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Sample records for combined chemoradiation therapy

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-01

    administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy

  3. Combined chemo-radiation therapy to adult patients with B-cell lymphoma in stage I and II

    International Nuclear Information System (INIS)

    Shimoyama, Masanori

    1988-01-01

    155 adult patients with B-lymphoma in stage I and II who were treated in National Cancer Center Hospital between 1975 and 1986 were analyzed for treatment outcome. 5-year survival rates were about 66 % in these patients and almost equal in the patients treated with radiation alone, doxorubicin-containing combination chemotherapy alone, or combined chemoradiation therapy. However, when analysis was limited to patients in stage I, patients treated with chemotherapy alone seemed to have better survival rate than those treated with radiation alone. In the patients who were in stage III or more and had bulky mass more than 10 cm in diameter, small residual tumor was sometimes detected by restaging procedure after achieving apparent remission by multi-drug chemotherapy. In these patients, additional radiation therapy was quite usefull to eradicate residual tumor cell to cure. (author)

  4. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

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    Kordes, Sil [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Hulshof, Maarten C. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Bergman, Jacques J.G.H.M. [Department of Gastroenterology, Academic Medical Center, Amsterdam (Netherlands); Vliet, Hans J. van der [Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam (Netherlands); Kapiteijn, Ellen [Department of Medical Oncology, Leiden University Medical Center, Leiden (Netherlands); Laarhoven, Hanneke W.M. van; Richel, Dick J. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Klinkenbijl, Jean H.G. [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Meijer, Sybren L. [Department of Pathology, Academic Medical Center, Amsterdam (Netherlands); Wilmink, Johanna W. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands)

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  5. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    International Nuclear Information System (INIS)

    Kordes, Sil; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.; Bergman, Jacques J.G.H.M.; Vliet, Hans J. van der; Kapiteijn, Ellen; Laarhoven, Hanneke W.M. van; Richel, Dick J.; Klinkenbijl, Jean H.G.; Meijer, Sybren L.; Wilmink, Johanna W.

    2014-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m 2 ) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%

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

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

    1978-12-01

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

  7. Novel minimally invasive chemoradiation therapy combined with biliary stenting for multidisciplinary approach to unresectable bile duct carcinoma

    International Nuclear Information System (INIS)

    Suzuki, Masanori; Sato, Takeaki; Umino, Noriaki

    2001-01-01

    Multidisciplinary treatment is a useful approach to unresectable non-metastatic bile duct carcinoma with invasion of the hepatic artery and portal vein. The authors developed a multidisciplinary treatment consisting of chemoradiation therapy combined with intraluminal bile duct irradiation plus external irradiation and systemic or local chemotherapy. The aim of this regimen was to improve the ability to locally control bile duct carcinoma by intraluminal irradiation and to shorten the treatment period compared to external irradiation therapy alone. According to the treatment schedule whole-body irradiation is performed first and followed by systemic administration of 5-fluorouracil (5-FU, 600 mg/m 2 /day) and cisplatin (CDDP, 10 mg/m 2 /day) after biliary stenting plus simultaneously intraluminal irradiation (8 Gy/week x 3, total 24 Gy) administered with 192 Ir-RALS (Remote After Loading System). Two novel types of applicators specifically designed by the authors for intraluminal radiation of the bile duct were improved. The authors have used this multidisciplinary approach to treat 3 patients with bile duct carcinoma. Its application has shortened the course of multidisciplinary therapy to about 6 weeks, and the patients have surviveed more than 6-8 months without recurrence. (K.H.)

  8. Chemoradiation therapy for esophageal cancer

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  9. Preoperative chemoradiation therapy for advanced rectal cancer

    International Nuclear Information System (INIS)

    Tsujinaka, Toshimasa; Murotani, Masahiro; Iihara, Keisuke

    1997-01-01

    Preoperative concurrent chemoradiation therapy with 5-fluorouracil and cisplatin was applied for advanced rectal cancer. Eligible criteria were as follows: no previous treatment, more than hemicircular occupation, T 3 or more, invasion to adjacent organs or lymph node metastasis on CT scan, tumor fixation by digital examination. Eleven patients were enrolled with this regimen consisting of 5-FU; 500 mg/day x 5/w x 4, CDDP; 10 mg/day x 5/w x 4 and radiation; 2 Gy x 5/w x 4. As a toxicity, grade 2 leukopenia in 2 cases, grade 2 GI symptoms in one case and radiation dermatitis was observed in 8 cases. As a local response, there were PR in 10 cases and NC in 1 case. Surgical resection was performed on 8 patients. Histological responses in the resected specimens were grade 2, 5 cases; grade 1b, 1 case; and grade 1a, 2 cases. Operative radicalities were grade A, 3 cases; grade B, 3 cases; and grade C, 2 cases. Preoperative chemoradiation is one of the effective options in multimodal treatment for advanced rectal cancer. (author)

  10. Serum Transforming Growth Factor-β1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy

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    Lu, Shao-Lun; Hsu, Feng-Ming; Tsai, Chiao-Ling; Wu, Jian-Kuan [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Koong, Albert C.; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China)

    2015-12-01

    Purpose: Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy. Methods and Materials: We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically. Results: Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-β1 (TGF-β1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-β1 concentration (−11,310 vs −5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-β1 concentration (−37.4% vs −25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-β1 >7040 pg/mL (P=.014) were independent factors associated with PPCs. Conclusions: Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.

  11. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

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

    1995-07-15

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

  12. 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.

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

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

    2015-09-01

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

  14. A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer

    International Nuclear Information System (INIS)

    Kusano, Toru; Inomata, Masafumi; Hiratsuka, Takahiro

    2014-01-01

    Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. In total, 33 patients were enrolled (open surgery group, n=14; laparoscopic surgery group, n=19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery. (author)

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  16. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  17. Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  18. Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

    Science.gov (United States)

    Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

    2017-08-01

    This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

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

    International Nuclear Information System (INIS)

    Mizutani, Yoshihide; Kitahara Tadashi

    2004-01-01

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

  20. Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

    Science.gov (United States)

    Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

    2014-01-01

    BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  2. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

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

  3. Chemoradiation therapy efficacy in patients with local cervical cancer

    International Nuclear Information System (INIS)

    Nemal'tsova, O.A.

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

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

    Science.gov (United States)

    Sanche, Léon

    2009-05-01

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

  6. Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Azria, David, E-mail: david.azria@icm.unicancer.fr [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); INSERM, U896, IRCM, Montpellier (France); Riou, Olivier [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Rebillard, Xavier [Department of Urology, Clinique Beausoleil, Montpellier (France); Thezenas, Simon [Biostatistics Unit, Montpellier Cancer Institute, Montpellier (France); Thuret, Rodolphe [Department of Urology, Montpellier University Hospital, Montpellier (France); Fenoglietto, Pascal [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Pouessel, Damien; Culine, Stephane [Department of Medical Oncology, AP-HP Saint-Louis, Paris (France)

    2014-03-15

    Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  9. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...

  10. Results of surgical treatment versus chemoradiation therapy in oropharyngeal early tumors

    Directory of Open Access Journals (Sweden)

    Chedid, Helma Maria

    2009-03-01

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

  11. A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer

    International Nuclear Information System (INIS)

    Hatae, Masayuki; Takahashi, Takeshi; Kodama, Shoji

    2005-01-01

    Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m 2 as Level 1 or at 90 mg/m 2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6 patients receiving 80 mg/m 2 of CDGP and in all 2 patients receiving 90 mg/m 2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was partial response (PR) or better in all patients. The complete response (CR) rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration CDGP at 80 mg/m 2 on Days 1 and 29 is safe and effective. (author)

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

    Science.gov (United States)

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

    2018-01-01

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

  13. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography Udgivelsesdato: 2008/1...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic...

  14. A clinical study of esophagectomy after chemo-radiation therapy for advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Takeda, Shigeru; Tokuno, Kazuhisa; Nishimura, Taku; Yoshino, Shigefumi; Oka, Masaaki

    2007-01-01

    The aim of this study was to evaluate the efficacy of preoperative neoadjuvant therapy (NAT) including chemo-radiation or radiation in patients with T3/T4 advanced esophageal squamous cell carcinoma. We reviewed 115 patients with T3/T4 tumors from January 1994 through August 2006. Forty-seven patients received NAT, and the remaining 68 patients had surgery alone. Of these 47 patients, 14 patients underwent esophagectomy following NAT, and 33 patients underwent consecutive chemoradiation. Patients treated with esophagectomy following NAT had a better two-year survival (45.5%) and the median survival time (486 days) was compared with patients treated with chemo-radiation only (10.4%, 242 days) (p=0.026). Of these patients treated with esophagectomy following NAT, the patients undergone curative resection had a better one-year survival rate (83.3%) and the median survival time (2,055 days) was compared with the patients received with non-curative resection (20.0%, 273 days) (p=0.042). Two patients having grade 3 effect by NAT had a long disease free survival. There was no significant difference in postoperative morbidity and mortality rate between the patients received NAT and the patients treated with surgery alone. These results suggest that NAT may be useful for advanced esophageal cancer. (author)

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Shen BJ

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Chemotherapy and molecular target therapy combined with radiation therapy

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo

    2012-01-01

    Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

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

    LENUS (Irish Health Repository)

    Abdul-Jalil, K I

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-01

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

  5. 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)

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  7. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.

    2013-01-01

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m 2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer

  8. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wood, Laura D. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda L. [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hidalgo, Manuel [Centro Nacional de Investigaciones Oncologicas, Madrid (Spain); Donehower, Ross C. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schulick, Richard D.; Edil, Barish H. [Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado (United States); Choti, Michael A. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hruban, Ralph H. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    2006-06-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Yoshida, Tomoyuki

    2010-01-01

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

  14. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-01-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  15. WE-FG-BRA-02: Docetaxel Eluting Brachytherapy Spacers for Local Chemo-Radiation Therapy in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Belz, J [Northeastern University, Boston, MA (United States); Kumar, R; Sridhar, S [Northeastern University & Dana Farber Cancer Institute, Boston, MA (United States); Makrigiorgos, G; Nguyen, P [Dana Farber Cancer Institute, Boston, MA (United States); D’Amico, A [Brigham & Women’s Hospital, Boston, MA (United States); Cormack, R [Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: We propose an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a sustained drug delivery platform in the form of a spacer to locally radio-sensitize the prostate with Docetaxel (DTX) enabling a synergistic cure with the use of lower radiation doses. These biodegradable spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but are now loaded with formulations of DTX. Methods: Spacers were loaded with ∼500µg Docetaxel (DTX) for prostate cancer studies. The implants were characterized in vitro using SEM and HPLC. The release kinetic studies were carried out in buffer (pH 6.0) at 37°C. Subcutaneous PC3 tumors were xenografted in nude mice. Prostate cancer studies were done with and without radiation using SARRP at 5Gy, 10Gy, and 15Gy. Drug-loaded implants were injected once intratumorally using an 18G brachytherapy needle. Results: The release study in vitro showed a highly sustained release for multiple weeks at therapeutically relevant doses. The monotherapy with local DTX spacer showed sustained tumor inhibition compared to empty implants and an equivalent DTX dose given systemically. At 40 days, 89% survival was observed for mice treated with DTX implants compared with 0% in all other treatment groups. The combined treatment with local DTX spacer and radiation (10Gy) showed the highest degree of tumor suppression (significant tumor growth inhibition by day 90). The control mice showed continuous tumor growth and were scarified by day 56. Groups of mice treated with DTX-spacer or radiation alone showed initial tumor suppression but growth continued after day 60. A larger experiment is ongoing. Conclusion: This approach provides localized delivery of the chemotherapeutic sensitizer directly to the tumor and avoids the toxicities associated with both brachytherapy and current systemic delivery of docetaxel. Sustained release of DTX is an effective chemotherapy option alone or

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

    Science.gov (United States)

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

    2014-11-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  18. Salvage lymphadenectomy of the right recurrent nerve node with tracheal involvement after definitive chemoradiation therapy for esophageal squamous cell carcinoma. Report of two cases

    International Nuclear Information System (INIS)

    Doki, Yuichiro; Yasuda, Takushi; Miyata, Hiroshi

    2007-01-01

    Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma. (author)

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

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

    2006-03-15

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-01

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

  4. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  9. PUVA combination therapy.

    Science.gov (United States)

    Morison, W L

    1985-08-01

    Various adjunctive treatments are now frequently used in combination with PUVA therapy with the aims of limiting adverse effects, improving efficacy and decreasing the cost of treatment. In the management of psoriasis, PUVA plus retinoids, PUVA plus methotrexate and PUVA plus UVB phototherapy are the most frequently used combinations. PUVA plus topical corticosteroids and PUVA plus anthralin are also efficacious but adverse effects and poor acceptance by patients are limiting factors. Combinations of PUVA plus nitrogen mustard and ionizing radiation are used in mycosis fungoides to treat tumors and residual disease in secluded sites. In the management of photodermatoses with PUVA therapy, prednisone is often required to prevent exacerbation of disease. A combination of prednisone and PUVA therapy can also be useful in lichen planus and atopic eczema. The selection of a suitable combination treatment, will depend upon the preferences of the clinician, the disease being treated, and the characteristics of the patient.

  10. Postoperative Chemoradiation Therapy in High-Risk Cervical Cancer: Re-evaluating the Findings of Gynecologic Oncology Group Study 109 in a Large, Population-Based Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, Daniel M. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Swisher-McClure, Samuel [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Hegarty, Sarah E. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grover, Surbhi, E-mail: Surbhi.grover@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2015-12-01

    Purpose: To review the National Cancer Database (NCDB) to evaluate postoperative high-risk cervical cancer patients for factors associated with a benefit from chemoradiation therapy (CRT) over external beam radiation therapy alone (EBRT). Methods and Materials: The National Cancer Database was queried for women with cervical cancer treated with hysterectomy and adjuvant EBRT from 2002 to 2012. Only patients with pathologic lymph node involvement (LN+), positive surgical margins, and/or parametrial invasion were included in our analysis (on the basis of Peter's criteria). Univariable and multivariable analyses (MVA) were performed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate for factors associated with of CRT utilization and overall survival (OS). Results: A total of 3053 patients met inclusion criteria, and 2479 received adjuvant CRT (81%), whereas 574 (19%) received EBRT alone. Factors associated with increased CRT utilization on MVA included age <69 years, year of diagnosis ≥2008, non-adenocarcinoma histology, and LN+. Use of CRT improved OS among the entire cohort on MVA (HR 0.76, CI 0.601-0.962; P=.022). On MVA, CRT improved OS in patients with LN+ as their sole Peter's criteria (HR 0.58, CI 0.413-0.814; P=.002). Chemoradiation therapy did not improve OS in patients with only positive margins (P=.73), only parametrial invasion (P=.95), or any combination of these 2 factors without LN+ (P=.63). Conclusions: The use of adjuvant CRT after hysterectomy improves OS in patients with high-risk cervical cancer compared with EBRT alone, but this benefit seems to be restricted to patients with LN+. The benefits of adjuvant CRT over EBRT alone in patients with parametrial invasion and/or positive margins (without nodal involvement) are unknown.

  11. Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?

    International Nuclear Information System (INIS)

    Dewas, Claire Vautravers; Créhange, Gilles; Maingon, Philippe; Dalban, Cécile; Petitfils, Aurélie; Peignaux, Karine; Truc, Gilles; Martin, Etienne; Khoury, Cédric; Dewas, Sylvain

    2012-01-01

    Chemoradiation is the standard treatment for anal cancer. 3D conformal radiotherapy (3D-CRT) is usually split in 2 sequences with a therapeutic break (gap) in between. Intensity-modulated radiation therapy (IMRT) makes it possible to reduce treatment time by abandoning this gap. The purpose of this study was to compare outcomes and toxicities in patients treated with either IMRT or 3D-CRT. Between 2004 and 2011, the data of 51 patients treated with exclusive radiotherapy with or without concomitant chemotherapy for non-metastatic anal carcinoma were retrospectively analyzed. Twenty-seven patients were treated with 3D-CRT and 24 patients with IMRT, with a median dose delivered to the tumor of 59.4Gy [30.6-66.6], whatever the radiotherapy technique (p= 0.99). The median follow-up was 40 months [26.4-51.6]. There was no difference between the two groups for response to treatment (p= 0.46). Two-year overall survival, locoregional relapse-free survival and colostomy-free survival rates were 88.5%, 63% and 60.3%, respectively for the IMRT group and 81%, 76.5% and 81.1% for the 3D-CRT group (all NS). Ten patients (37%) in 3D-CRT and 11 patients (45.8%) in IMRT (p= 0.524) had grade 3 acute toxicity. No grade 4 toxicity occurred. Our study suggests that further investigations concerning the use of IMRT to treat cancer of the anus are warranted. IMRT makes it possible to remove the gap, but with no impact on the prognosis. Nonetheless, a longer follow-up is essential to determine whether or not IMRT has an impact on late toxicity, local control and survival compared with conventional 3D-CRT

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  14. Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Noticewala, Sonal S.; Li, Nan; Williamson, Casey W. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Hoh, Carl K. [Division of Nuclear Medicine, Department of Radiology, University of California San Diego, La Jolla, California (United States); Shen, Hanjie [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T.; Saenz, Cheryl C. [Division of Gynecologic Oncology, Department of Reproductive Medicine, University of California San Diego, La Jolla, California (United States); Einck, John [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Plaxe, Steven [Division of Gynecologic Oncology, Department of Reproductive Medicine, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2017-03-15

    Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy

  15. Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Noticewala, Sonal S.; Li, Nan; Williamson, Casey W.; Hoh, Carl K.; Shen, Hanjie; McHale, Michael T.; Saenz, Cheryl C.; Einck, John; Plaxe, Steven; Vaida, Florin; Yashar, Catheryn M.; Mell, Loren K.

    2017-01-01

    Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m"2) and 14 were treated with cisplatin (40 mg/m"2) plus gemcitabine (50-125 mg/m"2) (C/G). Patients underwent "1"8F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were

  16. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma.

