ali

    2018-01-01

    Treatment-related toxicity and mortality are not uncommon during maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), especially in the low- and middle-income countries (LMIC). Undernutrition and micronutrient deficiencies are commonly seen in children from LMICs undergoing treatment for ALL. The present study examines the prevalence and clinical implications of folate deficiency in north Indian children with ALL during the maintenance phase of treatment in view of prolonged antifolate treatment and high population prevalence of folate deficiency. Pre-cycle folate levels/deficiency as well as weight for age z-score and serum albumin level were determined and correlated with complications of treatment and mortality encountered during the maintenance phase of treatment. Twenty-nine of 52 children enrolled in the study had folate deficiency at some point during maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002), thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29 vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7 of 21; P = 0.01) were more common in folate-deficient children. Maintenance deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02) in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate deficiency with maintenance deaths (P = 0.03). Folate deficiency was associated with treatment-related complications and adverse outcome in our patients. The risks and benefits of folate supplementation in deficient children during maintenance chemotherapy need to be explored with properly designed randomized studies in similar settings. © 2017 Wiley Periodicals, Inc.

  17. Treatment outcomes of different prognostic groups of patients on cancer and leukemia group B trial 39801: induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for unresectable stage III non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Hodgson, Lydia; Herndon, James E; Kelley, Michael J; Cicchetti, M Giulia; Ramnath, Nithya; Niell, Harvey B; Atkins, James N; Akerley, Wallace; Green, Mark R; Vokes, Everett E

    2009-09-01

    In Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival and demonstrated no significant benefit from the addition of induction chemotherapy. The primary objective of this analysis was to dichotomize patients into prognostic groups using factors predictive of survival and to investigate whether induction chemotherapy was beneficial in either prognostic group. A Cox proportional hazard model was used to assess the impact on survival of the following factors: (>or=70 versus or=13 g/dl), performance status (PS) (1 versus 0), weight loss (>or=5% versus or=5%, age >or=70 years, PS of 1, and hgb or=2 poor prognostic factors (n = 165) or or=2 versus patients with or=2 factors (HR = 0.86, 95% CI, 0.63-1.17; p = 0.34) or induction chemotherapy is beneficial in either prognostic group.

  18. 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.

  19. Sarcoma of the Ewing Family in Pregnancy: A Case Report of Intrauterine Fetal Death after Induction of Chemotherapy

    Directory of Open Access Journals (Sweden)

    S. Schur

    2012-11-01

    Full Text Available Ewing’s sarcoma is an ultra-orphan disease (2/1,000,000/year which requires a multimodal therapy approach in high-volume centers. Treatment consists of pre-operative therapy followed by surgery and post-operative combination of chemo-radiotherapy. Experience with diagnosis and therapy of Ewing’s sarcoma in pregnancy is very limited. We herein report the case of an atypical Ewing’s sarcoma detected in the second trimester of gestation. Neoadjuvant chemotherapy was initiated and resulted in substantial tumor shrinkage and intrauterine fetal death. The rare nature of this condition underlines once more the need for a multidisciplinary team to improve the quality of care for this highly special patient collective.

  20. Chemotherapy for Initial Induction Failures in Childhood Acute Lymphoblastic Leukemia: a Children’s Oncology Group Study (POG 8764)

    OpenAIRE

    Joyce, Michael; Pollock, Brad H.; Devidas, Meenakshi; Buchanan, George; Camitta, Bruce

    2013-01-01

    Children with acute lymphocytic leukemia (ALL) who fail to enter remission have a poor prognosis. In a previous study, 9 of 14 children with induction failure entered remission after teniposide (VM26) plus cytosine arabinoside (Ara-C). We attempted to confirm these results. Twenty children received teniposide (200 mg/m2/day IV) for 3 days and cytosine arabinoside (100 mg/m2/day continuous IV infusion) for 7 days. There were 3 complete and 3 partial responses. Two additional patients achieved ...

  1. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    International Nuclear Information System (INIS)

    Sher, David J.; Posner, Marshall R.; Tishler, Roy B.; Sarlis, Nicholas J.; Haddad, Robert I.; Holupka, Edward J.; Devlin, Phillip M.

    2011-01-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥ 70 Gy. Radiotherapy treatment time was analyzed as binary (≤ 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  2. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Posner, Marshall R. [Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Sarlis, Nicholas J. [Sanofi-Aventis US, Bridgewater, NJ (United States); Haddad, Robert I. [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Holupka, Edward J. [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA (Israel); Devlin, Phillip M. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States)

    2011-12-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  3. Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

    Science.gov (United States)

    Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

    2011-12-01

    To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc

  4. Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

    Science.gov (United States)

    Knauf, Wolfgang; Rieger, Kathrin; Blau, Wolfgang; Hegenbart, Ute; Von Gruenhagen, Ulrich; Niederwieser, Dietger; Thiel, Eckhard

    2004-12-01

    The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

  5. Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

    International Nuclear Information System (INIS)

    Bhide, Shreerang A.; Ahmed, Merina; Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate; Nutting, Christopher M.; Harrington, Kevin J.

    2009-01-01

    Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. 4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations

  6. Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

    Energy Technology Data Exchange (ETDEWEB)

    Bhide, Shreerang A; Ahmed, Merina [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate [Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Nutting, Christopher M [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Harrington, Kevin J [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom)], E-mail: kevinh@icr.ac.uk

    2009-02-01

    Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. <12 g/dL and NOUT 1-4 vs. >4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations.

  7. Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.

    Science.gov (United States)

    Park, Seongyeol; Ha, Seunggyun; Kwon, Hyun Woo; Kim, Woo Hyoung; Kim, Tae-Yong; Oh, Do-Youn; Cheon, Gi Jeong; Bang, Yung-Jue

    2017-06-01

    A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and 18 F-FDG PET, we assessed the tumor diameter, SUV max , and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched 18 F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUV max irrespective of tumor size ( P chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUV max reduction ( P chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  8. Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy

    Directory of Open Access Journals (Sweden)

    Shan E. Rauf

    2016-05-01

    Full Text Available Objective: Acute lymphoblastic leukemia (ALL encompasses a group of lymphoid neoplasms that are more common in children and arise from B-and T-lineage lymphoid precursor cells. The immature reticulocyte fraction (IRF, a new routine parameter in hematology analyzers, can give an indication of hemopoietic recovery like absolute neutrophil count (ANC. The purpose of this study was to evaluate IRF in excess of 5% was considered as IRF recovery. Materials and Methods: In this descriptive study, 2.5 to 3 mL of EDTA blood of 45 ALL patients undergoing the remission induction phase of their treatment was sampled and analyzed with a Sysmex XE-5000 on day 1 and every second day thereafter until the day of recovery. ANC of >0.5x109/L on the day corresponding to the first of the three consecutive counts was considered as the day of ANC recovery. IRF recovery was an IRF in excess of 5%. Results: The mean age of the patients was 12.04±5.30 years; 25 patients (55.6% were male and 20 patients (44.4% were female. On day 1 of induction remission, the mean IRF value was 9.68±1.41, while the mean ANC value was 0.077±0.061. Mean recovery day for IRF was 11.84±7.44 and mean recovery day for ANC was 17.67±8.77 (twotailed p-value <0.0001 with 95% confidence interval. By day 28, out of 45 patients 36 (80% showed ANC recovery, while 41 (91% showed IRF recovery. The remaining patients who had not shown recovery by day 28 were further followed up and all of them showed recovery of both parameters by day 39. Conclusion: This study concluded that postinduction bone marrow hemopoietic recovery was earlier by IRF than ANC in children with ALL on chemotherapy

  9. Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer

    International Nuclear Information System (INIS)

    Bhide, Shreerang A.; Gulliford, Sarah; Schick, Ulrike; Miah, Aisha; Zaidi, Shane; Newbold, Katie; Nutting, Christopher M.; Harrington, Kevin J.

    2012-01-01

    Dose–response curves (DRCs) and the quantitative parameters describing these curves were generated for grade 3 oral mucositis and dysphagia in 144 patients using individual patient DVHs. Curve fits to the oral mucositis clinical data yielded parameter values of mean dose in 2 Gy equivalent, MD 50 = 51 Gy (95% CI 40–61), slope of the curve, k = 1(95% CI 0.6–1.5). R 2 value for the goodness of fit was 0.80. Fits to the grade 3 dysphagia clinical data yielded parameter values of MD 50 = 44.5 Gy (95% CI 36–53), k = 2.6 (95% CI 0.8–4.5). R 2 value for the goodness of fit was 0.65. This is the first study to derive DRCs in patients receiving induction chemotherapy followed by chemo-radiation (IC-C-IMRT) for head and neck cancer. The dose–response model described in this study could be useful for comparing acute mucositis rates for different dose–fractionation schedules when using IMRT for head and neck cancer.

  10. Long-term functional and survival outcomes after induction chemotherapy and risk-based definitive therapy for locally advanced squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Hutcheson, Katherine A; Lewin, Jan S; Holsinger, F Christopher; Steinhaus, Ganene; Lisec, Asher; Barringer, Denise A; Lin, Heather Y; Villalobos, Sandra; Garden, Adam S; Papadimitrakopoulou, Vali; Kies, Merrill S

    2014-04-01

    The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). Forty-seven patients (stage IV; ≥N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. Copyright © 2013 Wiley Periodicals, Inc.

  11. Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination

    Directory of Open Access Journals (Sweden)

    Vijaya S Gadage

    2011-01-01

    Full Text Available Manifestations of parvovirus B19 vary even in the normal host from asymptomatic or subclinical infection to a spectrum of illness with symptoms during viremic and immune complex mediated stage of disease. We report the morphological findings of parvovirus B19 infection (confirmed on serology in a patient of T-acute lymphoblastic lymphoma (T-ALL who underwent induction phase of chemotherapy (MCP 842 protocol. Persistent pancytopenia in the bone marrow aspirate with mild increase in blasts was thought to be due to failure to achieve marrow remission. However, giant pronormoblasts with prominent intranuclear inclusions confirmed on trephine biopsy led to the suspicion of parvovirus B19 infection which was later confirmed on serology. This case is presented to report the rarely seen classical morphological feature of parvovirus infection on bone marrow examination which was incidentally the first investigation to diagnose the viremic phase of the infection, indicating that a high index of suspicion needs to be kept in mind while examining bone marrows of susceptible patients.

  12. Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy.

    Science.gov (United States)

    Huang, Huei-Ling; Lu, Pei-Hsuan; Yang, Hung-Chih; Lee, Gi-Da; Li, Han-Ru; Liao, Kuo-Chih

    2015-01-01

    The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs) using a 200 μm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81%) in the tumor than for free fluorophores (14%) at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

  13. Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice.

    Science.gov (United States)

    Elsea, Collin R; Kneiss, Janet A; Wood, Lisa J

    2015-10-01

    Cancer patients treated with cytotoxic chemotherapy experience fatigue and changes in body composition that can impact physical functioning and quality of life during and after treatment. Interleukin-6 (IL-6) is associated with fatigue in cancer survivors and plays an important role in the regulation of body composition. The purpose of the present study was to determine the specific role of IL-6 in cyclophosphamide-doxorubicin-5-fluorouracil (CAF)-induced changes in fatigue, food intake, and body composition using mice lacking IL-6. Female wild-type (WT) and IL-6 (-/-) mice were injected with four cycles of CAF or normal saline (NS) administered at 21-day intervals. Daily voluntary wheel-running activity (VWRA), used as a proxy for fatigue, and food intake were monitored daily up to 21 days after the fourth dose. Dual-energy X-ray absorptiometry (DEXA) was used to assess treatment-related changes in lean body mass (LBM), fat mass (FM), and bone mineral content (BMC). Patterns of change in fatigue and food intake did not differ between CAF-treated WT and IL-6 (-/-) mice. However, a Genotype × Drug interaction was observed for LBM (p = 0.047) and FM (p = 0.035) but not BMC (p = .569). Whereas WT mice lost LBM and FM during CAF treatment, IL-6-deficient mice did not. Treatment-related decreases in levels of the anabolic hormone insulin-like growth factor-1 (IGF-1) may contribute to LBM and FM loss since CAF decreased IGF-1 levels in an IL-6-dependent manner. These findings implicate IL-6 and possibly IGF-1 in the regulation of body composition in breast cancer patients exposed to cytotoxic chemotherapy. © The Author(s) 2014.

  14. “Treatment outcomes of different prognostic groups of patients on Cancer and Leukemia Group B trial 39801: Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for unresectable stage III non-small cell lung cancer”

    Science.gov (United States)

    Stinchcombe, Thomas E.; Hodgson, Lydia; Herndon, James E.; Kelley, Michael J.; Cicchetti, M. Giulia; Ramnath, Nithya; B.Niell, Harvey; Atkins, James N.; Akerley, Wallace; Green, Mark. R.; Vokes, Everett E.

    2009-01-01

    Background In Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival, and demonstrated no significant benefit from the addition of induction chemotherapy. The primary objective of this analysis was to dichotomize patients into prognostic groups using factors predictive of survival, and to investigate if induction chemotherapy was beneficial in either prognostic group. Patients and Methods A Cox proportional hazard model was used to assess the impact on survival of the following factors: (≥ 70 vs. < 70 years), gender, race, stage (IIIB vs. IIIA), hemoglobin (hgb) (< 13 vs. ≥13 g/dl), performance status (PS) (1 vs.0), weight loss (≥5% vs. < 5%), treatment arm, and the interaction between weight loss and hgb. Results Factors predictive of decreased survival were weight loss ≥ 5%, age ≥ 70 years, PS of 1, and hgb < 13 g/dl (p<0.05). Patients were classified as having ≥2 poor prognostic factors (n=165) or ≤ 1 factor (n=166). The hazard ratio (HR) for overall survival for the patients with ≥ 2 versus patients with ≤ 1 was 1.88 (95% CI, 1.49 to 2.37; p= < 0.0001); median survival times observed were 9 (95% CI, 8 to 11) and 18 (95% CI, 16 to 24) months, respectively. There was no significant difference in survival between treatment arms in patients with ≥ 2 factors (HR=0.86, 95% CI, 0.63 to 1.17; p=0.34) or ≤1 factor (HR=0.97, 95% CI, 0.70 to 1.35; p=0.87) Conclusions There is no evidence that induction chemotherapy is beneficial in either prognostic group. PMID:19652624

  15. Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy

    International Nuclear Information System (INIS)

    Huang, Pei-Yu; Zeng, Ting-Ting; Ban, Xiaojiao; Li, Meng-Qing; Zhang, Bao-Zhu; Zhu, Ying-Hui; Hua, Wen-Feng; Mai, Hai-Qiang; Zhang, Li; Guan, Xin-Yuan; Li, Yan

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes. The expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies. Positive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu. Our findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress. The online version of this article (doi:10.1186/s12885

  16. Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy

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    Maini PK

    2010-04-01

    Full Text Available Abstract Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial

  17. Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy

    Directory of Open Access Journals (Sweden)

    Huang HL

    2015-08-01

    Full Text Available Huei-Ling Huang,1 Pei-Hsuan Lu,1 Hung-Chih Yang,1 Gi-Da Lee,1,2 Han-Ru Li,1 Kuo-Chih Liao1 1Graduate Institute of Biomedical Engineering, National Chung Hsing University, 2Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan Abstract: The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs using a 200 µm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline, the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17% or AuNP-liposomes without excitation (21.92%±2.08% by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81% in the tumor than for free fluorophores (14% at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation. Keywords: fiber-optic guided excitation, light excitation triggered release, photo-thermal responsive liposome, gold nanoparticles, tunable release in vivo

  18. NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.

    Science.gov (United States)

    Mukherjee, Somnath; Hurt, Christopher Nicholas; Gwynne, Sarah; Sebag-Montefiore, David; Radhakrishna, Ganesh; Gollins, Simon; Hawkins, Maria; Grabsch, Heike I; Jones, Gareth; Falk, Stephen; Sharma, Ricky; Bateman, Andrew; Roy, Rajarshi; Ray, Ruby; Canham, Jo; Griffiths, Gareth; Maughan, Tim; Crosby, Tom

    2017-03-01

    Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m 2  day 1, 15, 29; capecitabine 625 mg/m 2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 2  day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m 2  day 1, capecitabine 625 mg/m 2 bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Based on pCR ≤ 15% not warranting future investigation, but pCR ≥ 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having ≥10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614). Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding R0 resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively. Both regimens were well tolerated. Only CarPacRT passed the predefined p

  19. Phase II study of induction chemotherapy followed by radiotherapy combined with daily cisplatin in stage III inoperable non-small cell lung cancer (NSCLC)

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    Scolaro, T; Ardizzoni, A; Giudici, S; Grossi, F; Cosso, M; Pennucci, M C; Bacigalupo, A; Rosso, R; Vitale, V

    1997-07-01

    Purpose: Results of radical radiotherapy in the treatment of inoperable NSCLC can be improved by either concurrent daily low-dose Cisplatin as radiosensitizer (Shaake-Koning, N Engl J Med, 1992; 326: 524) or by using neoadiuvant chemotherapy (Dillman, N Engl J Med, 1990; 323: 940). The aim of present study was to evaluate the activity and feasibility of a new chemo-radiotherapy (CT-RT) regimen in which both strategies of RT improvement will be used. Methods: Thirty consecutive patients (pts) were treated with induction CT (Cisplatin 100 mg/m{sup 2} i.v. day 1,22 + Vinblastine 5 mg/m{sup 2} i.v. day 1,8,15,22,29) followed by RT (60 Gy/30 fractions in 6 wks) combined with Cisplatin 5 mg/m{sup 2} daily before RT. Patients' characteristics were: 29 pts were male and 1 female; median age 60.5 yrs (range 44-69); median PS 1 (range 0-1); 21 squamous cell carcinoma and 9 adenocarcinoma; stage III A in 9 pts and stage IIIB in 21 pts. Results: Twenty-three pts were evaluable for RT plus daily Cisplatin toxicity and 29 for CT toxicity (according to WHO). For RT plus daily cisplatin hematological toxicity consisted of grade III leukopenia in 22%, grade III anemia 9% and grade III thrombocytopenia in 9% of pts. Only 2 patients developed severe esophagitis. Only one case of radiation pneumonitis was reported. For induction CT hematological toxicity consisted of grade III-IV leukopenia in 31%, grade II anemia 10% and grade IV thrombocitopenia in 14% of cases. Non-hematological toxicity consisted mainly of grade I peripheral neuropaty and occured in 17% of pts. One case of minor hearing loss and 4 cases of tinnitus were observed at the end of treatment. Twenty-seven pts were evaluable for response. Response rate was 59% with 7 CRs (26%) and 9 PRs (33%); 1 patient had SD (4%), 5 pts PD (20%) and 5 pts (19%) died early (3 for early progression, 1 for toxicity and 1 for cardiac failure). All pts with CR are still alive with a median event-free survival of 23.9 months (range 12

  20. Phase II study of induction chemotherapy followed by radiotherapy combined with daily cisplatin in stage III inoperable non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Scolaro, T.; Ardizzoni, A.; Giudici, S.; Grossi, F.; Cosso, M.; Pennucci, M.C.; Bacigalupo, A.; Rosso, R.; Vitale, V.

    1997-01-01

    Purpose: Results of radical radiotherapy in the treatment of inoperable NSCLC can be improved by either concurrent daily low-dose Cisplatin as radiosensitizer (Shaake-Koning, N Engl J Med, 1992; 326: 524) or by using neoadiuvant chemotherapy (Dillman, N Engl J Med, 1990; 323: 940). The aim of present study was to evaluate the activity and feasibility of a new chemo-radiotherapy (CT-RT) regimen in which both strategies of RT improvement will be used. Methods: Thirty consecutive patients (pts) were treated with induction CT (Cisplatin 100 mg/m 2 i.v. day 1,22 + Vinblastine 5 mg/m 2 i.v. day 1,8,15,22,29) followed by RT (60 Gy/30 fractions in 6 wks) combined with Cisplatin 5 mg/m 2 daily before RT. Patients' characteristics were: 29 pts were male and 1 female; median age 60.5 yrs (range 44-69); median PS 1 (range 0-1); 21 squamous cell carcinoma and 9 adenocarcinoma; stage III A in 9 pts and stage IIIB in 21 pts. Results: Twenty-three pts were evaluable for RT plus daily Cisplatin toxicity and 29 for CT toxicity (according to WHO). For RT plus daily cisplatin hematological toxicity consisted of grade III leukopenia in 22%, grade III anemia 9% and grade III thrombocytopenia in 9% of pts. Only 2 patients developed severe esophagitis. Only one case of radiation pneumonitis was reported. For induction CT hematological toxicity consisted of grade III-IV leukopenia in 31%, grade II anemia 10% and grade IV thrombocitopenia in 14% of cases. Non-hematological toxicity consisted mainly of grade I peripheral neuropaty and occured in 17% of pts. One case of minor hearing loss and 4 cases of tinnitus were observed at the end of treatment. Twenty-seven pts were evaluable for response. Response rate was 59% with 7 CRs (26%) and 9 PRs (33%); 1 patient had SD (4%), 5 pts PD (20%) and 5 pts (19%) died early (3 for early progression, 1 for toxicity and 1 for cardiac failure). All pts with CR are still alive with a median event-free survival of 23.9 months (range 12.3-41.9). Actuarial

  1. Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and guinea pig experimental models of tuberculosis.

    Science.gov (United States)

    Guirado, Evelyn; Gil, Olga; Cáceres, Neus; Singh, Mahavir; Vilaplana, Cristina; Cardona, Pere-Joan

    2008-08-01

    RUTI is a therapeutic vaccine that is generated from detoxified and liposomed Mycobacterium tuberculosis cell fragments that has demonstrated its efficacy in the control of bacillus reactivation after short-term chemotherapy. The aim of this study was to characterize the cellular immune response generated after the therapeutic administration of RUTI and to corroborate the lack of toxicity of the vaccine. Mouse and guinea pig experimental models were infected with a low-dose M. tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in both experimental models. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mouse and guinea pig models. This was not the case after Mycobacterium bovis BCG treatment. Cellular immunity was studied through the characterization of the intracellular gamma interferon (IFN-gamma)-producing cells after the splenocytes' stimulation with M. tuberculosis-specific structural and growth-related antigens. Our data show that the difference between the therapeutic administration of BCG and RUTI resides mainly in the stronger activation of IFN-gamma(+) CD4(+) cells and CD8(+) cells against tuberculin purified protein derivative, ESAT-6, and Ag85B that RUTI generates. Both vaccines also triggered a specific immune response against the M. tuberculosis structural antigens Ag16kDa and Ag38kDa and a marked mRNA expression of IFN-gamma, tumor necrosis factor, interleukin-12, inducible nitric oxide synthase, and RANTES in the lung. The results show that RUTI's therapeutic effect is linked not only to the induction of a Th1 response but also to the stimulation of a quicker and stronger specific immunity against structural and growth-related antigens that reduces both the bacillary load and the pulmonary pathology.

  2. The role of interim FDG PET-CT after induction chemotherapy as a predictor of concurrent chemoradiotherapy efficacy and prognosis for head and neck cancer

    International Nuclear Information System (INIS)

    Kim, Ka-Rham; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Chung, Ik-Joo; Park, Ki Seong; Kang, Sae-Ryung; Kwon, Seong Young; Chung, Woong-Ki; Bae, Woo Kyun

    2018-01-01

    Induction chemotherapy (ICT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) has the advantages of organ preservation and systemic control in head and neck cancer (HNC). Early prediction of CCRT efficacy may help identify patients who will benefit more from surgery than from CCRT. We investigated the role of interim 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (FDG PET-CT) after ICT to predict the efficacy of CCRT and clinical outcomes. Tumor responses were retrospectively reviewed after CCRT based on the Response Evaluation Criteria in Solid Tumors. FDG PET-CT imaging was performed before and after three cycles of TPF. We examined the associations between the metabolic response (percentage decrease in the maximum standardized uptake value [SUVmax] and total metabolic tumor volume [MTV]) after ICT and complete response (CR) to CCRT, progression-free survival (PFS), and overall survival (OS). We studied 43 HNC patients with a median follow-up of 32.7 months. Lymph node (LN) SUVmax and total MTV decreases from baseline after ICT were greater in patients with a CR to CCRT than in non-CR patients (LN SUVmax, 88.8% vs. 62.5%, respectively; total MTV, 99.7% vs. 89.9%, respectively). Decreases in total MTV ≥ 78% and LN SUVmax ≥73% after ICT predicted CR to CCRT and longer OS and PFS. Using interim FDG PET-CT to measure SUVmax and total MTV after three cycles of ICT may be a useful technique for identifying HNC patients who will benefit from CCRT and predicting survival outcomes. (orig.)

  3. Results of induction chemotherapy followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Wang Weihua; Bao Yong; Chen Ming; Zhang Li; Xu Guangchuan; Li Kaixin

    2008-01-01

    Objective: To evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3DCRT) plus concurrent weekly paclitaxel for inoperable non-small cell lung cancer (NSCLC). Methods: Patients with stage III NSCLC in favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC=5-6, d1) combined with paclitaxel (175 mg/m 2 , d1), then followed by weekly paclitaxel (40 mg/m 2 ) and concurrent 3DCRT within 34 weeks. The prescription dose of radiotherapy was given as high as possible while total lung V 20 ≤31% and total dose of the spinal cord ≤50 Gy. Results: ICT was well tolerated. During the concurrent chemoradiotherapy,the treatment of 4 patients was ended ahead of the schedule because of severe pulmonary and cardiac toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Leucopenia(33/56) was in grade 1-2 except 1 patient in grade 3. Lymphocytopenia was severe (54/56,42 in grade 3). Three patients developed grade 3 acute radiation-induced esophagitis, and 3 developed grade 3-4 radiation-induced pneumonitis. There was one patients each who developed grade 2,3, and 4 late esophageal damage, respectively. Nine developed grade 2 pulmonary fibrosis. The overall response rate was 69.7%. The 1-year overall survival rate was 72.3%. The 1-year local progression-free survival rate was 62.7%. Conclusions: The schedule of ICT followed by weekly paclitaxel and concurrent 3DCRT can be well tolerated by most of the favorable patients with stage III NSCLC, and the toxicity is tolerable. Results of this study are encouraging, though long-term results should be followed up. (authors)

  4. Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

    Science.gov (United States)

    Bozec, Alexandre; Benezery, Karen; Chamorey, Emmanuel; Ettaiche, Marc; Vandersteen, Clair; Dassonville, Olivier; Poissonnet, Gilles; Riss, Jean-Christophe; Hannoun-Lévi, Jean-Michel; Chand, Marie-Eve; Leysalle, Axel; Saada, Esma; Sudaka, Anne; Haudebourg, Juliette; Hebert, Christophe; Falewee, Marie-Noelle; Demard, François; Santini, José; Peyrade, Frédéric

    2016-09-01

    The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

  5. Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study

    International Nuclear Information System (INIS)

    Catalano, G.; Jereczek-Fossa, B.A.; Pas, T. de; Leon, M.E.; Cattani, F.; Spaggiari, L.; Veronesi, G.; Braud, F. de; Orecchia, R.