    Science.gov (United States)

    Mohammadianpanah, M; Gramizadeh, B; Omidvari, Sh; Mosalaei, A

    2004-01-01

    Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  17. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma

    Directory of Open Access Journals (Sweden)

    Mohammadianpanah M

    2004-07-01

    Full Text Available Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  18. SU-C-207B-06: Comparison of Registration Methods for Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Riyahi, S; Choi, W; Bhooshan, N; Tan, S; Zhang, H; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States)

    2016-06-15

    Purpose: To compare linear and deformable registration methods for evaluation of tumor response to Chemoradiation therapy (CRT) in patients with esophageal cancer. Methods: Linear and multi-resolution BSpline deformable registration were performed on Pre-Post-CRT CT/PET images of 20 patients with esophageal cancer. For both registration methods, we registered CT using Mean Square Error (MSE) metric, however to register PET we used transformation obtained using Mutual Information (MI) from the same CT due to being multi-modality. Similarity of Warped-CT/PET was quantitatively evaluated using Normalized Mutual Information and plausibility of DF was assessed using inverse consistency Error. To evaluate tumor response four groups of tumor features were examined: (1) Conventional PET/CT e.g. SUV, diameter (2) Clinical parameters e.g. TNM stage, histology (3)spatial-temporal PET features that describe intensity, texture and geometry of tumor (4)all features combined. Dominant features were identified using 10-fold cross-validation and Support Vector Machine (SVM) was deployed for tumor response prediction while the accuracy was evaluated by ROC Area Under Curve (AUC). Results: Average and standard deviation of Normalized mutual information for deformable registration using MSE was 0.2±0.054 and for linear registration was 0.1±0.026, showing higher NMI for deformable registration. Likewise for MI metric, deformable registration had 0.13±0.035 comparing to linear counterpart with 0.12±0.037. Inverse consistency error for deformable registration for MSE metric was 4.65±2.49 and for linear was 1.32±2.3 showing smaller value for linear registration. The same conclusion was obtained for MI in terms of inverse consistency error. AUC for both linear and deformable registration was 1 showing no absolute difference in terms of response evaluation. Conclusion: Deformable registration showed better NMI comparing to linear registration, however inverse consistency of

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

    Science.gov (United States)

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

    2009-11-01

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

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

    Science.gov (United States)

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

    2006-06-01

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

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

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

  2. Long-term functional outcome of patients treated with chemoradiation therapy for carcinoma of the anal canal

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah

    1996-01-01

    . No patient required a colostomy due to functional impairment. One patient with a history of rheumatoid arthritis required surgery without colostomy due to large bowel necrosis believed to be secondary to CRT. Thus, the overall severe late morbidity rate was 4% ((2(47))). Among 17 patients evaluated for quality of life and continence, the impact of concerns about sphincter function on patients' quality of life was minimal in 53%, moderate in 24%, and significant in 24%. All patients reported complete continence of gas, liquid stool and solid stool prior to therapy. Immediately following CRT, 41% of patients experienced incontinence of solid stool which resolved within 1 year. This acute effect was reported by(2(8)) patients who received ≤ 45 Gy RT, versus (5(9)) of those who received > 45 Gy. One patient developed intermittent incontinence 10 years following CRT. Eight of seventeen patients reported permanent incontinence of gas and liquid stool with long-term follow-up, and the effect did not appear dose-related. CONCLUSIONS: Combined chemoradiation therapy yields high cure rates in patients with Stage I and II disease. However, local failure remains problematic among patients with Stage III disease despite the use of > 45 Gy RT. RT dose escalation is an important consideration for patients with advanced disease and is being investigated in RTOG no. 9208. In our series, higher RT doses did not result in higher late morbidity rates. Qualitative assessment of sphincter function demonstrated that 41% of patients experience transient incontinence of solid stool following completion of CRT, and this effect appeared more pronounced in patients receiving > 45 Gy RT. However, with long-term follow-up, most recover continence of solid stool, and impairment of anal sphincter function did not significantly compromise quality of life for most patients

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

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Shibata

    2011-09-01

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

  4. SU-D-207B-07: Development of a CT-Radiomics Based Early Response Prediction Model During Delivery of Chemoradiation Therapy for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klawikowski, S; Christian, J; Schott, D; Zhang, M; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    Purpose: Pilot study developing a CT-texture based model for early assessment of treatment response during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily CT data acquired for 24 pancreatic head cancer patients using CT-on-rails, during the routine CT-guided CRT delivery with a radiation dose of 50.4 Gy in 28 fractions, were analyzed. The pancreas head was contoured on each daily CT. Texture analysis was performed within the pancreas head contour using a research tool (IBEX). Over 1300 texture metrics including: grey level co-occurrence, run-length, histogram, neighborhood intensity difference, and geometrical shape features were calculated for each daily CT. Metric-trend information was established by finding the best fit of either a linear, quadratic, or exponential function for each metric value verses accumulated dose. Thus all the daily CT texture information was consolidated into a best-fit trend type for a given patient and texture metric. Linear correlation was performed between the patient histological response vector (good, medium, poor) and all combinations of 23 patient subgroups (statistical jackknife) determining which metrics were most correlated to response and repeatedly reliable across most patients. Control correlations against CT scanner, reconstruction kernel, and gated/nongated CT images were also calculated. Euclidean distance measure was used to group/sort patient vectors based on the data of these trend-response metrics. Results: We found four specific trend-metrics (Gray Level Coocurence Matrix311-1InverseDiffMomentNorm, Gray Level Coocurence Matrix311-1InverseDiffNorm, Gray Level Coocurence Matrix311-1 Homogeneity2, and Intensity Direct Local StdMean) that were highly correlated with patient response and repeatedly reliable. Our four trend-metric model successfully ordered our pilot response dataset (p=0.00070). We found no significant correlation to our control parameters: gating (p=0.7717), scanner (p

  5. Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko, E-mail: midoris@med.kitasato-u.ac.jp

    2014-07-01

    Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

  6. SU-F-R-50: Radiation-Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

    International Nuclear Information System (INIS)

    Chen, X; Schott, D; Song, Y; Li, D; Hall, W; Erickson, B; Li, X

    2016-01-01

    Purpose: In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogram including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two-tailed t-test and the correlations were analyzed using Spearman rank correlation tests. Results: In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P<0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response. Conclusion: Significant changes in HU histogram and the histogram-based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.

  7. SU-F-R-50: Radiation-Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

    Purpose: In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogram including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two-tailed t-test and the correlations were analyzed using Spearman rank correlation tests. Results: In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P<0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response. Conclusion: Significant changes in HU histogram and the histogram-based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.

  8. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  9. Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

    Science.gov (United States)

    Chera, Bhishamjit S; Fried, David; Price, Alex; Amdur, Robert J; Mendenhall, William; Lu, Chiray; Das, Shiva; Sheets, Nathan; Marks, Lawrence; Mavroidis, Panayiotis

    2017-08-01

    To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m 2 ), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. Six months after CRT, patients reporting xerostomia severity (n=14) had an average D mean = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average D mean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and D mean =21 Gy. Six months after CRT, patients reporting xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-01

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

  11. Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fraunholz, Ingeborg, E-mail: inge.fraunholz@kgu.de [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Rödel, Franz; Kohler, Daniela [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Diallo-Georgiopoulou, Margarita [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Department of Radiation Oncology, Klinikum Offenbach, Offenbach/Main (Germany); Distel, Luitpold [Department of Radiation Oncology, Friedrich Alexander University, Erlangen (Germany); Falk, Stefan [Pathology Associates, Frankfurt/Main (Germany); Rödel, Claus [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany)

    2013-08-01

    Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.

  12. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-01-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-01

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

  16. Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Noel J. Aherne

    2014-01-01

    Full Text Available Purpose. Glioblastoma multiforme (GBM is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months. We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  17. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    Science.gov (United States)

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  20. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

    2010-01-01

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m 2 /day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  1. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-01

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

  3. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    International Nuclear Information System (INIS)

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-01-01

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities

  4. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-04-01

    Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

  5. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

    Science.gov (United States)

    Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

    2016-04-01

    To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  7. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Kim, Jin C.; Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun Y.; Kim, Tae W.; Kim, Jong H.; Kang, Tae W.; Kim, Seon Y.; Kim, Yong S.

    2013-01-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  9. Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dongryul [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan, E-mail: ycahn.ahn@samsung.com [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Seok Jin; Kim, Won Seog [Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ko, Young Hyeh [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-11-01

    Purpose: To evaluate the effectiveness of concurrent chemoradiation therapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. Methods and Materials: From August 2004 to August 2012, 62 patients with newly diagnosed stage IE to IIE ENKTL underwent CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin, 30 mg/m{sup 2}, was administered weekly during the RT course. Responders to CCRT were encouraged to undergo consolidation chemotherapy. Three different consolidation chemotherapy regimens were used consecutively: VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone); VIDL (etoposide, ifosfamide, and dexamethasone followed by intramuscular injection of L-asparaginase); and MIDLE (methotrexate, etoposide, ifosfamide, mesna, and L-asparaginase). Results: The median follow-up period was 49 months (range 8-112). After completion of CCRT, 56 patients (90.3%) had a complete response, 4 (6.4%) had a partial response, 1 (1.6%) had stable disease, and 1 patient (1.6%) had progressive disease (PD). Consolidation chemotherapy was recommended to 61 patients, after excluding the patient with PD, but was actually delivered to 58. Of these 58 patients, 56 (96.5%) had a complete response and 2 (3.5%) had PD. During the follow-up period, 17 patients (including 3 with PD) experienced progression. The median interval to progression was 11 months (range 1-61). Local failure developed in 6 patients, of whom, 2 had developed progression outside the RT field. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 83.1%, 77.1%, and 92.4%, respectively. Grade ≥3 nonhematologic toxicity developed in only 3 patients (4.8%). Conclusions: Excellent clinical outcomes were achieved using CCRT with 40 Gy followed by consolidation chemotherapy. Additional investigation, however, is warranted to confirm our findings.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  11. The new criteria of clinical response for the primary tumor based on the findings of histological response after chemoradiation therapy in esophageal cancer

    International Nuclear Information System (INIS)

    Okumura, Hiroshi; Natsugoe, Shoji; Yokomakura, Naoya; Matsumoto, Masataka; Aikou, Takashi

    2005-01-01

    The incidence of chemoradiation therapy (CRT) increased in order to improve the surgical resectabilty and clinical outcome. It is important to accurately assess the effect of CRT for selecting further treatment and predicting prognosis. We tried to make the new criteria for imaging diagnosis after we reevaluated the discrepancy between clinical and histological effect of CRT. Subjects were 36 patients with advanced esophageal cancer who underwent esophagectomy with lymphadenectomy after CRT that consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The clinical and histological response was firstly evaluated based on esophageal disease guidelines for clinical and pathologic studies on carcinoma of the esophagus by the Japanese Society of Clinical response in imaging was reassessed based on the histological response. The number of tumors judged as clinical complete response/partial response/no change (CR/PR/NC) was 0/26/10, and the histological grading 1/2/3 was 17/11/8, respectively. Imaging for Grade 1 tumors showed the existence of viable cancer cells in biopsy specimen. Of 16 patients with such finding, 14 (88%) were histologically judged as Grade 1. Imaging characteristics for grade 3 tumors was more than a 75% reduction in esophagography, and the existence of scar formation by esophagoscopy. All five (100%) patients with these findings were histologically judged as Grade 3. The findings of grade 1 and 3 based on new criteria were independent predictive factors for CRT effect. According to new criteria, it was possible to predict the histological effect by the combination of esophagography and endoscopy in more than 80% of patients after CRT. Our new criteria may offer important information on the selection of further treatment or the prediction of prognosis after CRT in patients with esophageal cancer. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  15. Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Palma, David A., E-mail: david.palma@uwo.ca [Department of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Dios, Núria Rodríguez de [Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Universidad Pompeu Fabra, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barriger, R. Bryan [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moreno-Jiménez, Marta [Department of Oncology, Radiation Oncology Division, Clínica Universidad de Navarra, University of Navarra, Pamplona (Spain); Kim, Tae Hyun [Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of); Ramella, Sara [Division of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Everitt, Sarah [Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Australia and Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University (Australia); Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); and others

    2013-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors

  16. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal 18F-FDG PET Features, Clinical Parameters, and Demographics

    International Nuclear Information System (INIS)

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV] max , tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than

  17. Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Deek, Matthew P.; Benenati, Brian [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Kim, Sinae [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Biometrics Division, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting; Ahmed, Inaya; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-01-01

    Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-01

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

  19. Chemoradiation therapy with or without salvage surgery for early squamous cell carcinoma of the hypopharynx

    International Nuclear Information System (INIS)

    Nakamura, Katsumasa; Shioyama, Yoshiyuki; Sasaki, Tomonari; Ohga, Saiji; Saku, Madoka; Urashima, Yusuke; Yoshitake, Tadamasa; Nakashima, Torahiko; Kuratomi, Yuichiro; Komune, Shizuo; Terashima, Hiromi; Honda, Hiroshi

    2005-01-01

    Purpose: Early squamous cell carcinoma of the hypopharynx is a rare clinical entity. Our objective was to analyze the outcome of patients with early hypopharyngeal cancer treated with curative radiotherapy or the combination of preoperative radiotherapy with surgery. Methods and Materials: Forty-three patients with Stage I-II hypopharyngeal cancer were initially treated with 30-40 Gy of irradiation with or without chemotherapy. Thirty-two patients (74.4%) who demonstrated a complete response continued to receive further radiotherapy, with a median total dose of 61.2 Gy. Eleven other patients (25.6%) received surgery. Results: Local control with laryngeal voice preservation was achieved in 8 (88.9%) of 9 patients with Stage I disease, and in 23 (67.6%) of 34 patients with Stage II disease. The overall and disease-specific 5-year survival rates for all patients were 70.4% and 89.5%, respectively. The disease-specific survival rates according to the T-category were 100% for patients with T1 disease and 87.2% for patients with T2 disease (p = 0.32). Twenty patients (46.5%) had synchronous or metachronous cancers. Four patients died of hypopharyngeal cancer, and 5 died of second-primary esophageal cancer. Conclusions: A majority of patients with early hypopharyngeal cancer was curable. However, second malignancies influenced the overall outcome of patients with early hypopharyngeal cancer

  20. Cancer nanomedicine: gold nanoparticle mediated combined cancer therapy

    Science.gov (United States)

    Yang, C.; Bromma, Kyle; Chithrani, B. D.

    2018-02-01

    Recent developments in nanotechnology has provided new tools for cancer therapy and diagnosis. Among other nanomaterial systems, gold nanoparticles are being used as radiation dose enhancers and anticancer drug carriers in cancer therapy. Fate of gold nanoparticles within biological tissues can be probed using techniques such as TEM (transmission electron microscopy) and SEM (Scanning Electron Microscopy) due to their high electron density. We have shown for the first time that cancer drug loaded gold nanoparticles can reach the nucleus (or the brain) of cancer cells enhancing the therapeutic effect dramatically. Nucleus of the cancer cells are the most desirable target in cancer therapy. In chemotherapy, smart delivery of highly toxic anticancer drugs through packaging using nanoparticles will reduce the side effects and improve the quality and care of cancer patients. In radiation therapy, use of gold nanoparticles as radiation dose enhancer is very promising due to enhanced localized dose within the cancer tissue. Recent advancement in nanomaterial characterization techniques will facilitate mapping of nanomaterial distribution within biological specimens to correlate the radiobiological effects due to treatment. Hence, gold nanoparticle mediated combined chemoradiation would provide promising tools to achieve personalized and tailored cancer treatments in the near future.

  1. Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

    Science.gov (United States)

    Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

    2012-11-01

    Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

  2. Strategies for combinational cancer therapies

    International Nuclear Information System (INIS)

    Khleif, Samir

    2014-01-01

    The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

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

    DEFF Research Database (Denmark)

    Kirchheiner, Kathrin; Pötter, Richard; Tanderup, Kari

    2016-01-01

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

  4. Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

    Science.gov (United States)

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

    2016-01-01

    Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT

  5. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    International Nuclear Information System (INIS)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

    2015-01-01

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

  6. Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report

    International Nuclear Information System (INIS)

    Florczynski, Matthew M.; Sanatani, Michael S.; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E.; Cao, Jeffrey; Louie, Alexander V.; Pope, Janet E.; Leung, Eric

    2016-01-01

    The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient’s myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient’s symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment

  7. Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report.

    Science.gov (United States)

    Florczynski, Matthew M; Sanatani, Michael S; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E; Cao, Jeffrey; Louie, Alexander V; Pope, Janet E; Leung, Eric

    2016-03-22

    The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Puchinina, E.A.

    1990-01-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  11. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    International Nuclear Information System (INIS)

    Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

    2015-01-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  12. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

    2015-06-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  13. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    International Nuclear Information System (INIS)

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-01-01

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation

  14. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    Energy Technology Data Exchange (ETDEWEB)

    Habr-Gama, Angelita, E-mail: gamange@uol.com.br [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); Gama-Rodrigues, Joaquim [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); São Julião, Guilherme P. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Colorectal Surgery Division, University of São Paulo School of Medicine, São Paulo (Brazil); Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Perez, Rodrigo O. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Ludwig Institute for Cancer Research, São Paulo Branch (Brazil)

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

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

    Science.gov (United States)

    McCullough, Ricky W

    2018-01-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-01

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

  18. Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

    Science.gov (United States)

    Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

    2015-01-01

    The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

  19. An opioid-based pain control program for head and neck cancer patients undergoing chemoradiation therapy achieves a high completion rate of radiation

    International Nuclear Information System (INIS)

    Kato, Kengo; Matsuura, Kazuto; Zenda, Sadamoto

    2011-01-01

    Appropriate supportive care is essential for intensive chemoradiation therapy (CRT), and pain management is an important supportive care for CRT for head and neck cancer. We developed an opioid-based pain control program for head and neck cancer patients undergoing CRT, and assessed its efficacy and safety. 110 head and neck cancer patients undergoing platinum-based concomitant CRT were enrolled from 10 cancer centers or university hospitals. Their pain caused by CRT was managed with a four-step opioid-based pain control program, and adverse events and usage of opioid were analyzed. 101 suitable cases of 110 patients were analyzed. 53% of cases suffered grade 3-4 mucositis. The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13%. The usage rate of opioid was 83% and the rate of compliance with the pain control program was 92%. The median maximum quantity of morphine used per day was 35 mg. No patient had to stop the opioid program or radiotherapy due to adverse effects of opioids. An opioid-based pain control program for head and neck cancer patients undergoing CRT achieves a high completion rate of radiation. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

  1. Cost-Effectiveness Analysis of Chemoradiation Therapy Versus Transoral Robotic Surgery for Human Papillomavirus–Associated, Clinical N2 Oropharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: david.sher@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Tishler, Roy B. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Stenson, Kerstin; Al-Khudari, Samer [Department of Otolaryngology, Rush University Medical Center, Chicago, Illinois (United States)

    2016-03-01

    Purpose: To perform a cost-effectiveness analysis of primary chemoradiation therapy (CRT) versus transoral robotic surgery (TORS) for clinical N2, human papillomavirus (HPV)-positive oropharyngeal carcinoma. Methods and Materials: We developed a Markov model to describe the health states after treatment with CRT or TORS, followed by adjuvant radiation therapy or CRT in the presence of high-risk pathology (positive margins or extracapsular extension). Outcomes, toxicities, and costs were extracted from the literature. One-way sensitivity analyses (SA) were performed over a wide range of parameters, as were 2-way SA between the key variables. Probabilistic SA and value of information studies were performed over key parameters. Results: The expected quality-adjusted life years (QALYs)/total costs for CRT and TORS were 7.31/$50,100 and 7.29/$62,200, respectively, so that CRT dominated TORS. In SA, primary CRT was almost always cost-effective up to a societal willingness-to-pay of $200,000/QALY, unless the locoregional recurrence risk after TORS was 30% to 50% lower, at which point it became cost effective at a willingness-to-pay of $50-100,000/QALY. Probabilistic SA confirmed the importance of locoregional recurrence risk, and the value of information in precisely knowing this parameter was more than $7M per year. If the long-term utility after TORS was 0.03 lower than CRT, CRT was cost-effective over nearly any assumption. Conclusions: Under nearly all assumptions, primary CRT was the cost-effective therapy for HPV-associated, clinical N2 OPC. However, in the hypothetical event of a large relative improvement in LRR with surgery and equivalent long-term utilities, primary TORS would become the higher-value treatment, arguing for prospective, comparative study of the 2 paradigms.

  2. Cost-Effectiveness Analysis of Chemoradiation Therapy Versus Transoral Robotic Surgery for Human Papillomavirus–Associated, Clinical N2 Oropharyngeal Cancer

    International Nuclear Information System (INIS)

    Sher, David J.; Fidler, Mary Jo; Tishler, Roy B.; Stenson, Kerstin; Al-Khudari, Samer

    2016-01-01

    Purpose: To perform a cost-effectiveness analysis of primary chemoradiation therapy (CRT) versus transoral robotic surgery (TORS) for clinical N2, human papillomavirus (HPV)-positive oropharyngeal carcinoma. Methods and Materials: We developed a Markov model to describe the health states after treatment with CRT or TORS, followed by adjuvant radiation therapy or CRT in the presence of high-risk pathology (positive margins or extracapsular extension). Outcomes, toxicities, and costs were extracted from the literature. One-way sensitivity analyses (SA) were performed over a wide range of parameters, as were 2-way SA between the key variables. Probabilistic SA and value of information studies were performed over key parameters. Results: The expected quality-adjusted life years (QALYs)/total costs for CRT and TORS were 7.31/$50,100 and 7.29/$62,200, respectively, so that CRT dominated TORS. In SA, primary CRT was almost always cost-effective up to a societal willingness-to-pay of $200,000/QALY, unless the locoregional recurrence risk after TORS was 30% to 50% lower, at which point it became cost effective at a willingness-to-pay of $50-100,000/QALY. Probabilistic SA confirmed the importance of locoregional recurrence risk, and the value of information in precisely knowing this parameter was more than $7M per year. If the long-term utility after TORS was 0.03 lower than CRT, CRT was cost-effective over nearly any assumption. Conclusions: Under nearly all assumptions, primary CRT was the cost-effective therapy for HPV-associated, clinical N2 OPC. However, in the hypothetical event of a large relative improvement in LRR with surgery and equivalent long-term utilities, primary TORS would become the higher-value treatment, arguing for prospective, comparative study of the 2 paradigms.

  3. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan); Sagawa, Tamotsu [Division of Gastroenterology, Hokkaido Cancer Center, Sapporo (Japan); Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi [Department of Radiology, Sapporo Medical University School of Medicine, Sapporo (Japan); Takayama, Tetsuji [Department of Gastroenterology and Oncology, University of Tokushima, Tokushima (Japan); Kato, Junji, E-mail: jkato@sapmed.ac.jp [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan)

    2015-10-01

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

  4. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    International Nuclear Information System (INIS)

    Topkan, Erkan; Parlak, Cem; Selek, Ugur

    2013-01-01

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT

  5. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    International Nuclear Information System (INIS)

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu; Sagawa, Tamotsu; Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi; Takayama, Tetsuji; Kato, Junji

    2015-01-01

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m 2 ) and nedaplatin (50 mg/m 2 ) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m 2 /day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m 2 . In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC

  6. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

    2013-07-15

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

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

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

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

  8. Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study

    International Nuclear Information System (INIS)

    Puerto-Nevado, Laura del; Marin-Arango, Juan Pablo; Fernandez-Aceñero, Maria Jesus; Arroyo-Manzano, David; Martinez-Useros, Javier; Borrero-Palacios, Aurea; Rodriguez-Remirez, Maria; Cebrian, Arancha; Gomez del Pulgar, Teresa; Cruz-Ramos, Marlid; Carames, Cristina; Lopez-Botet, Begoña; Garcia-Foncillas, Jesús

    2016-01-01

    Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. However, tumor response following NACRT varies, ranging from pathologic complete response to disease progression. We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and as such are potential predictors of tumor response and may aid in identifying patients who could benefit from NACRT. Sixty-seven pretreatment biopsies were examined for VRK1 and VRK2 expression using tissue microarrays. VRK1 and VRK2 Histoscores were combined by linear addition, resulting in a new variable designated as “composite score”, and the statistical significance of this variable was assessed by univariate and multivariate logistic regression. The Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC) analysis were carried out to evaluate calibration and discrimination, respectively. A nomogram was also developed. Univariate logistic regression showed that tumor size as well as composite score were statistically significant. Both variables remained significant in the multivariate analysis, obtaining an OR for tumor size of 0.65 (95 % CI, 0.45–0.94; p = 0.021) and composite score of 1.24 (95 % CI, 1.07–1.48; p = 0.005). Hosmer-Lemeshow test showed an adequate model calibration (p = 0.630) and good discrimination was also achieved, AUC 0.79 (95 % CI, 0.68–0.90). This study provides novel data on the role of VRK1 and VRK2 in predicting tumor response to NACRT, and we propose a model with high predictive ability which could have a substantial impact on clinical management of locally advanced rectal cancer. The online version of this article (doi:10.1186/s12885-016-2574-9) contains supplementary material, which is available to authorized users

  9. Cancer stem cells and chemoradiation resistance

    International Nuclear Information System (INIS)

    Ishii, Hideshi; Mori, Masaki; Iwatsuki, Masaaki; Ieta, Keisuke; Ohta, Daisuke; Haraguchi, Naotsugu; Mimori, Koshi

    2008-01-01

    Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer. (author)

  10. Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Chera, Bhishamjit S.; Amdur, Robert J.; Tepper, Joel; Qaqish, Bahjat; Green, Rebecca; Aumer, Shannon L.; Hayes, Neil; Weiss, Jared; Grilley-Olson, Juneko; Zanation, Adam; Hackman, Trevor

    2015-01-01

    Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus–associated oropharyngeal squamous cell carcinoma. Methods and Materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m"2). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. (ClinicalTrials.gov) ID: (NCT01530997).

  11. Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chera, Bhishamjit S., E-mail: bchera@med.unc.edu [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Amdur, Robert J. [Department of Radiation Oncology, University of Florida School of Medicine, Gainesville, Florida (United States); Shands Cancer Center, University of Florida School of Medicine, Gainesville, Florida (United States); Tepper, Joel [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Qaqish, Bahjat [Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina (United States); Green, Rebecca [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Aumer, Shannon L. [Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Hayes, Neil; Weiss, Jared; Grilley-Olson, Juneko [Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Division of Hematology Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Zanation, Adam; Hackman, Trevor [Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); and others

    2015-12-01

    Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus–associated oropharyngeal squamous cell carcinoma. Methods and Materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m{sup 2}). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. (ClinicalTrials.gov) ID: (NCT01530997).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-01

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

  13. [Combination drug therapy in leprosy].

    Science.gov (United States)

    Terencio de las Aguas, J

    1983-01-01

    The importance of polichemotherapy in multibacilar leprosy (LL and LD) in patients without any previous therapy as in those diagnosticated and under monotherapy most of all in the resistance patients is presented. Sulphones, clofazimine and rifampicine are selected as first rate drugs and protionamide-etionamide as second rate drugs. The therapy plans with the association of two and three drugs and the convenience of continuing indefinitely with at least one of the drugs are presented insisting on the advantages of the clofazimine-sulphones and rifampicine-sulphones associations. The necessity of immunotherapy for recover of celular immunity against the bacilus, is the only form of preventing relapses and drug resistance.

  14. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

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    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

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

    Directory of Open Access Journals (Sweden)

    Heeger S

    2005-10-01

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

  16. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  17. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

    Science.gov (United States)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-01-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits

  19. Secondary malignancies in patients with stage IA-IIIA Hodgkin's lymphoma after radiation (chemoradiation) therapy using accelerated dose fractionation

    International Nuclear Information System (INIS)

    Sinajko, V.V.; Minajlo, I.I.; Veyakin, I.V.

    2010-01-01

    The incidence of secondary malignancies was investigated in 367 patients with stage IA-IIIA Hodgkin's lymphoma after radiation therapy using accelerated fractionation. For 20 years of the observation 24 of them developed 27(7.4%) tumors, besides their frequency did not depend on the disease stage and method of treatment.

  20. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  1. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-01-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  7. SU-C-BRA-04: Use of Esophageal Wall Thickness in Evaluation of the Response to Chemoradiation Therapy for Esophageal Cancer

    International Nuclear Information System (INIS)

    Wang, J; Kligerman, S; Lu, W; Kang, M

    2015-01-01

    Purpose: To quantitatively evaluate the esophageal cancer response to chemoradiation therapy (CRT) by measuring the esophageal wall thickness in CT. Method: Two datasets were used in this study. The first dataset is composed of CT scans of 15 esophageal cancer patients and 15 normal controls. The second dataset is composed of 20 esophageal cancer patients who underwent PET/CT scans before (Pre-CRT) and after CRT (Post-CRT). We first segmented the esophagus using a multi-atlas-based algorithm. The esophageal wall thickness was then computed, on each slice, as the equivalent circle radius of the segmented esophagus excluding the lumen. To evaluate the changes of wall thickness, we computed the standard deviation (SD), coefficient of variation (COV, SD/Mean), and flatness [(Max–Min)/Mean] of wall thickness along the entire esophagus. Results: For the first dataset, the mean wall thickness of cancer patients and normal controls were 6.35 mm and 6.03 mm, respectively. The mean SD, COV, and flatness of the wall thickness were 2.59, 0.21, and 1.27 for the cancer patients and 1.99, 0.16, and 1.13 for normal controls. Statistically significant differences (p < 0.05) were identified in SD and flatness. For the second dataset, the mean wall thickness of pre-CRT and post-CRT patients was 7.13 mm and 6.84 mm, respectively. The mean SD, COV, and flatness were 1.81, 0.26, and 1.06 for pre-CRT and 1.69, 0.26, and 1.06 for post-CRT. Statistically significant difference was not identified for these measurements. Current results are based on the entire esophagus. We believe significant differences between pre- and post-CRT scans could be obtained, if we conduct the measurements at tumor sites. Conclusion: Results show thicker wall thickness in pre-CRT scans and differences in wall thickness changes between normal and abnormal esophagus. This demonstrated the potential of esophageal wall thickness as a marker in the tumor CRT response evaluation. This work was supported in part by

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  11. [Quantitative analysis of diffusion-weighted magnetic resonance images during chemoradiation therapy for cancer of the cervix uteri: Prognostic role of pretreatment diffusion coefficient values].

    Science.gov (United States)

    Kharuzhyk, S A

    2015-01-01

    to carry out a quantitative analysis of diffusion-weighted magnetic resonance images (DWI) in cancer of the cervix uteri (CCU) and to estimate the possibility of using pretreatment measured diffusion coefficient (MDC) to predict chemoradiation therapy (CRT). The investigation prospectively enrolled 46 women with morphologically verified Stages IB-IVB CCU. All the women underwent diffusion-weighted magnetic resonance imaging of pelvic organs before and after treatment. A semiautomatic method was used to determine tumor signal intensity (SI) on DWI at b 1000 s/mm2 (SI b1000) and tumor MDC. The reproducibility of MDC measurements was assessed in 16 randomly selected women. The investigators compared the pretreatment quantitative DWI measures in complete and incomplete regression (CR and IR) groups and the presence and absence of tumor progression during a follow-up. An association of MDC with progression-free and overall survivals (PFS and OS) was determined in the patients. A semiautomatic tumor segmentation framework could determine the pretreatment quantitative DMI measures with minimal time spent and high reproducibility. The mean tumor MDC was 0.82 +/- 0.14 x 10(-3) mm2/s. CR and IR were established in 28 and 18 women, respectively. The MDC < or = 0.83 x 10(-3) mm2/s predicted CR with a sensitivity of 64.3% and a specificity of 77.8% (p=0.007). The median follow-up was 47 months (range, 3-82 months). With the MDC < or = 0.86 x 10(-3) mm2/s, 5-year PFS was 74.1% versus 42.1% with a higher MDC (p=0.023) and 5-year OS was 70.4 and 40.6%, respectively (p=0.021). The survival difference was insignificant in relation to the degree of tumor regression. The pretreatment IS at b1000 was of no prognostic value. The pretreatment tumor MDC may serve as a biomarker for predicting the efficiency of CRT for CCU.

  12. Cone-beam computed tomography for lung cancer - validation with CT and monitoring tumour response during chemo-radiation therapy.

    Science.gov (United States)

    Michienzi, Alissa; Kron, Tomas; Callahan, Jason; Plumridge, Nikki; Ball, David; Everitt, Sarah

    2017-04-01

    Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical 'gold standard', CT. Tumour regression or progression on CBCT was also analysed. Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R 2 ). Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97-0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC. © 2016 The Royal Australian and New Zealand College of Radiologists.

  13. Advances in combination therapy of lung cancer

    DEFF Research Database (Denmark)

    Wu, Lan; Leng, Donglei; Cun, Dongmei

    2017-01-01

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

  14. Combination stem cell therapy for heart failure

    Directory of Open Access Journals (Sweden)

    Ichim Thomas E

    2010-04-01

    Full Text Available Abstract Patients with congestive heart failure (CHF that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a increasing stem cell migration to the heart; b augmenting stem cell activity; and c combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

  15. Artificial intelligence in drug combination therapy.

    Science.gov (United States)

    Tsigelny, Igor F

    2018-02-09

    Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  17. [Combination drug therapy in patients with BPH].

    Science.gov (United States)

    Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

    2018-03-01

    Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself

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

    International Nuclear Information System (INIS)

    Grassberger, C; Paganetti, H

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  20. [Combination therapy of chronic bacterial prostatitis].

    Science.gov (United States)

    Khryanin, A A; Reshetnikov, O V

    2016-08-01

    The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.

  1. Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2 : proposed applications and treatment protocols

    NARCIS (Netherlands)

    Zecha, J.A.E.M.; Raber-Durlacher, J.E.; Nair, R.G.; Epstein, J.B.; Elad, S.; Hamblin, M.R.; Barasch, A.; Migliorati, C.A.; Milstein, D.M.J.; Genot, M.T.; Lansaat, L.; van der Brink, R.; Arnabat-Dominguez, J.; van der Molen, L.; Jacobi, I.; van Diessen, J.; de Lange, J.; Smeele, L.E.; Schubert, M.M.; Bensadoun, R.J.

    2016-01-01

    Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together

  2. Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

    NARCIS (Netherlands)

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

    2016-01-01

    There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a

  3. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    Science.gov (United States)

    Kuranishi, Fumito; Ohno, Tadao

    2013-06-04

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

  4. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  7. Trial of radiation therapy combined with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Takegawa, Y; Fujiwara, K; Oe, J; Nagase, M; Akiyama, H [Tokushima Univ. (Japan). School of Medicine

    1978-08-01

    Nine patients were treated by the combination therapy of external irradiation and hyperthermia, 5 patients with metastatic lesions; two breast cancer, one lung cancer, one malignant melanoma, one vulva cancer, 1 patient with recurrent lesion of skin cancer and 3 patients with bladder cancer. All patients were treated by heating locally (42/sup 0/C, 30 min) followed by external irradiation with 4,000 - 5,000 rad over 4 to 5 weeks. No local recurrence was found in 4 of 9 patients.

  8. Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca [London Regional Cancer Program, London, Ontario (Canada); Hu, Chen [Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania (United States); Macdonald, David R. [London Regional Cancer Program, London, Ontario (Canada); Lesser, Glenn J. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Coons, Stephen W. [Barrow Neurological Institute, Phoenix, Arizona (United States); Brachman, David G. [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Ryu, Samuel [Henry Ford Hospital, Detroit, Michigan (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital Center, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, Quebec (Canada); Liu, Junfeng [GCE Solutions, Inc., Bloomington, Illinois (United States); Chakravarti, Arnab [The Ohio State University, The James, Columbus, Ohio (United States); Mehta, Minesh [University of Maryland Medical Systems, Baltimore, Maryland (United States)

    2015-03-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

  9. Combination Therapy for Airflow Limitation In COPD

    Directory of Open Access Journals (Sweden)

    Jafar Aslani

    2012-08-01

    Full Text Available Background and the purpose of the study Existing evidence confirms that no pharmacologic agent ameliorates the decline in the lung function or changes the prognosis of chronic obstructive pulmonary disease (COPD. We tried a critical combination therapy for management of COPD. Methods Current or past smoker (passive or active COPD patients with moderate to severe COPD who did not respond to primitive therapy (i.e., oral prednisolone (50 mg in the morning for 5 days; with Beclomethasone Fort (3 puff q12h, totally 1500 micrograms/day, Salmeterol (2 puffs q12h, 50 micrograms/puff and ipratropium bromide (4 puffs q8h for two months, enrolled to study. Furthermore they were received N-Acetylcysteine (1200 mg/daily, Azithromycin (tablet 250 mg/every other day and Theophylline (100 mg BD.Results The study group consisted of 44 men and 4 women, with a mean age and standard deviation of 63.6+/-12.7 years (range 22-86 years. Thirteen of 48 patients (27.0% was responder based on 15% increasing in FEV 1 (27.7+/-7.9 after 6.7+/-6.1 months (57.9+/-12.9 year old. There were statistically significant differences in age and smoking between responders and nonresponders (P value was 0.05 and 0.04 respectively. There was no difference in emphysema and air trapping between two groups (p=0.13. Conclusion Interestingly considerable proportion of patients with COPD can be reversible using combination drug therapy and patients will greatly benefit from different and synergic action of the drugs. The treatment was more effective in younger patients who smoke less.

  10. Phase I/II trial of vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02.

    Science.gov (United States)

    Galanis, Evanthia; Anderson, S Keith; Miller, C Ryan; Sarkaria, Jann N; Jaeckle, Kurt; Buckner, Jan C; Ligon, Keith L; Ballman, Karla V; Moore, Dennis F; Nebozhyn, Michael; Loboda, Andrey; Schiff, David; Ahluwalia, Manmeet Singh; Lee, Eudocia Q; Gerstner, Elizabeth R; Lesser, Glenn J; Prados, Michael; Grossman, Stuart A; Cerhan, Jane; Giannini, Caterina; Wen, Patrick Y

    2018-03-27

    Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown radiosensitizing properties in preclinical studies. This open-label, single-arm trial evaluated the maximum tolerated dose (MTD; phase I) and efficacy (phase II) of vorinostat combined with standard chemoradiation in newly diagnosed glioblastoma. Patients received oral vorinostat (300 or 400 mg/day) on days 1-5 weekly during temozolomide chemoradiation. Following a 4- to 6-week rest, patients received up to 12 cycles of standard adjuvant temozolomide and vorinostat (400 mg/day) on days 1-7 and 15-21 of each 28-day cycle. Association between vorinostat response signatures and progression-free survival (PFS) and overall survival (OS) was assessed based on RNA sequencing of baseline tumor tissue. Phase I and phase II enrolled 15 and 107 patients, respectively. The combination therapy MTD was vorinostat 300 mg/day and temozolomide 75 mg/m2/day. Dose-limiting toxicities were grade 4 neutropenia and thrombocytopenia and grade 3 aspartate aminotransferase elevation, hyperglycemia, fatigue, and wound dehiscence. The primary efficacy endpoint in the phase II cohort, OS rate at 15 months, was 55.1% (median OS 16.1 mo), and consequently, the study did not meet its efficacy objective. Most common treatment-related grade 3/4 toxicities in the phase II component were lymphopenia (32.7%), thrombocytopenia (28.0%), and neutropenia (21.5%). RNA expression profiling of baseline tumors (N = 76) demonstrated that vorinostat resistance (sig-79) and sensitivity (sig-139) signatures had a reverse and positive association with OS/PFS, respectively. Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials.

  11. The Role of 18F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Choi, Jiyoun; Kim, Hyun Jeong; Jeong, Yong Hyu; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Yong Bae; Kim, Young Tae; Kang, Won Jun

    2014-01-01

    To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p 18 F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor

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

    Science.gov (United States)

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

    2017-11-01

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

  13. The Role of {sup 18}F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jiyoun; Kim, Hyun Jeong; Jeong, Yong Hyu; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Yong Bae; Kim, Young Tae; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p <0.001). Persistent cervical FDG uptake in {sup 18}F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy

  14. Chemoradiation for adenocarcinoma of the anus

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  15. Concurrent chemoradiation for vaginal cancer.

    Directory of Open Access Journals (Sweden)

    David T Miyamoto

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

  16. PAM-OBG: A monoamine oxidase B specific prodrug that inhibits MGMT and generates DNA interstrand crosslinks, potentiating temozolomide and chemoradiation therapy in intracranial glioblastoma

    Science.gov (United States)

    Sharpe, Martyn A.; Raghavan, Sudhir; Baskin, David S.

    2018-01-01

    Via extensive analyses of genetic databases, we have characterized the DNA-repair capacity of glioblastoma with respect to patient survival. In addition to elevation of O6-methylguanine DNA methyltransferase (MGMT), down-regulation of three DNA repair pathways; canonical mismatch repair (MMR), Non-Homologous End-Joining (NHEJ), and Homologous Recombination (HR) are correlated with poor patient outcome. We have designed and tested both in vitro and in vivo, a monoamine oxidase B (MAOB) specific prodrug, PAM-OBG, that is converted by glioma MAOB into the MGMT inhibitor O6-benzylguanine (O6BG) and the DNA crosslinking agent acrolein. In cultured glioma cells, we show that PAM-OBG is converted to O6BG, inhibiting MGMT and sensitizing cells to DNA alkylating agents such as BCNU, CCNU, and Temozolomide (TMZ). In addition, we demonstrate that the acrolein generated is highly toxic in glioma treated with an inhibitor of Nucleotide Excision Repair (NER). In mouse intracranial models of primary human glioma, we show that PAM-OBG increases survival of mice treated with either BCNU or CCNU by a factor of six and that in a chemoradiation model utilizing six rounds of TMZ/2Gy radiation, pre-treatment with PAM-OBG more than doubled survival time. PMID:29844863

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

    Science.gov (United States)

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

    2012-02-01

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

  18. A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma

    International Nuclear Information System (INIS)

    Hong, Theodore S.; Ryan, David P.; Borger, Darrell R.; Blaszkowsky, Lawrence S.; Yeap, Beow Y.; Ancukiewicz, Marek; Deshpande, Vikram; Shinagare, Shweta; Wo, Jennifer Y.; Boucher, Yves; Wadlow, Raymond C.; Kwak, Eunice L.; Allen, Jill N.; Clark, Jeffrey W.; Zhu, Andrew X.; Ferrone, Cristina R.; Mamon, Harvey J.; Adams, Judith; Winrich, Barbara; Grillo, Tarin

    2014-01-01

    Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. Methods and Materials: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. Results: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). Conclusions: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS G12D status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival

  19. Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

    Science.gov (United States)

    Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

    2016-01-01

    To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings

  20. Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

    International Nuclear Information System (INIS)

    Menda, Yusuf; Boles Ponto, Laura L.; Dornfeld, Kenneth J.; Tewson, Timothy J.; Watkins, G. Leonard; Gupta, Anjali K.; Anderson, Carryn; McGuire, Sarah; Schultz, Michael K.; Sunderland, John J.; Graham, Michael M.; Buatti, John M.