    2005-01-01

    Purpose: to evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). Patients and methods: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. Results: from February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). Conclusion: in this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC. (orig.)

  6. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

    Science.gov (United States)

    Cohen, Ezra E W; Karrison, Theodore G; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H; Brockstein, Bruce E; Agulnik, Mark B; Mittal, Bharat B; Yunus, Furhan; Samant, Sandeep; Raez, Luis E; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y; Villaflor, Victoria M; Haraf, Daniel J; Vokes, Everett E

    2014-09-01

    Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. © 2014 by American Society of Clinical Oncology.

  7. Early restaging whole-body 18F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Yen, Ruoh-Fang; Chen, Tony Hsiu-Hsi; Ting, Lai-Lei; Tzen, Kai-Yuan; Pan, Mei-Hsiu; Hong, Ruey-Long

    2005-01-01

    This study was undertaken to evaluate the utility of whole-body 18 F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.9±11.9). Whole-body 18 F-FDG PET was performed in each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged on the basis of the 18 F-FDG PET results. Patients who were downstaged to stage I or II were classified as major responders; the rest were classified as non-major responders. Only 1 of the 23 major responders subsequently developed local recurrence. At the time of data analysis, all major responders were alive; by contrast, of the 27 non-major responders, 15 had locoregional recurrence or distant metastasis and nine had died (seven of NPC and two of treatment-related complications). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major responders (56.4±9.2 and 58.1±2.2 months) as compared with non-major responders (33.7±23.2 and 44.7±20.0 months), with p 18 F-FDG PET scan after the first or second course of IC is useful for predicting therapeutic response and outcome in patients with locoregionally advanced NPC. (orig.)

  8. Induction Chemotherapy Followed by Radiotherapy versus Concurrent Chemoradiotherapy in elderly patients with nasopharyngeal carcinoma: finding from a propensity-matched analysis

    International Nuclear Information System (INIS)

    Zeng, Qi; Wang, Jie; Lv, Xing; Li, Jie; Yin, Li-Jie; Xiang, Yan-Qun; Guo, Xiang

    2016-01-01

    To date, no guideline is proposed for elderly nasopharyngeal carcinoma (NPC) due to lack of prospective clinical trials. The present study comparing the survivals and toxicities in elderly NPC patients received either induction chemotherapy followed by radiotherapy(IC + RT) or concurrent chemoradiotherapy (CCRT) was therefore undertaken to provide a more accurate basis for future clinical practice. The eligible elderly NPC patients were retrospectively enrolled. Propensity score matching generated a matched cohort (1:2) composed from CCRT and IC + RT groups. The survivals and treatment-induced toxicities were compared between two groups. Multivariable analysis was carried to identify significant prognostic factors. The 5-year overall survival, cancer-specific survival, locoregional failure-free survival, distant failure-free survival for all patients were 58.3 %, 62.7 %, 88.7 %, 83.0 %, respectively. No significant survival differences were found between CCRT and IC + RT groups in the propensity-matched cohort. In comparison with the patients who received IC + RT, patients who underwent CCRT were associated with more severe acute toxicities including leucopenia (30 % vs. 6.8 %, P = 0.005), anemia (20 % vs. 4.1 %, P = 0.027), mucositis (63.3 % vs. 34.2 %, P = 0.007), weight loss (23.4 % vs. 4.1 %, P = 0.009). Basicranial bone involvement was an independent prognostic factor that predicted all-cause death (HR = 0.553, 95 % CI 0.329–0.929; P = 0.025) and cancer specific death (HR = 0.558, 95 % CI 0.321–0.969; P = 0.038) in elderly patients. In the context of no guideline for elderly NPC, the present study suggested IC + RT should be a preferable modality compared with CCRT, with similar treatment outcomes but less acute toxicities. The online version of this article (doi:10.1186/s12885-016-2661-y) contains supplementary material, which is available to authorized users

  9. The role of interim FDG PET-CT after induction chemotherapy as a predictor of concurrent chemoradiotherapy efficacy and prognosis for head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ka-Rham; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Chung, Ik-Joo [Chonnam National University Medical School, Department of Hemato-Oncology, Gwangju (Korea, Republic of); Park, Ki Seong; Kang, Sae-Ryung; Kwon, Seong Young [Chonnam National University Medical School, Department of Nuclear Medicine, Gwangju (Korea, Republic of); Chung, Woong-Ki [Chonnam National University Medical School, Department of Radiation-Oncology, Gwangju (Korea, Republic of); Bae, Woo Kyun [Chonnam National University Medical School, Department of Hemato-Oncology, Gwangju (Korea, Republic of); Chonnam National University Hwasun Hospital, Division of Hematology-Oncology, Department of Internal Medicine, Hwasun-gun, Jeollanam-do (Korea, Republic of)

    2018-02-15

    Induction chemotherapy (ICT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) has the advantages of organ preservation and systemic control in head and neck cancer (HNC). Early prediction of CCRT efficacy may help identify patients who will benefit more from surgery than from CCRT. We investigated the role of interim 18-fluoro-2-deoxy-glucose positron emission tomography computed tomography (FDG PET-CT) after ICT to predict the efficacy of CCRT and clinical outcomes. Tumor responses were retrospectively reviewed after CCRT based on the Response Evaluation Criteria in Solid Tumors. FDG PET-CT imaging was performed before and after three cycles of TPF. We examined the associations between the metabolic response (percentage decrease in the maximum standardized uptake value [SUVmax] and total metabolic tumor volume [MTV]) after ICT and complete response (CR) to CCRT, progression-free survival (PFS), and overall survival (OS). We studied 43 HNC patients with a median follow-up of 32.7 months. Lymph node (LN) SUVmax and total MTV decreases from baseline after ICT were greater in patients with a CR to CCRT than in non-CR patients (LN SUVmax, 88.8% vs. 62.5%, respectively; total MTV, 99.7% vs. 89.9%, respectively). Decreases in total MTV ≥ 78% and LN SUVmax ≥73% after ICT predicted CR to CCRT and longer OS and PFS. Using interim FDG PET-CT to measure SUVmax and total MTV after three cycles of ICT may be a useful technique for identifying HNC patients who will benefit from CCRT and predicting survival outcomes. (orig.)

  10. Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

    Science.gov (United States)

    Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

    2014-01-01

    Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

  11. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

    2012-10-01

    This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

  12. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

    2008-03-01

    Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

  13. Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

    Science.gov (United States)

    Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

    2017-07-01

    Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

  14. Phase II study of induction chemotherapy with TPF followed by radioimmunotherapy with Cetuximab and intensity-modulated radiotherapy (IMRT in combination with a carbon ion boost for locally advanced tumours of the oro-, hypopharynx and larynx - TPF-C-HIT

    Directory of Open Access Journals (Sweden)

    Mavtratzas Athanasios

    2011-05-01

    Full Text Available Abstract Background Long-term locoregional control in locally advanced squamous cell carcinoma of the head and neck (SCCHN remains challenging. While recent years have seen various approaches to improve outcome by intensification of treatment schedules through introduction of novel induction and combination chemotherapy regimen and altered fractionation regimen, patient tolerance to higher treatment intensities is limited by accompanying side-effects. Combined radioimmunotherapy with cetuximab as well as modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT and carbon ion therapy (C12 are able to limit toxicity while maintaining treatment effects. In order to achieve maximum efficacy with yet acceptable toxicity, this sequential phase II trial combines induction chemotherapy with docetaxel, cisplatin, and 5-FU (TPF followed by radioimmunotherapy with cetuximab as IMRT plus carbon ion boost. We expect this approach to result in increased cure rates with yet manageable accompanying toxicity. Methods/design The TPF-C-HIT trial is a prospective, mono-centric, open-label, non-randomized phase II trial evaluating efficacy and toxicity of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 50 patients with histologically proven locally advanced SCCHN following TPF induction chemotherapy. Patients receive 24 GyE carbon ions (8 fractions and 50 Gy IMRT (2.0 Gy/fraction in combination with weekly cetuximab throughout radiotherapy. Primary endpoint is locoregional control at 12 months, secondary endpoints are disease-free survival, progression-free survival, overall survival, acute and late radiation effects as well as any adverse events of the treatment as well as quality of life (QoL analyses. Discussion The primary objective of TPF-C-HIT is to evaluate efficacy and toxicity of cetuximab in combination with combined IMRT/carbon ion therapy following TPF induction in locally advanced SCCHN. Trial Registration

  15. Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

    2002-01-01

    Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

  16. Ovarian Damage during Chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility

    Directory of Open Access Journals (Sweden)

    Wendy Marder

    2012-01-01

    Full Text Available Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency (POI due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.

  17. Concomitant chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy as definitive, first line treatment of squamous cell carcinoma of the head and neck. A retrospective single center analysis

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, P.; Bauer, C.; Fraunholz, I.; Ottinger, A.; Fokas, E.; Roedel, C.; Weiss, C. [Goethe University Frankfurt, Department of Radiation Therapy and Oncology, Frankfurt am Main (Germany); Wagenblast, J.; Stoever, T. [Goethe University, Department of Otorhinolaryngology, Frankfurt am Main (Germany); Seitz, O. [Goethe University, Department of Oral Maxillofacial and Plastic Facial Surgery, Frankfurt am Main (Germany)

    2014-03-15

    Despite the lack of evidence to support its implementation in the clinical practice, induction chemotherapy (IC) before chemoradiotherapy (CRT) is often used in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). We retrospectively examined the tolerability, feasibility, and clinical outcome of both concepts in a single center analysis. In all, 83 patients were treated between 2007 and 2010 with IC + CRT (n = 42) or CRT alone (n = 41). IC consisted of docetaxel, cisplatin and 5-fluorouracil (TPF), or cisplatin and 5-fluorouracil (PF). All patients were scheduled to receive 2 cycles of PF during concurrent CRT. Adverse events were assessed according to the common toxicity criteria of adverse events (CTCAE v. 3.0). Associations were tested using the χ{sup 2} test, and survival estimates were calculated according to Kaplan-Meier. The median follow-up was 30.35 months (range 2.66-61.25 months). At 2 years, the overall survival rate was significantly higher for primary CRT compared to IC + CRT group (74.8 % vs. 54 %, respectively; p = 0.041). Significantly more treatment-related overall grade 4 toxicities were documented in the IC + CRT group compared to the CRT group (42.9% vs. 9.8%; p = 0.001). Renal toxicity ≥ grade 2 occurred in 52.4 % vs. 7.3 % (p < 0.001), respectively. In all, 93 % of the patients with primary CRT compared to 71 % with IC + CRT received the planned full radiotherapy dose (p = 0.012). This is, to our knowledge, the largest retrospective study to compare IC + CRT with primary CRT. IC showed high acute toxicity, compromised the feasibility of concurrent CRT, and was associated with reduced overall survival rates compared to primary CRT. The lack of clinical benefit in conjunction with the increased toxicity does not support implementation of IC. (orig.) [German] Trotz fehlender Studienergebnisse, die den Einsatz einer Induktionschemotherapie (IC) vor einer simultanen Radiochemotherapie (RCT) in der klinischen

  18. 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

  19. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    International Nuclear Information System (INIS)

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-01-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  20. 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

  1. The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer.

    Science.gov (United States)

    Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

    2016-10-01

    To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3). Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20). The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

  2. The impact of induction chemotherapy on the dosimetric parameters of subsequent radiotherapy: an investigation of 30 consecutive patients with locally-advanced non-small cell lung cancer and modern radiation planning techniques

    International Nuclear Information System (INIS)

    Grant, Jonathan D; Sobremonte, Angela; Hillebrandt, Evangeline; Allen, Pamela K; Gomez, Daniel R

    2015-01-01

    To investigate the influence of induction chemotherapy (ICT) on dosimetric outcomes in patients with inoperable non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT). 30 patients with inoperable stage II-III NSCLC treated with 2–4 cycles of ICT followed by definitive CRT to ≥ 60 Gy were selected. Tumor response to chemotherapy was scored by RECIST criteria. Treatment plans based on tumor extent prior to chemotherapy were generated based on equivalent planning constraints and techniques as the original post-chemotherapy plans. Dosimetric parameters predictive of toxicity for lung, esophagus, heart, and spinal cord were compared amongst the pre- and post-ICT plans. The majority of patients (70%) experienced an overall reduction in GTV size between the pre-ICT imaging and the time of simulation. Comparing pre-and post-ICT diagnostic imaging, 5 patients met the RECIST criteria for response, 23 were classified as stable, and 2 experienced disease progression on diagnostic imaging. Despite a significantly reduced GTV size in the post-ICT group, no systematic improvements in normal tissue doses were seen amongst the entire cohort. This result persisted amongst the subgroup of patients with larger pre-ICT GTV tumor volumes (>100 cc 3 ). Among patients with RECIST-defined response, a significant reduction in lung mean dose (1.9 Gy absolute, median 18.2 Gy to 16.4 Gy, p = 0.04) and V 20, the percentage of lung receiving 20 Gy (3.1% absolute, median 29.3% to 26.3%, p = 0.04) was observed. In the non-responding group of patients, an increased esophageal V 50 was found post-chemotherapy (median 28.9% vs 30.1%, p = 0.02). For patients classified as having a response by RECIST to ICT, modest improvements in V 20 and mean lung dose were found. However, these benefits were not realized for the cohort as a whole or for patients with larger tumors upfront. Given the variability of tumor response to ICT, the a priori impact of induction chemotherapy to

  3. Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

    Science.gov (United States)

    Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

    2013-12-01

    Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

  4. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    Science.gov (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  5. Anomalous directional behaviour of the real parts of the induction arrows in the Eastern Alps. Tectonic and palaeographical implications

    Energy Technology Data Exchange (ETDEWEB)

    Gurk, M.; Schnegg, P.-A. [Universite' de Neuchatel, Groupe de Geomagnetisme, Institut de Geologie, Neuchatel (Switzerland)

    2001-08-01

    The electromagnetic induction pattern in the Eastern Alps is characterised by a (continuous) large-scale zone on which the real parts of the induction arrows show anomalous directional behaviour. This zone extends from the Penninic Domain of Eastern Switzerland (Graubuenden) probably into the Carpathian ranges. A coarse mesh of a Magnetotelluric (MT) and Geomagnetic Deep Sounding (GDS) station in the Alps of Graubuenden and Valais (Western Switzerland) indicates that this electromagnetic anomaly is restricted to the Mesozoic sediments of the North Penninic Buendnerschiefer-facies that begins in Eastern Switzerland and extends towards the east beneath Austroalpine, South Penninic and Southalpine units. Striking similarities in position and arrangement between this zone and the magnetic signature in Eastern Alps are found. The analysis of the GDS data with the method of the Hypothetical Event Analysis (HEA) shows that current channelling affects the electromagnetic fields in this zone and causes the anomalous direction of induction arrows. Based on the combined interpretation of GDS data from the Eastern Alps and West Hungary together with the recent data from Switzerland, the following geological implications are discussed: i) a spatial decoupling of induction processes from the upper to the lower crust; ii) a lower crustal conductive structure caused by the identification of the Northern Adriatic promontory or terrane; iii) the eastward continuation of the Buendnerschiefer-facies at least to the tectonic window of Rechnitz.

  6. Anomalous directional behaviour of the real parts of the induction arrows in the Eastern Alps. Tectonic and palaeographical implications

    International Nuclear Information System (INIS)

    Gurk, M.; Schnegg, P.-A.

    2001-01-01

    The electromagnetic induction pattern in the Eastern Alps is characterised by a (continuous) large-scale zone on which the real parts of the induction arrows show anomalous directional behaviour. This zone extends from the Penninic Domain of Eastern Switzerland (Graubuenden) probably into the Carpathian ranges. A coarse mesh of a Magnetotelluric (MT) and Geomagnetic Deep Sounding (GDS) station in the Alps of Graubuenden and Valais (Western Switzerland) indicates that this electromagnetic anomaly is restricted to the Mesozoic sediments of the North Penninic Buendnerschiefer-facies that begins in Eastern Switzerland and extends towards the east beneath Austroalpine, South Penninic and Southalpine units. Striking similarities in position and arrangement between this zone and the magnetic signature in Eastern Alps are found. The analysis of the GDS data with the method of the Hypothetical Event Analysis (HEA) shows that current channelling affects the electromagnetic fields in this zone and causes the anomalous direction of induction arrows. Based on the combined interpretation of GDS data from the Eastern Alps and West Hungary together with the recent data from Switzerland, the following geological implications are discussed: i) a spatial decoupling of induction processes from the upper to the lower crust; ii) a lower crustal conductive structure caused by the identification of the Northern Adriatic promontory or terrane; iii) the eastward continuation of the Buendnerschiefer-facies at least to the tectonic window of Rechnitz

  7. Anomalous directional behaviour of the real parts of the induction arrows in the Eastern Alps: tectonic and palaeogeographic implications

    Directory of Open Access Journals (Sweden)

    P. A. Schnegg

    2001-06-01

    Full Text Available The electromagnetic induction pattern in the Eastern Alps is characterised by a (continuous large-scale zone on which the real parts of the induction arrows show anomalous directional behaviour. This zone extends from the Penninic Domain of Eastern Switzerland (Graubünden probably into the Carpathian ranges. A coarse mesh of a Magnetotelluric (MT and Geomagnetic Deep Sounding (GDS station in the Alps of Graubünden and Valais (Western Switzerland indicates that this electromagnetic anomaly is restricted to the Mesozoic sediments of the North Penninic Bündnerschiefer-facies that begins in Eastern Switzerland and extends towards the east beneath Austroalpine, South Penninic and Southalpine units. Striking similarities in position and arrangement between this zone and the magnetic signature in the Eastern Alps are found. The analysis of the GDS data with the method of the Hypothetical Event Analysis (HEA shows that current channelling affects the electromagnetic fields in this zone and causes the anomalous direction of induction arrows. Based on the combined interpretation of GDS data from the Eastern Alps and West Hungary together with our recent data from Switzerland, the following geological implications are discussed: i a spatial decoupling of induction processes from the upper to the lower crust; ii a lower crustal conductive structure caused by the indentation of the Northern Adriatic promontory or terrane; iii the eastward continuation of the Bündnerschiefer-facies at least to the tectonic window of Rechnitz.

  8. Implication of chemo-resistant memory T cells for immune surveillance in patients with sarcoma receiving chemotherapy.

    Science.gov (United States)

    Shibayama, Yuji; Tsukahara, Tomohide; Emori, Makoto; Murata, Kenji; Mizushima, Emi; Hirohashi, Yoshihiko; Kanaseki, Takayuki; Nakatsugawa, Munehide; Kubo, Terufumi; Yamashita, Toshihiko; Sato, Noriyuki; Torigoe, Toshihiko

    2017-09-01

    Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8 + memory T cell population with a chemo-resistance property, "young memory" T (T YM ) cells. In this study, we investigated the proportion and function of T YM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of T YM cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only T YM cells but also T CM and T EM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from T YM , T CM and T EM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from T YM cells but were hardly induced from T EM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from T YM cells but not from the T CM and T EM cells in sarcoma patients who received chemotherapy. The findings suggest that T YM cells are resistant to chemotherapy and can firstly recover from the nadir. T YM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. Biotransformation and induction: implications for toxicity, bioaccumulation and monitoring of environmental xenobiotics in fish

    International Nuclear Information System (INIS)

    Kleinow, K.M.; Melancon, M.J.; Lech, J.J.

    1987-01-01

    Biotransformation of xenobiotics in fish occurs by many of the same reactions as in mammals. These reactions have been shown to affect the bioaccumulation, persistence, residue dynamics, and toxicity of select chemicals in fish. P-450-dependent monooxygenase activity of fish can be induced by polycyclic aromatic hydrocarbons, but phenobarbital-type agents induce poorly, if at all. Fish monooxygenase activity exhibits ideal temperature compensation and sex-related variation. Induction of monooxygenase activity by polycyclic aromatic hydrocarbons can result in qualitative as well as quantitative changes in the metabolic profile of a chemical. Induction can also alter toxicity. In addition, multiple P-450 isozymes have been described for several fish species. The biotransformation productions of certain chemicals have been related to specific P-450 isozymes, and the formation of these products can be influenced by induction. Exposure of fish to low levels of certain environmental contaminants has resulted in induction of specific monooxygenase activities and monitoring of such activities has been suggested as a means of identifying areas of pollutant exposure in the wild

  10. Local recurrence and distant metastasis of supratentorial primitive neuro-ectodermal tumor in an adult patient successfully treated with intensive induction chemotherapy and maintenance temozolomide

    NARCIS (Netherlands)

    Terheggen, F.; Troost, D.; Majoie, C. B.; Leenstra, S.; Richel, D. J.

    2007-01-01

    Supratentorial primitive neuro-ectodermal tumors (PNET) in adults are very rare. Extraneural metastasis are unusual and the optimal palliative chemotherapy regimen is not established. We present a 26-year-old patient with local recurrence and distant metastasis of supratentorial PNET successfully

  11. Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukaemia

    NARCIS (Netherlands)

    Uyl-de Groot, CA; Lowenberg, B; Vellenga, E; Suciu, S; Willemze, R; Rutten, FFH

    We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin-cytosine arabinoside (control arm: rr = 161)

  12. Separation of Electric Fields Into Potential and Inductive Parts, and Implications for Radial Diffusion

    Science.gov (United States)

    Chan, A. A.; Ilie, R.; Elkington, S. R.; Albert, J.; Huie, W.

    2017-12-01

    It has been traditional to separate radiation belt radial-diffusion coefficients into two contributions: an "electrostatic" diffusion coefficient, which is assumed to be due to a potential (non-inductive) electric field, and an "electromagnetic" diffusion coefficient , which is assumed to be due to the combined effect of an inductive electric field and the corresponding time-dependent magnetic field. One difficulty in implementing this separation when using magnetospheric fields obtained from measurements, or from MHD simulations, is that only the total electric field is given; the separation of the electric field into potential and inductive parts is not readily available. In this work we separate the electric field using a numerical method based on the Helmholtz decomposition of the total motional electric field calculated by the BATS-R-US MHD code. The inner boundary for the electric potential is based on the Ridley Ionospheric Model solution and we assume floating boundary conditions in the solar wind. Using different idealized solar wind drivers, including a solar wind density that is oscillating at a single frequency or with a broad spectrum of frequencies, we calculate potential and inductive electric fields, electric and magnetic power spectral densities, and corresponding radial diffusion coefficients. Simulations driven by idealized solar wind conditions show a clear separation of the potential and inductive contributions to the power spectral densities and diffusion coefficients. Simulations with more realistic solar wind drivers are underway to better assess the use of electrostatic and electromagnetic diffusion coefficients in understanding ULF wave-particle interactions in Earth's radiation belts.

  13. Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

    Science.gov (United States)

    Pinkerton, C R; Blanc Vincent, M P; Bergeron, C; Fervers, B; Philip, T

    2000-09-01

    The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

  14. Feasibility, toxicity, and efficacy of short induction chemotherapy of docetaxel plus cisplatin or carboplatin (TP) followed by concurrent chemoradiotherapy for organ preservation in advanced cancer of the hypopharynx, larynx, and base of tongue. Early results

    International Nuclear Information System (INIS)

    Semrau, Sabine; Klautke, Gunther; Fietkau, Rainer; Waldfahrer, Frank; Iro, Heinrich; Lell, Michael; Uder, Michael; Linke, Rainer; Kuwert, Torsten

    2011-01-01

    Concurrent chemoradiotherapy (CRT) is standard treatment for advanced head and neck cancer. Whether short induction chemotherapy (ICT) provides additional benefit or, in particular, predictive benefit for the response to chemoradiotherapy is an open question. The present study aimed to assess the feasibility, toxicity, and efficacy of induction with docetaxel and platinum salt (TP) and subsequent CRT. A total of 25 patients with functionally inoperable cancer of the base of the tongue, hypopharynx, or larynx received 1 cycle of docetaxel (75 mg/m 2 , day 1) combined with either cisplatin (30 mg/m 2 , days 1-3; n = 23) or carboplatin (AUC 1.5 days 1-3; n = 2). Responders (n = 22, > 30% tumor reduction, graded by endoscopy) and 1 non-responder received CRT (target dose: 69-72 Gy) with cisplatin/paclitaxel, carboplatin/paclitaxel, or cisplatin/docetaxel. All patients completed ICT with acceptable toxicity (leukocytopenia grade 4: 8%). The remission rate of the primary tumor was 88% (22/25 patients). There was no need to delay CRT due to toxicity in any case. Each patient received the full radiation dose. Of the patients, 56% received > 80% of the chemotherapy. The acute toxicity of CRT was moderate, no grade 4 toxicities occurred, while grade 3 toxicities included the following: infection (39%), dermatitis (13%), leukocytopenia (30%), and thrombocytopenia (4%). The local control rate was 84.6% ± 8.5% and the survival rate was 89.6% ± 7.2% at 12 months. Organ preservation was possible in 22/23 (95%) cases. Short induction with a TP regimen and subsequent CRT with a taxan is feasible and associated with an encouraging local control rate. (orig.)

  15. Improvement of a predictive model in ovarian cancer patients submitted to platinum-based chemotherapy: implications of a GST activity profile.

    Science.gov (United States)

    Pereira, Deolinda; Assis, Joana; Gomes, Mónica; Nogueira, Augusto; Medeiros, Rui

    2016-05-01

    The success of chemotherapy in ovarian cancer (OC) is directly associated with the broad variability in platinum response, with implications in patients survival. This heterogeneous response might result from inter-individual variations in the platinum-detoxification pathway due to the expression of glutathione-S-transferase (GST) enzymes. We hypothesized that GSTM1 and GSTT1 polymorphisms might have an impact as prognostic and predictive determinants for OC. We conducted a hospital-based study in a cohort of OC patients submitted to platinum-based chemotherapy. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. GSTM1-null genotype patients presented a significantly longer 5-year survival and an improved time to progression when compared with GSTM1-wt genotype patients (log-rank test, P = 0.001 and P = 0.013, respectively). Multivariate Cox regression analysis indicates that the inclusion of genetic information regarding GSTM1 polymorphism increased the predictive ability of risk of death after OC platinum-based chemotherapy (c-index from 0.712 to 0.833). Namely, residual disease (HR, 4.90; P = 0.016) and GSTM1-wt genotype emerged as more important predictors of risk of death (HR, 2.29; P = 0.039; P = 0.036 after bootstrap). No similar effect on survival was observed regarding GSTT1 polymorphism, and there were no statistically significant differences between GSTM1 and GSTT1 genotypes and the assessed patients' clinical-pathological characteristics. GSTM1 polymorphism seems to have an impact in OC prognosis as it predicts a better response to platinum-based chemotherapy and hence an improved survival. The characterization of the GSTM1 genetic profile might be a useful molecular tool and a putative genetic marker for OC clinical outcome.