    2010-01-01

    Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[ 18 F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K FLT ) and the Patlak constant (K Patlak ) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, K FLT =0.045±0.016 min -1 and K Patlak =0.039±0.013 min -1 . After treatment, these values were SUV=0.74±0.19, K FLT =0.011±0.005 min -1 and K Patlak =0.005±0.002 min -1 . Compartmental analysis revealed a significant drop in k 3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-01

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

  4. A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Theodore S., E-mail: tshong1@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ryan, David P.; Borger, Darrell R.; Blaszkowsky, Lawrence S.; Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Deshpande, Vikram; Shinagare, Shweta [Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Wo, Jennifer Y.; Boucher, Yves [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Wadlow, Raymond C.; Kwak, Eunice L.; Allen, Jill N.; Clark, Jeffrey W.; Zhu, Andrew X. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ferrone, Cristina R. [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Mamon, Harvey J. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Adams, Judith; Winrich, Barbara; Grillo, Tarin [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); and others

    2014-07-15

    Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. Methods and Materials: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. Results: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). Conclusions: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS{sup G12D} status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

  5. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  6. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  7. A combination therapy with preoperative full-dose gemcitabine, concurrent 3-dimensional conformal radiation, surgery and postoperative liver perfusion chemotherapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Ohigashi, Hiroaki; Eguchi, Hidetoshi; Takahashi, Hidenori

    2009-01-01

    Due to the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of pancreatic cancer are extremely poor. For improving the survival of the patients, a combination of preoperative chemoradiation, surgery, and postoperative liver-perfusion chemotherapy (LPC) were performed. Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) in 98% of patients and negative nodal involvement in 85% of patients. The 5-year survival rate after pancreatectomy was 56%, with low incidences of both local recurrence (11%) and liver metastasis (9%). This combination therapy were able to effectively reduce the incidence of both local and liver recurrence and improved long-term outcomes for patients with T3-4 cancers of the pancreas. (author)

  8. National Patterns of Care and Outcomes after Combined Modality Therapy for Stage IIIA Non-small Cell Lung Cancer

    Science.gov (United States)

    Patel, Aalok P.; Crabtree, Traves D.; Bell, Jennifer M.; Guthrie, Tracey J.; Robinson, Clifford G.; Morgensztern, Daniel; Colditz, Graham A.; Kreisel, Daniel; Krupnick, A. Sasha; Bradley, Jeffrey D.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2014-01-01

    Introduction The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small cell lung cancer (NSCLC) remains controversial. Since there is limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally, and explored the outcomes with and without the addition of surgery. Methods Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation (CR) were compared to those undergoing chemotherapy, radiation, and surgery in any sequence (CRS). Results Between 1998 and 2010, 61339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51979 (84.7%) received CR while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely females and Caucasians, had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200/8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months vs. 15.7 months, p<.001) and matched analysis based on patient characteristics (34.3 months vs. 18.4months, p<.001). Conclusion There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy appear to have better long-term survival. PMID:24722151

  9. Combining Immunotherapy with Standard Glioblastoma Therapy

    Science.gov (United States)

    This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.

  10. Characteristic cytokine generation patterns in cancer cells and infiltrating lymphocytes in oral squamous cell carcinomas and the influence of chemoradiation combined with immunotherapy on these patterns.

    Science.gov (United States)

    Yamamoto, Tetsuya; Kimura, Tsuyoshi; Ueta, Eisaku; Tatemoto, Yukihiro; Osaki, Tokio

    2003-01-01

    Cytokines produced by tumor cells and tumor-infiltrating lymphocytes (TIL) appear to regulate tumor cell growth and the cytotoxic activity of TIL. The objectives of the present study were to investigate cytokine generation patterns in tumor cells and TIL and to examine the influence of cancer therapy on this cytokine production and the cytotoxic activity of TIL. We determined the levels of cytokines produced by tumor cells and TIL in vitro and measured the cytotoxic activity of TIL against Daudi cells in patients with oral squamous cell carcinoma (OSC) before and 1 week after the start of concomitant chemo-radio-immunotherapy. Before the therapy, OSC cells generated higher levels of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) than did oral keratinocytes isolated from the noninflamed gingivae of healthy individuals, but both kinds of cells generated similar levels of interleukin (IL)-1beta and IL-6. Compared with peripheral blood mononuclear cells (PBMC) of the patients, TIL produced higher levels of IL-1beta, IL-6, IL-10, TNF-alpha and TGF-beta, whereas their production of IL-12 and interferon-gamma (IFN-gamma) was only slightly higher than that in PBMC. After 1 week of therapy, the cytokine production by OSC cells had largely decreased, while the production of TNF-alpha, IFN-gamma, TGF-beta and IL-12 by TIL had increased greatly, although other cytokine levels were almost constant during the investigations. The cytotoxic activity of TIL was higher than that of PBMC before the therapy, and this activity was strongly increased by 1 week of therapy. These results suggest that the cytokine productivities of TIL and tumor cells differ from those of PBMC and normal keratinocytes, respectively, and that chemo-radio-immunotherapy modulates in situ cytokine generation, which is advantageous for inhibition of tumor cell growth and activation of TIL. Copyright 2003 S. Karger AG

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

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

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

  12. Combined therapy of urinary bladder radiation injury

    International Nuclear Information System (INIS)

    Zaderin, V.P.; Polyanichko, M.F.

    1982-01-01

    A scheme of therapy of radiation cystitis is suggested. It was developed on the basis of evaluation of literature data and clinical of 205 patients with radiation injury of the urinary bladder. The method is based on general and local therapy of damaged tissues by antiinflammatory drugs, anesthetics and stimulators of reparative regeneration. Severe ulcerative and incrustation cystites, refractory to conservative therapy, were treated by surgery, using antiseptics and reparation stimulators before, during and after operation. As a result, there were hardly any complications after reconstruction of the bladder with intestinal and peritoneal tissues. 104 patients (96.1%) were cured completely and ability to work was restored in 70 patients (76.9%) [ru

  13. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Science.gov (United States)

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

  14. Acute radiation oesophagitis associated with 2-deoxy-2-[18F]fluoro-d-glucose uptake on positron emission tomography/CT during chemo-radiation therapy in patients with non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Everitt, Sarah; Callahan, Jason; Obeid, Eman; Hicks, Rodney J.; MacManus, Michael; Ball, David

    2017-01-01

    Acute radiation oesophagitis (ARO) is frequently experienced by patients receiving concurrent chemo-radiation therapy (cCRT) for non-small-cell lung cancer (NSCLC). We investigated ARO symptoms (CTCAE v3.0), radiation dose and oesophageal FDG PET/CT uptake. Candidates received cCRT (60 Gy, 2 Gy/fx) and sequential FDG PET/CT (baseline FDG 0 , FDG wk2 and FDG wk4 ). Mean and maximum standardized uptake value (SUV mean and SUV max ) and radiation dose (O mean and O max ) were calculated within the whole oesophagus and seven sub-regions (5–60 Gy). Forty-four patients underwent FDG 0 and FDG wk2 , and 41 (93%) received FDG wk4 , resulting in 129 PET/CT scans for analysis. Of 29 (66%) patients with ≥ grade 2 ARO, SUVmax (mean ± SD) increased from FDG 0 to FDG wk4 (3.06 ± 0.69 to 3.83 ± 1.27, P = 0.0019) and FDG wk2 to FDG wk4 (3.10 ± 0.75 to 3.83 ± 1.27, P = 0.0046). Radiation dose (mean ± SD) was higher in grade ≥2 patients; O mean (47.5 ± 20 vs 53.9 ± 10.2, P = 0.0061), O max (13.7 ± 9.6 vs 20.1 ± 10.6, P = 0.0009) and V40 Gy (8.0 ± 8.2 vs 11.9 ± 7.3, P = 0.0185). FDG wk4 SUVmax and radiation dose were associated with ≥ grade 2 ARO. Compared to subjective assessments, future interim FDG PET/CT acquired for disease response assessment may also be utilized to objectively characterize ARO severity and image-guided oesophageal dose constraints.

  15. 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.

  16. Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients With Stage IV Non-Small Cell Lung Cancer Previously Treated With Radical Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Topkan, Erkan, E-mail: docdretopkan@gmail.com [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Yildirim, Berna Akkus; Guler, Ozan Cem; Parlak, Cem [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Pehlivan, Berrin [Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, and American Hospital, University of Texas MD Anderson Radiation Treatment Center, Istanbul (Turkey); Selek, Ugur [Medstar Hospital, Department of Radiation Oncology, Antalya (Turkey)

    2015-03-15

    Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

  17. Correlation Among Six Biologic Factors (p53, p21WAF1, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

    International Nuclear Information System (INIS)

    Yamashita, Hideomi; Murakami, Naoya; Asari, Takao; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2009-01-01

    Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.

  18. RTOG 0417: Efficacy of Bevacizumab in Combination With Definitive Radiation Therapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma

    International Nuclear Information System (INIS)

    Schefter, Tracey; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian Patrick; Small, William; Sause, William; Gaffney, David

    2014-01-01

    Purpose: Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS). Methods and Materials: Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m 2 ) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method. Results: 49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively. Conclusion: In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical cancer

  19. Radiation and chemoradiation treatment of esophagus cancer

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  20. Combination Therapy for Advanced Kaposi Sarcoma

    Science.gov (United States)

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  1. Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Christian Bressy

    2017-06-01

    Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

  2. Early diffusion weighted magnetic resonance imaging can predict survival in women with locally advanced cancer of the cervix treated with combined chemo-radiation

    International Nuclear Information System (INIS)

    Somoye, Gbolahan; Parkin, David; Harry, Vanessa; Semple, Scott; Plataniotis, George; Scott, Neil; Gilbert, Fiona J.

    2012-01-01

    To assess the predictive value of diffusion weighted imaging (DWI) for survival in women treated for advanced cancer of the cervix with concurrent chemo-radiotherapy. Twenty women treated for advanced cancer of the cervix were recruited and followed up for a median of 26 (range -3 /mm 2 /s), respectively, P = 0.02. The median change in ADC 14 days after treatment commencement was significantly higher in the alive group compared to non-survivors, 0.28 and 0.14 (x 10 -3 /mm 2 /s), respectively, P = 0.02. There was no evidence of a difference between survivors and non-survivors for pretreatment baseline or post-therapy ADC values. Functional DWI early in the treatment of advanced cancer of the cervix may provide useful information in predicting survival. (orig.)

  3. Is there really no benefit to combination therapy with colistin?

    Science.gov (United States)

    Pogue, Jason M; Kaye, Keith S

    2013-09-01

    Despite many theoretical and in vitro advantages, clinical data comparing combination therapy with colistin + rifampicin to colistin alone for infection due to extremely-drug resistant (XDR) Acinetobacter baumanni are scarce and limited by small numbers and/or low quality evidence. This article represents the first large, randomized, controlled, prospective study comparing colistin monotherapy and combination therapy. The reviewed article found no difference in all cause or infection related mortality, though there was an improved rate of microbiological clearance in the combination therapy arm. This study adds important new data to the literature and sets the stage for future studies that can be designed to overcome the limitations of this study, which are discussed in detail below. Based on this study, we cannot say definitively that combination therapy is not warranted for treatment of invasive infection due to A. baumannii, but the results do suggest that rifampicin is not an ideal agent to be combined with colistin.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. Asthma Severity in patients initiating controller monotherapy versus combination therapy.

    Science.gov (United States)

    Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

    2011-04-01

    Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

  6. Combination therapies in oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Krishnamurthi, S.; Shanta, V.

    1982-01-01

    The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

  7. Combination of radiation injuries: pathogenesis, clinic, therapy

    International Nuclear Information System (INIS)

    Tsyba, A.F.; Farshatova, M.N.

    1993-01-01

    Modern notions on combined radiation injuries (CRI) are presented. Characteristic of injurious factors of nuclear explosion and common regularities of the CRI origination is given. The data on the CRI clinical peculiarities, diagnostics and treatment, principles of medical assistance for the injured on the stages of medical evacuation and recommendations on rehabilitation are presented

  8. Survival of lung cancer patients after combined therapy with hyperglycemia

    International Nuclear Information System (INIS)

    Zharkov, V.V.; Demidchik, Yu.E.; Khodina, T.V.

    1991-01-01

    The results of a randomized study of combined therapy of lung cancer patients including large field radiotherapy (total irradiation of 20 Gy, daily fractionation of 4 Gy) and induced hyperglycemia (22-23 mmol/1) are presented. The use of new variants of combined therapy was shown to increase significantly the survival of patients, however therapeutic efficacy was different depending on the time of hyperglycemia: wheter it was used before radiotherapy sessions of after their discontinuation

  9. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation

    International Nuclear Information System (INIS)

    Antunes, Heliton S.; Herchenhorn, Daniel; Small, Isabele A.; Araújo, Carlos M.M.; Viégas, Celia Maria Pais; Cabral, Elida; Rampini, Mariana P.; Rodrigues, Pedro C.; Silva, Tereza G.P.; Ferreira, Elza M.S.; Dias, Fernando L.; Ferreira, Carlos G.

    2013-01-01

    Background: Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3–4 OM. Material and methods: From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3 weeks. A diode InGaAlP (660 nm–100 mW–1 J–4 J/cm 2 ) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). Results: A six-fold decrease in the incidence of grades 3–4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3–4 OM to a relative risk ratio of 0.158 (CI 95% 0.050–0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H and N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. Conclusion: Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3–4 OM. Efficacy data were corroborated by improvements seen in quality of life

  10. SU-F-T-106: A Dosimetric Study of Intensity Modulated Radiation Therapy to Decrease Radiation Dose to the Thoracic Vertebral Bodies in Patients Receiving Concurrent Chemoradiation for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiCostanzo, Dominic; Barney, Christian L.; Bazan, Jose G. [The Ohio State University, Columbus, Ohio (United States)

    2016-06-15

    Purpose: Recent clinical studies have shown a correlation between radiation dose to the thoracic vertebral bodies (TVB) and the development of hematologic toxicity (HT) in patients receiving chemoradiation (CRT) for lung cancer (LuCa). The feasibility of a bone-marrow sparing (BMS) approach in this group of patients is unknown. We hypothesized that radiation dose to the TVB can be reduced with an intensity modulated radiation therapy(IMRT)/volumetric modulated arc radiotherapy(VMAT) without affecting plan quality. Methods: We identified LuCa cases treated with curative intent CRT using IMRT/VMAT from 4/2009 to 2/2015. The TVBs from T1–T10 were retrospectively contoured. No constraints were placed on the TVB structure initially. A subset were re-planned with BMS-IMRT/VMAT with an objective or reducing the mean TVB dose to <23 Gy. The following data were collected on the initial and BMS plans: mean dose to planning target volume (PTV), lungs-PTV, esophagus, heart; lung V20; cord max dose. Pairwise comparisons were performed using the signed rank test. Results: 94 cases received CRT with IMRT/VMAT. We selected 11 cases (7 IMRT, 4 VMAT) with a range of initial mean TVB doses (median 35.7 Gy, range 18.9–41.4 Gy). Median prescription dose was 60 Gy. BMS-IMRT/VMAT significantly reduced the mean TVB dose by a median of 10.2 Gy (range, 1.0–16.7 Gy, p=0.001) and reduced the cord max dose by 2.9 Gy (p=0.014). BMS-IMRT/VMAT had no impact on lung mean (median +17 cGy, p=0.700), lung V20 (median +0.5%, p=0.898), esophagus mean (median +13 cGy, p=1.000) or heart mean (median +16 cGy, p=0.365). PTV-mean dose was not affected by BMS-IMRT/VMAT (median +13 cGy, p=0.653). Conclusion: BMS-IMRT/VMAT was able to significantly reduce radiation dose to the TVB without compromising plan quality. Prospective evaluation of BMS-IMRT/VMAT in patients receiving CRT for LuCa is warranted to determine if this approach results in clinically significant reductions in HT.

  11. Radiation and chemoradiation treatment of esophagus cancer

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  12. 18F-FDG-PET for evaluation of the response to concurrent chemoradiation therapy with intensity-modulated radiation technique for Stage T4 nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Yen, T.-C.; Lin, C.-Y.; Wang, H.-M.; Huang, S.-F.; Liao, C.-T.; Kang, C.-J.; Ng, S.-H.; Chan, S.-C.; Fan, K.-H.; Chen, I.-H.; Lin, W.-J.; Cheng, A.-J.; Chang, Joseph Tung-Chieh

    2006-01-01

    Purpose: This article evaluates [ 18 F] fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) findings as a predictor for local responders (R) vs. nonresponders (NR) in nasopharyngeal carcinoma (NPC) patients with Stage T4 lesions, before and at 3 months after completion of concurrent chemotherapy and radiation therapy (CCRT). Methods and Materials: From January 2002 to November 2003, 39 T4 NPC patients were enrolled. All had magnetic resonance imaging and 18 F-FDG-PET, both before and 3 months after CCRT. Any residual/recurrent lesions were confirmed histopathologically. Results: Of the 39 eligible patients, after a follow-up of 24.2 ± 9.5 months, 35 became disease-free and 4 had residual or recurrent disease. Marginal differences in standard uptake values (SUV) were observed (10.9 ± 5.3 vs. 15.6 ± 3.4, p = 0.058) between R and NR before treatment, and value changes of SUV before and after CCRT were not significantly different. However, highly significantly lower values of SUV were noted for R than for NR 3 months after completion of CCRT (2.1 ± 0.8 vs. 5.5 ± 3.2, p 0.001). One hundred percent positive and negative predictive values were observed for SUV values of 4.0, set 3 months after completion of CCRT. Conclusions: Neither the pretreatment SUV nor the changes of SUV between pretreatment and posttreatment were significant predictors for local response. SUV at 3 months after completion of CCRT was a significant determinator for local response. The cutoff of 4.0 for SUV at 3 months after completion of CCRT was useful to be offered as a diagnostic reference for recurrent or residual tumor for NPC treatment

  13. Neo-adjuvant chemo-radiation of rectal cancer with Volumetric Modulated Arc Therapy: summary of technical and dosimetric features and early clinical experience

    International Nuclear Information System (INIS)

    Richetti, Antonella; Fogliata, Antonella; Clivio, Alessandro; Nicolini, Giorgia; Pesce, Gianfranco; Salati, Emanuela; Vanetti, Eugenio; Cozzi, Luca

    2010-01-01

    To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc ® (RA) technology. Twenty-five consecutive patients (pts) were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44 Gy in 22 fractions (or 45 Gy in 25 fractions). Delivery was performed with single arc with a 6 MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC) is presented as well. From a dosimetric point of view, RA improved conformality of doses (CI 95% = 1.1 vs. 1.4 for RA and 3DC), presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of RA pts, 45% and 5% of 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC. RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects

  14. Neo-adjuvant chemo-radiation of rectal cancer with Volumetric Modulated Arc Therapy: summary of technical and dosimetric features and early clinical experience

    Directory of Open Access Journals (Sweden)

    Salati Emanuela

    2010-02-01

    Full Text Available Abstract Background To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc® (RA technology. Methods Twenty-five consecutive patients (pts were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44 Gy in 22 fractions (or 45 Gy in 25 fractions. Delivery was performed with single arc with a 6 MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC is presented as well. Results From a dosimetric point of view, RA improved conformality of doses (CI95% = 1.1 vs. 1.4 for RA and 3DC, presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of RA pts, 45% and 5% of 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC. Conclusion RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects.

  15. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  16. Cone-beam computed tomography for lung cancer – validation with CT and monitoring tumour response during chemo-radiation therapy

    International Nuclear Information System (INIS)

    Michienzi, Alissa; Kron, Tomas; Callahan, Jason; Plumridge, Nikki; Ball, David; Everitt, Sarah

    2017-01-01

    Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical ‘gold standard’, CT. Tumour regression or progression on CBCT was also analysed. Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R 2 ). Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97–0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC.

  17. Combination therapy of gastric carcinoma with radiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Hiroshi; Otawa, Hirokazu; Yamada, Shogo; Matsumoto, Ko [Miyagi Prefectural Adult Disease Center, Natori (Japan)

    1982-08-01

    The concurrent combination therapy of radiation and chemotherapy was performed in a total of 134 cases of stomach cancer. Radiation response of tumor was remarkable in 35 (37%) of 95 cases, irradiated more than 5,000 rad. Yearly survival rates in 81 cases, in which the scheduled curative treatment was completed, were 63% in one, 31% in two, 21% in three, 17% in four and 13% in five years. These rates were intimately correlated to tumor size and cancer type. However, this combination therapy accompanied some fatal complications in a few percent. From the results, it was concluded that this combination therapy should be valuable to prolong the life of patients with gastric cancer, and that the curable indications for this treatment should be T1-T3: M0 cases with radio-responsive tumor.

  18. A Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M; Kjær, Andreas; Langer, Seppo W; Aznar, Marianne C; Persson, Gitte F; Bentzen, Søren M

    2018-04-01

    The aim of the study was to build a model of first failure site- and lesion-specific failure probability after definitive chemoradiotherapy for inoperable NSCLC. We retrospectively analyzed 251 patients receiving definitive chemoradiotherapy for NSCLC at a single institution between 2009 and 2015. All patients were scanned by fludeoxyglucose positron emission tomography/computed tomography for radiotherapy planning. Clinical patient data and fludeoxyglucose positron emission tomography standardized uptake values from primary tumor and nodal lesions were analyzed by using multivariate cause-specific Cox regression. In patients experiencing locoregional failure, multivariable logistic regression was applied to assess risk of each lesion being the first site of failure. The two models were used in combination to predict probability of lesion failure accounting for competing events. Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than squamous cell carcinoma (HR = 0.45, 95% confidence interval [CI]: 0.26-0.76, p = 0.003). Distant failures were more common in the adenocarcinoma group (HR = 2.21, 95% CI: 1.41-3.48, p failure showed that primary tumors were more likely to fail than lymph nodes (OR = 12.8, 95% CI: 5.10-32.17, p failure (OR = 1.26 per unit increase, 95% CI: 1.12-1.40, p failure site-specific competing risk model based on patient- and lesion-level characteristics. Failure patterns differed between adenocarcinoma and squamous cell carcinoma, illustrating the limitation of aggregating them into NSCLC. Failure site-specific models add complementary information to conventional prognostic models. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  19. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    DEFF Research Database (Denmark)

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche

    2015-01-01

    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...

  20. Combined statin-fibrate therapy-induced rhabdomyolysis: Case report

    Directory of Open Access Journals (Sweden)

    Jozić Tanja L.

    2014-01-01

    Full Text Available Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2, CK 309 U/L (on day 2: 3476 U/L and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L. The patient was treated with thrombolysis medication therapy (Alteplase, anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg, which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L, but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.

  1. Risks and safety of combination therapy for hypothyroidism.

    Science.gov (United States)

    Jonklaas, Jacqueline

    2016-08-01

    Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

  2. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Science.gov (United States)

    Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

    2006-01-01

    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

  3. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    -naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

  4. Combined Therapy at Persistent Herpes Virus Infection in Sickly Children

    Directory of Open Access Journals (Sweden)

    F. S. Kharlamova

    2012-01-01

    Full Text Available We examined 40 sickly children with recurrent croup (RC — 28 and bronchial obstruction (ROB — 8, (RC + ROB — 4 aged from 18 months till 14 years. We found that high frequency of persistent herpes viruses usually occurs as associations with CMV, EBV and human herpes virus 6 type. We substantiated anti viral and immune corrective therapy in two schemes compared in efficacy: the 1st group was administered monotherapy with Viferon, and the 2nd group received combined therapy Viferon + Arbidol in doses according to the age during three months. We received a more expressed clinical immunologic effect from the therapy with decreased antigenic load and frequency of recurrence of RC and ROB with Viferon application in suppositories in combination with Arbidol per orally in the intermittent scheme during three months. 

  5. Atorvastatin/trimetazidine combination therapy in patients with ...

    African Journals Online (AJOL)

    Purpose: To explore the outcomes and safety of atorvastatin/trimetazidine combination therapy in patients with chronic cardiac failure. Methods: A total of 144 patients with chronic cardiac failure were divided into test group (n = 72) and control group (n = 72). In addition to conventional anti-heart failure treatment, all patients ...

  6. Combination therapy in patients with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Bojan Tršinar

    2006-11-01

    Full Text Available Background: The purpose of observational program of patients with lower urinary tract symptoms (LUTS because of benign prostatic hyperplasia (BPH (LUTS/BPH was to acquire additional pharmaco-epidemiological data on the safety and efficacy of combination therapy with finasteride and tamsulosin.Methods: Observational program of men with BPH was conducted in urological outpatient clinics in Slovenia from April 2004 until November 2005. In open-label, non-interventional program 1173 patients were observed, who had been treated because of LUTS/BPH with combination therapy with finasteride and tamsulosin, in the framework of common treatment. At baseline and after six months of treatment for each patient the International Prostatic Symptom Score (IPSS questionnaire and assessment of quality of life (QL were filled in. In addition, urinary flow rate and prostate volume were determined. Adverse effects of drugs were reported spontaneously. For statistical analysis the Student’s t-test was performed.Results: Combination therapy with finasteride and tamsulosin was well tolerated. 89 (7.6 % patients discontinued with medication because of lack of efficacy or because of adverse effects of drugs. Symptom score, assessment of quality of patients’ lives and volume of prostates were significantly lower (p < 0.0001, while urinary flow rate was significantly higher (p < 0.0001 after six months of treatment with finasteride and tamsulosin.Conclusions: Combination therapy of patients with LUTS/BPH with finasteride and tamsulosin is effective and safe.

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

    International Nuclear Information System (INIS)

    Mornex, F.; Chauffert, B.

    1998-01-01

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

  8. Building a roadmap for developing combination therapies for Alzheimer's disease.

    Science.gov (United States)

    Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia

    2015-03-01

    Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

  9. Effectiveness of medication / auricular therapy / phyto-therapy combination in the treatment of hypertensive patients

    Directory of Open Access Journals (Sweden)

    José Ramón Martínez Pérez

    2015-10-01

    Full Text Available Background: hypertension is one of the main cardiovascular risk factors, so its control improves the life expectancy of patients.Objective: to assess the effects of a treatment combining medication with auricular therapy and phyto-therapy in hypertensive patients assisted at the health area of ”Romárico Oro” Polyclinic, in Puerto Padre, Las Tunas province.Methods: an intervention study was carried out in 68 hypertensive patients of the health area of “Romárico Oro” Polyclinic in Puerto Padre from April, 2013 to April, 2014. The patients were distributed at random into two equal groups; the first received medication combined with auricular therapy and phyto-therapy, while the second one received only medication. The statistical analysis was done by means of Statistic system, t-student and Chi-Square tests were used and p< or =0.05 was considered as level of statistical significance.Results: by the end of the intervention, 73, 53% of the patients of the group with the combination of drug treatment and auricular therapy and phyto-therapy were controlled. In this group, the diastolic filling pressure diminished to 2, 2 mm Hg and the systolic gradient to 3, 66 mm, regarding the group treated only with drugs. Only one patient, representing the 2, 94% showed adverse reaction to the natural and traditional treatment.Conclusions: the combination of medication with auricular therapy and phyto-therapy proved to be effective, corroborated by a significant decrease of quantity of crisis, diastolic and systolic filling pressure values and increase of number of patients with their disease controlled; the report of only one complication shows the innocuousness of the auricular therapy and phyto-therapy treatment.

  10. Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

    Science.gov (United States)

    Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

    2017-06-01

    The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

  11. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  12. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Directory of Open Access Journals (Sweden)

    Ghosn Marwan G

    2010-06-01

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

  13. State of the art of radiation therapy for esophageal cancer

    International Nuclear Information System (INIS)

    Itasaka, Satoshi

    2014-01-01

    Radiation therapy has a critical role in the treatment of esophageal cancer. To improve the treatment outcome of radiotherapy, not only strengthening the treatment intensity but also decreasing the long term toxicity is needed. To reduce the long term cardiopulmonary toxicity of chemoradiation, JCOG is now running a clinical trial which combines three dimensional conformal radiation therapy (3D-CRT) and mild irradiation dose. New techniques of radiation therapy, such as intensity modulated radiation therapy (IMRT) or particle therapy are also promising in both treatment intensity and decreased toxicity. (author)

  14. Fixed-functional appliance treatment combined with growth hormone therapy.

    Science.gov (United States)

    Jung, Min-Ho

    2017-09-01

    The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  15. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    International Nuclear Information System (INIS)

    Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

    2009-01-01

    Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

  16. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  17. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  20. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

    1995-01-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  1. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

    1995-07-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  3. Combination Therapy Strategies Against Multiple-Resistant Streptococcus Suis

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2018-05-01

    Full Text Available Streptococcus suis is a major swine pathogen, an emerging zoonotic agent responsible for meningitis, endocarditis and septicaemia followed by deafness in humans. The development of antimicrobial resistance in S. suis increases the risk for therapeutic failure in both animals and humans. In this study, we report the synergism of combination therapy against multi-resistant S. suis isolates from swine. Twelve antibiotic profiles were determined against 11 S. suis strains. To investigate their synergistic/antagonistic activity, checkerboard assay was performed for all the possible combinations. In-vitro killing curves and in-vivo treatment trials were used to confirm the synergistic activity of special combinations against S. suis dominant clones. In this study, 11 S. suis isolates were highly resistant to erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and tetracycline with ratios of 80–100%, and the resistance percentages to enrofloxacin, florfenicol, and spectinomycin were ~50%. The checkerboard data identified two combination regimens, ampicillin plus apramycin and tiamulin plus spectinomycin which gave the greatest level of synergism against the S. suis strains. In-vitro kill-curves showed a bacterial reduction of over 3-logCFU with the use of combination treatments, whilst the application of mono-therapies achieve less than a 2-logCFU cell killing. In-vivo models confirm that administration of these two combinations significantly reduced the number of bacterial cells after 24 h of treatment. In conclusions, the combinations of ampicillin plus apramycin and tiamulin plus spectinomycin showed the greatest synergism and may be potential strategies for treatment of multi-resistant S. suis in animal.

  4. Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

    Science.gov (United States)

    Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

    2004-10-01

    An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.

  5. Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-01-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

  6. Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

    International Nuclear Information System (INIS)

    Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

    1979-01-01

    Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

  7. Biological basis of combination therapy with radiation and bleomycin

    International Nuclear Information System (INIS)

    Fukuda, Hiroshi; Matsuzawa, Taiju; Yokoyama, Kumiko; Okuyama, Shinichi; Yamaura, Hiroshi

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C 2 W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C 2 W cells were irradiated, incubated at 37 0 C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

  8. Radiotherapy in combination with vascular-targeted therapies

    International Nuclear Information System (INIS)

    Ciric, Eva; Sersa, Gregor

    2010-01-01

    Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

  9. Biological basis of combination therapy with radiation and bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, H; Matsuzawa, T; Yokoyama, K; Okuyama, S; Yamaura, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C/sub 2/W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C/sub 2/W cells were irradiated, incubated at 37/sup 0/C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising.

  10. Combined aquaretic and diuretic therapy in acute heart failure

    Directory of Open Access Journals (Sweden)

    Goyfman M

    2017-06-01

    Full Text Available Michael Goyfman,1 Paul Zamudio,2 Kristine Jang,3 Jennifer Chee,3 Catherine Miranda,2 Javed Butler,1 Nand K Wadhwa2 1Division of Cardiology, 2Division of Nephrology, 3Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Introduction: Acute heart failure (AHF is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and results: A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP was 4.1±2.0 L (range 1.8–10.5 L. There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10.Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe. Keywords: diuretics, aquaretic, acute heart failure, volume overload

  11. The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

    International Nuclear Information System (INIS)

    Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

    2013-01-01

    In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

  12. Combined cisplatin and radiation therapy for advanced bladder cancer

    International Nuclear Information System (INIS)

    Tajima, Masaharu; Sawamura, Yoshikatsu; Kase, Takahisa

    1991-01-01

    The combined effects of cisplatin and irradiation were investigated in 44 patients with bladder cancer accompanied by the infiltration of T 2 ∼T 4 cells, in a study commencing in September 1985. The antitumor effect and adverse reactions to the therapy were recorded. The majority of these patients had not undergone total bladder excision, for a variety of reasons. Thirty-two patients were male and 12 were female; the average age was 66.7 years, with ranging from 33∼83 years of age. Irradiation was performed using table cobalt 60 or a linear accelerator at a dose of 2 Gy per day, 5 days a week. The total radiation dose ranged from 40 to 70 Gy. Cisplatin was administered systemically at a dose of 20∼30 mg/day for 5 consecutive days during the first and fourth weeks of irradiation. At the time of final assessment of the antitumor effect, 24 out of 40 eligible patients (60%) had achieved complete remission (CR). The duration of CR averaged 18.8 months, with a range of 1∼50 months. The actual survival rates were as follows: 81% at 1 year, 69% at 2 years, and 52% at 3 and 4 years. Regarding adverse reactions, anorexia occurred in 28 patients (70%), nausea and vomiting in 21 (53%), diarrhea in 8 (20%), leukopenia in 16 (40%), mild thrombocytopenia in 5 (13%), and dermatitis in 8 (20%). All of these adverse reactions were mild and were alleviated after completion of the combined therapy. The present investigation demonstrated that combined therapy with cisplatin and irradiation is effective for the regional treatment of invasive bladder cancer. (author)

  13. Myxedema coma associated with combination aripiprazole and sertraline therapy.

    Science.gov (United States)

    Church, Chelsea O; Callen, Erin C

    2009-12-01

    To describe a case of myxedema coma (MC) associated with combination aripiprazole and sertraline therapy. A 41-year-old male presented to the emergency department with confusion, right-sided numbness and tingling, slurred speech, dizziness, and facial edema. His blood pressure was 160/113 mm Hg, with a pulse of 56 beats/min and temperature of 35.4 degrees C. Initial abnormal laboratory values included creatine kinase (CK) 439 U/L; serum creatinine 1.6 mg/dL; aspartate aminotransferase 85 U/L; and alanine aminotransferase 35 U/L. Repeat cardiac markers revealed an elevated CK level of 3573 U/L with a CK-MB of 24 ng/mL. Thyroid function tests showed thyroid-stimulating hormone 126.4 microIU/mL and free thyroxine 0.29 ng/dL. Home medications of unknown duration were sertraline 200 mg and aripiprazole 20 mg daily. He was admitted to the intensive care unit and initially treated with intravenous levothyroxine and dexamethasone. By hospital day 4, the patient was clinically stable and discharged to home. Myxedema coma, the most significant form of hypothyroidism (HT), is a rare but potentially fatal condition. The known precipitating causes of MC were ruled out in this patient, which left his home medications as the likely cause. Cases of HT caused by certain atypical antipsychotics and antidepressants are found in the literature, but none was reported with aripiprazole therapy. There are also no reported cases of sertraline or aripiprazole inducing MC. Use of the Naranjo probability scale indicates that the combination of aripiprazole and sertraline was a probable inducer of MC in this patient. Due to the widespread use of psychotropic medications, clinicians should be reminded of the rare, yet life-threatening, occurrence of MC when treating patients, especially with combination therapies such as sertraline and aripiprazole.

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

    NARCIS (Netherlands)

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

    2016-01-01

    There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a

  15. Combination therapy of acne in women: searching for optimum solutions

    Directory of Open Access Journals (Sweden)

    M. V. Goryachkina

    2014-01-01

    Full Text Available Current data on the acne pathogenesis are given. According to the authors, dermatosis is becoming more prevalent among women of mature age. Issues related to the clinical picture, effect of exogenous and endogenous factors on the course of acne, and psychosocial characteristics of delayed acne manifestations in women are described in detail. The essential role of medical and cosmetic products for the complex therapy of acne is discussed. The authors describe their own experience of treating delayed acne using the Hyseac line of medical and cosmetic products in a combination with microdermabrasion and no-needle mesotherapy using the vitaPeel/vital О2 device.

  16. Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

    International Nuclear Information System (INIS)

    Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

    2011-01-01

    Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors

  17. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  18. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    National Research Council Canada - National Science Library

    Johnson, Leigh G; Rohan, Kelly J

    2005-01-01

    ...), group cognitive-behavioral therapy (CBT), or combination therapy (CBT+LT). Atypical and typical symptoms were assessed using subscales of the Structured Interview Guide for the Hamilton Rating Scale for Depression - SAD Version (SIGH-SAD...

  19. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  20. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  1. Improved outcome in solitary bone plasmacytomata with combined therapy.

    Science.gov (United States)

    Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

    1996-09-01

    Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

  2. Multicomponent Pharmaceutical Cocrystals: A Novel Approach for Combination Therapy.

    Science.gov (United States)

    Fatima, Zeeshan; Srivastava, Dipti; Kaur, Chanchal Deep

    2018-03-05

    Cocrystallization is a technique for modifying the physicochemical and pharmacokinetic properties of an active pharmaceutical ingredient (API) embodying the concept of supramolecular synthon. Most of the examples cited in the literature are of cocrystals formed between an API and a coformer chosen from the generally recognized as safe (GRAS) substance list, however, few examples exist where a cocrystal consists of two or more APIs. These cocrystals are commonly known as multi API, multi drug or drug- drug cocrystals. The formation of such cocrystals is feasible by virtue of non covalent interactions between the APIs, which help them in retaining their biologic activity. In addition, drug- drug cocrystals also offer the potential solution to the limitations such as solubility, stability differences and chemical interaction between the APIs which is often faced during the traditional combination therapy. Cocrystallization of two or more APIs can be employed for delivery of combination drugs for the better and efficacious management of many complex disorders where existing monotherapies do not furnish the desired therapeutic effect. This review on the existing drug-drug cocrystals is to gain insight for better designing of multi API cocrystals with improved physicochemical and pharmacokinetic profile and its application in multiple target therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Severe Rhabdomyolysis Associated with the Cerivastatin-Gemfibrozil Combination Therapy

    Science.gov (United States)

    Lau, Theodore K.; Leachman, D. Richard; Lufschanowski, Roberto

    2001-01-01

    Cerivastatin is the new 3rd-generation of the synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, the 1st drugs of choice for treating hypercholesterolemia. A potent inhibitor of HMG-CoA reductase, it possesses a high affinity for liver tissue and decreases plasma low-density lipoprotein cholesterol at microgram doses. Cerivastatin produces reductions in low-density lipoprotein cholesterol of 31.3% and 36.1% at doses of 0.3 and 0.4 mg/day, respectively. It is an uncomplicated agent with regard to its pharmacokinetic profile, low potential for interaction with other drugs, and suitability for use in those with impaired renal function. Most other statins have been implicated in causing rhabdomyolysis, either as mono-therapy or in combination with other agents. We report what to our knowledge is the most profound case yet in the literature of rhabdomyolysis in association with ceriva-statin-gemfibrozil combination therapy, in regard both to the extreme elevation in serum creatinine kinase and to the patient's near-paralytic weakness. PMID:11453128

  4. A study on radiation therapy combined with superselective intraarterial infusion therapy for maxillary sinus carcinoma

    International Nuclear Information System (INIS)

    Okamoto, Isaku; Ito, Hiroyuki; Shimizu, Akira; Shimizu, Shigetaka; Suzuki, Mamoru; Yoshida, Tomoyuki; Nakamura, Kazuhiro; Tsukahara, Kiyoaki

    2010-01-01

    The data of 14 patients with squamous cell carcinoma of the maxillary sinus who were admitted to our hospital and received radiation therapy and concurrent superselective intraarterial infusion therapy between 1998 and 2008 were analyzed to determine the effect of the primary treatment and the adverse events. The subjects were between 43 and 79 years old (median, 61 years old), and there were 10 male and 4 female patients. Superselective intraarterial infusion therapy was administered using the Seldinger method, and cisplatin (CDDP) was administered by intraarterial infusion at a total of 200 mg/m 2 . 5-fluorouracil (FU) was systemically administered by intravenous infusion at the dose of 800 mg/m 2 from day 2 to day 5. In addition, radiation therapy was given concurrently, beginning on day 2. At 4 weeks after completion of the scheduled radiation therapy combined with superselective intraarterial infusion therapy, the treatment effect was judged based on macroscopic, radiological and histopathological findings. The response rates to the primary treatment were as follows: 57.1%, complete response (CR) (8 patients) and 42.9%, partial response (PR) (6 patients). Thus, the overall response rate was 100%. As for the adverse events, while grade 4 cerebral infarction occurred in one patient, all of the other adverse events were reversible and not serious. The safety of the treatment was therefore considered to be acceptable. We are planning to investigate the long-term outcomes in a future study. (author)

  5. FLUORESCENCE DIAGNOSIS AND PHOTODYNAMIC THERAPY IN COMBINED TREATMENT OF CHOLANGIOCARCINOMA

    Directory of Open Access Journals (Sweden)

    A. A. Shiryaev

    2016-01-01

    Full Text Available The results of the pilot study of combined treatment for non-resectable cholangiocarcinoma complicated with obstructive jaundice are represented this paper. Method included percutaneous transhepatic biliary drainage, endoscopic fluorescence diagnosis, photodynamic therapy of tumor stricture, and stenting of bile ducts. Fourteen patients who underwent the treatment in the surgery department clinic of I.M. Sechenov First Moscow State Medical University were enrolled in the study. Fluorescence diagnosis and photodynamic therapy were carried out using photosensitizers photosens (0.5 mg/kg, fotolon (1 mg/kg, and radachlorin (1 mg/kg. The average light dose for one session was 115±5 J/cm2. Fluorescence diagnosis using endoscopic video-fluorescence system for endoscopy and minimally invasive surgery allowed to obtain videoassisted fluorescence image of the tumor and to measure level of photosensitizer fluorescence in tumor in all patients. Malignant tumor was confirmed by morphological study in 12 patients, biopsy of material for morphological study failed in 2 patients with Klatskin tumor. The preliminary results of combined minimally invasive treatment were assessed as promising. The survival time in 4 patients after treatment accounted for 21, 17, 13 and 11 months, respectively. For now 5 patients are under follow-up. Follow-up periods are 13 and 19 months in 2 of them and from 4 to 6 months in 3 of them. Five patients with multiple distant metastases before the treatment died in 3±1 months after therapy. The average lifetime in the treatment group is 9.5 months up to date, however the duration is expected to belonger because 5 of 14 patients are alive.