  16. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  17. Effects of intensive induction and consolidation chemotherapy with idarubicin and high dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kenneth F. Bradstock

    2016-12-01

    Full Text Available An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL. Patients achieving a complete response (CR were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity. Grades 3–4 diarrhoea occurred in 47% of patients during induction. Two patients (11% died during induction therapy, and 2 were withdrawn due to resistant disease or prolonged marrow hypoplasia. Fifteen patients achieved CR (79%, but levels of minimal residual disease (MRD after induction were comparable with those previously observed using a modified pediatric protocol. Overall survival at 5 years was 36.8% while leukemia-free survival was 44.1%. An intensive AML protocol used in adults with ALL resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes.

  18. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    International Nuclear Information System (INIS)

    Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

    2011-01-01

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  19. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  20. A Retrospective, Multicenter Study of the Tolerance of Induction Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Radiotherapy With Concomitant Cetuximab in 46 Cases of Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Buiret, Guillaume; Combe, Claire; Favrel, Veronique; Pommier, Pascal; Martin, Laurent; Ecochard, Rene; Fayette, Jerome; Tartas, Sophie; Ramade, Antoine; Ceruse, Philippe

    2010-01-01

    Purpose: To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. Results: The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. Conclusion: The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.

  1. Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection

    OpenAIRE

    Yu, Yong-Qiang; Liu, Lian-Cheng; Wang, Fa-Cai; Liang, Yan; Cha, Da-Qin; Zhang, Jing-Jing; Shen, Yu-Jun; Wang, Hai-Ping; Fang, Shengyun; Shen, Yu-Xian

    2009-01-01

    Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion w...

  2. Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

    Science.gov (United States)

    Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

    2013-08-01

    While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients. Copyright © 2013 Wiley Periodicals, Inc.

  3. Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy.

    Science.gov (United States)

    Valdez, Benigno C; Li, Yang; Murray, David; Brammer, Jonathan E; Liu, Yan; Hosing, Chitra; Nieto, Yago; Champlin, Richard E; Andersson, Borje S

    2016-09-27

    HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased. Other HDAC inhibitors - panobinostat, belinostat and suberoylanilide hydroxamic acid (SAHA) - had similar effects on these transporters. The protein level of MRP1 correlated with cellular resistance to busulfan and chlorambucil, and Rom exposure sensitized cells to these DNA alkylators. The decrease in MRP1 correlated with decreased cellular drug export activity, and increased level of MDR1 correlated with increased export of daunorubicin. A similar decrease in the level of MRP1 protein, and increase in MDR1, were observed when mononuclear cells derived from patients with T-cell malignancies were exposed to Rom. Decreased MRP1 and increased MDR1 expressions were also observed in blood mononuclear cells from lymphoma patients who received SAHA-containing chemotherapy in a clinical trial. This inhibitory effect of HDAC inhibitors on the expression of MRP1 suggests that their synergism with DNA alkylating agents is partly due to decreased efflux of these alkylators. Our results further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy.

  4. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  5. Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. A hellenic cooperative oncology group phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Fountzilas, G.; Kalogera-Fountzila, A.; Karanikiotis, C.; Nicolaou, A.; Plataniotis, G.; Daniilidis, J. [AHEPA Hospital, Aristotle Univ. of Thessaloniki, Thessaloniki (Greece); Tolis, C.; Bai, M.; Tsekeris, P. [Univ. of Ioannina Medical School, Ioannina (Greece); Misailidou, D. [' ' Papageorgiou' ' Hospital, Thessaloniki (Greece); Samantas, E.; Athanassiou, E. [' ' Agii Anargiri' ' Cancer Hospital, Athens (Greece); Papamichael, D.; Catodritis, N. [Bank of Cyprus Oncology Center, Nicosia (Cyprus); Makatsoris, T. [' ' Rio' ' Hospital, Univ. of Patras Medical School, Rio, Patras (Greece); Papakostas, P. [' ' Ippokration' ' Hospital, Athens (Greece); Zamboglou, N. [Dept. of Radiotherapy, Klinikum Offenbach, Offenbach (Germany)

    2005-04-01

    Background: clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control. Patients and methods: untreated patients with stage IIB-IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m{sup 2} followed by paclitaxel 175 mg/m{sup 2} as 3-h infusion on day 1 and cisplatin 75 mg/m{sup 2} on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m{sup 2}. Results: from November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet. Conclusion: IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions. (orig.)

  6. S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Brown, P D; Diamant, M; Jensen, P O

    1999-01-01

    Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential....../kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had....../kg and 5 micrograms/kg respectively. Immunophenotypic assessment demonstrated that rhIL-6 increased the expression of CD20 in all CLL patients with a reversal after cessation of rhIL-6. We conclude that rhIL-6, in the dosage and schedule used in this study, did not increase the proportion of the cells in S...

  7. Treatment of patients with unresectable squamous head and neck cancer with induction chemotherapy followed by hyperfractionated radiotherapy; Traitement de patients atteints d'un cancer irresecable de la tete et du cou avec une chimiotherapie d'induction suivie d'une radiotherapie hyperfractionnee

    Energy Technology Data Exchange (ETDEWEB)

    Mesia, R.; Majem, M.; Barretina Ginesta, M.P.; Montes, A.; Cardenal, F. [Institut Catala d' Oncologia-Duran i Reynals, Dept. of Medical Oncology, L' Hospitalet de LLobregat-Barcelona (Spain); Galiana, R.; Guedea, F. [Institut Catala d' Oncologia-Duran i Reynals, Dept. of Radiation Oncology, L' Hospitalet de LLobregat-Barcelona (Spain); Manos, M. [Institut Catala d' Oncologia-Duran i Reynals, Dept. of ENT, L' Hospitalet de LLobregat-Barcelona (Spain); Monner, A. [Institut Catala d' Oncologia-Duran i Reynals, Dept. of Dept. of Maxillofacial Surgery, L' Hospitalet de LLobregat-Barcelona (Spain); Perez, J. [Institut Catala d' Oncologia-Duran i Reynals, Clinical Investigation Unit, L' Hospitalet de LLobregat-Barcelona (Spain)

    2008-03-15

    Purpose: the contribution of induction chemotherapy (CT) followed by hyperfractionated radiotherapy (h.f.R.T.) in unresectable squamous head and neck cancer has been evaluated in a single institution as an assistancial protocol. Patients and methods: from March 1994 to June 2000 all consecutive patients with unresectable disease were treated with four courses of platin plus fluorouracil based CT followed by h.f.R.T.. Tumor resectability and response was assessed by a multidisciplinary committee. Results: ninety-nine patients (pts) were treated. All of them had stage IV-M0 disease: 67 T4, 88 N2-N3. Tumor location: 62 oropharynx, 22 hypopharynx, eight oral cavity and seven larynx. Tumor response at the end of treatment: 61 patients complete response, 17 partial response, two stable disease, 10 progressive disease and nine unevaluated. With a median follow-up of 70 months the 5-year loco-regional control and overall survival was 30.3% (95% CI: 21.9-38.6) and 21.6% (95% CI: 13.4-29.8), respectively. Loco-regional control and overall survival is significantly influenced by prior response to induction CT. Main grade 3-4 toxicity related to CT was stomatitis, but there were five patients with an ischemic event. Grade 3-4 acute toxicity related to h.f.R.T.: 47 stomatitis, 20 epithelitis. Chronic toxicity related to h.f.R.T.: six emergency tracheotomies due to laryngeal edema, five pneumonia and one mucous/soft-tissue necrosis. There were eight toxic related deaths. Conclusion: induction CT followed by h.f.R.T. might increase the overall survival rate in unresectable disease. H.f.R.T. resulted in a high rate of acute toxicity and its use would not be warranted in those patients with no response to induction CT who had a low probability of long-term control. (authors)

  8. Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Lin, Yu-Lin [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Wang, Hsiu-Po [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chiu, Yen-Feng [Institute of Public Health Sciences, National Health Research Institutes, Miaoli, Taiwan (China); Chang, Ming-Chu [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Tien, Yu-Wen [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Jen-Shi [Department of Internal Medicine, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); Hsieh, Ruey-Kuen [Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (China); Lin, Pin-Wen; Shan, Yan-Shen [Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan (China); Cheng, Ann-Lii [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Jang-Yang [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China); Whang-Peng, Jacqueline [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Cancer Center Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Hwang, Tsann-Long, E-mail: hwangtl@adm.cgmh.org.tw [Department of Surgery, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); and others

    2011-12-01

    Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaieve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m{sup 2}) infusion at a fixed dose rate (10 mg/m{sup 2}/min), followed by 85 mg/m{sup 2} oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m{sup 2}) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m{sup 2} gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18

  9. 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

  10. Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

    International Nuclear Information System (INIS)

    Ch’ang, Hui-Ju; Lin, Yu-Lin; Wang, Hsiu-Po; Chiu, Yen-Feng; Chang, Ming-Chu; Hsu, Chih-Hung; Tien, Yu-Wen; Chen, Jen-Shi; Hsieh, Ruey-Kuen; Lin, Pin-Wen; Shan, Yan-Shen; Cheng, Ann-Lii; Chang, Jang-Yang; Whang-Peng, Jacqueline; Hwang, Tsann-Long

    2011-01-01

    Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaïve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m 2 ) infusion at a fixed dose rate (10 mg/m 2 /min), followed by 85 mg/m 2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m 2 ) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m 2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2–42.5%) and 70% (95% CI, 44.4–99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8–12.8) months and 14.5 (95% CI, 11.9–17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1–80.9%) and 20.6% (95% CI, 8.7–32.5%), respectively. Neutropenia was the most common Grade 3–4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion

  11. 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

  12. Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Khalid J.H. Alzahrani

    2017-08-01

    Full Text Available Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU and 5F,2′deoxyuridine (5F,2′dUrd, and was designated uridine-uracil transporter 1 (UUT1; the other transporter mediated uptake of adenosine, uridine, 5F,2′dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1. To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2′dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2′dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Keywords: Leishmania, Pyrimidine metabolism, Uracil

  13. FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

    Science.gov (United States)

    Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

    2018-04-13

    Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of

  14. 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.

  15. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1

    Directory of Open Access Journals (Sweden)

    Oertel Katrin

    2012-10-01

    Full Text Available Abstract Background Induction chemotherapy (ICT with docetaxel, cisplatin and fluorouracil (TPF followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. Methods Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0 and 30 mg/m2 (DL −1, plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. Results Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50% showed complete pathologic regression. Conclusions A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. Trial registration number NCT01108042 (ClinicalTrials.gov Identifier

  16. Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

    Science.gov (United States)

    Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

    2016-03-01

    In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

  17. Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.

    Science.gov (United States)

    Alzahrani, Khalid J H; Ali, Juma A M; Eze, Anthonius A; Looi, Wan Limm; Tagoe, Daniel N A; Creek, Darren J; Barrett, Michael P; de Koning, Harry P

    2017-08-01

    Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [ 3 H]-uridine but not of [ 3 H]-inosine. Conversely, the NT2-like genes mediated uptake of [ 3 H]-inosine but not [ 3 H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2'dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2'dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights

  18. Metronomic chemotherapy.

    Science.gov (United States)

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  19. Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Tuyet A Nguyen

    2011-08-01

    Full Text Available Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposureMiliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin

  20. Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation in First Complete Remission Can Abrogate the Poor Outcomes of Children with Acute Myeloid Leukemia Resistant to the First Course of Induction Chemotherapy.

    Science.gov (United States)

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-12-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy option for children with acute myeloid leukemia (AML) resistant to the first course of induction chemotherapy (IC 1st ). We aimed to identify the efficacy of unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first complete remission and whether children resistant (IC 1st -resistant; n = 38) or sensitive (IC 1st -sensitive; n = 59) to the IC 1st can achieve comparable outcomes. The cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) and severe chronic GVHD was .0% versus 20.1% (P = .038) and 21.7% versus 13.2% (P = .238), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was 22.2% versus 7.6% (P = .061) and 5.3% versus 10.8% (P = .364), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year probability of overall survival and disease-free survival was 76.3% versus 83.0% (P = .657) and 72.5% versus 81.6% (P = .396), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. Multivariate analysis failed to show significant differences in survival rates between the groups. Thus, our results show that unmanipulated haplo-HSCT may overcome the poor prognostic significance of IC 1st -resistance in children with AML, and it is valid as a postremission treatment for children with IC 1st -resistant AML lacking an HLA-matched donor. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Recovery from inhibition by UV-irradiation of ornithine decarboxylase induction in human cells: implication of excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Hur, E.; Prager, A. (Nuclear Research Centre-Negev, Beer-Sheva (Israel)); Buonaguro, F. (Argonne National Lab., IL (USA))

    1982-05-01

    Exposure of stationary-phase human breast carcinoma (T-47D) cells to far-UV light (254nm) inhibited the appearance of induced ornithine decarboxylase (ODC) activity. The fluence response curve had a shoulder (Dsub(q)=2Jm/sup -2/) followed by an exponential decline (D/sub 0/=4.2Jm/sup -2/). The cells could recover from this inhibition when the stimulus of induction of ODC was delayed for 20-24h after irradiation. Hydroxyurea (HU) when present at 3mM during the recovery period eliminated completely the ability of the cells to recover. This effect of HU on ODC induction was partially reversed by 50..mu..M of the four deoxyribonucleosides required for DNA synthesis. Neither HU nor the deoxyribonucleosides by themselves affected ODC induction in unirradiated cells. Since HU inhibited the recovery from potentially lethal UV damage and is a known inhibitor of excision repair, it is suggested that recovery from UV-induced inhibition of ODC induction depends on excision-repair of DNA damage. This interpretation is strongly supported by the finding that specific photolysis of 5-bromodeoxyuridine, incorporated into DNA during the recovery period, inhibited recovery of ODC induction from inhibition by UV light.

  2. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

    International Nuclear Information System (INIS)

    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi

    1997-01-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  3. Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis.

    Science.gov (United States)

    Fan, Yu; Wang, Ye; Wang, Ke

    2015-12-18

    Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2-induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell

  4. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

    Science.gov (United States)

    Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

    2014-11-11

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

  5. Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer. Results of a randomized phase II study

    International Nuclear Information System (INIS)

    Takacsi-Nagy, Zoltan; Polgar, Csaba; Major, Tibor; Fodor, Janos; Hitre, Erika; Remenar, Eva; Kasler, Miklos; Oberna, Ferenc; Goedeny, Maria

    2015-01-01

    Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63 % following ICT + CRT, whereas 70 % after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %), and PFS (41 vs. 50 %) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12 %; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42 % in the ICT + CRT and CRT groups, respectively. The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of

  6. Progress in treatment of head and neck cancer. Pt. 1. Chemotherapy

    International Nuclear Information System (INIS)

    Stupp, R.; Vokes, E.E.; Chicago Univ., IL

    1995-01-01

    Cancer of the head and neck is commonly diagnosed in an advanced stage with a poor prognosis. New active agents and combinations have recently been identified. By adding chemotherapy to a multimodality approach with surgery and radiation therapy the outcome may be altered. We reviewed the more recently published literature on induction and adjuvant chemotherapy. No survival advantage has been shown for adjuvant chemotherapy. Organ preservation can be achieved with induction chemotherapy followed by limited surgery and radiation in approximately two thirds of the patients with laryngeal carcinoma. Patients achieving a complete response after induction chemotherapy have a better prognosis. Chemotherpy has consistently shown to reduce the frequency of distant metastases. Chemotherapy is indicated only in recurrent or metastatic disease. Induction chemotherapy is limited to laryngeal carcinoma with organ preservation as intent. Local recurrences and intercurrent morbidity are the main reasons for treatment failures. (orig.) [de

  7. Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

    Science.gov (United States)

    Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

    2017-12-29

    To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

    Science.gov (United States)

    Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu

    2010-03-01

    The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

  9. Types of chemotherapy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html . Updated February 15, ...

  10. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  11. Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

    International Nuclear Information System (INIS)

    Park, Anthony; Govindaraj, Chindu; Xiang, Sue D.; Halo, Julene; Quinn, Michael; Scalzo-Inguanti, Karen; Plebanski, Magdalena

    2012-01-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25 hi Foxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients

  12. Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Anthony; Govindaraj, Chindu; Xiang, Sue D., E-mail: Sue.Xiang@monash.edu [Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria 3004 (Australia); Halo, Julene; Quinn, Michael [Department of Oncology, Royal Women’s Hospital, Melbourne, Victoria 3052 (Australia); Scalzo-Inguanti, Karen; Plebanski, Magdalena, E-mail: Sue.Xiang@monash.edu [Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria 3004 (Australia)

    2012-06-18

    Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25{sup hi}Foxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.

  13. DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy.

    Science.gov (United States)

    Nadin, Silvina Beatriz; Vargas-Roig, Laura M; Drago, Gisela; Ibarra, Jorge; Ciocca, Daniel R

    2006-07-28

    Drug resistance is considered the main impediment to successful cancer chemotherapy. The quest for a method useful to predict individual responses to chemotherapy prior to treatment is highly desired. This study was designed to determine the individual influences of doxorubicin and cisplatin on the degree of DNA damage, DNA repair and hMSH2 and the hMLH1 protein expression in peripheral blood lymphocytes (PBL) and their correlations with the clinical response. PBL were obtained from 25 cancer patients (pre- and post-chemotherapy) and from 10 healthy persons, cultured and exposed to doxorubicin or cisplatin. Cells were collected at T0 (immediately after drug treatment) and 24h after damage (T24). The alkaline comet assay was employed to assess the DNA damage and repair function, and immunocytochemistry to study hMLH1 and hMSH2 expression. Clinical response was evaluated after three cycles of chemotherapy. Pre-chemotherapy PBL from cancer patients showed significantly higher levels of basal DNA damage than healthy persons, with appreciable interindividual variations between them. The in vivo administration of antineoplasic drugs was accompanied by significant DNA damage, and an increased in the number of apoptotic cells. Cancer patients with complete response showed a high number of apoptotic cells. The DNA migration increased at T0 and at T24 in cisplatin-treated patients, reflecting a decreased rate of cisplatin adducts repair than that observed in healthy individuals. The ability to repair DNA lesions in doxorubicin-damaged cells was very similar between healthy individuals and cancer patients. Cisplatin-treated patients that died by the disease showed lower DNA migration than the mean value. The expression of hMLH1 and hMSH2 was practically identical between healthy individuals and cancer patients. Nevertheless, chemotherapy induced a depletion mostly of hMLH1. In 83% of cisplatin-treated patients with CR the hMLH1 and hMSH2 expression at T24 was higher than the

  14. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

    Directory of Open Access Journals (Sweden)

    Elena López

    Full Text Available Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43 than fluoroquinolone-susceptible strains (49/70 (P = 0.0018. In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25; CC63 (2/20, and CC81 (1/19], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21, CC230 (5/20, CC62 (9/21, and CC180 (21/30]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11. Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance.

  15. Tolerance induction to cytoplasmic beta-galactosidase by hepatic AAV gene transfer: implications for antigen presentation and immunotoxicity.

    Directory of Open Access Journals (Sweden)

    Ashley T Martino

    2009-08-01

    Full Text Available Hepatic gene transfer, in particular using adeno-associated viral (AAV vectors, has been shown to induce immune tolerance to several protein antigens. This approach has been exploited in animal models of inherited protein deficiency for systemic delivery of therapeutic proteins. Adequate levels of transgene expression in hepatocytes induce a suppressive T cell response, thereby promoting immune tolerance. This study addresses the question of whether AAV gene transfer can induce tolerance to a cytoplasmic protein.AAV-2 vector-mediated hepatic gene transfer for expression of cytoplasmic beta-galactosidase (beta-gal was performed in immune competent mice, followed by a secondary beta-gal gene transfer with E1/E3-deleted adenoviral Ad-LacZ vector to provoke a severe immunotoxic response. Transgene expression from the AAV-2 vector in approximately 2% of hepatocytes almost completely protected from inflammatory T cell responses against beta-gal, eliminated antibody formation, and significantly reduced adenovirus-induced hepatotoxicity. Consequently, approximately 10% of hepatocytes continued to express beta-gal 45 days after secondary Ad-LacZ gene transfer, a time point when control mice had lost all Ad-LacZ derived expression. Suppression of inflammatory T cell infiltration in the liver and liver damage was linked to specific transgene expression and was not seen for secondary gene transfer with Ad-GFP. A combination of adoptive transfer studies and flow cytometric analyses demonstrated induction of Treg that actively suppressed CD8(+ T cell responses to beta-gal and that was amplified in liver and spleen upon secondary Ad-LacZ gene transfer.These data demonstrate that tolerance induction by hepatic AAV gene transfer does not require systemic delivery of the transgene product and that expression of a cytoplasmic neo-antigen in few hepatocytes can induce Treg and provide long-term suppression of inflammatory responses and immunotoxicity.

  16. Malaria chemotherapy.

    Science.gov (United States)

    Winstanley, Peter; Ward, Stephen

    2006-01-01

    Most malaria control strategies today depend on safe and effective drugs, as they have done for decades. But sensitivity to chloroquine, hitherto the workhorse of malaria chemotherapy, has rapidly declined throughout the tropics since the 1980s, and this drug is now useless in many high-transmission areas. New options for resource-constrained governments are few, and there is growing evidence that the burden from malaria has been increasing, as has malaria mortality in Africa. In this chapter, we have tried to outline the main pharmacological properties of current drugs, and their therapeutic uses and limitations. We have summarised the ways in which these drugs are employed, both in the formal health sector and in self-medication. We have briefly touched on the limitations of current drug development, but have tried to pick out a few promising drugs that are under development. Given that Plasmodium falciparum is the organism that kills, and that has developed multi-drug resistance, we have tended to focus upon it. Similarly, given that around 90% of global mortality from malaria occurs in Africa, there is the tendency to dwell on this continent. We give no apology for placing our emphasis upon the use of antimalarial drugs in endemic populations rather than their use for prophylaxis in travellers.

  17. Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a cancer and leukemia group B study

    International Nuclear Information System (INIS)

    Coleman, Morton; Rafla, Sameer; Propert, Kathleen J.; Glicksman, Arvin; Peterson, Bruce; Nissen, Nis; Brunner, Kurt; Holland, James F.; Anderson, James R.; Gottlieb, Arlan; Kaufman, Thomas

    1998-01-01

    Purpose: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. Patient and Methods: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. Results: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. Conclusion: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment

  18. Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

    International Nuclear Information System (INIS)

    Ishikawa, Masashi; Miyauchi, Takayuki; Kashiwagi, Yutaka

    2008-01-01

    A number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU) metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU. This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT) chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT) activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors. While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity. TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT

  19. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    International Nuclear Information System (INIS)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-01-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

  20. Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development

    Directory of Open Access Journals (Sweden)

    Sze-Wah Tse

    2011-08-01

    Full Text Available CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs, these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.

  1. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    International Nuclear Information System (INIS)

    Lorenzen, Sylvie; Debus, Jürgen; Jäger, Dirk; Münter, Marc W; Gall, Carl von; Stange, Annika; Haag, Georg M; Weitz, Jürgen; Haberkorn, Uwe; Lordick, Florian; Weichert, Wilko; Abel, Ulrich

    2011-01-01

    18-Fluorodeoxyglucose-PET ( 18 F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a < 35% decrease of SUV two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18 FDG-PET scans will be performed before (= Baseline) and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUV Baseline - SUV PET1 )/SUV Baseline

  2. Radio-chemotherapy in advanced tumors of the oral cavity, oro- and hypopharynx

    International Nuclear Information System (INIS)

    Schmitt, G.; Schnabel, T.

    1992-01-01

    Among combined radio-chemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radio-chemotherapy, 3. adjuvant chemotherapy, 4. accelerated-hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radio-chemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cis-platin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. (orig.) [de

  3. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    Science.gov (United States)

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer. Results of a randomized phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Takacsi-Nagy, Zoltan; Polgar, Csaba; Major, Tibor; Fodor, Janos [National Institute of Oncology, Center of Radiotherapy, Budapest (Hungary); Hitre, Erika [National Institute of Oncology, Department of Chemotherapy and Clinical Pharmacology, Budapest (Hungary); Remenar, Eva; Kasler, Miklos [National Institute of Oncology, Department of Head and Neck and Maxillofacial Surgery, Budapest (Hungary); Oberna, Ferenc [Bacs-Kiskun County Hospital, Department of Oral, Maxillofacial and Head and Neck Surgery, Kecskemet (Hungary); Goedeny, Maria [National Institute of Oncology, Department of Radiology, Budapest (Hungary)

    2015-08-15

    Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63 % following ICT + CRT, whereas 70 % after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %), and PFS (41 vs. 50 %) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12 %; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42 % in the ICT + CRT and CRT groups, respectively. The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of

  5. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG: The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2011-06-01

    Full Text Available Abstract Background 18-Fluorodeoxyglucose-PET (18F-FDG-PET can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. Methods/Design The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a 18FDG-PET scans will be performed before ( = Baseline and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1 and at the end of radiochemotherapy (PET2. Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV. The percentage difference ΔSUV = 100 (SUVBaseline - SUV PET1/SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference

  6. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1997-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients with unresectable disease; advanced larynx or hypopharynx cancer with the intent of larynx preservation, or advanced nasopharynx cancer. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Veterans Administration and EORTC larynx preservation studies. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  7. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1995-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients seeking to avoid potentially morbid surgical procedures or with unresectable disease. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Memorial Hospital experience with larynx preservation and the Veterans Administration larynx preservation study. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  8. Labor Induction

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ154 LABOR, DELIVERY, AND POSTPARTUM CARE Labor Induction • What is labor induction? • Why is labor induced? • What is the Bishop score? • What is “ripening ...

  9. Chemotherapy to Treat Cancer

    Science.gov (United States)

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  10. Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia.

    Science.gov (United States)

    Wang, Zhican; Lin, Yvonne S; Dickmann, Leslie J; Poulton, Emma-Jane; Eaton, David L; Lampe, Johanna W; Shen, Danny D; Davis, Connie L; Shuhart, Margaret C; Thummel, Kenneth E

    2013-05-01

    Long-term therapy with certain drugs, especially cytochrome P450 (P450; CYP)-inducing agents, confers an increased risk of osteomalacia that is attributed to vitamin D deficiency. Human CYP24A1, CYP3A4, and CYP27B1 catalyze the inactivation and activation of vitamin D and have been implicated in the adverse drug response. In this study, the inducibility of these enzymes and monohydroxylation of 25-hydroxyvitamin D3 (25OHD3) were evaluated after exposure to P450-inducing drugs. With human hepatocytes, treatment with phenobarbital, hyperforin, carbamazepine, and rifampin significantly increased the levels of CYP3A4, but not CYP24A1 or CYP27B1 mRNA. In addition, rifampin pretreatment resulted in an 8-fold increase in formation of the major metabolite of 25OHD3, 4β,25(OH)2D3. This inductive effect was blocked by the addition of 6',7'-dihydroxybergamottin, a selective CYP3A4 inhibitor. With human renal proximal tubular HK-2 cells, treatment with the same inducers did not alter CYP3A4, CYP24A1, or CYP27B1 expression. 24R,25(OH)2 D3 was the predominant monohydroxy metabolite produced from 25OHD3, but its formation was unaffected by the inducers. With healthy volunteers, the mean plasma concentration of 4β,25(OH)2D3 was increased 60% (p osteomalacia. Copyright © 2013 American Society for Bone and Mineral Research.