  6. Aliskiren and valsartan combination therapy for the management of hypertension

    Directory of Open Access Journals (Sweden)

    Benjamin J Epstein

    2010-08-01

    Full Text Available Benjamin J EpsteinDepartments of Pharmacotherapy and Translational Research and Medicine, Colleges of Pharmacy and Medicine, University of Florida, Gainesville, Florida, USA and East Coast Institute for Research, Jacksonville, Florida, USAAbstract: Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA, a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.Keywords: aliskiren, valsartan, single-pill combination, hypertension, renin

  7. Hydrotherapy combined with Snoezelen multi-sensory therapy.

    Science.gov (United States)

    Lavie, Efrat; Shapiro, Michele; Julius, Mona

    2005-01-01

    The aim of this article is to present a new and challenging model of treatment that combines two therapeutic interventions: hydrotherapy and Snoezelen or controlled multisensory stimulation. The combination of the two therapeutic approaches enhances the treatment effect by utilizing the unique characteristics of each approach. We believe that this combined model will further enhance each media to the benefit of the clients and create a new intervention approach. This article relates to a hydrotherapy swimming pool facility that has been established at the Williams Island Therapeutic Swimming and Recreation Center, Beit Issie Shapiro, Raanana in Israel, after acquiring many years of experience and gaining substantial knowledge both in the field of hydrotherapy and Snoezelen intervention. Beit Issie Shapiro is a non-profit community organization providing a range of services for children with developmental disabilities and their families. The organization provides direct services for nearly 6,000 children and adults each year. This article provides an overview of hydrotherapy and Snoezelen and presents a case study, which will demonstrate the new model of treatment and show how this new and innovative form of therapy can be used as a successful intervention. We believe it will open a path to enriching the repertoire of therapists helping people with special needs. This article is also addressed to researchers to provide ideas for further studies in this area.

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  9. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-01

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

  10. Radiation therapy combined with hyperthermia in advanced cancer

    International Nuclear Information System (INIS)

    Okuma, Akiko; Terashima, Hiromi; Torii, Yoshikuni; Nakata, Hajime; Inatomi, Hisato

    1986-01-01

    Radiation therapy combined with radiofrequency (RF) hyperthermia was performed on 5 advanced cancer patients. Included were one each with urinary bladder cancer, hepatoma with left axillary node metastasis, breast cancer, tongue cancer with left cervical metastasis, and mandibular cancer. All had large tumors, which were judged to be uncontrollable by radiotherapy alone. They were treated with irradiation (Linac: 10 MV X-ray 1.8 - 2.0 Gy/day, 5 days/week), followed within an hour by RF hyperthermia once or twice a week. Partial response was obtained in the urinary bladder cancer patient. Surface overheating around the margin of electrodes occurred in all but no severe complications were observed. (author)

  11. Therapeutic Advances using Combinational Therapy in the Treatment of Glioblastoma

    DEFF Research Database (Denmark)

    Staberg, Mikkel

    2017-01-01

    Glioblastoma is the most malignant brain tumor in adults. Median survival is only about 15 months despite aggressive treatment, consisting of surgery followed by radio- and chemotherapy, stressing the need for new therapies. Development of glioblastoma is thought to be a result of both genetic...... and epigenetic alterations, ultimately leading to oncogenic transformation of normal glia cells. Several features are suggested to give rise to the poor prognosis of glioblastoma including treatment resistance, a high degree of abnormal blood vessels, and high heterogeneity, both within the single tumor and from...... patient to patient. Thus, investigations are needed to identify the genetic-molecular alterations that glioblastoma tumors depend on in order to overcome treatment and regrow after initial surgery. The findings presented in this thesis illustrate the promising potential of combinational treatments...

  12. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    But-Hadzic, Jasna, E-mail: jbut@onko-i.si [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Anderluh, Franc [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Brecelj, Erik; Edhemovic, Ibrahim [Division of Surgery, Institute of Oncology, Ljubljana (Slovenia); Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Kozelj, Miran; Krebs, Bojan [Division of Surgery, University Medical Centre Maribor, Maribor (Slovenia); Oblak, Irena [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Omejc, Mirko [Division of Surgery, University Medical Centre Lubljana, Ljubljana (Slovenia); Vogrin, Andrej [Division of Diagnostics, Institute of Oncology, Ljubljana (Slovenia); Velenik, Vaneja [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia)

    2016-12-01

    Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

  13. Combination therapy in the management of atrophic acne scars

    Directory of Open Access Journals (Sweden)

    Shilpa Garg

    2014-01-01

    Full Text Available Background: Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. Objective: To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA peel in the management of atrophic scars. Materials and Methods: Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Results: Out of 16 patients with Grade 4 scars, 10 (62.5% patients improved to Grade 2 and 6 (37.5% patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7% patients were left with no scars, 2 (9.1% patients improved to Grade 1and 15 (68.2% patients improved to Grade 2. All 11 (100% patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. Conclusion: This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars.

  14. Spillover adherence effects of fixed-dose combination HIV therapy

    Directory of Open Access Journals (Sweden)

    Kauf TL

    2012-02-01

    Full Text Available Teresa L Kauf1, Keith L Davis2, Stephanie R Earnshaw2, E Anne Davis31Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, 2RTI Health Solutions, Research Triangle Park, NC, 3Independent consultant, Pittsboro, NC, USAAbstract: The impact of fixed-dose combination (FDC products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI backbone consisting of the FDC Epzicom®, GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group versus NRTI combinations taken as two separate pills (NRTI Combo group using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR. Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001. In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03. None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.Keywords

  15. Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

    2013-01-01

    Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

  16. Combined radio- and hormone therapy of the prostate carcinoma

    International Nuclear Information System (INIS)

    Papic, R.

    1979-08-01

    Intention of this study is to detect in 49 patients suffering from prostate carcinomas, effects and side effects of radiotherapy. According to the present results, there is not any doubt that prostate carcinomas are radiosensitive. In all patients radiotherapy induced a prostate shrinkage and an increasing of consistency. It resulted that a prostate biopsy must be carried out in order to control the success of therapy. The success of the treatment depends upon tumour spreading and on its degree of differentiation. Within the observation period only in four cases metastasation of the prostate carcinoma occurred after radiotherapy. According to literature, the 5-year survival rate with an organ-defined prostate carcinoma ranges between 70 and 80% when radiotherapeutic methods are applied. The same authors indicate a 5-year survival rate between 42 and 48% for scattered carcinomas. Only minor side effects are provoked by radiotherapy. In 75% of the patients pollakisuria and dysuria resulted. After irradiation was finished, the symptoms disappeared and did not cause in any case any late complications. In 12% of the cases proctitic pain occurred during irradiation, which in 6% remained even after the treatment was terminated. We could prove unequivocally on our patients that passage impairments caused by a prostate carcinoma are improved by radiotherapy. Finally it can be said that this treatment is applicable for curing carcinoma which is localised on the prostate. In the case of an undefined, scattered carcinoma radiotherapy combined with hormone therapy is the treatment of choice. With regards to undesired side effects radiotherapy is superior to other therapeutic measures. (orig./MG) [de

  17. Outcome of urinary bladder cancer after combined therapies.

    Science.gov (United States)

    Anghel, R M; Gales, L N; Trifanescu, O G

    2016-01-01

    Rationale: Urinary bladder cancer is the fourth most common cancer in men and the eighth in women, being an important public health issue. Methods: : Medical files of 155 patients (132M/ 23F) with urinary bladder cancer treated between 2006 and 2012 were retrospectively analyzed. The median age at diagnosis was 65 years (range: 19-85 years). Disease free survival (DFS) for patients with complete tumor resection receiving adjuvant treatment and progression free survival (PFS) for patients with post-operative residual disease was estimated. Results: The distribution of the stage disease was: 50 patients (32.2%) stage II, 47 (30.3%) stage III, 58 (37.4%) stage IV. Radical cystectomy was performed in 56 patients (36.1%), while 99 patients (63.9%) underwent repeated transurethral resection of the urinary bladder tumor (TURBT). Postoperative treatment included multimodal therapy in 47 patients (30.3%) (chemotherapy and external beam radiation), external beam radiation alone in 57 patients (36.8%) and chemotherapy alone (methotrexate, vinblastine, doxorubicin, and cisplatin-MVAC or gemcitabine+platinum) in 51 patients (32.9%). After a median follow-up of 31 months (range: 3-79 months), 51 patients (32.9%) presented local recurrence, 32 patients (21%) distant recurrence (metastases), 10 patients (6.4%) both local and distant recurrence, and 62 patients (40%) were free of disease. The median duration until progression was 27 months. Discussion: Despite the combined therapy approaches, urinary bladder carcinoma remains an aggressive disease, with a high relapse rate. Earlier diagnosis, aggressive radical surgery in intention to cure (cystectomy), and adjuvant multimodal treatment (radiotherapy and chemotherapy) are needed for survival improvement.

  18. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, Joseph W., E-mail: jwshelt@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waxweiler, Timothy V.; Landry, Jerome; Gao, Huiying; Xu, Yanbo; Wang, Lanfang [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Shu, Hui-Kuo G. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.

  19. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Colonic exclusion and combined therapy for refractory constipation.

    Science.gov (United States)

    Peng, Hong-Yun; Xu, Ai-Zhong

    2006-12-28

    To investigate the therapeutic effectiveness of colonic exclusion and combined therapy for refractory constipation. Thirty-two patients with refractory constipation were randomly divided into treatment group (n = 14) and control group (n = 18). Fourteen patients in treatment group underwent colonic exclusion and end-to-side colorectal anastomosis. Eighteen patients in control group received subtotal colectomy and end-to-end colorectal anastomosis. The therapeutic effects of the operations were assessed by comparing the surgical time, incision length, volume of blood losses, hospital stay, recovery rate and complication incidence. All patients received long-term follow-up. All operations were successful and patients recovered fully after the operations. In comparison of treatment group and control group, the surgical time (h), incision length (cm), volume of blood losses (mL), hospital stay (d) were 87 +/- 16 min vs 194 +/- 23 min (t = 9.85), 10.4 +/- 0.5 cm vs 21.2 +/- 1.8 cm (t = 14.26), 79.5 +/- 31.3 mL vs 286.3 +/- 49.2 mL (t = 17.24), and 11.8 +/- 2.4 d vs 18.6 +/- 2.6 d (t = 6.91), respectively (P 0.05), 21.4% vs 33.3% (P = 0.73 > 0.05), respectively. Colonic exclusion has better therapeutic efficacy on refractory constipation. It has many advantages such as shorter surgical time, smaller incision, fewer blood losses and shorter hospital stay.

  1. Combined therapy for 129 patients with second primary lung cancer

    International Nuclear Information System (INIS)

    Liang Jun; Feng Qinfu; Wang Luhua; Zhang Yaohong; Zhao Hongfa; Weng Xinran

    2004-01-01

    Objective: To analyze the clinical characteristics and prognosis of the second primary lung cancer. Methods: The interval between the second primary lung cancer and the previous primary cancer ranged from 10 days to 317 months (median 49 months). Of the 129 patients treated from 1971 to 1997 by surgery only, radiotherapy only and chemotherapy only or combined therapy, 11 (8.5%) patients had stage I, 29 (22.5%) stage II, 75 (58.1%) stage III and 14 (10.9%) stage IV; 30 patients received surgery alone, 54 radiotherapy alone, 8 chemotherapy alone, 12 surgery plus radiotherapy, 20 radiotherapy plus chemotherapy, 4 surgery plus chemotherapy and 1 surgery plus radiotherapy plus chemotherapy. Results: The overall 2-, 3- and 5-year survival rates were 40.2%, 27.2% and 15.3%. The stage I, II, III and IV 2-year survival rates were 71.6%, 60.7%, 32.9% and 0%, respectively (P 49 and ≤49 months of the interval between the second primary lung cancer and the previous primary cancer (P>0.05). Conclusions: Second primary lung cancer are similar to the first primary lung cancer in clinical characteristics and prognosis. The main cause of failure is lung cancer perse. Stage and being able to operation are prognostic factors

  2. Correlating HIV tropism with immunological response under combination antiretroviral therapy.

    Science.gov (United States)

    Bader, J; Schöni-Affolter, F; Böni, J; Gorgievski-Hrisoho, M; Martinetti, G; Battegay, M; Klimkait, T

    2016-09-01

    A significant percentage of patients infected with HIV-1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV-1 envelope during periods of suppressive cART. Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period. Patients with CCR5-tropic CC-motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4-tropic CXC-motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5-tropic viruses at follow-up. Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5-tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4-tropic viruses during cART. © 2016 British HIV Association.

  3. Acute toxicity of chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  4. Combination of vascular targeting agents with thermal or radiation therapy

    International Nuclear Information System (INIS)

    Horsman, Michael R.; Murata, Rumi

    2002-01-01

    Purpose: The most likely clinical application of vascular targeting agents (VTAs) is in combination with more conventional therapies. In this study, we report on preclinical studies in which VTAs were combined with hyperthermia and/or radiation. Methods and Materials: A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was treated when at 200 mm 3 in size. The VTAs were combretastatin A-4 disodium phosphate (CA4DP, 25 mg/kg), flavone acetic acid (FAA, 150 mg/kg), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), and were all injected i.p. Hyperthermia and radiation were locally administered to tumors of restrained, nonanesthetized mice, and response was assessed using either a tumor growth or tumor control assay. Results: Heating tumors at 41.5 degree sign C gave rise to a linear relationship between the heating time and tumor growth with a slope of 0.02. This slope was increased to 0.06, 0.09, and 0.08, respectively, by injecting the VTAs either 30 min (CA4DP), 3 h (FAA), or 6 h (DMXAA) before heating. The radiation dose (±95% confidence interval) that controls 50% of treated tumors (the TCD 50 value) was estimated to be 53 Gy (51-55 Gy) for radiation alone. This was decreased to 48 Gy (46-51 Gy), 45 Gy (41-49 Gy), and 42 Gy (39-45 Gy), respectively, by injecting CA4DP, DMXAA, or FAA 30-60 min after irradiating. These values were further decreased to around 28-33 Gy if the tumors of VTA-treated mice were also heated to 41.5 degree sign C for 1 h, starting 4 h after irradiation, and this effect was much larger than the enhancement seen with either 41.5 degree sign C or even 43 degree sign C alone. Conclusions: Our preclinical studies and those of others clearly demonstrate that VTAs can enhance tumor response to hyperthermia and/or radiation and support the concept that such combination studies should be undertaken clinically for the full potential of VTAs to be realized

  5. Treatment of selective mutism based on cognitive behavioural therapy, psychopharmacology and combination therapy - a systematic review.

    Science.gov (United States)

    Østergaard, Kasper Rud

    2018-02-15

    Selective mutism (SM) is a debilitating childhood anxiety disorder characterized by a persistent lack of speech in certain social settings and is considered hard to treat. Cognitive behavioral therapy (CBT) and pharmacological treatments are the best described treatments in the literature. To test whether there is evidence on treatment based on CBT, medication or a combination of these. Systematic and critical review of the literature on CBT and/or pharmacological treatments of SM. Literature was sought on PubMed, Embase and Psycinfo in March 2017. Of the included studies, six examined CBT, seven pharmacologic treatment and two a combination of these. Using CBT 53/60 children improved symptomatically whilst respectively 55/67 and 6/7 improved using pharmacologic- and combination-treatment. Pharmacologic treatment and especially CBT showed promising results supported by some degree of evidence, which combination treatment lacks. Yet small numbers, few RCTs, heterogeneous study designs, lack of consistent measures, short treatment and follow-up periods, generally limits the evidence. This needs focus in future research.

  6. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  7. Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

    Science.gov (United States)

    Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

    2016-10-28

    Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Analysis of toxicity in a group of patients treated for pancreatic cancer with combined modality 3D radiation therapy

    International Nuclear Information System (INIS)

    Fine, Robert M.; Fernandez-Vicioso, Eduardo; Higgins, Patrick; Schell, Michael; Sohn, Jason; Pelley, Robert; Walsh, R. M.; Vogt, David; Hermann, Robert

    1995-01-01

    patients (11%) had a minimal KPS =/< 70. Seven of the 37 patients (19%) either lost no weight or gained weight during the chemo-RT, while the mean weight lost was 6.9 lb. with a median weight loss of 6.0 lb. for the entire group. Eighteen patients (49%) required narcotic analgesics during chemo-RT, 9 patients (24%) had ECOG grade 1 or 2 thrombocytopenia. Of those 16 patients receiving a 3 day bolus of 5-FU, 6 of 16 (38%) had thrombocytopenia while of the 96 hr infusion group 4 of 19 (21%) patients had thrombocytopenia. Eight patients had leukopenia of whom 3 had ECOG grade 3 and 4 (both on 3 day bolus 5-FU). Of 6 of 37 (16%) patients developing anemia during chemo-RT 5 were treated with 3 day bolus and one with the 96 hr infusion 5-FU. Nine of 37 (24%) patients suffered grade 0 or 1 diarrhea. Of the two patients treated with prolonged venous infusion 5-FU (225 mg/m2/d) during RT, neither developed any hematologic toxicity. Conclusions: Noncoplanar, nonopposed, conformal radiation therapy can be used with acceptable acute toxicity in the treatment of pancreatic cancer, whether the chemo-radiation is delivered preoperatively, postoperatively, or as the only treatment. The relatively acceptable acute toxicity with the 3D RT approach may allow for more effective and maybe even more potentially toxic treatment strategies to be used in combination with 3D RT

  9. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  10. Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis.

    NARCIS (Netherlands)

    Tuyl, L.H.D. van; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

    2008-01-01

    Objective. The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to

  11. Zonisamide Combined with Cognitive Behavioral Therapy in Binge Eating Disorder

    Science.gov (United States)

    Castellini, Giovanni; Lo Sauro, Carolina; Rotella, Carlo M.; Faravelli, Carlo

    2009-01-01

    Objective. Binge eating disorder is a serious, prevalent eating disorder that is associated with overweight. Zonisamide is an antiepileptic drug that can promote weight loss. We evaluated the efficacy and safety of zonisamide as augmentation to individual cognitive behavioral therapy in the treatment of binge eating disorder patients. Design: controlled open study. Participants: Twenty four threshold and subthreshold binge eating disorder patients were enrolled in the cognitive behavioral therapy treatment group, and 28 patients in the cognitive behavioral therapy plus zonisamide group. Measurements: At the beginning (T0), at the end (T1) of treatment, and one year after the end of treatment (T2), body mass index was measured and Eating Disorder Examination-Questionnaire, Binge Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory were administered. Results. At T1 the cognitive behavioral therapy plus zonisamide group showed a higher mean reduction of body mass index, Eating Disorder Examination-Questionnaire, Beck Depression Inventory, and Binge Eating Scale scores. At T2, the cognitive behavior therapy group regained weight, while the cognitive behavioral therapy plus zonisamide group reduced their body mass and showed a higher reduction in binge eating frequency and Binge Eating Scale, Eating Disorder Examination-Questionnaire Restraint, and State and Trait Anxiety Inventory scores. Conclusion. The zonisamide augmentation to individual cognitive behavior therapy can improve the treatment of binge eating disorder patients, reducing body weight and the number of binge eating episodes. These results are maintained one year after the end of treatment. PMID:20049147

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

    Science.gov (United States)

    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.