  11. Characteristics of users and implications for the use of complementary and alternative medicine in Ghanaian cancer patients undergoing radiotherapy and chemotherapy: a cross- sectional study

    Directory of Open Access Journals (Sweden)

    Yarney Joel

    2013-01-01

    Full Text Available Abstract Background There is widespread use of Complementary and Alternative Medicine (CAM in Ghana, driven by cultural consideration and paradigm to disease causation. Whether there is concurrent use of conventional medicine and CAM in cancer patients is unknown. This study investigates the prevalence, pattern and predictors of CAM use in cancer patients. Overlapping toxicity, sources of information, and whether users inform their doctor about CAM use is examined. Method Cross-sectional study using a questionnaire administered to cancer patients, who were receiving radiotherapy and or chemotherapy or had recently completed treatment at a single institution was used. Results Ninety eight patients participated in the study with a mean age of 55.5 (18–89, made up of 51% females. Married individuals formed 56% of the respondents, whilst 49% had either secondary or tertiary education. Head and neck cancer patients were 15.3%, breast (21.4%, abdomen/pelvic cancers constituted (52%.Seventy seven (78.6% patients received radiotherapy only, 16.3% received radiation and chemotherapy and 5.3% had chemotherapy only. Ninety five patients were diagnosed of cancer within the past 24 months,73.5% were CAM users as follows; massage(66.3%, herbal(59.2%, mega vitamins(55.1%, Chinese medicine(53.1%,and prayer(42.9%. Sixty eight percent were treated with curative intent. Overlapping toxicity was reported. Majority (83.3% of users had not informed their doctor about CAM use. On univariate analysis, female (p=0.004 and palliative patients, p=0.032 were more likely to be CAM users. Multivariate analysis identified female (p Friends and Media are the main sources of information on CAM. There was increase in CAM use after the diagnosis of cancer mainly for Chinese Medicine and vitamins. Conclusion There is high CAM usage among Cancer patients, comparable to use in the general population, there is concurrent use of CAM and conventional medicine with reported

  12. Induction linacs

    International Nuclear Information System (INIS)

    Keefe, D.

    1986-07-01

    The principle of linear induction acceleration is described, and examples are given of practical configurations for induction linacs. These examples include the Advanced Technology Accelerator, Long Pulse Induction Linac, Radial Line Accelerator (RADLAC), and Magnetically-Insulated Electron-Focussed Ion Linac. A related concept, the auto accelerator, is described in which the high-current electron-beam technology in the sub-10 MeV region is exploited to produce electron beams at energies perhaps as high as the 100 to 1000 MeV range. Induction linacs for ions are also discussed. The efficiency of induction linear acceleration is analyzed

  13. Inductive reasoning 2.0.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan

    2018-05-01

    Inductive reasoning entails using existing knowledge to make predictions about novel cases. The first part of this review summarizes key inductive phenomena and critically evaluates theories of induction. We highlight recent theoretical advances, with a special emphasis on the structured statistical approach, the importance of sampling assumptions in Bayesian models, and connectionist modeling. A number of new research directions in this field are identified including comparisons of inductive and deductive reasoning, the identification of common core processes in induction and memory tasks and induction involving category uncertainty. The implications of induction research for areas as diverse as complex decision-making and fear generalization are discussed. This article is categorized under: Psychology > Reasoning and Decision Making Psychology > Learning. © 2017 Wiley Periodicals, Inc.

  14. Anticancer Activity of Linalool Terpenoid: Apoptosis Induction and ...

    African Journals Online (AJOL)

    Induction and Cell Cycle Arrest in Prostate Cancer Cells. Xiu-Bin Sun1,2, ... Keywords: Prostate cancer, Linalool, Chemotherapy, Cell cycle, Apoptosis, DNA fragmentation, Sub-. G1 phase ..... receptors, regulate expression of various genes.

  15. Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

    International Nuclear Information System (INIS)

    Savva-Bordalo, Joana; Henrique, Rui; Jerónimo, Carmen; Ramalho-Carvalho, João; Pinheiro, Manuela; Costa, Vera L; Rodrigues, Ângelo; Dias, Paula C; Veiga, Isabel; Machado, Manuela; Teixeira, Manuel R

    2010-01-01

    Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity

  16. Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

    Directory of Open Access Journals (Sweden)

    Savva-Bordalo Joana

    2010-09-01

    Full Text Available Abstract Background Severe toxicity to 5-fluorouracil (5-FU based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD. Methods In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Results Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A, and one case carrying the 1845 G > T missense mutation (c.1845G > T in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Conclusions Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.

  17. Inductive reasoning.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan; Swendsen, Haruka

    2010-03-01

    Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category-based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge-based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  18. Patterns of failure following high-dose chemotherapy and stem cell rescue for relapsed/refractory non-Hodgkin's lymphoma: implications for the use of adjuvant involved field radiotherapy

    International Nuclear Information System (INIS)

    Mundt, Arno J.; Williams, Stephanie F.; Hallahan, Dennis; Weichselbaum, Ralph R.

    1996-01-01

    Purpose: Recent data have suggested a benefit to involved-field radiotherapy (IFRT) in conjunction with high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) in patients with metastatic breast cancer, advanced neuroblastoma and relapsed/refractory Hodgkin's disease. The purpose of this study is to determine whether a similar role exists for IFRT in patients with relapsed/refractory Non-Hodgkin's Lymphoma (NHL) undergoing HDCT. Methods/Materials: Forty-nine adult patients with refractory (17) or relapsed (32) NHL underwent HDCT with SCR between 9/90 and 9/95. The most common histology was diffuse large cell (42.8%). Initial stages were I (3), II (23), III (5) and IV (18). All patients had a history of conventional chemotherapy (median regimens 2, range 1-3), 17 (34.7%) had previous RT. Treatment consisted of conventional dose induction chemotherapy followed by high-dose intensification with cytoxan, busulfan and either ara-C or VP-16. Seven patients (14.3%) received IFRT (median dose 34.5 Gy, range 20-45 Gy) to eleven sites of persistent disease following HDCT (HDCT+IFRT). Patients treated with RT to sites of progressive disease following HDCT (salvage RT) were not included in the HDCT+IFRT group. No patient received total body irradiation (TBI). One hundred sixty four sites were identified. Sites were designated as amenable or not to IFRT and divided into those achieving a complete response to induction (IndCR) and those which did not (non-IndCR). An amenable site is defined as disease localized to either an organ or nodal chain and encompassable within a standard RT portal. Relapse sites were designated as in previous (involved) sites (present prior to HDCT) or in new (uninvolved) sites. Median followup was 19.7 months (range, 1-57.3 months). Results: The 4-year actuarial progression-free (PFS), cause-specific (CSS) and overall (OS) survivals of the entire group were 36.4%, 45.9% and 34.9%, respectively. Excluding toxic deaths, 20 (47.6%) patients

  19. Whole-body vibration as a modality for the rehabilitation of peripheral neuropathies: implications for cancer survivors suffering from chemotherapy-induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Anna L.J. Verhulst

    2015-02-01

    Full Text Available The objective was to study the effect of whole-body vibration (WBV on strength, balance and pain in patients with peripheral neuropathies and to consider its significance for the rehabilitation of patients suffering from chemotherapy-induced peripheral neuropathy (CIPN. Using a broad search strategy, PubMed was searched for clinical trials on WBV interventions aimed at improving strength, balance or pain in patients with peripheral neuropathies, which were published in English until 5th June 2014. The search was performed by the first author and generated a total of 505 results, which yielded 5 articles that met the inclusion criteria, being studies: i published in English; ii involving adult human subjects’ peripheral neuropathies; iii evaluating the effect of WBV as a therapeutic intervention; and iv reporting findings for at least one of the following outcomes: strength, balance or pain. Methodological quality of included studies was assessed independently by first and second author, using the physiotherapy evidence database scale. The overall methodological quality of included studies was low. Two studies found a beneficial effect of WBV on neuropathic pain, but another study failed to find the same effect. One study found significant improvements in both muscle strength and balance, while another study found improvements only in some, but not all, of the applied tests to measure muscle strength and balance. The results of this literature search suggest insufficient evidence to assess the effectiveness for the effects of WBV on neuropathic pain, muscle strength and balance in patients with peripheral neuropathies. More high-quality trials are needed to guide the optimization of rehabilitation programs for cancer survivors with CIPN in particular.

  20. Adult population as potential reservoir of NTD infections in rural villages of Kwale district, Coastal Kenya: implications for preventive chemotherapy interventions policy.

    Science.gov (United States)

    Njenga, Sammy M; Mwandawiro, Charles S; Muniu, Erastus; Mwanje, Mariam T; Haji, Fatma M; Bockarie, Moses J

    2011-09-14

    Neglected tropical diseases (NTDs) are major public health problems in developing countries where they contribute to suffering of populations living in poor settings. As part of a research project started in September 2009 in Kwale district, Coast Region, Kenya, a baseline cross-sectional survey was conducted in 5 rural villages to provide information on the status of NTDs, including urinary schistosomiasis, soil-transmitted helminthiasis (STH), and lymphatic filariasis. This paper presents the results of a parasitological investigation among adults in the study villages. A total of 599 adults in the 5 study villages were tested for NTD infections in urine, stool and blood. The presence of Schistosoma haematobium infection was determined by the urine filtration method. The presence of STH in stool was determined by Kato-Katz method while filarial antigenaemia was determined using immunochromatographic (ICT) test. The study revealed high prevalence of hookworm (41.7%) and schistosomiasis (18.2%) infections among adults in the study villages. Of the 599 individuals examined, 50.1% had one or more helminthic infections. There was low level of polyparasitism with helminthic NTDs in the study population with 9.5% and 1.7% of the participants having two and three infections, respectively. In the current study, hookworm and schistosomiasis infections were identified as important infections among adults living in areas of high endemicity for these infections. Thus, if this section of the population is left untreated it may remain an important potential reservoir and a source of re-infection for school-age children treated in school deworming programmes. Therefore, there is a need to design novel strategies for preventive chemotherapy interventions that could allow inclusion of adults in an effort to reduce force of infection in high endemic communities.

  1. Teacher induction

    NARCIS (Netherlands)

    Beijaard, D.; Buitink, J.; Kessels, C.; Peterson, P.; Baker, E.; McGraw, B.

    2010-01-01

    Teacher induction programs are intended to support the professional development of beginning teachers and thereby contribute to the reduction of teacher attrition during the early teaching years. Teacher induction programs are often based upon a deficit model with a focus on the better organization

  2. Chemotherapy disruption of efficient radiotherapy

    International Nuclear Information System (INIS)

    Nervi, C.; Friedman, M.

    1974-01-01

    Studies on the use of chemotherapy in combination with radiotherapy are reviewed. Some topics discussed are: indications for the use of combined chemotherapy and radiotherapy; improvement of the therapeutic ratio following the use of methotrexate; advantages of preirradiation and postirradiation chemotherapy; side effects following simultaneous chemotherapy and radiotherapy; and effects of chemotherapy on cure rate of radiosensitive and radioresistant tumors. (U.S.)

  3. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Hilbe

    Full Text Available Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2 and docetaxel (75 mg/m2 d1 q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly. The primary endpoint was radiological response according to RECIST.40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95% underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

  4. Platelet-derived growth factor (PDGF-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

    Directory of Open Access Journals (Sweden)

    Bethel-Brown Crystal

    2012-12-01

    Full Text Available Abstract Chemokine (C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1 is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND. The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS via the disrupted blood-brain barrier (BBB. We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK1/2, c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein (MAP kinases and phosphatidylinositol 3-kinase (PI3K/Akt pathways and the downstream transcription factor, nuclear factor κB (NFκB. Chromatin immunoprecipitation (ChIP assays demonstrated increased binding of NFκB to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs, an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R blocker. PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte

  5. Postoperative Chemotherapy for Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-03-01

    Full Text Available The survival rate and cognitive function of 43 children, age <3 years, with medulloblastoma treated with intensive postoperative chemotherapy alone, without radiotherapy, were determined at the University of Wurzburg and other centers in Germany Chemotherapy consisted of three two-month cycles of cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide.

  6. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

    Science.gov (United States)

    Huddart, Robert A; Gabe, Rhian; Cafferty, Fay H; Pollock, Philip; White, Jeff D; Shamash, Jonathan; Cullen, Michael H; Stenning, Sally P

    2015-03-01

    Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU). Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data

  7. Practicing induction:

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Rohde, Nicolas

    2009-01-01

    We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning.......We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning....

  8. 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.

  9. Coping strategies used by hospitalized children with cancer undergoing chemotherapy.

    Science.gov (United States)

    Sposito, Amanda Mota Pacciulio; Silva-Rodrigues, Fernanda Machado; Sparapani, Valéria de Cássia; Pfeifer, Luzia Iara; de Lima, Regina Aparecida Garcia; Nascimento, Lucila Castanheira

    2015-03-01

    To analyze coping strategies used by children with cancer undergoing chemotherapy during hospitalization. This was an exploratory study to analyze qualitative data using an inductive thematic analysis. Semistructured interviews using puppets were conducted with 10 children with cancer, between 7 and 12 years old, who were hospitalized and undergoing chemotherapy. The coping strategies to deal with chemotherapy were: understanding the need for chemotherapy; finding relief for the chemotherapy's side effects and pain; seeking pleasure in nourishment; engaging in entertaining activities and having fun; keeping the hope of cure alive; and finding support in religion. Children with cancer undergoing chemotherapy need to cope with hospitalizations, pain, medication side effects, idle time, and uncertainty regarding the success of treatment. These challenges motivated children to develop their own coping strategies, which were effective while undergoing chemotherapy. By gaining knowledge and further understanding about valid coping strategies during chemotherapy treatment, health professionals can mobilize personal and material resources from the children, health teams, and institutions aiming to potentiate the use of these strategies to make treatments the least traumatic. © 2015 Sigma Theta Tau International.

  10. Chemotherapy in eye cancer

    African Journals Online (AJOL)

    is a drug used in a wide range of cancers, which produces ... lesions. In a 10-year retrospective review of .... disease and focal chemotherapy for selected high-risk ... of focal drug delivery methods to reduce recurrence .... the protein tubulin.

  11. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.

  12. Lost at Sea: Summary Results of a Meta-Analysis of the Efficacy of Teacher Induction and Implications for Administrative Practice

    Science.gov (United States)

    Shockley, Robert; Watlington, Eliah; Felsher, Rivka

    2011-01-01

    This paper summarizes a qualitative meta-analysis of the empirical research on the effectiveness of teacher induction programs over the last decade for the purpose of identifying the essential elements that make them effective in reducing teacher attrition. The study used Herzberg's two-factor theory of motivation as the theoretical framework for…

  13. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

    Full Text Available Platinum-based chemotherapy is commonly used for the treatment of locally advanced and metastatic bladder cancer. However, there are currently no methods to predict chemotherapy response in this disease setting. A better understanding of the biology of bladder cancer has led to developments of molecular biomarkers that may help guide clinical decision making. These biomarkers, while promising, have not yet been validated in prospective trials and are not ready for clinical applications. As alkylating agents, platinum drugs kill cancer cells mainly through induction of DNA damage. A microdosing approach is currently being tested to determine if chemoresistance can be identified by measuring platinum-induced DNA damage using highly sensitive accelerator mass spectrometry technology. The hope is that these emerging strategies will help pave the road towards personalized therapy in advanced bladder cancer.

  14. Induction practice -

    DEFF Research Database (Denmark)

    Rohde, Nicolas; Sprogøe, Jonas

    2007-01-01

    that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and the organization, what we call agenerative dance, ignites both kinds of learning. We focus on and describe the interplay , ignites both kinds...

  15. Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia.

    Science.gov (United States)

    Chamberlain, Marc C; Raizer, Jeffrey

    2009-06-01

    A case series of gliomas treated with alkylator-based chemotherapy who subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic leukemia (AML). Alkylator-based chemotherapy is recognized to be leukemogenic; however, it is infrequently described as a delayed consequence of anti-glioma treatment. Seven patients (4 men; 3 women) ages 34-69 years (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all but one with involved-field radiotherapy and all with alkylator-based chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5 patients). Exposure to alkylator-based chemotherapy ranged from 8 to 30 months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in 7 patients. Seven patients showed chromosomal abnormalities consistent with chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two determined by bone marrow and one at autopsy). Interval from last chemotherapy exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months). Two patients were treated with bone marrow transplantation and 5 received supportive care only. Five patients have died, 2 as a consequence of recurrent brain tumor, 1 as a complication of transplantation, and 2 due to AML. Although rare, induction of tMDS/AML following extended use of alkylator-based chemotherapy may become more relevant with the evolving practice to treat gliomas for protracted periods. Future work to determine at risk patients would be important.

  16. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    , or if the hottest area is located outside the joint interface, a number of defects may appear: the braze metal may flow away from the joint, the flux may burn off, poor binding of the braze metal may appear or the braze metal may be overheated. Joint geometry as well as electro-magnetic properties of the work piece...... presents a combined numerical and experimental method for determination of appropriate/optimiged coil geometry and position in induction brazing tube-to-plate joints of different ratios between tube and plate thickness and different combinations of the materials stainless steel, brass and copper....... The method has proven to give successful results in brazing tube-plate joints of copper-brass, copper-stainless steel, stainless steel-brass, and stainless steel-stainless steel. A new design of an adjustable flux concentrator for induction heating tube-to-plate joints is proposed and tested on a variety...

  17. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  18. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  19. Chemotherapy in thyroid carcinoma

    International Nuclear Information System (INIS)

    Samuel, A.M.; Shah, D.H.

    1999-01-01

    Chemotherapy alone, either as a single drug or a combination of drugs with or without external radiation (ER) is useful for treatment of locally advanced disease and non iodine concentrating metastasis in differentiated thyroid cancers (DTC). The reported response is not encouraging, but the absence of better alternatives leave no choice for the treatment of such cases. However, for treatment of anaplastic thyroid cancers (ANC), chemotherapy (CT) in combination with ER results in local control. In medullary thyroid cancers (MTC), the results obtained with multimodal treatment are encouraging

  20. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...... to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane....

  1. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  2. Chemotherapy-induced hypocalcemia.

    Science.gov (United States)

    Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

    2010-01-01

    To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

  3. After chemotherapy - discharge

    Science.gov (United States)

    You had chemotherapy treatment for your cancer. Your risk of infection, bleeding, and skin problems may be high. You may have mouth sores, an upset stomach, and diarrhea. You will probably get tired easily. Your appetite may be poor, but you should be able ...

  4. Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Shueng, Pei-Wei; Hsieh, Chen-Hsi; Shen, Bing-Jie; Wu, Le-Jung; Liao, Li-Jen; Hsiao, Chi-Huang; Lin, Yu-Chin; Cheng, Po-Wen; Lo, Wu-Chia; Jen, Yee-Min

    2011-01-01

    To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC). Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction. After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively. HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings

  5. Nail toxicity induced by cancer chemotherapy.

    Science.gov (United States)

    Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

    2009-09-01

    To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

  6. DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy

    International Nuclear Information System (INIS)

    Grishina, Olga; Schmoor, Claudia; Döhner, Konstanze; Hackanson, Björn; Lubrich, Beate; May, Annette M.; Cieslik, Caroline; Müller, Michael J.; Lübbert, Michael

    2015-01-01

    Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of decitabine (DAC) in the European Union (EU) in 2012 for the treatment of patients with AML ≥65 years marks the potential for hypomethylating agents in elderly AML. Nevertheless the situation is dissatisfactory and the quest for novel treatment approaches, including combination epigenetic therapy is actively ongoing. The given randomized trial should be helpful in investigating the question whether combinations of DAC with the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and/or all-trans retinoic acid (ATRA), which in vitro show a very promising synergism, are superior to the DAC monotherapy. The accompanying translational research project will contribute to find surrogate molecular end points for drug efficacy and better tailor epigenetic therapy. An additional aim of the study is to investigate the prognostic value of geriatric assessments for elderly AML patients treated non-intensively. DECIDER is a prospective, randomized, observer blind, parallel group, multicenter, Phase II study with a 2x2 factorial design. The primary endpoint is objective best overall response (complete remission (CR) and partial remission (PR)). The target population is AML patients aged 60 years or older and unfit for standard induction chemotherapy. Patients are randomized to one of the four treatment groups: DAC alone or in combination with VPA or ATRA or with both add-on drugs. One interim safety analysis was planned and carried out with the objective to stop early one or more of the treatment arms in case of an unacceptable death rate. This analysis showed that in all treatment arms the critical stopping rule was not reached. No important safety issues were observed. The Data Monitoring Committee (DMC) recommended continuing the study as planned. The first patient was included in December 2011. A total of 189 out of 200 planned patients were randomized

  7. Liposome-encapsulated chemotherapy

    DEFF Research Database (Denmark)

    Børresen, B.; Hansen, A. E.; Kjær, A.

    2018-01-01

    Cytotoxic drugs encapsulated into liposomes were originally designed to increase the anticancer response, while minimizing off-target adverse effects. The first liposomal chemotherapeutic drug was approved for use in humans more than 20years ago, and the first publication regarding its use...... to inherent issues with the enhanced permeability and retention effect, the tumour phenomenon which liposomal drugs exploit. This effect seems very heterogeneously distributed in the tumour. Also, it is potentially not as ubiquitously occurring as once thought, and it may prove important to select patients...... not resolve the other challenges that liposomal chemotherapy faces, and more work still needs to be done to determine which veterinary patients may benefit the most from liposomal chemotherapy....

  8. Combined radiotherapy-chemotherapy

    International Nuclear Information System (INIS)

    Steel, G.G.

    1989-01-01

    This paper presents the clinically confirmed benefits of combined chemotherapy-radiotherapy. They have been found in a small group of diseases that respond to chemotherapy alone. According to the author, only when a drug or drug combination has the ability to eradicate occult disease or substantially to reduce the size of objectively measurable disease is there likely to be an demonstrable benefit from its use in conjunction with radiotherapy. It is the author's belief that the immediate future lies in selecting drugs and patients in which a good chemotherapeutic response can be expected, avoiding drugs that seriously enhance radiation damage to normal tissues and keeping drug and radiation treatments far enough apart in time to minimize interactions

  9. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    2011-10-24

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.  Created: 10/24/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 10/24/2011.

  10. Full dose CHOP chemotherapy

    International Nuclear Information System (INIS)

    Tominaga, Shinichi; Kondo, Makoto; Ando, Yutaka; Yamashita, Shoji; Uematsu, Minoru; Shigematsu, Naoyuki; Nishiguchi, Iku; Hashimoto, Shozo

    1985-01-01

    Since 1982, we have performed 125 courses of CHOP chemotherapy for 27 patients of malignancy, adhering to the original regimen as strictly as possible. CHOP chemotherapy consisted of Cyclophosphamide 750 mg/m 2 , iv, on day 1; Adriamycin 50 mg/m 2 , iv, on day 1; Vincristine 1.4 mg/m 2 , iv, on day 1 (maximum single dose 2.0 mg) and Prednisolone 50 mg/m 2 , po, day 1 through 5. The cycle was repeated every 21 days. As side effects, myelosuppression, hair loss, fever, nausea, vomiting, liver dysfunction, stomatitis, neuropathy, herpes zoster, arrhythmia and hemorrhagic cystitis were seen. Due to myelosuppression, twenty patients experienced febrile episodes at each nadir of WBC counts on 40 courses. However, any febrile patient did not have life threatening infection. Other side effects were also reversible. The radiotherapy of most patients was carried out as initially scheduled, except for 3 patients in whom irradiation was interrupted due to severe stomatitis or herpes zoster. We consider that CHOP chemotherapy is excellent in feasibility even when combined with radiotherapy. (author)

  11. Concurrent radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Fu, K.K.

    1985-01-01

    The principal objective of combining chemotherapy with radiotherapy (XRT) for the treatment of advanced head and neck cancer is to improve the therapeutic ratio through the enhancement of local control and reduction of distant metastases without excessively enhancing normal tissue effects. Improved tumour control can result from sole additivity of either therapy or direct interactions between drug and radiation leading to increased tumour cell kill. Chemotherapy may sensitize the cells to radiation, interfere with repair of sublethal or potentially lethal radiation damage, induce cell synchrony, and reduce tumour mass leading to reoxygenation and decreased fraction of resistant hypoxic cells. Radiation may improve drug accessibility to tumour cells and reduce tumour volume leading to increased cell proliferation and chemosensitivity. If the enhanced effects of combined therapy are purely additive, then the two modalities can be administered either sequentially or concurrently with the same results. However, if the enhanced effects result from the direct interaction between drug and radiation, it is necessary that the two modalities be administered concurrently and in close temporal proximity. This review summarizes the results of clinical studies in which chemotherapy was administered concurrently during the course of radiotherapy for patients with previously untreated advanced squamous cell carcinoma in the head and neck

  12. Induction and persistence of chromosome aberrations in human lymphocytes exposed to neutrons in vitro or in vivo: Implications of findings in 'retrospective' biological dosimetry

    International Nuclear Information System (INIS)

    Littlefield, L.G.; McFee, A.F.; Sayer, A.M.; O'Neill, J.P.; Kleinerman, R.A.; Maor, M.H.

    2000-01-01

    The induction and persistence were evaluated of chromosome aberrations in lymphocytes exposed in vitro to highly efficient 1 MeV monoenergetic neutrons and in patients who received fast neutrons as therapy for tumours. For the in vitro studies, lymphocytes were exposed to various doses of neutrons and cultured for one or 20 cell cycles. Aberrations were quantified in painted chromosome pairs 1, 2 or 4. These 1 MeV neutrons were highly efficient in inducing aberrations, and dicentrics as well as one-way and two-way translocations increased as a linear function of dose. About 30% of the aberrant metaphases displayed complex aberrations. After multiple in vitro cell divisions, virtually all asymmetrical aberrations had been eliminated from the cell population, and the frequency of one-way translocations was reduced dramatically. In contrast, most two-way translocations apparently survived through multiple cell divisions and still displayed excellent correlation with dose after 20 cell cycles. Classical methods were used to evaluate persistence of aberrations in patients who received fractionated neutron therapy to tumours located in many different sites. Neutron induced dicentrics and rings disappeared from the peripheral circulation within the first three years after exposure, while translocations persisted for more than 17 y. However, considerable variability in numbers of aberrations were observed between patients who had received similar 'average bone marrow doses'. Results of these studies are discussed in relation to the possible use of translocations as retrospective dosemeters in persons exposed to radiation many years ago. (author)

  13. Sequential response patterns to chemotherapy and radiotherapy in head and neck cancer

    International Nuclear Information System (INIS)

    Hong, W.K.; O'Donoghue, G.M.; Sheetz, S.

    1985-01-01

    Surgery and/or radiotherapy have been the standard therapies for locally advanced squamous cell carcinoma of the head and neck region. Despite major improvement in these therapeutic techniques, the control rate in cases of advanced cancer remains poor. More recently, induction chemotherapy as initial treatment has been used in previously untreated squamous cell carcinoma of the head and neck. For the last 6 years at the Boston Veterans Administration (V.A.) Medical Center, initial induction chemotherapy followed by surgery and/or radiotherapy has been employed in the treatment of advanced head and neck cancer. The use of chemotherapy and radiotherapy has allowed the authors to monitor and correlate sequential response patterns produced by each modality of treatment. The authors have observed that responders to chemotherapy can be predicted to have further response to subsequent radiotherapy

  14. Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease

    International Nuclear Information System (INIS)

    Arriagada, R.; Le Chevalier, T.; Baldeyrou, P.

    1985-01-01

    Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85%. Local control at 2 years was 61% in the first study and 82% in the second. Acute and delayed toxicity effects are discussed

  15. Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

    Science.gov (United States)

    Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

    2018-01-15

    Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Stochastic Inversion of Geomagnetic Observatory Data Including Rigorous Treatment of the Ocean Induction Effect With Implications for Transition Zone Water Content and Thermal Structure

    Science.gov (United States)

    Munch, F. D.; Grayver, A. V.; Kuvshinov, A.; Khan, A.

    2018-01-01

    In this paper we estimate and invert local electromagnetic (EM) sounding data for 1-D conductivity profiles in the presence of nonuniform oceans and continents to most rigorously account for the ocean induction effect that is known to strongly influence coastal observatories. We consider a new set of high-quality time series of geomagnetic observatory data, including hitherto unused data from island observatories installed over the last decade. The EM sounding data are inverted in the period range 3-85 days using stochastic optimization and model exploration techniques to provide estimates of model range and uncertainty. The inverted conductivity profiles are best constrained in the depth range 400-1,400 km and reveal significant lateral variations between 400 km and 1,000 km depth. To interpret the inverted conductivity anomalies in terms of water content and temperature, we combine laboratory-measured electrical conductivity of mantle minerals with phase equilibrium computations. Based on this procedure, relatively low temperatures (1200-1350°C) are observed in the transition zone (TZ) underneath stations located in Southern Australia, Southern Europe, Northern Africa, and North America. In contrast, higher temperatures (1400-1500°C) are inferred beneath observatories on islands, Northeast Asia, and central Australia. TZ water content beneath European and African stations is ˜0.05-0.1 wt %, whereas higher water contents (˜0.5-1 wt %) are inferred underneath North America, Asia, and Southern Australia. Comparison of the inverted water contents with laboratory-constrained water storage capacities suggests the presence of melt in or around the TZ underneath four geomagnetic observatories in North America and Northeast Asia.

  17. High Precision Seawater Sr/Ca Measurements in the Florida Keys by Inductively Coupled Plasma Atomic Emission Spectrometry: Analytical Method and Implications for Coral Paleothermometry

    Science.gov (United States)

    Khare, A.; Kilbourne, K. H.; Schijf, J.

    2017-12-01

    Standard methods of reconstructing past sea surface temperatures (SSTs) with coral skeletal Sr/Ca ratios assume the seawater Sr/Ca ratio is constant. However, there is little data to support this assumption, in part because analytical techniques capable of determining seawater Sr/Ca with sufficient accuracy and precision are expensive and time consuming. We demonstrate a method to measure seawater Sr/Ca using inductively coupled plasma atomic emission spectrometry where we employ an intensity ratio calibration routine that reduces the self- matrix effects of calcium and cancels out the matrix effects that are common to both calcium and strontium. A seawater standard solution cross-calibrated with multiple instruments is used to correct for long-term instrument drift and any remnant matrix effects. The resulting method produces accurate seawater Sr/Ca determinations rapidly, inexpensively, and with a precision better than 0.2%. This method will make it easier for coral paleoclimatologists to quantify potentially problematic fluctuations in seawater Sr/Ca at their study locations. We apply our method to test for variability in surface seawater Sr/Ca along the Florida Keys Reef Tract. We are collecting winter and summer samples for two years in a grid with eleven nearshore to offshore transects across the reef, as well as continuous samples collected by osmotic pumps at four locations adjacent to our grid. Our initial analysis of the grid samples indicates a trend of decreasing Sr/Ca values offshore potentially due to a decreasing groundwater influence. The values differ by as much as 0.05 mmol/mol which could lead to an error of 1°C in mean SST reconstructions. Future work involves continued sampling in the Florida Keys to test for seasonal and interannual variability in seawater Sr/Ca, as well as collecting data from small reefs in the Virgin Islands to test the stability of seawater Sr/Ca under different geologic, hydrologic and hydrographic environments.

  18. Differential induction of apoptosis and autophagy by pyrrolizidine alkaloid clivorine in human hepatoma Huh-7.5 cells and its toxic implication

    Science.gov (United States)

    Fang, Shoucai; Ho, Wenzhe; Chen, Hui; Liang, Hao; Ye, Li; Tang, Jun

    2017-01-01

    Growing evidence suggests that the pyrrolizidine alkaloids (PAs)-induced hepatotoxicity is mediated by multiple cell death/defence modalities. However, the detailed mechanisms are still lacking. In this study, the hepatotoxic effects of four PAs including three retronecine-type ones (senecionine, seneciphylline and monocrotaline) and one otonecine-type (clivorine) on the proliferation of Huh-7.5 cells and the possible mechanisms were investigated. The results showed that all the PAs could inhibit cell proliferation and induce apoptosis in a concentration-dependent manner. Among them clivorine was the most significant one. In addition to its effect on apoptosis, clivorine treatment could promote autophagy in Huh-7.5 cells, as evidenced by the accumulation of autophagosomes, the enhancement of LC3B expression at the concentrations close to its IC0 value, and the increased conversion of LC3B-I to LC3B-II in the presence of lysosomal inhibitor (chloroquine) and decreased formation of green fluorescent protein (GFP)-LC3 positive puncta in the presence of autophagic sequestration inhibitor (3-methyladenine). Among the other tested PAs, senecionine and seneciphylline also activated autophagy at the same concentrations used for clivorine but monocrotaline did not. Furthermore, our study demonstrated that suppression or enhancement of autophagy resulted in the remarkable enhancement or suppression of senecionine, seneciphylline and clivorine-induced apoptosis at the concentration close to the IC10 for clivorine, respectively, indicating a protective role of autophagy against the PA-induced apoptosis at the low level of exposure. Collectively, our data suggest that PAs in different structures may exert different toxic disturbances on the liver cells. Apoptosis may be one of the most common models of the PA-induced cytotoxicity, while autophagy may be a structure-dependent defence model in the early stage of PA intoxication. Differential induction of apoptosis and autophagy

  19. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  20. Adjuvant chemotherapy for osteosarcoma.

    Science.gov (United States)

    Eilber, F R; Rosen, G

    1989-08-01

    From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at

  1. MVP Chemotherapy and Hyperfractionated Radiotherapy for Stage III Unresectable Non-Small Cell Lung Cancer - Randomized for maintenance Chemotherapy vs. Observation; Preliminary Report-

    International Nuclear Information System (INIS)

    Choi, Euk Kyung; Chang, Hye Sook; Suh, Cheol Won

    1991-01-01

    To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991. Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGY following 3 cycles of induction MVP (Mitomycin C 6 mg/m 2 , vinblastine 6 mg/m 2 , Cisplatin 60 mg/m 2 ) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 16 were analyzed for this preliminary report. The response rate of induction chemotherapy was 62.5%; partial response, 50% and minimal response, 12.5%. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue

  2. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML.

    Science.gov (United States)

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C

    2016-02-18

    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. © 2016 by The American Society of Hematology.

  3. Physical exercise during adjuvant chemotherapy

    NARCIS (Netherlands)

    van Waart, H.

    2017-01-01

    This thesis evaluates the effect of physical exercise during chemotherapy. In chapter two the study design, rationale and methods of the Physical exercise during Adjuvant Chemotherapy Study (PACES) are described. Chapter three presents the effects of the randomized controlled trial evaluating a

  4. Chromonychia Secondary to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Marien Lopes

    2013-06-01

    Full Text Available Chemotherapy drugs can affect the skin and its appendages. Several clinical presentations can be observed, depending on the affected structure. The most common dermatological side effect is chromonychia. The main causative agents are: (1 cyclophosphamide, which can provoke a diffuse, black pigmentation, longitudinal striae and dark grey pigmentation located proximally on the nails; (2 doxorubicin, which promotes dark brown bands alternating with white striae and dark brown pigmentation in transverse bands, and (3 hydroxyurea, which produces a distal, diffuse, dark brown pigmentation. In the majority of cases, the effects are reversible after the suspension of the causative agent for a few months. We report a patient who developed chromonychia while undergoing treatment with cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine for acute lymphocytic leukemia.

  5. Butyrate down regulates BCL-XL and sensitizes human fibroblasts to radiation and chemotherapy induced apoptosis

    International Nuclear Information System (INIS)

    Chung, Diana H.; Ljungman, Mats; Zhang Fenfen; Chen Feng; McLaughlin, William P.

    1997-01-01

    Purpose/Objective: Butyrate is a short chain fatty acid that has been implicated in the induction of cell cycle arrest, cell differentiation and apoptosis. The purpose of this study was to determine if butyrate treatment sensitizes cells to radiation or chemotherapy induced apoptosis. Materials and Methods: Normal neonatal human diploid fibroblasts were used throughout this study. Apoptosis was scored and quantified using three different methods. First, cell morphology using propidium iodide and fluorescence microscopy was used to qualitatively determine apoptosis and to quantify the percentage of cells undergoing apoptosis. Second, apoptosis induced DNA degradation was scored by quantifying the amount of cells appearing in a sub-G1 peak using fixed and PI-stained cells and flow cytometry. Third, apoptosis-induced DNA degradation was examined by using an assay involving direct lysis of cells in the wells of agarose gels followed by conventional gel electrophoresis. Western blotting was used to quantify the cellular levels of the apoptosis regulators, Bcl-2, Bcl-XL and Bax. Results: Human diploid fibroblasts, which were resistant to radiation induced apoptosis, were found to undergo massive apoptosis when radiation was combined with butyrate treatment. Sensitization was obtained when butyrate was added before or after radiation although the combination of both pre and post-treatment was the most effective. Butyrate was also found to enhance UV light and cisplatin-induced apoptosis. These findings correlated with a reduction of the apoptosis antagonist Bcl-XL. Bcl-XL levels significantly dropped in a time and dose dependent manner. In addition, butyrate effectively blocked UV-induced accumulation of p53. Conclusion: Our results suggest that butyrate may be an attractive agent to use in combination with radiation or chemotherapy to lower the apoptotic threshold of tumor cells, regardless of the p53 status of the tumor cells

  6. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Sanambar Sadighi

    2015-06-01

    Full Text Available To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years. Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%. No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014. Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

  7. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  8. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... with Your Treatment Team Treatment Surgery Surgical Staging Pathology of Ovarian Cancer Chemotherapy Radiation Therapy Hormone Therapy ... 20, 2016 January 17, 2017 February 21, 2017 March 22, 2017 April 18, 2017 May 16, 2017 ...

  9. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  10. Inductive Reasoning and Writing

    Science.gov (United States)

    Rooks, Clay; Boyd, Robert

    2003-01-01

    Induction, properly understood, is not merely a game, nor is it a gimmick, nor is it an artificial way of explaining an element of reasoning. Proper understanding of inductive reasoning--and the various types of reasoning that the authors term inductive--enables the student to evaluate critically other people's writing and enhances the composition…

  11. Twice-a-day fractionated radiotherapy with chemotherapy for advanced laryngeal cancer

    International Nuclear Information System (INIS)

    Karasawa, Kumiko; Okawa, Tomohiko

    1998-01-01

    Twenty-five patients with advanced laryngeal cancer were treated with twice-a-day fractionated radiotherapy (TDFR) to a total dose of 65 Gy to 82 Gy combined with chemotherapy of CDDP and 5-FU between 1994 and 1997. Twenty-two cases (88%) became complete response and 9 cases recurred. The relapse-free rate at 2 years was 49.8%. The laryngeal conserving rate at 2 years was 71.0%, the actuarial 2-year survival rate was 89.9%. In induction chemotherapy (12 cases) no severe toxicity has been observed. In TDFR with concurrent chemotherapy (22 cases), grade 3 hematological toxicity was observed in 4 cases and grade 4 mucosal toxicity in 16 cases. Based on this investigation, it is concluded that TDFR with chemotherapy is a promising modality for advanced laryngeal cancer and toxicity is acceptable. (author)

  12. Combination chemotherapy concurrent with small dose radiation therapy for small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Tada, Toshihiko; Fujita, Hiroji; Shintomi, Takenori

    1987-01-01

    Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500 cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81 % (29 % complete) and the 2 year survival rate was 28.6 %. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000 cGy) and 3 recieved surgical treatment. Radiation therapy improved the 2-year survival rate (42.2 %) when compared with those patients who received no radiation therapy (18.2 %). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy. (author)

  13. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  14. Crianças/adolescentes em quimioterapia ambulatorial: implicações para a enfermagem Niños y adolescentes en quimioterapia ambulatoria: implicaciones para enfermería Children and adolecents in outpatient clinic chemotherapy: nursing implications

    Directory of Open Access Journals (Sweden)

    Juliana Cardeal da Costa

    2002-06-01

    , comunicación ineficiente, alteración de la autoimagen y reacción adversa a la quimioterapia. Este trabajo hizo posible el acceso a informaciones de interés real para la atención al niño y al adolescente con cáncer y sus familias. A partir de los datos empíricos elaboramos una cartilla de orientación para el cuidado domiciliario.Hospitalization was common in the care to the child with cancer. However, a great focus is being given to dehospitalization, whose viability occurred through the outpatient clinic follow up, the outpatient clinic chemotherapy, the day-hospitals and/or home care. This paper aims at analyzing the difficulties that the families face at the home environment when their children or adolescents are submitted to the outpatient clinic chemotherapy. The study was developed at the chemotherapy room of the University of São Paulo Hospital at Ribeirão Preto School of Medicine and the empirical data were collected through semi-structured interviews with the children's parents in January and February, 2000. Results showed the following difficulties: changes in family daily life, health team inefficient communication; self-image alteration and chemotherapy side effects. This work enabled access to information that is of real interest in the care to children and/or adolescents with cancer and their families. Based on empirical data, authors elaborated a booklet on home care.

  15. Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.

    Science.gov (United States)

    Goswami, Meghali; Prince, Gabrielle; Biancotto, Angelique; Moir, Susan; Kardava, Lela; Santich, Brian H; Cheung, Foo; Kotliarov, Yuri; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Golding, Hana; Manischewitz, Jody; King, Lisa; Kunz, Lauren M; Noonan, Kimberly; Borrello, Ivan M; Smith, B Douglas; Hourigan, Christopher S

    2017-07-10

    Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.

  16. Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

    Directory of Open Access Journals (Sweden)

    Michael L. Wang

    2017-07-01

    Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

  17. Experimental and theoretical investigations about the vaporization of laser-produced aerosols and individual particles inside inductively-coupled plasmas — Implications for the extraction efficiency of ions prior to mass spectrometry

    International Nuclear Information System (INIS)

    Flamigni, Luca; Koch, Joachim; Günther, Detlef

    2012-01-01

    Current quantification capabilities of laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) are known to be restricted by elemental fractionation as a result of LA-, transport-, and ICP-induced effects which, particularly, may provoke inaccuracies whenever calibration strategies on the basis of non-matrix matched standard materials are applied. The present study is dealing with the role of ICP in this complex scenario. Therefore, the vaporization process of laser-produced aerosols and subsequent diffusion losses occurring inside ICP sources were investigated using 2-D optical emission spectrometry (OES) and ICP-quadrupole (Q)MS of individual particles. For instance, Na- and Ca-specific OES of aerosols produced by LA of silicate glasses or metals revealed axial shifts in the onset and maximum position of atomic emission which were in the range of a few millimeters. The occurrence of these shifts was found to arise from composition-dependent particle/aerosol penetration depths, i.e. the displacement of axial vaporization starting points controlling the ion extraction efficiency through the ICP-MS vacuum interface due to a delayed, diffusion-driven expansion of oxidic vs. metallic aerosols. Furthermore, ICP-QMS of individual particles resulted in 1/e half-value signal durations of approximately 100 μs, which complies with modeled values if OES maxima are assumed to coincide with positions of instantaneous vaporization and starting points for atomic diffusion. To prove phenomena observed for their consistency, in addition, “ab initio” as well as semi-empirical simulations of particle/aerosol penetration depths followed by diffusion-driven expansion was accomplished indicating differences of up to 15% in the relative ion extraction efficiency depending on whether analytes are supplied as metals or oxides. Implications of these findings on the accuracy achievable by state-of-the-art LA-ICP-MS systems are outlined. - Highlights: ► Specification

  18. Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.

    Science.gov (United States)

    Stram, D O; Matthay, K K; O'Leary, M; Reynolds, C P; Haase, G M; Atkinson, J B; Brodeur, G M; Seeger, R C

    1996-09-01

    To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT). Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells. One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%). Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.

  19. Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

    International Nuclear Information System (INIS)

    Øyan, Anne Margrete; Ånensen, Nina; Bø, Trond Hellem; Stordrange, Laila; Jonassen, Inge; Bruserud, Øystein; Kalland, Karl-Henning; Gjertsen, Bjørn Tore

    2009-01-01

    The molecular changes in vivo in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response. The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting. Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells. Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex

  20. Chemotherapy for carcinoma of stomach

    International Nuclear Information System (INIS)

    Salek, T.

    2011-01-01

    Of all patients with gastric cancer 80 % to 90 % are either diagnosed at an advanced stage when the tumour is inoperable, or develop a recurrence within five years after surgery. Chemotherapy clearly improves survival in comparison to best supportive care only. No chemotherapy regimen showed a survival benefit better than 5-fluorouracil alone in a phase III trial for advanced gastric cancer in 1990s, and several new cytotoxic agents became available in late 1990s. Thereafter, a couple of phase III trials supported the substitution of infusional 5-fluorouracil by orally administered agents and the replacement of cisplatin by oxaliplatin in early 2000s. Trastuzumab has succeeded in showing a survival benefit for patients with Her-2 positive gastric cancer which accounts for about 10 - 20 % of the cancer. This means that the door is opened to the new era of chemotherapy with molecular target agents and with individualization for advanced gastric cancer. (author)

  1. Adjuvant chemotherapy and cancer cure

    International Nuclear Information System (INIS)

    Bertino, J.R.

    1983-01-01

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  2. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

    International Nuclear Information System (INIS)

    Pignon, Jean-Pierre; Le Maitre, Aurelie; Maillard, Emilie; Bourhis, Jean

    2009-01-01

    Background: Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000. Methods: The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment + chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated. Results: Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p = 0.003, test for trend). Conclusion: The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.

  3. The use of chemomodification for tumor apoptosis ceramide pathway induction

    International Nuclear Information System (INIS)

    Myitryajeva, N.A.; Bakaj, T.S.; Segeda, T.V.; Staren'kij, V.P.

    2012-01-01

    Comparative analysis of the clinical findings of pre-operative radiation therapy in patients with non-small-cell lung cancer with chemomodification (Taxotere, Etoposide, Cisplatin) and without it demonstrated the advantages of the combination therapy. Experimental investigation of chemomodifying effect of chemotherapy drugs (Taxotere, Etoposide, Cisplatin) on Guerin's carcinoma showed various mechanisms of accumulation of pro-apoptosis ceramides and their potential role in apoptosis induction and tumor regression.

  4. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis.

    Science.gov (United States)

    Savage, Philip

    2016-11-21

    take on a significant aspect of the biological characteristics of their parent cancer cells. This action includes for the chemotherapy curable malignancies the heightened pro-apoptotic sensitivity linked to their respective associated unique genetic events. For the chemotherapy curable malignancies the combination of the relationship of their cancer stem cells combined with the extreme inherent sensitivity to induction of apoptosis from DNA damaging agents plays a key role in determining their overall curability with chemotherapy.

  5. Managing Chemotherapy Side Effects: Bleeding Problems

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Bleeding Problems “My nurse said that chemotherapy could make ... with a clean cloth. Keep pressing until the bleeding stops. If you bruise: Put ice on the ...

  6. Fertility preservation after chemotherapy for Hodgkin lymphoma

    NARCIS (Netherlands)

    van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

    2010-01-01

    Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause

  7. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD

    2017-01-01

    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  8. Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2012-02-01

    Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.

  9. Managing Chemotherapy Side Effects: Constipation

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds Turn this ...

  10. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    Joseph, D.; Dubashi, B.; Karthikeyan, B.; Jain, A.

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

  11. Radiation oxidative stress in cancer induction and prevention

    International Nuclear Information System (INIS)

    Meher, Prabodha Kumar; Mishra, Kaushala Prasad

    2017-01-01

    Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stress or agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy. (author)

  12. Urofollitropin and ovulation induction

    NARCIS (Netherlands)

    van Wely, Madelon; Yding Andersen, Claus; Bayram, Neriman; van der Veen, Fulco

    2005-01-01

    Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has

  13. Inductance loop and partial

    CERN Document Server

    Paul, Clayton R

    2010-01-01

    "Inductance is an unprecedented text, thoroughly discussing "loop" inductance as well as the increasingly important "partial" inductance. These concepts and their proper calculation are crucial in designing modern high-speed digital systems. World-renowned leader in electromagnetics Clayton Paul provides the knowledge and tools necessary to understand and calculate inductance." "With the present and increasing emphasis on high-speed digital systems and high-frequency analog systems, it is imperative that system designers develop an intimate understanding of the concepts and methods in this book. Inductance is a much-needed textbook designed for senior and graduate-level engineering students, as well as a hands-on guide for working engineers and professionals engaged in the design of high-speed digital and high-frequency analog systems."--Jacket.

  14. Half Bridge Inductive Heater

    Directory of Open Access Journals (Sweden)

    Zoltán GERMÁN-SALLÓ

    2015-12-01

    Full Text Available Induction heating performs contactless, efficient and fast heating of conductive materials, therefore became one of the preferred heating procedure in industrial, domestic and medical applications. During induction heating the high-frequency alternating currents that heat the material are induced by means of electromagnetic induction. The material to be heated is placed inside the time-varying magnetic field generated by applying a highfrequency alternating current to an induction coil. The alternating electromagnetic field induces eddy currents in the workpiece, resulting resistive losses, which then heat the material. This paper describes the design of a power electronic converter circuit for induction heating equipment and presents the obtained results. The realized circuit is a low power half bridge resonant inverter which uses power MOS transistors and adequate driver circuits.

  15. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  16. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  17. Long term survival with the combination of interferon and chemotherapy in metastatic melanoma

    International Nuclear Information System (INIS)

    Karagoz, B.; Bilgi, O.; Ozgun, A.; Emirzeoglu, L.; Celika, S.; Ozet, A.

    2015-01-01

    The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-α (IF-α) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-α plus chemotherapy and IF-α maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-α plus chemotherapy and IF-α maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of auto immunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-α treatment with concurrent chemotherapy and maintenance. IF-α plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs

  18. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...

  19. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    Raza, S.; Ahmed, P.; Khan, B.

    2008-01-01

    To compare survival in Acute Promyelocytic Leukemia (APL) patients treated with or without All-Trans Retinoic Acid (ATRA). Longitudinal, comparative study. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or PML/RAR macro re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other retinoids). All patients having history of cardiac failure (LVEF 150 macro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox (Proportional hazard) regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival (OS), Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality. (author)

  20. TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells and enhance chemotherapy effects.

    Science.gov (United States)

    Sommariva, Michele; De Cecco, Loris; De Cesare, Michelandrea; Sfondrini, Lucia; Ménard, Sylvie; Melani, Cecilia; Delia, Domenico; Zaffaroni, Nadia; Pratesi, Graziella; Uva, Valentina; Tagliabue, Elda; Balsari, Andrea

    2011-10-15

    Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as "CpG-like" for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as "CpG-untreated-like," indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response.

  1. Chemotherapy-induced Spontaneous Pneumothorax: Case Series

    Directory of Open Access Journals (Sweden)

    Een Hendarsih

    2016-09-01

    The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1 the rupture of a subpleural bulla after chemotherapy; 2 the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3 tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency.

  2. Cancer cell adaptation to chemotherapy

    International Nuclear Information System (INIS)

    Di Nicolantonio, Federica; Johnson, Penny; Somers, Shaw S; Toh, Simon; Higgins, Bernie; Lamont, Alan; Gulliford, Tim; Hurren, Jeremy; Yiangou, Constantinos; Cree, Ian A; Mercer, Stuart J; Knight, Louise A; Gabriel, Francis G; Whitehouse, Pauline A; Sharma, Sanjay; Fernando, Augusta; Glaysher, Sharon; Di Palma, Silvana

    2005-01-01

    Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation

  3. Effect of Intensive Chemotherapy on Physical, Cognitive, and Emotional Health of Older Adults with Acute Myeloid Leukemia.

    Science.gov (United States)

    Klepin, Heidi D; Tooze, Janet A; Pardee, Timothy S; Ellis, Leslie R; Berenzon, Dmitriy; Mihalko, Shannon L; Danhauer, Suzanne C; Rao, Arati V; Wildes, Tanya M; Williamson, Jeff D; Powell, Bayard L; Kritchevsky, Stephen B

    2016-10-01

    To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML). Prospective observational study. Single academic institution. Individuals aged 60 and older with newly diagnosed AML who received induction chemotherapy (N = 49, mean age 70 ± 6.2, 56% male). Geriatric assessment (GA) was performed during inpatient examination for AML and within 8 weeks after hospital discharge after induction chemotherapy. Measures were the Pepper Assessment Tool for Disability (activity of daily living, instrumental activity of daily living (IADL), mobility questions), Short Physical Performance Battery (SPPB), grip strength, Modified Mini-Mental State examination, Center for Epidemiologic Studies Depression Scale, and the Distress Thermometer. Changes in GA measures were assessed using paired t-tests. Analysis of variance models were used to evaluate relationships between GA variables and change in function over time. After chemotherapy, IADL dependence worsened (mean 1.4 baseline vs 2.1 follow-up, P physical function. These data support the importance of interventions to maintain physical function during and after chemotherapy. Depressive symptoms before and during chemotherapy may be linked to potentially modifiable physical function declines. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  4. Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

    Science.gov (United States)

    Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

    2018-04-01

    The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Review of induction LINACS

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1981-10-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  6. Review of induction linacs

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1982-01-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of several kiloamps of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  7. Properties of inductive reasoning.

    Science.gov (United States)

    Heit, E

    2000-12-01

    This paper reviews the main psychological phenomena of inductive reasoning, covering 25 years of experimental and model-based research, in particular addressing four questions. First, what makes a case or event generalizable to other cases? Second, what makes a set of cases generalizable? Third, what makes a property or predicate projectable? Fourth, how do psychological models of induction address these results? The key results in inductive reasoning are outlined, and several recent models, including a new Bayesian account, are evaluated with respect to these results. In addition, future directions for experimental and model-based work are proposed.

  8. Experimental studies on cancer chemotherapy

    International Nuclear Information System (INIS)

    1976-08-01

    The further development of the chemotherapy of cancer in the experimental and clinical fields necessitates a profound knowledge of its chemical, biochemical and pharmacological fundamentals and the mechanism of physiological and pathological growth processes. The 'Arbeitsgemeinschaft Zytostatika' includes chemists, biochemists, pharmacologists, molecular biologists, physicians and immunologists of various scientific institutes and clinics in the Federal Republic of Germany and in West Berlin. It is their aim to carry out basic research as well as clinical-orientated research in the field of the chemotherapy of cancer. In the 15 years of cooperation, fundamental knowledge was gained, especially in the field of the cytotoxic specificity and cancerotoxic selectivity of alkylating cytostatics. New cytostatics with a greater oncostatic selectivity and an altered spectrum of activity were tested and greater knowledge was won on the molecular-biological prerequisites of a rational drug design. (orig.) [de

  9. [Chemotherapy and women fertility preservation].

    Science.gov (United States)

    Gauthier, Tristan; Piver, Pascal; Durand, Lise-Marie; Donadel, Lorène; Pech, Jean-Christophe; Roux, Christophe; Aubard, Yves

    2010-01-01

    Agressive chemotherapy can lead to premature ovarian failure and loss of fertility in women and children. Embryo cryopreservation is an established clinical procedure of fertility preservation but with several limitations. Others options are available. Cryopreservation ovarian cortex tissu have to be suggested in case of high gonadotoxic treatment. It doesn't require puberty and delay in initiation of chemotherapy. The first birth in France after orthotopic graft of ovarian tissu thawed have been recently described with a promising process. Oocyte cryopreservation is available for women without partner but the experience is limited. Gonadotrophin-releasing hormone (GnRH) agonist therapy as ovarian protectants seem interesting. Follicular growth and maturation in vitro are still experimental. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  10. Chemotherapy for advanced gastric cancer.

    Science.gov (United States)

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

  11. Metastatic hidradenocarcinoma: Surgery and chemotherapy.

    Science.gov (United States)

    Amel, Trabelsi; Olfa, Gharbi; Faten, Hammedi; Makrem, Hochlef; Slim, Ben Ahmed; Moncef, Mokni

    2009-12-01

    Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms.

  12. Metastatic hidradenocarcinoma: Surgery and chemotherapy

    OpenAIRE

    Trabelsi Amel; Gharbi Olfa; Hammedi Faten; Hochlef Makrem; Ben Ahmed Slim; Mokni Moncef

    2009-01-01

    Context: Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. Case report: We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Conclusion: Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies parti...

  13. Non-medical prescribing of chemotherapy: engaging stakeholders to maximise success?

    Science.gov (United States)

    Lennan, Elaine

    2014-01-01

    introduced over the past decade.Little research has been conducted in acute care and none in the chemotherapy setting.Cancer policy recommends the introduction of nurse-led chemotherapy clinics.What this paper addsNon-medical prescribing (NMP) in chemotherapy is appropriate with the right model of practice.Well-established professional relationships are a key to success.NMP is not appropriate in isolation of the multidisciplinary team (MDT).Implications for practice and/or policyNurses need to demonstrate the value of non-medical prescribing in chemotherapy using available metrics.Models of practice need to ensure good communication channels, MDT working, and transparency of prescribing.

  14. Multimodal treatment with ALL-like chemotherapy, Auto-SCT and radiotherapy for lymphoblastic lymphoma.

    Science.gov (United States)

    Bersvendsen, Hanne; Kolstad, Arne; Blystad, Anne Kirsti; Aurlien, Ellen; Fosså, Alexander; Kvaløy, Stein O; Holte, Harald; Lauritzsen, Grete F

    2014-05-01

    Recommended treatment for lymphoblastic lymphomas, a highly aggressive, relatively rare lymphoma entity predominantly seen in teenagers and young adults, includes acute lymphoblastic leukemia (ALL)-like induction chemotherapy. Whether these patients should be consolidated with maintenance chemotherapy or autologous stem cell transplantation (Auto-SCT) and the use of radiotherapy are matters of debate. We reviewed treatment and outcome for 25 consecutive patients above the age of 15 years with lymphoblastic lymphoma (T-lineage; T-LBL, n = 19; B-lineage; B-LBL, n = 6) seen at a single center during a 12-year period (1999-2011). Patients were given an ALL-like chemotherapy induction regimen, and responding patients were consolidated with Auto-SCT and local radiotherapy when applicable. Median age at diagnosis was 33 years (range 15-65). Seventeen of the T-LBL patients had a mediastinal mass, three patients had central nervous system (CNS) involvement. Chemotherapy with intensified CNS prophylaxis induced an overall response rate of 92% (CR 84%, PR 8%). In total 23/25 (92%) patients underwent Auto-SCT in first remission while 13 of 14 eligible patients with mediastinal involvement received local radiotherapy. Twenty percent of the patients had hepatotoxicity grade 3-4 and 32% thromboembolic events (TE). Two patients (8%) died of treatment-related toxicity. One patient had progressive disease and died of lymphoma. Three patients have relapsed, but two of these (both B-LBL) are currently alive in second CR after Allo-SCT. With a median follow-up of 98 months (range 1-163) the 5- and 8-year PFS and OS are 76% and 84%, respectively. Combined intensive ALL-like induction and early consolidation chemotherapy followed by Auto-SCT and local radiation therapy resulted in high sustained cure rates.

  15. Induction melter apparatus

    Science.gov (United States)

    Roach, Jay A [Idaho Falls, ID; Richardson, John G [Idaho Falls, ID; Raivo, Brian D [Idaho Falls, ID; Soelberg, Nicholas R [Idaho Falls, ID

    2008-06-17

    Apparatus and methods of operation are provided for a cold-crucible-induction melter for vitrifying waste wherein a single induction power supply may be used to effect a selected thermal distribution by independently energizing at least two inductors. Also, a bottom drain assembly may be heated by an inductor and may include an electrically resistive heater. The bottom drain assembly may be cooled to solidify molten material passing therethrough to prevent discharge of molten material therefrom. Configurations are provided wherein the induction flux skin depth substantially corresponds with the central longitudinal axis of the crucible. Further, the drain tube may be positioned within the induction flux skin depth in relation to material within the crucible or may be substantially aligned with a direction of flow of molten material within the crucible. An improved head design including four shells forming thermal radiation shields and at least two gas-cooled plenums is also disclosed.

  16. Rapid COJEC Induction Therapy for High-risk Neuroblastoma Patients - Cochrane Review.

    Science.gov (United States)

    Peinemann, F; van Dalen, E C; Berthold, F

    2016-04-01

    Neuroblastoma is a rare malignant disease and patients with high-risk neuroblastoma have a poor prognosis. Rapid COJEC induction chemotherapy means (almost) the same total doses given within a shorter time period. In theory, rapid COJEC could reduce the risk of drug resistance and it has been considered as a potential candidate for improving the outcome. The objective was to evaluate effects of rapid COJEC compared to standard induction chemotherapy in patients with high-risk neuroblastoma. We searched the databases CENTRAL, MEDLINE, and EMBASE from inception to 11 November 2014 and included randomized controlled trials. We identified one relevant randomized controlled trial with 130 participants receiving rapid COJEC and 132 participants receiving standard OPEC/COJEC induction chemotherapy. There was no statistically significant difference between the treatment groups in complete response (risk ratio 0.99, 95% confidence interval 0.71 to 1.38, P=0.94) and treatment-related mortality (risk ratio 1.21, 95% confidence interval 0.33 to 4.39, P=0.77). A statistically significant difference in favor of the standard treatment arm was identified for the following early toxicities: febrile neutropenia, septicemia, and renal toxicity. The differences in complete response and treatment-related mortality between treatment alternatives were not statistically significantly different. Based on the currently available evidence, we are uncertain about the effects of rapid COJEC induction chemotherapy in patients with high-risk neuroblastoma. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Linear induction accelerator

    Science.gov (United States)

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  18. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  19. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    International Nuclear Information System (INIS)

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-01-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy

  20. 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)

  1. Linear induction accelerators

    International Nuclear Information System (INIS)

    Briggs, R.J.

    1986-06-01

    The development of linear induction accelerators has been motivated by applications requiring high-pulsed currents of charged particles at voltages exceeding the capability of single-stage, diode-type accelerators and at currents too high for rf accelerators. In principle, one can accelerate charged particles to arbitrarily high voltages using a multi-stage induction machine, but the 50-MeV, 10-kA Advanced Test Accelerator (ATA) at LLNL is the highest voltage machine in existence at this time. The advent of magnetic pulse power systems makes sustained operation at high-repetition rates practical, and this capability for high-average power is very likely to open up many new applications of induction machines in the future. This paper surveys the US induction linac technology with primary emphasis on electron machines. A simplified description of how induction machines couple energy to the electron beam is given, to illustrate many of the general issues that bound the design space of induction linacs

  2. 5FU and oxaliplatin-containing chemotherapy in two dihydropyrimidine dehydrogenase-deficient patients

    NARCIS (Netherlands)

    Reerink, O; Mulder, NH; Szabo, BG; Hospers, GAP

    2004-01-01

    Patients with a germline mutation leading to a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme are at risk from developing severe toxicity on the administration of 5FU-containing chemotherapy. We report on the implications of this inborn genetic error in two patients who received 5FU

  3. Genotyping panel for assessing response to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Hampel Heather

    2008-06-01

    Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

  4. Chemotherapy-Induced Nausea and Vomiting Mitigation With Music Interventions
.

    Science.gov (United States)

    Kiernan, Jason M; Conradi Stark, Jody; Vallerand, April H

    2018-01-01

    Despite three decades of studies examining music interventions as a mitigant of chemotherapy-induced nausea and vomiting (CINV), to date, no systematic review of this literature exists.
. PubMed, Scopus, PsycInfo®, CINAHL®, Cochrane Library, and Google Scholar were searched. Keywords for all databases were music, chemotherapy, and nausea.
. All studies were appraised for methodology and results.
. 10 studies met inclusion criteria for review. Sample sizes were generally small and nonrandomized. Locus of control for music selection was more often with the investigator rather than the participant. Few studies controlled for the emetogenicity of the chemotherapy administered, nor for known patient-specific risk factors for CINV.
. The existing data have been largely generated by nurse scientists, and implications for nursing practice are many, because music interventions are low-cost, easily accessible, and without known adverse effects. However, this specific body of knowledge requires additional substantive inquiry to generate clinically relevant data.

  5. Nanotechnology for Cancer Therapy Based on Chemotherapy

    OpenAIRE

    Chen-Yang Zhao; Rui Cheng; Zhe Yang; Zhong-Min Tian

    2018-01-01

    Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover,...

  6. Overview, prevention and management of chemotherapy extravasation

    OpenAIRE

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-01-01

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracycl...

  7. Combined radiotherapy and chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

    1988-01-01

    There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

  8. [Oral complications of chemotherapy of malignant neoplasms].

    Science.gov (United States)

    Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

    1999-01-01

    Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

  9. Chemotherapy in combined and multimodality treatment

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    It is shown that chemotherapy of tumors of various localizations developes intensively in the last few years. It is connected with discovery and adoption of new active antitumoral preparations, such as alkylating preparations, antimetabolites, antitumoral antibiotics, hormonal preparations. To create the rational effective conditions of chemotherapy a study was made on kinetics of tumor gowth, molecular mechanisms of interaction of cytostatics and cells of malignant tumor. Main factors of chemotherapy combination with radiotherapy when treating numerous malignant tumors were considered. Effectiveness of using chemotherapy in combination with other methods of treatment was shown

  10. Chemotherapy

    Science.gov (United States)

    ... Central venous catheter Central venous catheter with a port Percutaneously inserted central catheter (PICC) A central line ... pain or numbness from nerve damage Have a dry mouth , mouth sores, or swelling in the mouth ...

  11. Chemotherapy

    Science.gov (United States)

    ... cause nerve problems and burning, numbness, tingling, or shooting pain in the fingers and toes. Certain types ... more comfortable wearing hats, scarves, or wigs to school or other events. Or, you may look great ...

  12. Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma.

    Science.gov (United States)

    Baranski, Zuzanna; Booij, Tijmen H; Cleton-Jansen, Anne-Marie; Price, Leo S; van de Water, Bob; Bovée, Judith V M G; Hogendoorn, Pancras C W; Danen, Erik H J

    2015-07-01

    Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Parsons, James T; Greene, Bruce D

    2015-01-01

    To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  14. Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients.

    Science.gov (United States)

    Black, David S; Peng, Cheng; Sleight, Alix G; Nguyen, Nathalie; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-08-15

    The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients. A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness. An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (β = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P mindfulness practice during chemotherapy can reduce the blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Inductive dielectric analyzer

    International Nuclear Information System (INIS)

    Agranovich, Daniel; Popov, Ivan; Ben Ishai, Paul; Feldman, Yuri; Polygalov, Eugene

    2017-01-01

    One of the approaches to bypass the problem of electrode polarization in dielectric measurements is the free electrode method. The advantage of this technique is that, the probing electric field in the material is not supplied by contact electrodes, but rather by electromagnetic induction. We have designed an inductive dielectric analyzer based on a sensor comprising two concentric toroidal coils. In this work, we present an analytic derivation of the relationship between the impedance measured by the sensor and the complex dielectric permittivity of the sample. The obtained relationship was successfully employed to measure the dielectric permittivity and conductivity of various alcohols and aqueous salt solutions. (paper)

  16. A theory evaluation of an induction programme

    Directory of Open Access Journals (Sweden)

    Kenrick Hendricks

    2012-07-01

    Full Text Available Orientation: An induction programme is commonly used to help new employees understand their job within the organisation. Research purpose: The main aim of this study was to examine whether or not the programme theory of an induction programme was plausible and would lead to the intended outcomes as described by the programme manager. Motivation for the study: Induction training is one of the most common training programmes in an organisation. However, there is little research to evaluate whether or not the activities of an induction programme will lead to the intended outcomes of such a programme. Research design, approach and method: This theory evaluation used a descriptive design. One hundred and thirteen employees of a media company completed a ten-item, five-point Likert scale which measured their perceptions of the programme’s outcome, identification with the organisation and intentions to stay with the organisation. Main findings: From this theory evaluation it was apparent that an induction programme based on an implausible programme theory could be problematic. An implausible programme theory affects the design of the programme activities and unsuitable activities may not deliver the desired outcomes. Practical/managerial implications: The intention of the evaluation is to guide human resource managers through a process of replacing an implausible programme theory with one that is plausible, and which ensures better alignment of programme activities and outcomes. Contribution/value-add: The evaluators showed how a plausible programme theory could improve programme design. This redesigned induction programme may lead to benefits, such as staff retention and company identification, rather than the vague assumption that it has been conforming to a legal obligation.

  17. A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

    Science.gov (United States)

    de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M

    2014-11-01

    Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. ©2014 American Association for Cancer Research.

  18. Platinum-based chemotherapy followed by radiation therapy of locally advanced nasopharyngeal cancer; A retrospective analysis of 39 cases

    Energy Technology Data Exchange (ETDEWEB)

    Fountzilas, G.; Danilidis, J.; Kosmidis, P.; Srihar, K.S.; Kalogera-Fountzila, A.; Nicolaou, A.; Makrantonakis, P.; Banis, K.; Dimitriadis, A.; Sombolos, K.; Zaramboukas, T.; Themelis, C.; Vritsios, A.; Tourkantonis, A. (Ahepa Univ. Hospital, Thessaloniki (Greece) Metaxa Cancer Hospital, Piraeaus (Greece) Miami School of Medicine and VA Hospital, FL (United States). Sylvester Comprehensive Cancer Center)

    1991-01-01

    A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplating 100 mg/m{sup 2} day 1, 5-FU 1000 mg/m{sup 2} days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4 mg/m{sup 2} day 22 and hydroxyurea 1000 mg/m{sup 2} daily days 23-27) or regimen B (carboplatin 300 mg/m{sup 2} day 1, 5-FU 1000 mg/m{sup 2} days 1-5 as continuous infusion and methotrexate 1.2 g/m{sup 2} day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials. (orig.).

  19. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    Directory of Open Access Journals (Sweden)

    Tetu Bernard

    2008-02-01

    Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

  20. Combination chemotherapy and radiotherapy of small cell lung cancer

    International Nuclear Information System (INIS)

    Saito, Yasuo; Chohtoh, Shuichi; Nishijima, Hiroshi; Kobayashi, Akihiko; Hirose, Jin-ichiro; Kamimura, Ryoichi; Takashima, Tsutomu; Konishi, Hideo; Miyata, Samon.

    1986-01-01

    Treatment results of 49 patients (25, limited disease, LD, 24, extensive disease, ED) with small cell lung cancer were retrospectively analyzed. Fifteen patients received chemotherapy with Cyclophosphamide (CPM) and Vincristine (VCR) following thoracic radiotherapy (RT). Twenty-two patients were given induction chemotherapy with CPM, Adriamycin (ADM), and VCR and were followed by thoracic RT. Other chemotherapy consisted of CPM, VCR, Methotrexate, and ADM in 2 patients, 5-FU, CPM, Mitomycin C, and Toyomycin in 1 patient. The remaining 9 patients (2, LD, 7, ED) were treated with RT alone. The response rate was 80 % (64 % CR; 16 % PR) for LD patients and 33 % (4 % CR; 29 % PR) for ED patients (P < 0.001). The three-year survival (Kaplan-Meier's product) of all patients was 14 %, with a median survival time (MST) of 8 months. For patients with LD, the 3-year survival was 27 % (MST 15 months). Survival of patients with ED was 14 % at 1 year, 0 % at 2 year (MST 5.5 months). The difference between these figures was statistically significant (P < 0.0003). The 3-year survival and relapse-free survival for complete responders with LD were 43 % (MST 21 months) and 36 % (median CR duration, 11.5 months) respectively. Six of 16 complete responders with LD are alive and well at over 2 years. Local recurrence rate of the complete responders with LD was 28.8 %. None of the 7 complete responders given more than 48 Gy relapsed within the radiation field. We believe that the addition of thoracic RT to patients with LD is necessary for the control of the primary tumors and for long-term disease-free survival. (author)

  1. Second malignancies after chemotherapy and radiotherapy for Hodgkin disease.

    Science.gov (United States)

    Chronowski, Gregory M; Wilder, Richard B; Levy, Larry B; Atkinson, Edward N; Ha, Chul S; Hagemeister, Fredrick B; Barista, Ibrahim; Rodriguez, Maria A; Sarris, Andreas H; Hess, Mark A; Cabanillas, Fernando; Cox, James D

    2004-02-01

    The purpose of this preliminary study was to determine the incidence of second malignancies after combined-modality therapy for adults with Hodgkin disease and relate it to the details of initial treatment. We retrospectively studied 286 patients ranging in age from 16 to 88 years with stage I or II Hodgkin disease who were treated between 1980 and 1995 with chemotherapy followed 3 to 4 weeks later by radiotherapy. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone was used in 161 cases, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 67 cases, Adriamycin, bleomycin, vinblastine, and dacarbazine in 19 cases, lomustine, vinblastine, procarbazine, and prednisone/doxorubicin, bleomycin, dacarbazine, and lomustine in 18 cases, and other chemotherapeutic regimens in the remaining 21 cases. The median radiotherapy dose was 40 Gy given in 20 daily 2-Gy fractions. Median follow-up of surviving patients was 7.4 years. There were 2,230 person-years of observation. Significantly increased relative risks (RR) were observed for acute myeloid leukemia (RR, 69.3; 95% CI, 14.3-202.6) and melanoma (RR, 7.3; 95% CI, 1.5-21.3). The 5-, 10-, and 15-year actuarial risks of acute myeloid leukemia were 0.8%, 1.3%, and 1.3%, respectively. Patients treated with MOPP had the highest 15-year actuarial risk of leukemia (1.6%). The 5-, 10-, and 15-year actuarial risks of solid tumors were 1.9%, 9.3%, and 16.8%, respectively. Consolidative radiotherapy to both sides of the diaphragm resulted in a trend toward an increased risk of solid tumors relative to radiotherapy to only one side of the diaphragm (p = 0.08). In an effort to reduce the risk of second malignancies, we have stopped using the alkylating agents nitrogen mustard and procarbazine and elective paraaortic and splenic radiotherapy after chemotherapy.

  2. Gut microbiota modulation of chemotherapy efficacy and toxicity.

    Science.gov (United States)

    Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

    2017-06-01

    Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

  3. Comparison of chemotherapy and hematopoietic stem cell ...

    African Journals Online (AJOL)

    Aims: Chemotherapy is frequently used as a conditioning regimen to destroy malignant marrow cells before transplantation. Xerostomia, dysphagia, altered taste perception, mucositis, soft‑tissue ulceration, and infection are common adverse oral effects of chemotherapy. The study was aimed to compare decayed, missing, ...

  4. Paradox of Prescribing Late Chemotherapy: Oncologists Explain.

    Science.gov (United States)

    Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J

    2016-12-01

    The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.

  5. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system d...

  6. Nanotechnology for Cancer Therapy Based on Chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen-Yang Zhao

    2018-04-01

    Full Text Available Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

  7. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma (Review)

    DEFF Research Database (Denmark)

    Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

    2017-01-01

    BACKGROUND: Combined modality treatment consisting of chemotherapy followed by localised radiotherapy is the standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long- term adverse effects such as secondary malignancies the role of radiotherapy has been questioned...... recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: To assess the effects of chemotherapy alone compared to chemotherapy plus radiotherapy in adults with early stage HL . SEARCH METHODS: For the or i ginal version of this review, we searched MEDLINE, Embase......-related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. CRR rate was not reported. AUTHORS' CONCLUSIONS: This systematic review compared the effects of chemotherapy alone...

  8. High current induction linacs

    International Nuclear Information System (INIS)

    Barletta, W.; Faltens, A.; Henestroza, E.; Lee, E.

    1994-07-01

    Induction linacs are among the most powerful accelerators in existence. They have accelerated electron bunches of several kiloamperes, and are being investigated as drivers for heavy ion driven inertial confinement fusion (HIF), which requires peak beam currents of kiloamperes and average beam powers of some tens of megawatts. The requirement for waste transmutation with an 800 MeV proton or deuteron beam with an average current of 50 mA and an average power of 40 MW lies midway between the electron machines and the heavy ion machines in overall difficulty. Much of the technology and understanding of beam physics carries over from the previous machines to the new requirements. The induction linac allows use of a very large beam aperture, which may turn out to be crucial to reducing beam loss and machine activation from the beam halo. The major issues addressed here are transport of high intensity beams, availability of sources, efficiency of acceleration, and the state of the needed technology for the waste treatment application. Because of the transformer-like action of an induction core and the accompanying magnetizing current, induction linacs make the most economic sense and have the highest efficiencies with large beam currents. Based on present understanding of beam transport limits, induction core magnetizing current requirements, and pulse modulators, the efficiencies could be very high. The study of beam transport at high intensities has been the major activity of the HIF community. Beam transport and sources are limiting at low energies but are not significant constraints at the higher energies. As will be shown, the proton beams will be space-charge-dominated, for which the emittance has only a minor effect on the overall beam diameter but does determine the density falloff at the beam edge

  9. Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy.

    Science.gov (United States)

    Laoprasopwattana, Kamolwish; Khwanna, Thida; Suwankeeree, Pussayaban; Sujjanunt, Tipwan; Tunyapanit, Wanutsanun; Chelae, Sureerat

    2013-03-01

    Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, -23.0%; 95% confidence interval: -45.0% to -0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

  10. Use of recombinant granulocyte-macrophage colony-stimulating factor during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia (AML) : Final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer (EORTC-LCG) and the Dutch Belgian Hemato-Oncology Cooperative Group (HOVON)

    NARCIS (Netherlands)

    Lowenberg, B; Suciu, S; Archimbaud, E; Ossenkoppele, G; Verhoef, GEG; Vellenga, E; Wijermans, P; Berneman, Z; Dekker, AW; Stryckmans, P; Jehn, U; Muus, P; Sonneveld, P; Dardenne, M; Zittoun, R

    1997-01-01

    We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were

  11. Splenic abscess in cancer chemotherapy.

    Science.gov (United States)

    Ismail, Essadi; El Barni, Rachid; Lahkim, Mohamed; Rokhsi, Redouane; Atmane, Elmehdi; El Fikri, Abdelghani; Bouchama, Rachid; Achour, Abdessamad; Zyani, Mohamed

    2015-11-11

    Splenic abcess is an uncommon complication for cancer treatment. It occurs more frequently in immunocompromised patients. They are characterized by high mortality. The classic triad (fever, pain of the left hypochondrium, and sensitive mass left) is only present in one-third of cases the clinical spectrum ranging from no symptoms to events such as fever, nausea, vomiting, weight loss, abdominal pain left, splenomegaly. Treatment options are limited, but must be discussed and adapted to the patient profile. We report the case of a 62-year-old Arabic male, diagnosed with metastatic lung adenocarcinoma, who, after several cycles of chemotherapy, presented symptoms and signs of splenic abcess. Splenic abcess is rare situation, which must be actively researched, to have access to an optimal therapeutic approach.

  12. Inductive Communication System Design Summary

    Science.gov (United States)

    1978-09-01

    The report documents the experience obtained during the design and development of the Inductive Communications System used in the Morgantown People Mover. The Inductive Communications System is used to provide wayside-to-vehicle and vehicle-to-waysid...

  13. Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

    Full Text Available Background: The incidence of different malignancies is increasing among the world populations. Acute lymphoblastic leukaemia (ALL is the most common of all the paediatric malignancies. Response to induction therapy is one of the most important predictors of long term outcome of ALL. Objective: To see the immediate outcome of paediatric ALL patients following induction therapy. Materials and Methods: This retrospective study was conducted from January 2013 to December 2015. Total 221 paediatric ALL patients were included in this study. Diagnosis was based on history, examination, blast cells count on peripheral blood film and bone marrow study, CSF study and immunophenotyping of peripheral blood/bone marrow aspirate in patients who were financially capable. Among them, parents of 40 (18% patients did not agree to start chemotherapy. According to Modified UK ALL 2003 protocol (Regimen A & B 181 patients were given induction therapy (vincristine, prednisolone, L-asparaginase, and daunomycin in high risk patients. Among them 14 patients discontinued, 10 patients died during chemotherapy and rest 157 patients completed induction phase. Bone marrow study was repeated after completion of induction therapy and remission pattern was seen. Results: Out of 157 chemotherapy completed patients, 137 (87% went into complete remission (25% blast cells in the bone marrow. Ten (5.5% patients died due to bleeding, febrile neutropenia and sepsis during the course of induction therapy. Conclusion: ALL in children is curable with effective chemotherapy. Poverty, ignorance and misconception regarding outcome are responsible for refusal and discontinuation of chemotherapy in third world countries like Bangladesh. Mortality and treatment cost can be reduced with the improvement of the facilities for isolation, barrier nursing and supportive treatment, and by creating awareness.

  14. Maintaining normality and support are central issues when receiving chemotherapy for ovarian cancer.

    Science.gov (United States)

    Ekman, Inger; Bergbom, Ingegerd; Ekman, Tor; Berthold, Harrieth; Mahsneh, Sawsan Majali

    2004-01-01

    The aim of this study was to enrich the understanding of patients' perspective of being diagnosed and treated for ovarian cancer. A qualitative approach was used to obtain knowledge and insight into patients' experiences and thoughts. Ten Swedish women, diagnosed with ovarian cancer, participated in a total of 23 interviews on 3 occasions: at the time of diagnosis, during chemotherapy, and after completion of chemotherapy. The results of the interpretation of the interviews were formulated in the form of 3 themes: (1) feeling the same despite radical castrating surgery, (2) accepting chemotherapy, and (3) maintaining normality and support. Suggestions of caring implications from our interpretation of the interview data underscore the need to support these women in learning to cope with their feelings of weakness and anxiety. The findings further indicate the potential in narrative methods to identify important issues in comprehensive cancer care.

  15. Induction technology optimization code

    International Nuclear Information System (INIS)

    Caporaso, G.J.; Brooks, A.L.; Kirbie, H.C.

    1992-01-01

    A code has been developed to evaluate relative costs of induction accelerator driver systems for relativistic klystrons. The code incorporates beam generation, transport and pulsed power system constraints to provide an integrated design tool. The code generates an injector/accelerator combination which satisfies the top level requirements and all system constraints once a small number of design choices have been specified (rise time of the injector voltage and aspect ratio of the ferrite induction cores, for example). The code calculates dimensions of accelerator mechanical assemblies and values of all electrical components. Cost factors for machined parts, raw materials and components are applied to yield a total system cost. These costs are then plotted as a function of the two design choices to enable selection of an optimum design based on various criteria. (Author) 11 refs., 3 figs

  16. Glass manufacturing through induction

    International Nuclear Information System (INIS)

    Boen, R.; Paya, B.; Roscini, M.; Fautrelle, Y.; Tuaz, F.; Delage, D.

    1991-01-01

    Oxides and glasses are electrical and thermal insulators, but show the characteristic of being weakly conductors of electricity when they are melt. It is then possible to heat them through HF induction. This interesting property allows the development of a melting process in cold crucible induction furnace. The process is being studied and developed by a consortium made up of CFEI, CEA Marcoule, ELECTRICITE DE FRANCE and MADYLAM laboratory. The studies include 2 parts: a) One experimental part to develop the technology and research for satisfying configurations, through a small size platform (10 to 30 kg/h). The long run continuous pouring melting tests made on different kinds of glass allow to go-on with industrial range units. b) One theoretical part to understand the magneto-thermo-hydraulic phenomenon hardly in relation with the heavy dependence of the physical characteristics (electrical and heat conductivities, viscosity) according to temperature. 6 refs., 4 figs [fr

  17. Inductive energy storage commutator

    International Nuclear Information System (INIS)

    Gavrilov, I.M.

    1987-01-01

    An inductive energy storage commutator is described. The value of commutated current is up to 800 A, the voltage amplitude in the load is up to 50 kV, the working frequency is equal to 1-50 Hz, the commutated power is up to 40 MW. The commutating device comprises of the first stage commutator having two in-series connected modules of the BTSV - 800/235 high-voltage thyristor unit, the second stage commutator containing three GMI-43A parallel connected powerful pulsed triodes, a commutating capacitor, an induction coil, two supplementary high-voltage thyristor keys (20 in-series connected thyristors T2-300 (13 class)), load, control pulse shapers, thyristor keys, power supply

  18. Pulse induction heating

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, A S; Kachanov, B Y; Kogan, B V

    1993-12-31

    Induction heating and three types of pulse processes were studied. It was found that in pulse processes the frequency and pulse duration of heat treatments do not remain constant. High frequency pulse heat treatments can be used on sprayed coatings; such treatments will result in stronger surfaces with no cracks. For induction hardening, the rate of specific power was 1 to 1.5 kW/sq.cm, for forging it was 0.2 to 0.3 kW/sq.cm and for melting it was 0.05 to 0.1 kW/sq.cm. The application of pulse heating will result in higher rates of specific power.

  19. Inductive Reasoning: A Training Approach

    Science.gov (United States)

    Klauer, Karl Josef; Phye, Gary D.

    2008-01-01

    Researchers have examined inductive reasoning to identify different cognitive processes when participants deal with inductive problems. This article presents a prescriptive theory of inductive reasoning that identifies cognitive processing using a procedural strategy for making comparisons. It is hypothesized that training in the use of the…

  20. Lexicographic Path Induction

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Sarnat, Jeffrey

    2009-01-01

    Programming languages theory is full of problems that reduce to proving the consistency of a logic, such as the normalization of typed lambda-calculi, the decidability of equality in type theory, equivalence testing of traces in security, etc. Although the principle of transfinite induction......, and weak normalization for Gödel’s T follows indirectly; both have been formalized in a prototypical extension of Twelf....

  1. Exercise and chemotherapy-induced amenorrhea.

    Science.gov (United States)

    Mathis, Katlynn M; Sturgeon, Kathleen M; Winkels, Renate M; Wiskemann, Joachim; Williams, Nancy I; Schmitz, Kathryn

    2018-07-01

    Chemotherapy-induced amenorrhea (CIA) is the temporary or permanent loss of menses experienced by premenopausal women undergoing chemotherapy treatment for cancer. Two possible mechanisms through which chemotherapy induces CIA have been identified: systemic endothelial dysfunction, resulting in decreased blood flow to the ovaries, and increased oxidative stress within the ovaries, both of which are proposed to lead to apoptosis of follicles. Endothelial dysfunction in ovarian arteries in women undergoing or who have undergone chemotherapy treatment is characterized by prothrombotic changes and thickening of the vascular wall. These changes result in occlusion of the blood vessels. Oxidative stress is increased and antioxidants decreased in the ovaries secondary to chemotherapy drugs, specifically cyclophosphamide. It is hypothesized that low to moderate intensity aerobic exercise during chemotherapy may prevent these changes and lessen the risk for developing CIA in premenopausal women. Low to moderate intensity aerobic exercise has been shown to improve endothelial function and blood flow in patients with cardiovascular disease-a disease state characterized by endothelial dysfunction and for which patients who have undergone chemotherapy are at increased risk. In mice, moderate intensity aerobic exercise has been shown to decrease the amount of oxidative stress within the ovaries, and in humans, chronic aerobic exercise has been shown to increase antioxidant production systemically. This hypothesis should be tested in both a mouse model, using sedentary and exercising mice treated with chemotherapy drugs that commonly result in CIA, as well as a human model to determine the effects of low to moderate intensity aerobic exercise on ovarian function in premenopausal women undergoing chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960's to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore's Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail

  3. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1997-01-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at Lawrence Livermore National Laboratory (LLNL) from the early 1960s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400-ns pulses. The Advanced Test Accelerator (ATA) built at Livermore close-quote s Site 300 produced 10,000-Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and Lawrence Berkeley National Laboratory (LBNL). This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high-current, short-pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail. copyright 1997 American Institute of Physics

  4. Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

    Science.gov (United States)

    Gerber, David E.; Schiller, Joan H.

    2013-01-01

    Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

  5. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....

  6. A taxonomy of inductive problems.

    Science.gov (United States)

    Kemp, Charles; Jern, Alan

    2014-02-01

    Inductive inferences about objects, features, categories, and relations have been studied for many years, but there are few attempts to chart the range of inductive problems that humans are able to solve. We present a taxonomy of inductive problems that helps to clarify the relationships between familiar inductive problems such as generalization, categorization, and identification, and that introduces new inductive problems for psychological investigation. Our taxonomy is founded on the idea that semantic knowledge is organized into systems of objects, features, categories, and relations, and we attempt to characterize all of the inductive problems that can arise when these systems are partially observed. Recent studies have begun to address some of the new problems in our taxonomy, and future work should aim to develop unified theories of inductive reasoning that explain how people solve all of the problems in the taxonomy.

  7. Cancer chemotherapy and biotherapy: principles and practice

    National Research Council Canada - National Science Library

    Chabner, Bruce; Longo, Dan L

    2011-01-01

    "Updated to include the newest drugs and those currently in development, Cancer Chemotherapy and Biotherapy, Fifth Edition is a comprehensive reference on the preclinical and clinical pharmacology of anticancer agents...

  8. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. ... and anywhere on your body may fall out. Hair loss is called alopecia. When will my hair start ...

  9. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  10. Managing Chemotherapy Side Effects: Nausea and Vomiting

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Nausea and Vomiting “I take medicine so I won’t feel sick ...

  11. Managing Chemotherapy Side Effects: Swelling (Fluid Retention)

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Swelling (Fluid retention) “My hands and feet were swollen and puffy. My nurse helped me understand why I had to stop eating salty ...

  12. Nanoscale drug delivery for targeted chemotherapy.

    Science.gov (United States)

    Xin, Yong; Huang, Qian; Tang, Jian-Qin; Hou, Xiao-Yang; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

    2016-08-28

    Despite significant improvements in diagnostic methods and innovations in therapies for specific cancers, effective treatments for neoplastic diseases still represent major challenges. Nanotechnology as an emerging technology has been widely used in many fields and also provides a new opportunity for the targeted delivery of cancer drugs. Nanoscale delivery of chemotherapy drugs to the tumor site is highly desirable. Recent studies have shown that nanoscale drug delivery systems not only have the ability to destroy cancer cells but may also be carriers for chemotherapy drugs. Some studies have demonstrated that delivery of chemotherapy via nanoscale carriers has greater therapeutic benefit than either treatment modality alone. In this review, novel approaches to nanoscale delivery of chemotherapy are described and recent progress in this field is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  14. The role of chemotherapy in brain metastases

    International Nuclear Information System (INIS)

    Ohori, Hisatsugu; Takahashi, Shin; Ishioka, Chikashi

    2007-01-01

    Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases have a very poor prognosis with a median survival of 1-2 months. Despite the use of surgery and radiotherapy including whole-brain radiation and stereotactic radiosurgery to locally control brain metastases, survival times for those patients has not improved. Although chemotherapy plays a limited role in the treatment of brain metastases, metastases from lung or breast cancer are often well-controlled by chemotherapy. Accumulating evidence suggest that brain metastases are equally sensitive to chemotherapy as are metastases elsewhere in the body in particular chemotherapy-naive cases. Finally, since nearly a half of patients with brain metastases die from progression of systemic disease, control of systemic disease as well as intracranial disease are both important. (author)

  15. Chemotherapy-induced sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, K.; Alazmi, W.M.; Tann, M.; Fogel, E.L.; McHenry, L.; Lehman, G.A

    2006-08-15

    Aim: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). Methods: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. Results: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5 cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n = 1) or confluent fibrosis (n = 0) were uncommon findings. Conclusion: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.

  16. EXPERIENCE WITH INTRAPERITONEAL CHEMOTHERAPY USING ASCITIC FLUID AS A SOLVENT OF CHEMICALS IN THE TREATMENT OF OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2009-01-01

    Full Text Available Thirty two with the ascitic form of Stages IIIC—IV ovarian cancer underwent 1 to 3 courses of intraperitoneal multidrug therapy using a protein ascitic fluid concentrate (PAFC as a solvent of drugs (cisplatin, cyclophosphan, doxorubicin according to the CAP regimen. The induction chemotherapy allowed remission to be achieved in 78.1% of cases (against 40% with standard intraperitoneal therapy, the stan- dard volume of surgical treatment was performed in 28 (87.5% patients (21 (70% receiving the control regime; with the use of PAFC, the size of minimum residual tumour (less than 1 cm was achieved in 81.3% versus 63.3% with standard intraperitoneal chemotherapy. This treatment enables the use large-dose chemotherapy regimens that cause no severe systemic toxic reactions. The method is highly-effective, low-toxic and may be recommended for the treatment of patients with the ascitic form of Stages III—IV ovarian cancer.

  17. Mechanisms of chemotherapy-induced behavioral toxicities

    Directory of Open Access Journals (Sweden)

    Elisabeth G Vichaya

    2015-04-01

    Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  18. Chemotherapy for intracranial ependymoma in adults

    International Nuclear Information System (INIS)

    Gramatzki, Dorothee; Roth, Patrick; Felsberg, Jörg; Hofer, Silvia; Rushing, Elisabeth J.; Hentschel, Bettina; Westphal, Manfred; Krex, Dietmar; Simon, Matthias; Schnell, Oliver; Wick, Wolfgang; Reifenberger, Guido; Weller, Michael

    2016-01-01

    Ependymal tumors in adults are rare, accounting for less than 4 % of primary tumors of the central nervous system in this age group. The low prevalence of intracranial ependymoma in adults limits the ability to perform clinical trials. Therefore, treatment decisions are based on small, mostly retrospective studies and the role of chemotherapy has remained unclear. We performed a retrospective study on 17 adult patients diagnosed with intracranial World Health Organisation grade II or III ependymoma, who were treated with chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by applying Macdonald criteria. Progression-free (PFS) and overall survival (OS) were calculated from start of chemotherapy, using the Kaplan-Meier method. Eleven patients had supratentorial and 6 infratentorial tumors. Ten patients were treated with temozolomide (TMZ), 3 with procarbazine/lomustine/vincristine (PCV), 3 with platinum-based chemotherapy and 1 patient received epirubicin/ifosfamide. Response rates were as follows: TMZ 8/10 stable disease; PCV 3/3 stable disease; platinum-based chemotherapy 1/3 partial response; epirubicin/ifosfamide 1/1 complete response. PFS rates at 6, 12 and 24 months were 52.9, 35.3 and 23.5 %. OS rates at 6, 12 and 24 months were 82.4, 82.4 and 70.1 %. There was no indication for a favourable prognostic role of O 6 -methylguanyl-DNA-methyltransferase (MGMT) promoter methylation which was detected in 3/12 investigated tumors. Survival outcomes in response to chemotherapy in adult intracranial ependymoma patients vary substantially, but individual patients may respond to any kind of chemotherapy. There were too few patients to compare survival data between chemotherapeutic subgroups. The online version of this article (doi:10.1186/s12885-016-2323-0) contains supplementary material, which is available to authorized users

  19. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Blake, Mónika; Mata-Moya, María Dolores de la; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

    2014-01-01

    Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

  20. Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Salem, Mohamed Labib; El-Shanshory, Mohamed R; Abdou, Said H; Attia, Mohamed S; Sobhy, Shymaa M; Zidan, Mona F; Zidan, Abdel-Aziz A

    2018-04-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (T regs ) which we and others have reported to mediate suppression of anti-tumor immune responses. In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients. Peripheral blood samples withdrawn from B-ALL pediatric patients (n = 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin - HLA-DR - CD33 + CD11b + ; and T reg cells were defined as CD4 + CD25 + CD127 -/low . Early diagnosed B-ALL patients showed significant increases in the numbers of MDSCs and T regs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and T reg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and T reg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy. Our results indicate that B-ALL patients harbor high numbers of both MDSCs and T regs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

  1. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

    2010-01-01

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  2. Impact of adjuvant chemotherapy for gliomatosis cerebri

    International Nuclear Information System (INIS)

    Kong, Doo-Sik; Nam, Do-Hyun; Kim, Sung Tae; Lee, Jung-Il; Suh, Yeon-Lim; Lim, Do Hoon; Kim, Won Seog; Kwon, Ki-Hoon; Park, Kwan; Kim, Jong Hyun

    2010-01-01

    Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

  3. Cancer occurring after radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Holm, L.E.

    1990-01-01

    Radiotherapy and chemotherapy can effectively control cancer but can also cause new cancers to develop as long-term complications. Almost all types of cancer have been associated with radiotherapy. The breast, thyroid, and bone marrow are the organs most susceptible to radiation carcinogenesis. The bone marrow is also most frequently involved by chemotherapy and the leukemia risk is much higher than after radiotherapy. The combination of intensive radiotherapy and chemotherapy is particularly leukemogenic. The latent period between radiotherapy/chemotherapy and the appearance of a second primary cancer ranges from a few years to several decades. The risk for a second primary cancer following radiotherapy or chemotherapy emphasizes the need for life long follow-up of patients receiving such treatments. This is particularly the case in individuals with long life expectancy, for example, patients treated for childhood neoplasms. The benefits of radiotherapy and chemotherapy in oncology exceed the risks for second primary cancers. Efforts should be directed towards identifying those patients who will benefit from the treatments so that only they are exposed to the risk. 33 references

  4. Photon buildup factors of some chemotherapy drugs.

    Science.gov (United States)

    Kavaz, Esra; Ahmadishadbad, Nader; Özdemir, Yüksel

    2015-02-01

    Everyday more and more people are diagnosed with some form of cancer. Some are treatable with chemotherapy alone, while others need radiotherapy and occasionally surgery. Recently, concurrent administration of chemotherapy and radiotherapy has been increasingly used in cancer treatment, leading to improvements in survival as well as quality of life. Accordingly, interaction of chemotherapy drugs with radiation will be meaningful to examine. In the present study, gamma ray energy absorption and exposure of buildup factors were computed using the five-parameter geometric progression (G-P) fitting formula for some chemotherapy drugs in the energy range 0.015-15 MeV, and for penetration depths up to 40 mean free path (mfp). The generated energy absorption (EABF) and exposure buildup factors (EBF) of chemotherapy drugs have been studied as a function of penetration depth and incident photon energy. The significant variations in EABF and EBF for chemotherapy drugs have been observed at the moderate energy region. It has been concluded that the buildup of photons is less in azathioprine and is more in vinblastine compared with other drugs. Buildup factors investigated in the present work could be useful in radiation dosimetry and therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Linear induction motor

    International Nuclear Information System (INIS)

    Barkman, W.E.; Adams, W.Q.; Berrier, B.R.

    1978-01-01

    A linear induction motor has been operated on a test bed with a feedback pulse resolution of 5 nm (0.2 μin). Slewing tests with this slide drive have shown positioning errors less than or equal to 33 nm (1.3 μin) at feedrates between 0 and 25.4 mm/min (0-1 ipm). A 0.86-m (34-in)-stroke linear motor is being investigated, using the SPACO machine as a test bed. Initial results were encouraging, and work is continuing to optimize the servosystem compensation

  6. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation....... OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register...... to identify additional trials. SELECTION CRITERIA: We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should...

  7. Analysis of cortical bone porosity using synchrotron radiation microtomography to evaluate the effects of chemotherapy

    Science.gov (United States)

    Alessio, R.; Nogueira, L. P.; Salata, C.; Mantuano, A.; Almeida, A. P.; Braz, D.; de Almeida, C. E.; Tromba, G.; Barroso, R. C.

    2015-11-01

    Microporosities play important biologic and mechanical roles on health. One of the side effects caused by some chemotherapy drugs is the induction of amenorrhea, temporary or not, in premenopausal women, with a consequent decrease in estrogen production, which can lead to cortical bone changes. In the present work, the femur diaphysis of rats treated with chemotherapy drugs were evaluated by 3D morphometric parameters using synchrotron radiation microtomography. Control animals were also evaluated for comparison. The 3D tomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the ELETTRA Synchrotron Laboratory in Trieste, Italy. Results showed significant differences in morphometric parameters measured from the 3D images of femur diaphysis of rats.

  8. Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

    Science.gov (United States)

    Niho, Seiji; Ohe, Yuichiro; Ohmatsu, Hironobu; Umemura, Shigeki; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

    2017-06-01

    We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC). Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m 2 twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate. The efficacy/toxicity of switch maintenance chemotherapy with S-1 and S-1+Bev was evaluated separately. The primary end point of this study was the treatment success rate at three months after the start of S-1 treatment. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities. Copyright © 2017. Published by Elsevier B.V.

  9. Cybernetic systems based on inductive logic

    International Nuclear Information System (INIS)

    Fry, Robert L.

    2001-01-01

    Recent work in the area of inductive logic suggests that cybernetics might be quantified and reduced to engineering practice. If so, then there are considerable implications for engineering, science, and other fields. This paper attempts to capture the essential ideas of cybernetics cast in the light of inductive logic. The described inductive logic extends conventional logic by adding a conjugate logical domain of questions to the logical domain of assertions intrinsic to Boolean Algebra with which most are familiar. This was first posited and developed by Richard Cox. Interestingly enough, these two logical domains, one of questions and the other of assertions, only exist relative to one another with each possessing natural measures of entropy and probability, respectively. Examples are given that highlight the utility of cybernetic approaches to neuroscience, algorithm design, system engineering, and the design and understanding of defensive and offensive systems. For example, the application of cybernetic approaches to defense systems suggests that these systems possess a wavefunction which like quantum mechanics, collapses when we 'look' through the eyes of the system sensors such as radars and optical sensors

  10. Quality of life of lung cancer patients receiving outpatient chemotherapy

    OpenAIRE

    MATSUDA, AYAKO; KOBAYASHI, MIKA; SAKAKIBARA, YUMI; TAMAOKA, MEIYO; FURUIYE, MASASHI; INASE, NAOHIKO; MATSUSHIMA, EISUKE

    2011-01-01

    An increasing number of cancer patients receive outpatient chemotherapy as an alternative to inpatient chemotherapy. The aim of this study was to investigate whether quality of life (QOL) during outpatient chemotherapy was better than QOL prior to hospital discharge, and to explore possible related factors prior to hospital discharge that affected the QOL of lung cancer patients who received outpatient chemotherapy. Lung cancer inpatients who were scheduled for outpatient chemotherapy were as...

  11. n-3 polyunsaturated fatty acid supplementation during cancer chemotherapy

    OpenAIRE

    Morland, Sarah Louise; Martins, Karen J.B.; Mazurak, Vera C.

    2016-01-01

    Evidence from several clinical trials suggests that n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation during cancer chemotherapy improves patient outcomes related to chemotherapy tolerability, regardless of the type of chemotherapy used. While the effects of n-3 PUFA supplementation during chemotherapy have been the subject of several reviews, the mechanisms by which n-3 PUFA improve patient responses through improved chemotherapy tolerability are unclear. There are several barriers c...

  12. Lauren classification and individualized chemotherapy in gastric cancer.

    Science.gov (United States)

    Ma, Junli; Shen, Hong; Kapesa, Linda; Zeng, Shan

    2016-05-01

    Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.

  13. Acute memory deficits in chemotherapy-treated adults.

    Science.gov (United States)

    Lindner, Oana C; Mayes, Andrew; McCabe, Martin G; Talmi, Deborah

    2017-11-01

    Data from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients' first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically relevant implications.

  14. Role of chemotherapy of taeniasis in prevention of neurocysticercosis.

    Science.gov (United States)

    Pawlowski, Zbigniew S

    2006-01-01

    Neurocysticercosis (NC) is a serious public health problem in Taenia solium endemic areas and in some immigrants and international travelers. A key intervention in preventing NC is elimination of taeniasis by chemotherapy. Currently, two safe and effective taenicides, namely niclosamide and praziquantel, are available. Both are on WHO Essential Drug list, but are often inaccessible in T. solium endemic areas. Natural remedies, still widely used in some endemic areas, are frequently carcinogenic or highly toxic and as such should be discontinued. Chemotherapeutic intervention to control T. solium taeniasis/cysticercosis, whilst theoretically feasible, has several practical obstacles. These include poor public awareness, problems with diagnosing Taenia carriers, poor availability of taenicides where needed and low priority afforded to the control of NC. These can be overcome, respectively, by effective health education, wider use of newly developed coproantigen tests, strengthening of health services infrastructure and essential drugs distribution, and increasing the priority given to prevention of NC, as a leading cause of epilepsy in T. solium endemic areas. Information is accumulating on rational approaches to population-based short-term chemotherapeutic control measures. These are: widely available modern diagnostic tools and taenicides, treatment of any case of taeniasis, confirmed or probable, focus-oriented chemotherapy, irrespective of Taenia species implicated, improved sanitation, cooperation of veterinary and medical services, linkage with programs against epilepsy and cooperation of better educated communities. Now, it remains to take an advantage of existing tools and experience.

  15. Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

    Science.gov (United States)

    Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

    2011-01-13

    Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

  16. Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

    Science.gov (United States)

    Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

    2018-04-24

    While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

  17. Pulsed inductive HF laser

    Energy Technology Data Exchange (ETDEWEB)

    Razhev, A M; Kargapol' tsev, E S [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation); Churkin, D S; Demchuk, S V [Novosibirsk State University, Novosibirsk (Russian Federation)

    2016-03-31

    We report the results of experimentally investigated dependences of temporal, spectral and spatial characteristics of an inductive HF-laser generation on the pump conditions. Gas mixtures H{sub 2} – F{sub 2}(NF{sub 3} or SF6{sub 6}) and He(Ne) – H{sub 2} – F{sub 2}(NF{sub 3} or SF{sub 6}) were used as active media. The FWHM pulse duration reached 0.42 μs. This value corresponded to a pulsed power of 45 kW. For the first time, the emission spectrum of an inductive HF laser was investigated, which consisted of seven groups of bands with centres around the wavelengths of 2732, 2736, 2739, 2835, 2837, 2893 and 2913 nm. The cross section profile of the laser beam was a ring with a diameter of about 20 mm and width of about 5 mm. Parameters of laser operation in the repetitively pulsed regime were sufficiently stable. The amplitude instability of light pulses was no greater than 5% – 6%. (lasers)

  18. Benefit of adjuvant chemotherapy after resection of stage II (T1-2N1M0) non-small cell lung cancer in elderly patients.

    Science.gov (United States)

    Berry, Mark F; Coleman, Brooke K; Curtis, Lesley H; Worni, Mathias; D'Amico, Thomas A; Akushevich, Igor

    2015-02-01

    We evaluated the use and efficacy of adjuvant chemotherapy after resection of T1-2N1M0 non-small cell lung cancer (NSCLC) in elderly patients. Factors associated with the use of adjuvant chemotherapy in patients older than 65 years of age who underwent surgical resection of T1-2N1M0 NSCLC without induction chemotherapy or radiation in the Surveillance, Epidemiology, and End Results-Medicare database from 1992 to 2006 were assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census tract characteristics. Overall survival (OS) was analyzed using the Kaplan-Meier approach and inverse probability weight-adjusted Cox proportional hazard models. Overall, 2,781 patients who underwent surgical resection as the initial treatment for T1-2N1M0 NSCLC and survived at least 31 days after surgery were identified, with adjuvant chemotherapy given to 784 patients (28.2 %). Factors that predicted adjuvant chemotherapy use were younger age and higher T status. The 5-year OS was significantly better for patients who received adjuvant chemotherapy compared with patients not given adjuvant chemotherapy: 35.8 % (95 % confidence interval [CI] 31.9-39.6) vs. 28.0 % (95 % CI 25.9-30.0) (p = 0.008). In the inverse probability weight-adjusted Cox proportional hazard regression model, adjuvant chemotherapy use predicted significantly improved survival (hazard ratio 0.84; 95 % CI 0.76-0.92; p = 0.0002). Adjuvant chemotherapy after resection of T1-2N1M0 NSCLC is associated with significantly improved survival in patients older than 65 years. These data can be used to provide elderly patients with realistic expectations of the potential benefits when considering adjuvant chemotherapy in this setting.

  19. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Ou Guangfei; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Feng Qinfu; Zhou Zongmei; Lv Jima; Liang Jun; Wang Mei; Yin Weibo

    2007-01-01

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  20. The efficacy of superselective intra-arterial infusion in patients with T4 oral cancer. Comparison with conventional chemotherapy

    International Nuclear Information System (INIS)

    Arakaki, Keiichi; Arasaki, Akira; Kano, Takeshi

    2009-01-01

    Since 1985, we have applied systematic treatment to improve radicality and postoperative oral dysfunction, as well as maxillofacial deformity. However, most T4 cases of oral cancer have remained difficult to treat, and diverse methods and results for progressive cancer have been reported by many institutions. For high-grade malignancy cases, we changed the treatment from bleomycin or cisplatin in induction chemotherapy to targeted intra-arterial infusions of carboplatin with radiation-combined therapy. In this study, we compared the effects of conventional therapy with targeted intra-arterial infusions of carboplatin for T4 cases of oral cancer. In this retrospective review, we analyzed a subset of patients who were treated with induction chemotherapy using bleomycin (BLM) and targeted intra-arterial infusions of carboplatin (CBDCA) with radiation-combined therapy patients who received treatment between June 1985 and December 2006. Of the 105 patients who had T4 disease, the proportion with grade IIb to IV in the carboplatin with radiation-combined therapy (88.9%) was higher than that in induction chemotherapy (45.0%). Targeted chemoradiation therapy followed by surgical salvage is a highly effective approach for the regional control of patients with T4, although additional strategies are required to address the problem of distant metastases. (author)

  1. Adapting immunisation schedules for children undergoing chemotherapy.

    Science.gov (United States)

    Fernández-Prada, María; Rodríguez-Martínez, María; García-García, Rebeca; García-Corte, María Dolores; Martínez-Ortega, Carmen

    2018-02-01

    Children undergoing chemotherapy for cancer have special vaccination needs after completion of the treatment. The aim of this study was to evaluate the adaptation of post-chemotherapy vaccination schedules. An observational study was performed on a retrospective cohort that included all children aged from 0 to 14 years, who completed chemotherapy in a tertiary hospital between 2009 and 2015. Inclusion and exclusion criteria were applied. Immunisation was administered in accordance with the guidelines of the Vaccine Advisory Committee of the Spanish Association of Paediatrics. Primary Care immunisation and clinical records of the Preventive Medicine and Public Health Department were reviewed. Of the 99 children who had received chemotherapy, 51 (70.6% males) were included in the study. As regards the type of tumour, 54.9% had a solid organ tumour, and 45.1% had a haematological tumour. Post-chemotherapy immunisation was administered to 70.6%. The most common vaccines received were: diphtheria-tetanus-pertussis or diphtheria-tetanus (54.9%), meningococcus C (41.2%), and seasonal influenza (39.2%). The rate of adaptation of the immunisation schedule after chemotherapy was 9.8%. The pneumococcal conjugate vaccine against 7v or 13v was administered to 21.6% of study subjects. However, only 17.6% received polysaccharide 23v. None received vaccination against hepatitis A. No statistically significant differences were observed between adherence to immunisation schedules and type of tumour (P=.066), gender (P=.304), or age (P=.342). Post-chemotherapy immunisation of children with cancer is poor. The participation of health professionals in training programs and referral of paediatric cancer patients to Vaccine Units could improve the rate of schedule adaptation and proper immunisation of this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  3. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    Energy Technology Data Exchange (ETDEWEB)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Medicine. Div. of Solid Tumor Oncology; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States).Dept. of Surgery. Head and Neck Service; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiation Oncology]. E-mail: pfisterd@mskcc.org

    2000-06-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  4. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    International Nuclear Information System (INIS)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G.; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P.; Zelefsky, Michael J.

    2000-01-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  5. Borehole induction coil transmitter

    Science.gov (United States)

    Holladay, Gale; Wilt, Michael J.

    2002-01-01

    A borehole induction coil transmitter which is a part of a cross-borehole electromagnetic field system that is used for underground imaging applications. The transmitter consists of four major parts: 1) a wound ferrite or mu-metal core, 2) an array of tuning capacitors, 3) a current driver circuit board, and 4) a flux monitor. The core is wound with several hundred turns of wire and connected in series with the capacitor array, to produce a tuned coil. This tuned coil uses internal circuitry to generate sinusoidal signals that are transmitted through the earth to a receiver coil in another borehole. The transmitter can operate at frequencies from 1-200 kHz and supplies sufficient power to permit the field system to operate in boreholes separated by up to 400 meters.

  6. Inductive circuit arrangements

    International Nuclear Information System (INIS)

    Mansfield, Peter; Coxon, R.J.

    1987-01-01

    A switched coil arrangement is connected in a bridge configuration of four switches S 1 , S 2 , S 3 and S 4 which are each shunted by diodes D 1 , D 2 , D 3 and D 4 so that current can flow in either direction through a coil L depending on the setting of the switches. A capacitor C is connected across the bridge through a switch S 5 to receive the inductive energy stored in coil L on breaking the current flow path through the coil. The electrostatic energy stored in capacitor C can then be used to supply current through the coil in the reverse direction either immediately or after a time delay. Coil L may be a superconductive coil. Losses in the circuit can be made up by a trickle charge of capacitor C from a separate supply V 2 . The device may be used in nuclear magnetic resonance imaging. (author)

  7. Induction heating using induction coils in series-parallel circuits

    Science.gov (United States)

    Matsen, Marc Rollo; Geren, William Preston; Miller, Robert James; Negley, Mark Alan; Dykstra, William Chet

    2017-11-14

    A part is inductively heated by multiple, self-regulating induction coil circuits having susceptors, coupled together in parallel and in series with an AC power supply. Each of the circuits includes a tuning capacitor that tunes the circuit to resonate at the frequency of AC power supply.

  8. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  9. Autophagy induction for the treatment of cancer.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Maiuri, Maria Chiara; Madeo, Frank; Kroemer, Guido

    2016-10-02

    Cancer can be viewed in 2 rather distinct ways, namely (i) as a cell-autonomous disease in which malignant cells have escaped control from cell-intrinsic barriers against proliferation and dissemination or (ii) as a systemic disease that involves failing immune control of aberrant cells. Since macroautophagy/autophagy generally increases the fitness of cells as well as their resistance against endogenous or iatrogenic (i.e., relating to illness due to medical intervention) stress, it has been widely proposed that inhibition of autophagy would constitute a valid strategy for sensitizing cancer cells to chemotherapy or radiotherapy. Colliding with this cell-autonomous vision, however, we found that immunosurveillance against transplantable, carcinogen-induced or genetically engineered cancers can be improved by pharmacologically inducing autophagy with caloric restriction mimetics. This positive effect depends on autophagy induction in cancer cells and is mediated by alterations in extracellular ATP metabolism, namely increased release of immunostimulatory ATP and reduced adenosine-dependent recruitment of immunosuppressive regulatory T cells into the tumor bed. The combination of autophagy inducers and chemotherapeutic agents is particularly efficient in reducing cancer growth through the stimulation of CD8 + T lymphocyte-dependent anticancer immune responses.

  10. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  11. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    International Nuclear Information System (INIS)

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-01-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92–1.01). The median V 30 (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V 20 (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V 40 (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate pathologic

  12. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

    Science.gov (United States)

    Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2016-12-01

    The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  13. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  14. Modelling of tumour repopulation after chemotherapy

    International Nuclear Information System (INIS)

    Marcu, Loredana; Bezak, Eva

    2010-01-01

    Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

  15. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  16. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

    Science.gov (United States)

    Saunders, John H; Bowman, Christopher R; Reece-Smith, Alex M; Pang, Vincent; Dorrington, Matthew S; Mumtaz, Errum; Soomro, Irshad; Kaye, Philip; Madhusudan, Srinivasan; Parsons, Simon L

    2017-06-01

    For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity. © 2017 Wiley Periodicals, Inc.

  17. Probabilistic inductive inference: a survey

    OpenAIRE

    Ambainis, Andris

    2001-01-01

    Inductive inference is a recursion-theoretic theory of learning, first developed by E. M. Gold (1967). This paper surveys developments in probabilistic inductive inference. We mainly focus on finite inference of recursive functions, since this simple paradigm has produced the most interesting (and most complex) results.

  18. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  19. Sampling Assumptions in Inductive Generalization

    Science.gov (United States)

    Navarro, Daniel J.; Dry, Matthew J.; Lee, Michael D.

    2012-01-01

    Inductive generalization, where people go beyond the data provided, is a basic cognitive capability, and it underpins theoretical accounts of learning, categorization, and decision making. To complete the inductive leap needed for generalization, people must make a key "sampling" assumption about how the available data were generated.…

  20. From Inductive Reasoning to Proof

    Science.gov (United States)

    Yopp, David A.

    2009-01-01

    Mathematical proof is an expression of deductive reasoning (drawing conclusions from previous assertions). However, it is often inductive reasoning (conclusions drawn on the basis of examples) that helps learners form their deductive arguments, or proof. In addition, not all inductive arguments generate more formal arguments. This article draws a…

  1. Covariation in Natural Causal Induction.

    Science.gov (United States)

    Cheng, Patricia W.; Novick, Laura R.

    1991-01-01

    Biases and models usually offered by cognitive and social psychology and by philosophy to explain causal induction are evaluated with respect to focal sets (contextually determined sets of events over which covariation is computed). A probabilistic contrast model is proposed as underlying covariation computation in natural causal induction. (SLD)

  2. Fructose and NAFLD: metabolic implications and models of induction in rats Frutose e NAFLD: implicações metabólicas e modelos de indução em ratos

    Directory of Open Access Journals (Sweden)

    Gabriela S. F. Castro

    2011-01-01

    Full Text Available PURPOSE: The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63% fructose. Another group of rats was fed an diet with 63% fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100% of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal. In liver plates of Wistar rats fed 63% fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20% of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones.OBJETIVO: O aumento do consumo de frutose é concomitante a maior incidência mundial de obesidade. Este monossacarídeo está relacionado à Síndrome Metabólica, sendo vinculado à hipertrigliceridemia, hipertensão arterial, resistência à insulina e diabetes mellitus.

  3. Safe and feasible outpatient treatment following induction and consolidation chemotherapy for patients with acute leukaemia

    DEFF Research Database (Denmark)

    Møller, Tom; Nielsen, Ove Juul; Welinder, Pernille

    2010-01-01

    incorporating comprehensive patient education for self-care management at home during pancytopenia and involvement of patients in care of their tunnelled central venous catheter (CVC). During neutropenia, patients are treated with prophylactic ciprofloxacine, amoxicillin/clavulanic acid and fluconazole. Herein...

  4. Placing of tunneled central venous catheters prior to induction chemotherapy in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Møller, Jens Kjølseth; Frydenberg, Morten

    2010-01-01

    BACKGROUND: Tunneled central venous catheters (CVCs) are inevitable in children with acute lymphoid leukemia (ALL). The aim of this study was to evaluate the risk of CVC-related complications in children with ALL in relation to timing of catheter placement and type of catheter. PROCEDURE: All...

  5. Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice

    International Nuclear Information System (INIS)

    Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R.

    2001-01-01

    Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

  6. Metaplastic carcinoma. Breast. Relapse. Chemotherapy and Radiotherapy

    International Nuclear Information System (INIS)

    Marquez, A.; Terrasa, J.; Garcia, J.M.; Rifa, J.

    1996-01-01

    Metaplastic carcinoma of the breast is a rare tumor. The appearance of unexpected mesenchymal elements within the epithelial tumors is the squamous metaplasia. These tumors have a different clinical behaviour that classical breast carcinoma. We present a case of metaplastic mammary carcinoma with multiple relapses treated with a combination of chemotherapy and radiotherapy. The use of chemotherapy after local treatment has enhanced the relapse-free survival. The combined treatment modality seems to produce some benefit in the management of the local relapses of this neoplasms

  7. Retinoblastoma: Achieving new standards with methods of chemotherapy

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available The management of retinoblastoma (RB has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  8. Change of SPARC expression after chemotherapy in gastric cancer

    International Nuclear Information System (INIS)

    Gao, Yong-Yin; Han, Ru-Bing; Wang, Xia; Ge, Shao-Hua; Li, Hong-Li; Deng, Ting; Liu, Rui; Bai, Ming; Zhou, Li-Kun; Zhang, Xin-Yuan; Ba, Yi; Huang, Ding-Zhi

    2015-01-01

    The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes after chemotherapy in gastric cancer (GC) is unclear. This study investigated the influence of chemotherapy on SPARC expression in GC. Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy

  9. Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Ursula Winter

    Full Text Available Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure or metronomic (7-day continuous exposure treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50 was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks and metronomic (5 days a week for 2 weeks topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3-23 was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p0.05. In mice, continuous topotecan lead to significantly lower tumor volumes compared to conventional treatment after 14 days of treatment (p<0.05. Continuous exposure to melphalan or topotecan increased the chemosensitivity of retinoblastoma and endothelial cells to both chemotherapy agents with lower IC50 values compared to short-term treatment. These findings were validated in an in vivo model. None of the dosing modalities induced

  10. Defining optimal duration and predicting benefit from chemotherapy in patients with luminal-like subtypes.

    Science.gov (United States)

    Hart, Christopher D; Sanna, Giuseppina; Siclari, Olimpia; Biganzoli, Laura; Di Leo, Angelo

    2015-11-01

    The molecular subtypes of breast cancer have individual patterns of behaviour, prognosis and sensitivity to treatment, with subsequent implications for the choice of, or indeed role for adjuvant therapy. The luminal A and B subtypes make up the majority of breast cancers, but despite sharing expression of the oestrogen receptor (ER), they are molecularly distinct. It follows then that they would have different sensitivities to chemotherapy. Clinically, luminal A disease has a better prognosis than luminal B, and may not derive significant benefit from adjuvant chemotherapy. However no prospective trials have specifically investigated the benefit of adjuvant chemotherapy in each subtype, nor do we know if certain agents are more or less effective. This paper will briefly summarise the role of molecular profiles in assessing the need for chemotherapy and predicting its effectiveness, followed by an assessment of the relative value of newer anthracycline- or taxane-containing regimes in the luminal-like subtypes, providing a review of retrospective analyses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.

    Science.gov (United States)

    Marx, Wolfgang; Ried, Karin; McCarthy, Alexandra L; Vitetta, Luis; Sali, Avni; McKavanagh, Daniel; Isenring, Liz

    2017-01-02

    Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT 3 , substance P, and acetylcholine receptor antagonism; antiinflammatory properties; and modulation of cellular redox signaling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro, and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing CINV.

  12. Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

    Science.gov (United States)

    Dobrila-Dintinjana, Renata; Trivanovic, Dragan; Zelić, Marko; Radić, Mladen; Dintinjana, Marijan; Petranović, Duška; Toni, Valković; Vukelic, Jelena; Matijasic, Nusa

    2013-05-01

    Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

  13. Interferon induction by adenoviruses

    Energy Technology Data Exchange (ETDEWEB)

    Beladi, I; Bakay, M; Pusztai, R; Mucsi, I; Tarodi, B [University Medical School, Szeged (Hungary). Inst. of Microbiology

    1979-02-01

    All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and there-fore the adenovirus-specific T antigen was resitant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.

  14. Chemotherapy and Hair Loss: What to Expect during Treatment

    Science.gov (United States)

    Chemotherapy and hair loss: What to expect during treatment Your doctor can tell you whether your particular chemotherapy treatment is likely to cause hair loss. This allows you to plan ahead for head ...

  15. Chemotherapy and Sex: Is Sexual Activity OK during Treatment?

    Science.gov (United States)

    ... OK during treatment? Is it safe to have sex with my husband while undergoing chemotherapy? Answers from ... best to discuss any concerns about chemotherapy and sex with your doctor, who's familiar with your individual ...

  16. Side Effects of Chemotherapy and Radiation (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Side Effects of Chemotherapy and Radiation KidsHealth / For Parents / Side Effects of Chemotherapy and Radiation What's in this article? What to ...

  17. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Women “Talk with your doctor before you start treatment. Ask how chemotherapy could affect your ability to have ...

  18. Management of chemotherapy-induced nausea and vomiting.

    LENUS (Irish Health Repository)

    Zubairi, Ishtiaq H

    2006-08-01

    Chemotherapy-induced nausea and vomiting are symptoms that cause major concern to oncology patients. This article explores the types of nausea and vomiting in the context of chemotherapy, and discusses their pathogenesis and management.

  19. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

  20. Inductive line energy storage generator

    Energy Technology Data Exchange (ETDEWEB)

    Choi, P [Ecole Polytechnique, Palaiseau (France). Laboratoire de Physique des Milieux Ionises

    1997-12-31

    The inductive energy storage (IES) generator has long been considered to be the most efficient system for energy usage in large pulsed power system at the MA level. A number of parameters govern the efficiency of energy transfer between the storage capacitors and the load, and the level of current deliverable to the load. For high power system, the energy storage capacitors are arranged as a Marx generator. The primary constraints are the inductances in the various parts of the circuit, in particular, the upstream inductance between the Marx and the POS, and the downstream inductance between the POS and the load. This paper deals with the effect of replacing part of the upstream inductance with a transmission line and introduces the new concept of an inductive line for energy storage (ILES). Extensive parametric scans were carried out on circuit simulations to investigate the effect of this upstream transmission line. A model was developed to explain the operation of the ILES design based on the data obtained. Comparison with an existing IES generator shows that the ILES design offers a significant improvement in the maximum current and hence energy delivered to an inductive load. (author). 5 figs., 1 ref.

  1. [Supportive care during chemotherapy for lung cancer in daily practice].

    Science.gov (United States)

    Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

    2012-09-01

    Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

  2. Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

    Science.gov (United States)

    Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

    2015-11-01

    Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

  3. Radiation recall supraglottitis. A hazard in head and neck chemotherapy

    International Nuclear Information System (INIS)

    Wallenborn, P.A.; Postma, D.S.

    1984-01-01

    The enhanced effects of chemotherapy on previously irradiated tissue have been well demonstrated. When chemotherapy is given some time after irradiation and elicits a tissue reaction in the radiation field, the reaction is termed radiation recall. We review known interactions between chemotherapy and radiotherapy and report, to our knowledge, the first case of a supraglottitis radiation recall reaction. Familiarity with this phenomenon and potential complications of chemotherapy following head and neck irradiation may expedite early diagnosis and appropriate lifesaving treatment

  4. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients

  5. Comparison of chemotherapy and hematopoietic stem cell ...

    African Journals Online (AJOL)

    2013-02-19

    Feb 19, 2013 ... scores before and after hematopoietic stem cell transplantation (HSCT) and chemotherapy. Materials and Methods: Thirty-six patients undergoing HSCT were included in the study. A pre-HSCT dental treatment protocol was implemented that consisted of restoration of all active carious lesions, treatment of ...

  6. Pathological response for neoadjuvant chemotherapy in locally ...

    African Journals Online (AJOL)

    Background: Breast cancer is the leading cancer in Sudanese females. Objectives: This study was done to evaluate the clinical response to neoadjuvant chemotherapy for patients treated at National Cancer Institute (NCI) and to compare it with the published literature. Methods: This is a retrospective study conducted in ...

  7. Antimicrobial chemotherapy and Sustainable Development: The ...

    African Journals Online (AJOL)

    Antimicrobial chemotherapy and Sustainable Development: The past, The Current Trend, and the futu. ... Within the past half century, a wide variety of antimicrobial substances have been discovered, designed and synthesized; literally hundreds of drugs have been successfully used in some fashion over the years. Today ...

  8. Chemotherapy of gastric cancer - a radiological control

    International Nuclear Information System (INIS)

    Theobaldy, S.; Hofmann-Preiss, K.; Walter, M.

    1987-01-01

    In most cases of metastatic gastric cancer, treatment with cytostatic drugs seems to be justified. Responsiveness to chemotherapy, according to the MAF-schedule (Methotrexat, Adriamycin, 5-Fluorouracil) was reported to be successful in 50% of this cancer type. (orig.) [de

  9. Haemorheological changes in cancer patients on chemotherapy

    International Nuclear Information System (INIS)

    Omoti, C.E.; Osime, E.

    2007-01-01

    To assess the rheological changes in haematological and non-haematological cancer patients pre and post chemotherapy. It is a prospective study of 50 patients comprising 16(32%) haematological and 34(68%) non-haematological cancers of various types from March to December 2005 at University of Benin Teaching Hospital, Nigeria. Rheologic parameters estimated by the various specific diagnostic methods were determined in cancer patient's pre and post chemotherapy. The rheological tests estimated were relative plasma viscosity (RPV) measured by means of a capillary viscometer, whole blood viscosity (WBV), erythrocyte sedimentation rate (ESR) and plasma fibrinogen concentration (PFC) estimated by the Ingram's Clot weight method. The RPV in pre chemotherapy (p=0.006) and WBV in post chemotherapy (p=0.0231) patients measured revealed a significant difference when compared to controls. The fibrinogen concentration (P<0.0001) and ESR values (P<0.0001) were significantly increased in cancer patients when compared to controls. We conclude that total reduction of hyperviscosity and hyperfibrinogenaemia may contribute to effective treatment strategies in cancer patients. (author)

  10. Default from neoadjuvant chemotherapy in premenopausal female ...

    African Journals Online (AJOL)

    Seventeen (38.6%) patients dropped out of treatment, before, during or after completing NAC. Ten of these defaulted due to inadequate funds to procure chemotherapy, three patients because they insisted on immediate mastectomy, and four of these patients refused surgery when they achieved complete clinical response, ...

  11. Combined radiotherapy-chemotherapy in clinical practice

    International Nuclear Information System (INIS)

    Horwich, A.

    1989-01-01

    This paper investigates the combination of radiotherapy and chemotherapy performed over the last 15 years. The improvement of the therapeutic ratio of anti- cancer effect to normal tissue toxicity and its requirement of a thorough understanding of the biological effects of each modality and of how these effects may interact is presented. Early studies and conclusions are examined

  12. Patient expectancy and post-chemotherapy nausea

    DEFF Research Database (Denmark)

    Colagiuri, Ben; Zachariae, Robert

    2010-01-01

    to determine the strength of the relationship between expectancy and post-chemotherapy nausea. METHODS: The findings from 17 relevant studies (n = 2,400) identified through systematic searches of Medline, PsycInfo, and Cinhal were analyzed using a combination of meta-analytic techniques. RESULTS: Overall...

  13. Contralateral paradoxical response to chemotherapy in tuberculous ...

    African Journals Online (AJOL)

    Pleural effusions may occur as a complication of primary tuberculosis or an established pulmonary or extrapulmonary infection. New formation or expansion of a tuberculous lesion during chemotherapy is referred to as paradoxical response. Paradoxical response has been described to occur weeks or months after starting ...

  14. Overview of Bearingless Induction Motors

    Directory of Open Access Journals (Sweden)

    Xiaodong Sun

    2014-01-01

    Full Text Available Bearingless induction motors combining functions of both torque generation and noncontact magnetic suspension together have attracted more and more attention in the past decades due to their definite advantages of compactness, simple structure, less maintenance, no wear particles, high rotational speed, and so forth. This paper overviews the key technologies of the bearingless induction motors, with emphasis on motor topologies, mathematical models, and control strategies. Particularly, in the control issues, the vector control, independent control, direct torque control, nonlinear decoupling control, sensorless control, and so forth are investigated. In addition, several possible development trends of the bearingless induction motors are also discussed.

  15. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

    2011-01-01

    BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... chemotherapy regimen plus radiotherapy. SELECTION CRITERIA: Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also...... excluded. DATA COLLECTION AND ANALYSIS: Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none...

  16. Combination chemotherapy with cyclophosphamide adriamycin and vincristine for small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Edralin, A.C.

    1992-01-01

    Between January, 1988 and January, 1991, 29 patients were treated with cyclophosphamide, adriamycin and vincristine (CAV) chemotherapy and were evaluable after a median follow-up of 7.5 months. Of the 29 patients, 25 had limited disease (LD) and 4 had extensive disease (ED). Three patients had a complete remission (CR), 19 had a partial remission (PR) and 7 were non-responders. All the complete responders are still alive at 8, 10 and 40.8 months. The median survival time (MST) of all the patients was 8.5 months. The patients with LD had an MST of 8.5 months while those with ED had an MST of 5.5 months. The chemotherapy regimen produced a total response rate and median survival comparable to those achieved with other regimens. The complete response rate, however, was low and needed to be improved with other approaches. In partial responders, continuation of chemotherapy beyond the 3 courses given for induction did not improve the CR rate. Drug resistance was a limiting factor to the efficacy of this CAV regimen. Prophylactic cranial irradiation is recommended. (auth.). 21 refs.; 2 figs.; 2 tabs

  17. The effect of chemotherapy on rat brain PET: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)

    2010-10-15

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  18. The effect of chemotherapy on rat brain PET: preliminary study

    International Nuclear Information System (INIS)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min

    2010-01-01

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  19. Chemotherapy-induced peripheral neuropathy : Impact on quality of life

    NARCIS (Netherlands)

    Scheel, A.; Beijers, A.J.M.; Mols, F.; Faber, C.G.; Vreugdenhil, G.

    2014-01-01

    Peripheral neuropathy is a frequently occurring side-effect of chemotherapy as a cancer treatment. The incidence of chemotherapy-induced peripheral neuropathy (CIPN) is increasing as a consequence of better treatment of cancer becoming available and increasing use of chemotherapy, and because CIPN

  20. Chemotherapy Agents: A Primer for the Interventional Radiologist

    OpenAIRE

    Mihlon, Frank; Ray, Charles E.; Messersmith, Wells

    2010-01-01

    In this article, the authors review the basic principles of cancer chemotherapy and provide an overview of each of the general classes of chemotherapeutic agents with a target audience of interventional radiologists in mind. Special attention is paid to agents used in regional chemotherapy as well as agents commonly included in systemic chemotherapeutic regimens for patients who also require regional chemotherapy.

  1. Routine surgery in addition to chemotherapy for treating spinal tuberculosis

    NARCIS (Netherlands)

    Jutte, PC; Van Loenhout-Rooyackers, JH; Loenhout-Rooyackers, J.H.

    2006-01-01

    Background Tuberculosis is generally curable with chemotherapy, but there is controversy in the literature about the need for surgical intervention in the one to two per cent of people with tuberculosis of the spine. Objectives To compare chemotherapy plus surgery with chemotherapy alone for

  2. Cystic craniopharyngioma: intratumoral chemotherapy with