  13. Therapeutic Results of Concurrent Chemoradiation in Locally Advanced Uterine Cervical Cancer

    International Nuclear Information System (INIS)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2018-04-27

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

  15. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy.

    Science.gov (United States)

    Bomback, Andrew S; Rekhtman, Yelena; Klemmer, Philip J; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B

    2012-01-01

    Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension

  16. Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

    International Nuclear Information System (INIS)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

    1983-01-01

    Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

  17. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.

    OpenAIRE

    Gaskill, C L; Cribb, A E

    2000-01-01

    In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

  18. Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

    International Nuclear Information System (INIS)

    Leong, Trevor; Joon, Daryl Lim; Willis, David; Jayamoham, Jayasingham; Spry, Nigel; Harvey, Jennifer; Di Iulio, Juliana; Milner, Alvin; Mann, G. Bruce; Michael, Michael

    2011-01-01

    Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.

  19. Combined use of Dexa-Scheroson and Primobolan-Depot in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, J [Shizuoka Rosai Hospital (Japan)

    1976-05-01

    Dexa-Scheroson and Primobolan-Depot were used together with radiation therapy (Linac therapy) required in 13 cases. The following results were obtained. The decrease in white cell counts, which often occurs in radiation therapy, was inhibited by the drugs. There was no case in which radiation therapy should necessarily withdraw because the number of leuckocytes was decreased to less than 3,000. The patients whose liver function was poor should be treated with both drugs at the beginning of radiation therapy. It was found that the combined use of the drugs is effective in the prevention and the treatment of cerebral edema in radiation therapy of intracranial lesion.

  20. Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial.

    Science.gov (United States)

    Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D'Angelo, Valerio; Urso, Viviana

    2015-01-01

    The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization.

  1. Effect of Polycosanol, a grape seed extract and its combined therapy on oxidation markers in rats

    International Nuclear Information System (INIS)

    Oyarzabal Yera, Ambar; Molina Cuevas, Vivian; Jimenez Despaigne, Sonia

    2010-01-01

    The Polycosanol, a mixture of superior primary aliphatic alcohols obtained from the sugarcane wax (Sacharum officinarum, L.) and the grape seeds extract (Vitis vinifera, L.) produces antioxidant effects experimentally and clinically demonstrated. The aim of present paper was to compare the effects of Polycosanol, the grape seed extract, and its combined therapy on oxidative markers in plasma and liver of rats. The rats were distributed into 4 groups: a control one and three treated with Polycosanol, grape seed extract and its combined therapy, respectively, using a 25 mg/kg dose over 4 weeks. The single-therapies significantly reduced the plasmatic concentrations of malonyldialdehyde and of protein-associated carbonyl groups regarding the control, showing a similar efficacy. Combined therapy reduced in a more effective way (p < 0,001) the malonyldialdehyde concentrations of carbonyl groups, and also decreased (p < 0,01) the concentrations of carbonyl groups, but no more than the single-therapies. Each single-therapy reduced the malonyldialdehyde concentrations generated by spontaneous oxidant system in liver homogenate. The effect of combined therapy was higher (p < 0,05) than the grape seed extract, but no more than that of polycosanol. We concluded that oral single-therapies using polycosanol and grape seed extract, administered during 4 weeks, decreased in a similar way, the lipid peroxidation in plasma and liver of rats. Combined therapy was more effective to inhibits the lipid peroxidation in plasma than each single-therapy, separately

  2. Concurrent chemoradiation for unresectable pancreatic cancer

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  3. Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

    Science.gov (United States)

    Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

    2015-12-01

    Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

    Science.gov (United States)

    Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

    2015-03-01

    An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

  5. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    International Nuclear Information System (INIS)

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-01-01

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  6. Combination Therapy in Asthma: A Review | Saleh | Nigerian ...

    African Journals Online (AJOL)

    Background: Asthma can be defined as a chronic inflammatory disease of the airways that is reversible either spontaneously or by treatment. Despite the exponential increase in asthma research, the prevalence of asthma is on the increase, especially in children and young adults in the western societies. Inhaled therapies

  7. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Whittington, Richard; Malkowicz, S Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M; Broderick, Gregory A; Wein, Alan J

    1997-10-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  8. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    International Nuclear Information System (INIS)

    Whittington, Richard; Malkowicz, S. Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M.; Broderick, Gregory A.; Wein, Alan J.

    1997-01-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  9. 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

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

    Science.gov (United States)

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

    2017-05-01

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

  11. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  12. Combined treatment of unresectable pancreatic carcinoma

    International Nuclear Information System (INIS)

    Ohashi, Kazuhiko; Yamao, Kenji; Watanabe, Yoshihiro; Morimoto, Takeshi

    1999-01-01

    For patients with unresectable pancreatic carcinoma, a few kind of treatment including chemoradiation, intraoperative radiation and intra-arterial chemotherapy was done. Chemoradiation using 5FU, CDDP, ADM and radiation to the lesion and liver was performed in 16 patients, showing a response rate of 10%. One-year survivals rate and mean a survival period of this group was 11.7% and 6.6 months respectively. Postmortem autopsy in 6 cases revealed insufficient therapeutic effects in both primary and metastatic site. Because of above-mentioned reasons, chemoradiation therapy to the pancreatic carcinoma, which we did, was estimated as ineffective. (author)

  13. IMMUNOLOGICAL REACTIVITY IN PATIENTS WITH UROLOGICAL PROFILE UNDER COMBINED THERAPY

    Directory of Open Access Journals (Sweden)

    A. V. Esipov

    2017-01-01

    Full Text Available Prevention and treatment of postoperative purulent-inflammatory complications in urological practice remains a subject for study and improvement in all medical centers. The principle of evidence must be taken as a basis of effectiveness of therapy. In this study the quality criteria of demonstrated therapy are immunological parameters.The purpose of this study is to identify the effectiveness of using monooxidase (NO containing a gas stream replenishing the deficiency of endogenous NO in a group of patients; and to investigate immunological reactivity in patients under complex therapy included nitrogen monoxide and immunomodulators.Materials and methods. In this experimental study we determined the functioning of the main links of the patient’s immunological system. They were determined on the basis of the levels of general T-lymphocytes (T-total, T-helper (T-h, T-suppressor (T-s, natural killer (NK, B-lymphocyte and immunoglobulin G, M, A, circulating immune complexes (CIC.Results. Based on the obtained data, we concluded that the traditional treatment of patients with postoperative complications was less effective than the one proposed in our study. Immunological picture of patient’s condition come back to normal almost from the first day of treatment, and under traditional treatment it was only on the 7th day. Under using complex treatment with nitrogen monoxide, parameters of humoral immunity corresponded to the norm already on the 7–14th day from the beginning of treatment.Conclusion. NO-containing gas flow application in complex prevention of purulent-inflammatory complications made possible to eliminate wound infection in shorter terms and to shorten the period of patient’s hospitalization. The best results were obtained in terms of immunological reactivity in a clinical trial in patients who received complex therapy included nitrogen monoxide and lymphotropic administration of the immunomodulators.

  14. Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

    Directory of Open Access Journals (Sweden)

    Nnennaya Anthony Ajayi

    2013-07-01

    Full Text Available Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

  15. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  16. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Postow, Michael A.

    2014-01-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study

  17. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  18. Combined therapy of radiation and hyperthermia on a metastatic tumor of angiosarcoma

    International Nuclear Information System (INIS)

    Yasuda, Hiroshi; Kitayama, Yoshiaki

    1987-01-01

    A combined therapy of radiation and hyperthermia is said to be fairly effective when applied to certain malignant tumors. However, the utility of this therapy for the treatment of angiosarcoma has not been well discussed. Recently, we have had a chance to treat a patient with metastatic angiosarcoma of the neck by using this combined therapy. In this paper, the clinical course of this patient and the availability of this combined therapy for angiosarcoma is reported. The patient was a 77-year-old man, having a primary lesion on the head and a metastatic tumor over the left cheek and neck. This combined therapy was used for the treatment of the metastatic tumor which caused severe pain and uncontrollable bleeding. The results were considered good ; the tumor decreased in size, pain disappeared and no further bleeding or severe side effects were observed. Though the patient died of another metastatic lesion which could not be treated with this combined therapy because the area of its localization could not allow placement in our hyperthermal apparatus, it is concluded that the combined therapy of radiation and hyperthermia is useful selectively for the treatment for angiosarcoma. (author)

  19. Biological basis of chemo-radiation

    International Nuclear Information System (INIS)

    Mornex, F.; Van Houtte, P.; Cosset, J.M.

    1997-01-01

    Radiation therapy has been for years treatment of choice of locally advanced non small cell lung cancer. Improvement due to the combination of radiation and chemotherapy has been shown recently through several randomized trials and a recent meta-analysis. These results may be explained by biological mechanisms, yet un-completely explored, which are detailed in this review and applied to lung cancer. The optimal combination scheme is not yet defined, even trough the concurrent approach is promising, at the expense of an increased toxicity which is the limiting factor of treatment escalation doses. Biological findings and future results of randomized trials will hopefully open new avenues in the therapeutic strategy of this poor prognosis disease. (authors)

  20. Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Seema Gupta

    2016-12-01

    Conclusion: Our results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.

  1. Experimental study of chemical embolus therapy combined with radiotherapy for VX2 bone tumors

    International Nuclear Information System (INIS)

    Yamaguchi, Hiroshi; Mochizuki, Kazuo; Ishii, Yoshiaki

    2000-01-01

    We conducted an experimental study, using a combination of coarse crystal cisplatin and radiotherapy for bone tumors, to evaluate the possibility of the clinical application of chemical embolus therapy in the field of orthopedic surgery. Experimental femoral bone tumors were produced, in rabbits, using VX2 carcinoma. The rabbits were allocated to five groups: untreated control, embolus, chemical embolus, irradiation alone, and chemical embolus and irradiation combination. These therapies were evaluated comparatively, in terms of local antitumor effects (including body weight, X-ray findings, angiography, and histopathology) and in terms of inhibition of pulmonary metastasis. Local antitumor effects, as evaluated by all parameters, except for body weight, were significantly greater for the chemical and irradiation combination group than for the chemical embolus, irradiation alone, untreated control, and embolus groups. There was no significant difference in the inhibition of pulmonary metastasis among the chemical embolus and irradiation combination, chemical embolus, and irradiation alone groups. These findings demonstrated the synergistic effect of the combination of chemical embolus therapy and radiotherapy. In this study, however, no significant difference was found between the chemical embolus therapy alone and the combination therapy groups in the inhibitory effect on pulmonary tumor metastasis, suggesting the need to conduct combination therapy repeatedly in the clinical setting. (author)

  2. Combining Voice Therapy and Physical Therapy: A Novel Approach to Treating Muscle Tension Dysphonia

    Science.gov (United States)

    Craig, Jennifer; Tomlinson, Carey; Stevens, Kristin; Kotagal, Kiran; Fornadley, Judith; Jacobson, Barbara; Garrett, C. Gaelyn; Francis, David O.

    2015-01-01

    Objective This study investigated the role of a specialized physical therapy program for muscle tension dysphonia patients as an adjunct to standard of care voice therapy. Study Design Retrospective Cohort Study Methods Adult MTD patients seen between 2007 and 2012 were identified from the clinical database. They were prescribed voice therapy and, if concomitant neck pain, adjunctive physical therapy. In a pragmatic observational cohort design, patients underwent one of four potential treatment approaches: voice therapy alone (VT), voice therapy and physical therapy (VT+PT), physical therapy alone (PT), or incomplete/no treatment. Voice handicap outcomes were compared between treatment approaches. Results Of 153 patients meeting criteria (Median age 48 years, 68% female, and 30% had fibromyalgia, chronic pain, chronic fatigue, depression, and/or anxiety), there was a similar distribution of patients with moderate or severe pre-treatment VHI scores across treatment groups (VT 45.5%, VT+PT 43.8%, PT 50%, no treatment 59.1%; p=0.45). Patients treated with VT alone had significantly greater median improvement in VHI than those not treated: 10-point vs. 2-point (p=0.02). Interestingly, median VHI improvement in patients with baseline moderate-severe VHI scores was no different between VT (10), VT+PT (8) and PT alone (10; p=0.99). Conclusions Findings show voice therapy to be an effective approach to treating MTD. Importantly, other treatment modalities incorporating physical therapy had a similar, albeit not significant, improvement in VHI. This preliminary study suggests that physical therapy techniques may have a role in the treatment of a subset of MTD patients. Larger, comparative studies are needed to better characterize the role of physical therapy in this population. PMID:26012419

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  5. Well-established and more recent aspects of combined therapy of gynaecological tumours

    International Nuclear Information System (INIS)

    Ladner, H.A.

    1981-01-01

    The question of superiority concerning operative or radiation therapy should not make us forget that the combined therapy of gynaecologic carcinomas was proven to be good. The differing therapy results are due to the problems of classifying the phases, the ages of the patients, the histology, and, not less important, the radiation sensibility of gynaecologic tumours. The psychological and psychosomatic aspects of treating gynaecologic tumours are discussed. (APR) [de

  6. Ethical hot spots of combined individual and group therapy: applying four ethical systems.

    Science.gov (United States)

    Brabender, Virginia M; Fallon, April

    2009-01-01

    Abstract Combined therapy presents ethical quandaries that occur in individual psychotherapy and group psychotherapy, and dilemmas specifically associated with their integration. This paper examines two types of ethical frameworks (a classical principle-based framework and a set of context-based frameworks) for addressing the ethical hot spots of combined therapy: self-referral, transfer of information, and termination. The principle-based approach enables the practitioner to see what core values may be served or violated by different courses of action in combined therapy dilemmas. Yet, the therapist is more likely to do justice to the complexity and richness of the combined therapy situation by supplementing a principle analysis with three additional ethical frameworks. These approaches are: virtue ethics, feminist ethics, and casuistry. An analysis of three vignettes illustrates how these contrasting ethical models not only expand the range of features to which the therapist attends but also the array of solutions the therapist generates.

  7. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy

    DEFF Research Database (Denmark)

    Abdulla, Salim; Achan, Jane; Adam, Ishag

    2016-01-01

    Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are importa...

  8. Combined therapy of corpus carcinoma with special regard to radiotherapy

    International Nuclear Information System (INIS)

    Wilhelm, C.

    1980-01-01

    From 496 case reports of patients with a corpus carcinoma collected between 1970 and 1976, the clinical findings, separation into clinical stages and the various therapy forms were compiled and evaluated. As a mean age of 62.3 years, 56.9 per cent of patients reached an average five-year, recidivation-free survival periods. Metastases occurred in 19.1 per cent of all treated women, vaginal recidivations in 1.8 per cent. Particular attention was given to the side effects of radiation therapy and retarded harmful effects. In this connexion an increase in complications following treatment with newly introduced radiation qualities had to be recorded. 21.9 per cent of all radiation-treated patients differed side-effects, and in 11.7 per cent of all radiation-treated women retarded harmful effects were found. Owing to the experience collected meanwhile in radiotherapy with ultra-hard X-rays and to the use of computerized tomography establishing the adequate quantity of radiation, complications following radiation treatment are expected to occur less frequently in future. (orig./MG) [de

  9. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  10. Resolution of orbitocerebral aspergillosis during combination treatment with voriconazole and amphotericin plus adjunctive cytokine therapy.

    Science.gov (United States)

    Bethell, Delia; Hall, Georgina; Goodman, T Robin; Klein, Nigel; Pollard, Andrew J

    2004-05-01

    Orbitocerebral aspergillosis has a very high fatality rate and cure is unusual. We describe the successful management of a child with cereberal aspergillosis who had a dramatic response to therapy with a combination of liposomal amphotericin and voriconazole with adjunctive cytokine therapy during immunosuppresive chemotherapy for acute lymphoblastic leukaemia.

  11. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial

    NARCIS (Netherlands)

    van Tubergen, A.; Landewé, R.; van der Heijde, D.; Hidding, A.; Wolter, N.; Asscher, M.; Falkenbach, A.; Genth, E.; Thè, H. G.; van der Linden, S.

    2001-01-01

    To determine the efficacy of combined spa-exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS). A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean

  12. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Neratinib Versus Lapatinib Plus Capecitabine For ErbB2 Positive Advanced Breast Cancer Active, not recruiting No Results Available YES neratinib -9...Drug: Neratinib |Drug: Lapatinib|Drug: Capecitabine Efficacy and Safety of BMS-690514 in Combination With Letrozole to Treat Metastatic Breast Cancer

  13. [Control of blood pressure in hypertensive patients on combination therapy].

    Science.gov (United States)

    de la Sierra, Alejandro; Oliveras, Anna; Armario, Pedro; Lucas, Silvia

    2015-02-20

    The impact of antihypertensive treatment on blood pressure (BP) control is fairly unknown. The aim of the study was to evaluate the degree of BP control and its relationship with treatment-related factors in hypertensive patients treated with 2 or 3 agents and attended in referral units. We studied 1,337 hypertensive subjects (41% women) with a mean age (SD) of 63 (12) years, who were receiving 2 or 3 antihypertensive drugs. The degree of BP control was estimated in a single visit by the proportion of patients with BP below 140/90mmHg. BP was controlled in 767 patients (57%). Lack of BP control was related to older age (12% risk for each 10-year increase) and the presence of microalbuminuria (64% risk increase). In those treated with 2 agents, BP control was 61%, without differences between those treated with fixed-drug or free combinations. BP control in those treated with 3 agents was 55%, higher in those receiving 3 agents in a fixed-drug combination (68%) compared with those on 3 agents administered separately (52%; P=.025). Drug classes used in combinations did not influence the degree of BP control. The degree of BP control in patients treated with 2 or 3 agents is 57%. Microalbuminuria is related to a lack of BP control. In those receiving 3 agents, the use of fixed-drug combinations is associated with better BP control. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

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

  16. Combination therapy in chronic periodontitis: a case report

    Directory of Open Access Journals (Sweden)

    Omid Taherpour

    2018-04-01

    Full Text Available Background: The aim of periodontal treatment is to provide healthy and functional dentition for the whole life.Cases Report: A 42 year old female with sever chronic periodontitis, treated medically and surgically, is reported. She initially received antibiotic, Scaling and root planning in addition to oral hygiene instruction. After four weeks, periodontal Surgery, root canal Therapy, extraction of excess tooth and restoration of some teeth were performed, because of remaining residual pockets, and bone loss, flap Surgery and Access flap, with papilla preservation flap method, also modified Widmann flap, were done. After one month, favorable clinical improvement was obtained.Conclusion: It can be concluded that high oral hygiene level in accompanied with Suitable medical and surgical treatment, enhanced the success of periodontal treatment outcomes even in sever disease. 

  17. Healing the wounded self: combining hypnotherapy with ego state therapy.

    Science.gov (United States)

    Alladin, Assen

    2013-07-01

    The purpose of this article is to formulate a theoretical conceptualization for utilizing ego state therapy (EST) as an adjunct with cognitive hypnotherapy (CH) for depression. As the relationship between life events and onset of depression is very complex, it is not clear from current literature how stressors cause depressive symptoms. The notion of "wounded self," derived from the work of Wolfe (2005, 2006), is examined as a potential unifying concept for binding the role of risk factors in the precipitation of depression. By incorporating wounded self, the circular feedback model of depression, on which CH for depression is based, is expanded. This revised version provides conceptual and empirical underpinnings for integrating EST with CH in the management of depression.

  18. Locally advanced cervix carcinoma - innovation in combined modality therapy

    International Nuclear Information System (INIS)

    Swift, Patrick S.

    1996-01-01

    Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

  19. Enhanced tumor responses through therapies combining CCNU, MISO and radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, S.A.

    1984-01-01

    Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

  20. Two drugs are better than one. A short history of combined therapy of ovarian cancer.

    Science.gov (United States)

    Bukowska, Barbara; Gajek, Arkadiusz; Marczak, Agnieszka

    2015-01-01

    Combined therapy of ovarian cancer has a long history. It has been applied for many years. The first drug which was commonly combined with other chemotherapeutics was cisplatin. It turned out to be effective given together with alkylating agents as well as with taxanes. Another drug which is often the basis of first-line therapy is doxorubicin. The use of traditional chemotherapy is often limited due to side effects. This is why new drugs, targeted specifically at cancer cells (e.g. monoclonal antibodies or epidermal growth factor receptor inhibitors), offer a welcome addition when used in combination with conventional anticancer agents. Drugs applied in combination should be synergistic or at least additive. To evaluate the type of interaction between drugs in a plausible sequence, isobolographic analysis is used. This method allows one to assess whether the two agents could make an efficient combination, which might improve the therapy of ovarian cancer.

  1. Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

    International Nuclear Information System (INIS)

    Mizusawa, Hirokazu; Takahashi, Toshio

    1983-01-01

    Twelve cases of carcinoma of the rectum were treated preoperatively by combination therapy with 5-fluorouracil (5-FU) suppository (100 mg twice a day consecutively, a total dose of more than 4,000 mg) and irradiation (300 rad x 3/week, a total dose of 3,000 rad). This group was compared with 34 cases given single preoperative 5-FU therapy and 24 control cases given no preoperative adjuvant modality. The group treated by preoperative combination therapy showed marked antitumor effects macroscopically and histologically. In addition, decrease in local recurrence was expected for this group, compared with the other two groups. (Chiba, N.)

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  4. Nutraceuticals as an Important Part of Combination Therapy in Dyslipidaemia.

    Science.gov (United States)

    Patti, Angelo M; Toth, Peter P; Giglio, Rosaria V; Banach, Maciej; Noto, Marcello; Nikolic, Dragana; Montalto, Giuseppe; Rizzo, Manfredi

    2017-01-01

    Several risk factors such as abnormality of lipid metabolism (e.g. high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C)) play a central role in the aetiology of cardiovascular disease (CVD). Nutraceutical combination together with a cholesterol- lowering action, when associated with suitable lifestyle, should furnish an alternative to pharmacotherapy in patients reporting statin-intolerance and in subjects at low cardiovascular risk. The present review is focused on nutraceuticals and their synergetic combinations demonstrating a beneficial effect in the management of dyslipidaemia. Several nutraceuticals have been shown to positively modulate lipid metabolism having different functions. Plant sterols and soluble fibres can, for example, decrease the intestinal assimilation of lipids and increase their elimination. Furthermore, berberine and soybean proteins improve the cholesterol uptake in the liver. Policosanols, monacolins and bergamot inhibit hydroxy-methyl-glutaryl coenzyme A reductase (HMGCoA reductase) enzyme action determining the cholesterol hepatic synthesis. Moreover, pomegranate can decrease LDL oxidation and positively affect subclinical atherosclerosis; red yeast rice and berberine play, instead, an important role on endothelial dysfunction and psyllium, plant sterols and bergamot have positive effects on LDL subclasses. To the best of our knowledge, there are no long-term large-scale studies on the anti-atherogenic effect of the nutraceuticals that are available on the market. Thus, further clinical studies should investigate in order to achieve long term tolerability and safety and to provide a better nutraceutical combination tailored to the patient needs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  6. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  8. Efficacy of intense pulse light therapy and tripple combination cream versus intense pulse light therapy and tripple combination cream alone in epidermal melasma treatment

    International Nuclear Information System (INIS)

    Shakeeb, N.; Noor, S.M.; Paracha, M.M.; Ullah, G.

    2018-01-01

    Objective:To compare the efficacy of intense pulse light therapy (IPL) and triple combination cream (TCC) versus intense pulse light therapy and triple combination cream alone in epidermal melasma treatment, downgrading MASI score to more than 10. Study Design:Randomized controlled trial. Place and Duration of Study:Dermatology Department, Lady Reading Hospital, Peshawar, from August 2014 to January 2015. Methodology:Patients of 18-45 years were included in the study with Fitzpatrick skin type II-V. Sample of 96 patients was divided in to three groups of 32 each, through consecutive (non-probability) sampling method. Detailed history was taken, Woods Lamp Examination done, and melasma area and severity index (MASI) score was calculated. TCC had to be applied daily at night for two months by group A patients while group B was consigned for IPL therapy fortnightly, and those in group C were given both for two months. Efficacy was compared by recalculating MASI score at treatment end as well as at follow-up after 4 weeks, using Chi-square test with significance at p < 0.05. Results:Male and female patients were 10 (31.2%) and 22 (68.8%) in group A, 7 (21.9%) and 25 (78.1%) in group B, while in group C were 12 (37.5%) and 20 (62.5%). The average age was 28.70 +8.70 years. MASI score reduction was achieved in 22 (68.8%) patients in group A; whereas, in 20 (62.5%) and 30(93.8%) patients in group B and C, respectively. Efficacy-wise distribution was significant (p=0.009). Conclusion:Intense pulse light therapy and triple combination cream are more efficacious in epidermal melasma treatment than intense pulse light therapy and triple combination cream alone. (author)

  9. Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

    Science.gov (United States)

    Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Supuran, Claudiu T; Fais, Stefano

    2017-12-23

    Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities compared with unicellular microorganisms. These systems are also involved in the unresponsiveness or resistance to chemotherapy, leading to the protection of cancer cells from the vast majority of drugs, that when protonated in the acidic tumor microenvironment, do not enter into cancer cells. Indeed, as usually occurs in the progression versus malignancy, resistant tumor clones emerge and proliferate, following a transient initial response to a therapy, thus giving rise to more malignant behavior and rapid tumor progression. Recent studies are supporting the use of a cocktail of proton exchanger inhibitors as a new strategy against cancer.

  10. Research advances in traditional Chinese medicine combined with interventional therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LIU Yang

    2015-01-01

    Full Text Available Interventional therapy has become the first choice of non-surgical treatment for hepatocellular carcinoma (HCC due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti-cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage.

  11. Anti-tumor effects of Egr-IFN γ gene therapy combined with 125I-UdR radionuclide therapy

    International Nuclear Information System (INIS)

    Zhao Jingguo; Ni Yanjun; Song Xiangfu; Li Yanyi; Yang Wei; Sun Ting; Ma Qingjie; Gao Fengtong

    2008-01-01

    Objective: To explore the anti-tumor effects of Egr-IFNγ gene therapy combined with 125 I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNγ mixed with liposome was injected into tumor. 48 h later, 370 kBq 125 I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNγ in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNγ + 125 I-UdR group were obviously lower than those of control group, 125 I-UdR group and pcDNAEgr-1 + 125 I-UdR group 6-15 d after gene-radionuclide therapy. IFNγ protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNγ + 125 I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNγ + 125 I-UdR group was significantly higher than that in the other groups (P 125 I-UdR radionuclide therapy are better than those of 125 I-UdR therapy. (authors)

  12. Combined doxorubicin and radiation therapy in malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Sinoff, C.; Falkson, G.; Sandison, A.G.; De Muelenaere, G.

    1982-01-01

    Ten patients with histologically confirmed inoperable malignant mesothelioma of the pleura were treated with doxorubicin and fractionated radiotherapy courses. Three patients derived significant clinical benefit from this treatment, although only one of the three had measureable tumor shrinkage that could be defined as partial response. Two of the ten patients showed only progressive disease, while the remaining five showed disease stabilization for 30--100 weeks. The treatment was subjectively well-tolerated and hematopoietic toxicity was acceptable. Radiation pneumonitis did not occur. Two of the four patients who lived greater than or equal to 94 weeks developed fibrosis of the irradiated hemithorax. The median survival time for all patients was 46 weeks. Although the combined treatment could be given with acceptable toxic effects and although four patients benefited from it, the best objective assessment, namely, survival time, did not appear to be adequately influenced to justify an extension of this series

  13. Epigenetic polypharmacology: from combination therapy to multitargeted drugs.

    Science.gov (United States)

    de Lera, Angel R; Ganesan, A

    The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.

  14. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rebecca J Faleiro

    2016-02-01

    Full Text Available Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of

  15. FIRST EXPERIENCE OF CYMEVEN IN THE COMBINED THERAPY OF RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    R M Balabanova

    2001-01-01

    Full Text Available Ummary Objective. To reveal J'reguency of accompaning virus infection and possibility to use antivirus therapy together in therapy RA. Material. 40 patients with RA at the age of 17-45 were studied. The duration of disease was not more than 6 months; patients had 2-3 degrees of activity. Every one had a positive rheumatoid factor. Results. 78,2% of the examined patients connected the beginning of the illness with virus infection they have had. The most difficalt variant of RA course and uneffectiveness of basic therapy were registerd among the patients with combination HSV and CMV infection. Inclusion of Cymevene in complex therapy RA has exerted positive influence on clinical-laboratory, signs stregthened effect of basic therapy. Conclusion. The most difficult variant of RA course was registered among the patients with virus infection. Inclusion of antivirus drugs had a positive influence on effectiveness of basic therapy.

  16. Early use of negative pressure therapy in combination with silver dressings in a difficult breast abscess.

    Science.gov (United States)

    Richards, Alastair J; Hagelstein, Sue M; Patel, Girish K; Ivins, Nicola M; Sweetland, Helen M; Harding, Keith G

    2011-12-01

    Combining silver-based dressings with negative pressure therapy after radical excision of chronically infected breast disease is a novel application of two technologies. One patient with complex, chronic, infected breast disease underwent radical excision of the affected area and was treated early with a combination of silver-based dressings and topical negative pressure therapy. The wound was then assessed sequentially using clinical measurements of wound area and depth, pain severity scores and level of exudation. It is possible to combine accepted techniques with modern dressing technologies that result in a positive outcome. In this case, the combination of a silver-based dressing with negative pressure therapy following radical excision proved safe and was well tolerated by the patient. Full epithelisation of the wound was achieved and there was no recurrence of the infection for the duration of the treatment. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  17. Assessment of immunomodulating action of combined therapy with UHF-hyperthermia in children with osteogenic sarcoma

    International Nuclear Information System (INIS)

    Neprina, G.S.; Panteleeva, E.S.; Vatin, O.E.; Bizer, V.A.; Bojko, I.N.

    1989-01-01

    The paper is concerned with immunological evaluation of different stages of combined therapy with local UHF-hyperthermia in children with osteogenic sarcoma. Combined therapy (polychemo- and raditherapy) was shown to cause a decrease in the number of immunocompetent cells, to enhance dysbalance of immunoregulatory T-lymphocytes, to weaken T-lymphocyte function on PHA; immunosuppressive action of combined therapy did not depend on a tumor site. The incorporation of UHF-hyperthermia in the therapeutic scheme weakened the manifestations of secondary immunodeficiency, got back to normal structure of T-lymphocyte population. A favorable immunomodulating effect of hyperthermia was more frequently observed in patients with crural bone tumors. The effect of hyperthermia was revealed after direct influence of thermotherapy but it was absent in continuation of combined treatment

  18. Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

    2018-05-20

    This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

  19. Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, N.; Hubeck-Graudal, T.; Tarp, S.

    2014-01-01

    identified in a search of electronic archives of biomedical literature and included in a star-shaped network meta-analysis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. Effects are reported as standardized mean differences (SMD......). The effects of data from 39 trials published in the period 1989-2012 were as follows: Double DMARD: -0.32 SMD (CI: -0.42, -0.22); triple DMARD: -0.46 SMD (CI: -0.60, -0.31); 1 DMARD plus TNFi: -0.30 SMD (CI: -0.36, -0.25); 1 DMARD plus abatacept: -0.20 SMD (CI: -0.33, -0.07); 1 DMARD plus tocilizumab: -0.......34 SMD (CI: -0.48, -0.20); 1 DMARD plus CD20i: -0.32 SMD (CI: -0.40, -0.24). The indirect comparisons showed similar effects between combination treatments apart from triple DMARD being significantly better than abatacept plus methotrexate (2 0.26 SMD (CI: -0.45, -0.07)) and TNFi plus methotrexate (-0...

  20. Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

    Science.gov (United States)

    Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

    2017-11-25

    The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

  1. Ultrasound elastography in patients with rectal cancer treated with chemoradiation

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  3. Therapy of combined radiation injuries with hemopoietic growth factors

    International Nuclear Information System (INIS)

    Boudagov, R.; Oulianova, L.

    1996-01-01

    Radiation accidents of the 5-7 th levels according to IAEA scale lead to life-threatening acute radiation syndrome and many patients will probably suffer from additional thermal burns. These combined injuries (CI) will be among the most difficult to achieve survival. Present therapeutic means need to augment with new approaches to stimulate host defence mechanisms, blood system recovery and to enhance survival. The evaluation of therapeutic properties of human recombinant G-CSF, IL-1,IL-2 and other so called 'biological response modifiers' on survival and blood recovery after CI was the purpose of this work. Experiments carried out with mice CBA x C57BL6 receiving 7 Gy total body irradiation followed by a full-thickness thermal bum of 10% of body surface. It established that G-CSF does not exhibit a positive modifying action on the damage level and on hematopoietic recovery. I.p two-four/fold infusion of IL-2 during the initial 2 days has provided a significant statistically survival increase from 40% (untreated mice with CI) to 86%. Single s.c IL-1 injection resulted in abrupt deterioration of the outcome when dealing with CI; three/fold administration of IL-1 in 2,4 and 6 days after CI did not increase survival. Extracellular yeast polysaccharides resulted only a 15 to 30% increase in survival it given 1 h after CI. The best results obtained when mixture of heat-killed L.acidophilus injected s.c immediately alter CI - survival has increased from 27% (untreated mice) to 80%. Revealed beneficial effects of IL-2 and biological response modifiers did not accompany by a corresponding correction of depressed hematological parameters

  4. Combined Antirelapse Therapy in Patients with Schizoaffective Disorder: A Prospective Cohort Study

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    Zhanna R. Gardanova

    2016-06-01

    Full Text Available Background: In most studies, patients with schizoaffective disorder (SAD are often combined into one group along with schizophrenia patients or less commonly with those suffering from affective disorders, which makes it difficult to obtain data about the peculiarities of SAD treatment. Articles dedicated to SAD treatment in the interictal period are rare. Methods and Results: The prospective cohort study was conducted from 2011 to 2015. The study involved 86 patients diagnosed with SAD according to ICD-10. Patients received neuroleptics (NLs as antirelapse therapy for 2 years (NL therapy; then mood stabilizers (MSs were added to the antirelapse treatment (NL+MS therapy. The results of this combined therapy with MSs were evaluated after 2 years of treatment. Our results suggest that the use of combination therapy that includes antipsychotics and MSs leads to maintenance of a higher quality remission. Remission becomes more prolonged and affective swings less pronounced, resulting in improved quality of life in SAD patients. Improving the quality of remission can be attributed to the following characteristics of the combined therapy: a the use of lower doses of neuroleptics; b a reduction in the frequency and severity of mood swings; and c an increase in patient compliance. Conclusion: The use of combined pharmacotherapy including antipsychotics and MSs produces a longer, high-quality remission. The inclusion of MSs in the scheme of treatment increases the patient adherence to a medication regimen. The use of MSs in combination therapy reduces affective fluctuations, thereby increasing the probability of maintaining remission with complete symptom relief.

  5. Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

    Science.gov (United States)

    Amato, Dominick; Patterson, Mary Anne

    2018-01-27

    Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

  6. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

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    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  7. Potential utility of combination therapy with nateglinide and telmisartan for metabolic derangements in Zucker Fatty rats.

    Science.gov (United States)

    Kajioka, T; Miura, K; Kitahara, Y; Yamagishi, S

    2007-12-01

    The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular disease. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial hyperglycemia. In this study, we investigated the potential utility of combination therapy with telmisartan, an angiotensin II receptor blocker and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial hyperglycemia and metabolic derangements in Zucker Fatty (ZF) rats. ZF rats fed twice daily were given vehicle, 50 mg/kg of nateglinide, 5 mg/kg of telmisartan, or both for 6 weeks. Combination therapy with nateglinide and telmisartan for 2 weeks ameliorated postprandial hyperglycemia in ZF rats fed twice daily. Furthermore, 6-week treatment with nateglinide and telmisartan not only decreased fasting plasma insulin, triglycerides, and free fatty acid levels, but also improved the responses of blood glucose to insulin and subsequently reduced the decremental glucose areas under the curve in the ZF rats. Combination therapy also restored the decrease of plasma adiponectin levels in the ZF rats. Monotherapy with nateglinide or telmisartan alone didnot significantly improve these metabolic parameters. These observations demonstrate that combination therapy with nateglinide and telmisartan may improve the metabolic derangements by ameliorating early phase of insulin secretion as well as insulin resistance in ZF rats fed twice daily. Our present findings suggest that the combination therapy with nateglinide and telmisartan could be a promising therapeutic strategy for the treatment of the metabolic syndrome.

  8. Fixed-dose combination for adults accessing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    SA HIV Clinicians Society

    2013-02-01

    Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  10. A clinical study on combined modality therapy, radio-hyperthermo-chemotherapy, for pancreatic cancer

    International Nuclear Information System (INIS)

    Yamamoto, Yoshikazu

    1989-01-01

    A new multimodality therapy, radio-hyperthermo-chemotherapy, has been performed in a total of 31 pancreatic cancer patients with the purpose of improving treatment outcome. Combination of hyperthermia and chemotherapy was given as a pre-irradiation therapy in 7 resectable cancer patients. Among 24 unresectable cancer patients, 17 had irradiation in combination with hyperthermia and chemotherpay. Although both degeneration and necrosis of cancer cells were observed in all resectable cases at biopsy, these were not predictive of a better outcome. Of evaluable 17 patients with unresectable cancer, tumor regression was observed in 5 (29.4%). Although 22 patients had pain before therapy, 8 and 5 patients had remarkable and moderate pain relief, respectively, with therapy. Performance status was improved in 7 patients (29.2%). Survival rate at 12 months was still low (8.3%). However, the radio-hyperthermo-chemotherapy appears to help in increasing the quality of life in view of pain relief. (N.K.)

  11. Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Gong DJ

    2013-07-01

    Full Text Available Dao-Jun Gong,1 Jia-Min Zhang,1 Min Yu,1 Bo Zhuang,1 Qing-Qu Guo21Department of Hepatobiliary-Pancreatic Surgery, Jinhua Hospital of Zhejiang University, Jinhua, People's Republic of China; 2Department of Surgery, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of ChinaBackground: Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods.Methods: Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo.Results: The cleaved poly ADP ribose polymerase (PARP-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05 and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05.Conclusion: Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single

  12. Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes.

    Science.gov (United States)

    Raskin, P

    2008-12-01

    Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

  13. Nonstent Combination Interventional Therapy for Treatment of Benign Cicatricial Airway Stenosis

    OpenAIRE

    Xiao-Jian Qiu; Jie Zhang; Ting Wang; Ying-Hua Pei; Min Xu

    2015-01-01

    Background: Benign cicatricial airway stenosis (BCAS) is a life-threatening disease. While there are numerous therapies, all have their defects, and stenosis can easily become recurrent. This study aimed to investigate the efficacy and complications of nonstent combination interventional therapy (NSCIT) when used for the treatment of BCAS of different causes and types. Methods: This study enrolled a cohort of patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and othe...

  14. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

    Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

  15. The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.

    Science.gov (United States)

    An, Jingang; Zhang, Dingwei; Wu, Jiawen; Li, Jiong; Teng, Xiu; Gao, Xiaomin; Li, Ruilian; Wang, Xiuying; Xia, Linlin; Xia, Yumin

    2017-07-01

    Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control. Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs. Human primary keratinocytes and hepatic stellate cells were used for analyzing their effect in vitro. The results showed that the combination therapy exhibited higher effectiveness in remitting skin lesion, but did not significantly affect the liver function of both patients and mice. Moreover, the combination groups showed less elevation of profibrotic factors in sera when compared with methotrexate alone groups accordingly. Furthermore, primary keratinocytes expressed more involucrin as well as loricrin and proliferated more slowly on the combined stimulation. Interestingly, such combination treatment induced lower expression of profibrotic factors in hepatic stellate cells. In conclusion, the acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve higher effectiveness and result in less liver fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The role of combination medical therapy in the treatment of acromegaly.

    Science.gov (United States)

    Lim, Dawn Shao Ting; Fleseriu, Maria

    2017-02-01

    Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

  17. Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

    Science.gov (United States)

    Nakanishi, Asako; Hakamada, Arata; Isoda, Ken-ichi; Mizutani, Hitoshi

    2005-05-01

    Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

  18. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy.

    Science.gov (United States)

    Hay, Jodie F; Lappin, Katrina; Liberante, Fabio; Kettyle, Laura M; Matchett, Kyle B; Thompson, Alexander; Mills, Ken I

    2017-09-15

    Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML.