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Sample records for hyperfractionated accelerated chemoradiotherapy

  1. A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

    SciTech Connect

    Tada, Takuhito; Chiba, Yasutaka; Tsujino, Kayoko; Fukuda, Haruyuki; Nishimura, Yasumasa; Kokubo, Masaki; Negoro, Shunichi; Kudoh, Shinzoh; Fukuoka, Masahiro; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2012-05-01

    Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

  2. [The results of chemoradiotherapy for locally advanced laryngeal cancer with hyperfractionated radiotherapy].

    PubMed

    Kurpeshev, O K; Gulidov, V A; Andreev, V G; Pankratov, I A; Orlova, A V

    2014-01-01

    Single chemoradiotherapy (CRT) was performed in 27 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy (RT) was carried out in hyperfractionated mode 1+1 Gy (every 4-5 hours), 5 times a week to CFD 60 Gy with a 2-week break after CFD 30-40 Gy. Courses of polychemotherapy (PCT) were performed simultaneously with RT at each stage of treatment. Overall 5-year survival of patients in the whole by the group (T3-4N0-3) was 44.6%, for patients with T3N0--72.7%, T3N1-20--42.9%, T4N1-2--40.0% with an average life expectancy 38.1; 50.8; 39.0 and 39.8 months respectively. During a 5-year follow-up the local control of the primary tumor at T3 was equal to 61%, T4--25% with a median remission of 40.6 and 13.5 months respectively. During this period the regional control at metastases N1 was 50%, with a median remission of 32.7 months. In 4 patients of 5 with N2 and in all 3 patients with N3 during the first year after CRT continued growth or tumor recurrence was diagnosed. Thus, conservative CRT provides relatively satisfactory 5-year outcomes in patients with tumors T3N0-1. PMID:25552069

  3. Late course accelerated hyperfractionated radiotherapy plus concurrent chemotherapy for squamous cell carcinoma of the esophagus: A phase III randomized study

    SciTech Connect

    Zhao Kuaile; Shi Xuehui; Jiang Guoliang . E-mail: jianggl@21cn.com; Yao Weiqiang; Guo Xiaomao; Wu Gendi; Zhu Longxiang

    2005-07-15

    Purpose: Late course accelerated hyperfractionated (LCAF) radiotherapy (RT) is as effective as standard chemoradiotherapy for nonsurgical management of locally advanced esophageal squamous cell carcinoma (SCC). We have evaluated further the efficacy of concurrent LCAF RT and chemotherapy. Methods and Materials: In all, 111 eligible patients with esophageal SCC were randomized to receive LCAF alone (LCAF) or concurrent LCAF and chemotherapy (LCAT+CT) between March 1998 and July 2000. All patients received conventional fractionation irradiation of 1.8 Gy per day, to a dose of 41.4 Gy/23 fractions in 4-5 weeks, followed by accelerated hyperfractionated irradiation using reduced fields, 1.5 Gy/fractions twice a day, to a dose of 27 Gy in 18 days. Thus, the total dose was 68.4 Gy/41 fractions in 44 days. Fifty-four patients in the LCAF+CT arm had an additional four cycles of chemotherapy using cisplatin 25 mg/m{sup 2} daily and fluorouracil (5-FU) 600 mg/m{sup 2} daily on Days 1-3 every 4 weeks starting on the same day that LCAF was delivered. Results: The median survival was 23.9 months (95% confidence [CI], 20.1-27.7) for the LCAF arm and 30.8 months (95% CI, 17.6-44.1) for the LCAF+CT arm, respectively. Survival rates at 1, 3, and 5 years of the LCAF arm were 77%, 39%, and 28%, respectively, while those of the LCAF+CT arm were 67%, 44%, and 40%, respectively (p = 0.310). Grades 3 and 4 acute toxicities occurred in 46% and 25% of the patients in the LCAF arm and the LCAF+CT arm, respectively; 6% of the patients in the combined arm had Grade 5 acute toxicities, whereas none was noted in the LCAF alone arm. Conclusions: Late course accelerated hyperfractionation was effective for locally advanced esophageal SCC. There was a trend toward better survival among patients who received intensified treatment with concurrent chemotherapy. Further randomized studies with a larger number of patients should be carried out, but additional measures must be taken to reduce the higher

  4. Accelerated Hyperfractionated Radiotherapy for Cervical Cancer: Multi-Institutional Prospective Study of Forum for Nuclear Cooperation in Asia Among Eight Asian Countries

    SciTech Connect

    Ohno, Tatsuya Nakano, Takashi; Kato, Shingo

    2008-04-01

    Purpose: To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer. Methods and Materials: A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors {>=}6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%. Conclusion: The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.

  5. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  6. Mature Results of a Randomized Trial of Accelerated Hyperfractionated Versus Conventional Radiotherapy in Head-and-Neck Cancer

    SciTech Connect

    Saunders, Michele I.; Rojas, Ana M.; Parmar, Mahesh K.B.; Dische, Stanley

    2010-05-01

    Purpose: To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck. Methods and Materials: Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events. Results: The 10-year estimates (+-1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% +- 2% for CHART and 50% +- 3% with CRT (log-rank p = 0.2); 26% +- 2% and 29% +- 3% (p = 0.4), respectively; 41% +- 2% and 46% +- 3% (p = 0.3), respectively; and 56% +- 3% and 58% +- 3% (p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART (p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART (p = 0.02 to 0.05). Conclusions: Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy.

  7. A feasibility study of [sup 252]Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer

    SciTech Connect

    Murayama, Y.; Wierzbicki, J. Univ. of Kentucky Medical Center, Lexington, KY ); Bowen, M.G.; Van Nagell, J.R.; Gallion, H.H.; DePriest, P. )

    1994-06-15

    The purpose was to evaluate the feasibility and toxicity of [sup 252]Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with [sup 252]Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m[sup 2]) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m[sup 2]/day [times] 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq by external and intracavitary therapy and 60 Gy at the pelvic sidewalls. Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the [sup 252]Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). [sup 252]Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of [sup 252]Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. The authors found chemotherapy was more effective with the improved local tumor control. 18 refs., 2 tabs.

  8. Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

    SciTech Connect

    Das, Prajnan; Delclos, Marc E.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Bedi, Manpreet; Krishnan, Sunil; Crane, Christopher H.

    2010-05-01

    Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <=2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

  9. Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

    PubMed Central

    Mauguen, Audrey; Le Péchoux, Cécile; Saunders, Michele I.; Schild, Steven E.; Turrisi, Andrew T.; Baumann, Michael; Sause, William T.; Ball, David; Belani, Chandra P.; Bonner, James A.; Zajusz, Aleksander; Dahlberg, Suzanne E.; Nankivell, Matthew; Mandrekar, Sumithra J.; Paulus, Rebecca; Behrendt, Katarzyna; Koch, Rainer; Bishop, James F.; Dische, Stanley; Arriagada, Rodrigo; De Ruysscher, Dirk; Pignon, Jean-Pierre

    2012-01-01

    Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity. PMID:22753901

  10. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  11. Short treatment time and excellent treatment outcome in accelerated hyperfractionated radiotherapy for T1 glottic cancer

    PubMed Central

    Tamaki, Yukihisa; Hieda, Yoko; Yoshida, Rika; Yoshizako, Takeshi; Fuchiwaki, Takafumi; Aoi, Noriaki; Sekihara, Kazumasa; Kitajima, Kazuhiro; Kawauchi, Hideyuki; Kitagaki, Hajime; Sasaki, Ryohei; Inomata, Taisuke

    2015-01-01

    ABSTRACT Accelerated hyperfractionated radiotherapy was performed as treatment for patients with T1 glottic cancer, and its utility was evaluated based on treatment outcomes and adverse effects. Fifty-eight men who had undergone radiotherapy were retrospectively reviewed. Tumor classification was Tis in 4 patients, T1a in 38, and T1b in 16. Histological examination revealed squamous cell carcinoma in 55 patients. Travel time from home to hospital was 0–1 hour for 24 patients, 1–2 hours for 9, and >2 hours for 25. Laser vaporization was performed prior to radiotherapy in 38 patients, and 19 patients received concurrent chemotherapy with an agent such as S-1. Patients were irradiated twice daily using an irradiation container. Most patients received a dose of 1.5 Gy/fraction up to a total of 60 Gy. The median overall treatment time was 30 days, with a median observation period of 59.6 months. A complete response was observed in all patients. The 5-year overall survival, disease-free survival, and local control rates were 97.2%, 93.2%, and 97.8%, respectively. Although grade 3 pharyngeal mucositis was observed in 2 patients, there were no other grade 3 or higher acute adverse events. As late toxicity, grade 2 laryngeal edema and grade 1 laryngeal hemorrhage were observed in 1 patient each, but no serious events such as laryngeal necrosis or laryngeal stenosis were observed. In conclusion, this treatment method brings excellent outcome and will substantially reduce the treatment duration among patients who need to stay at nearby hotels while undergoing treatment at hospitals in rural areas. PMID:26663937

  12. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

    SciTech Connect

    De Crevoisier, Renaud . E-mail: rdecrevo@mdanderson.org; Baudin, Eric; Bachelot, Anne; Leboulleux, Sophie; Travagli, Jean-Paul; Caillou, Bernard; Schlumberger, Martin

    2004-11-15

    Purpose: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. Methods and materials: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m{sup 2}) and cisplatin (120 mg/m{sup 2}) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. Results: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. Conclusions: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.

  13. Short treatment time and excellent treatment outcome in accelerated hyperfractionated radiotherapy for T1 glottic cancer.

    PubMed

    Tamaki, Yukihisa; Hieda, Yoko; Yoshida, Rika; Yoshizako, Takeshi; Fuchiwaki, Takafumi; Aoi, Noriaki; Sekihara, Kazumasa; Kitajima, Kazuhiro; Kawauchi, Hideyuki; Kitagaki, Hajime; Sasaki, Ryohei; Inomata, Taisuke

    2015-11-01

    Accelerated hyperfractionated radiotherapy was performed as treatment for patients with T1 glottic cancer, and its utility was evaluated based on treatment outcomes and adverse effects. Fifty-eight men who had undergone radiotherapy were retrospectively reviewed. Tumor classification was Tis in 4 patients, T1a in 38, and T1b in 16. Histological examination revealed squamous cell carcinoma in 55 patients. Travel time from home to hospital was 0-1 hour for 24 patients, 1-2 hours for 9, and >2 hours for 25. Laser vaporization was performed prior to radiotherapy in 38 patients, and 19 patients received concurrent chemotherapy with an agent such as S-1. Patients were irradiated twice daily using an irradiation container. Most patients received a dose of 1.5 Gy/fraction up to a total of 60 Gy. The median overall treatment time was 30 days, with a median observation period of 59.6 months. A complete response was observed in all patients. The 5-year overall survival, disease-free survival, and local control rates were 97.2%, 93.2%, and 97.8%, respectively. Although grade 3 pharyngeal mucositis was observed in 2 patients, there were no other grade 3 or higher acute adverse events. As late toxicity, grade 2 laryngeal edema and grade 1 laryngeal hemorrhage were observed in 1 patient each, but no serious events such as laryngeal necrosis or laryngeal stenosis were observed. In conclusion, this treatment method brings excellent outcome and will substantially reduce the treatment duration among patients who need to stay at nearby hotels while undergoing treatment at hospitals in rural areas. PMID:26663937

  14. Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Gandola, Lorenza; Spreafico, Filippo; Luksch, Roberto; Collini, Paola; Giangaspero, Felice; Simonetti, Fabio; Casanova, Michela; Cefalo, Graziella; Pignoli, Emanuele; Ferrari, Andrea; Terenziani, Monica; Podda, Marta; Meazza, Cristina; Polastri, Daniela; Poggi, Geraldina; Ravagnani, Fernando; Fossati-Bellani, Franca

    2006-03-15

    Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.

  15. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin for locally advanced head and neck carcinomas: A preliminary report

    SciTech Connect

    Arias, F.; Dominguez, M.A.; Illarramendi, J.J.

    1995-10-15

    The feasibility and activity of an intensive chemoradiotherapeutic scheme for patients with locally advanced squamous cell head and neck cancers were tested in a single institution Phase II pilot study. Between January 1990 and February 1992, 40 patients were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64-67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. All of the 40 patients are evaluable for response and survival. Toxicity was significant, but tolerable. A complete tumor response to this treatment was achieved by 37 patients (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 patients have died, 2 without tumor. The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49-79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95, 39-73%). This treatment obtains a high rate of complete responses with increased acute toxicity but tolerable late effects. Preliminary results are encouraging for laryngeal neoplasms. A longer follow-up is needed to evaluate the impact of this treatment on patient survival. 47 refs., 3 figs., 3 tabs.

  16. Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

    PubMed

    Doi, Hiroshi; Beppu, Naohito; Odawara, Soichi; Tanooka, Masao; Takada, Yasuhiro; Niwa, Yasue; Fujiwara, Masayuki; Kimura, Fumihiko; Yanagi, Hidenori; Yamanaka, Naoki; Kamikonya, Norihiko; Hirota, Shozo

    2013-11-01

    The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials. PMID:23658415

  17. Routine Use of Continuous, Hyperfractionated, Accelerated Radiotherapy for Non-Small-Cell Lung Cancer: A Five-Center Experience

    SciTech Connect

    Din, Omar S. Lester, Jason; Cameron, Alison; Ironside, Janet; Gee, Amanda; Falk, Stephen; Morgan, Sally A.; Worvill, Jackie; Hatton, Matthew Q.F.

    2008-11-01

    Purpose: To report the results from continuous, hyperfractionated, accelerated radiotherapy (CHART) used as the standard fractionation for radical RT in the management of non-small cell lung cancer (NSCLC) in five United Kingdom centers. Methods and Materials: In 2005, the CHART consortium identified six U.K. centers that had continued to use CHART after the publication of the CHART study in 1997. All centers had been using CHART for >5 years and agreed to use a common database to audit their results. Patients treated with CHART between 1998 and December 2003 were identified to allow a minimum of 2 years of follow-up. Patient demographics, tumor characteristics, treatment details, and survival were recorded retrospectively. Five centers completed the data collection. Results: A total of 583 patients who had received CHART were identified. Of these patients, 69% were male, with a median age of 68 years (range, 31-89); 83% had performance status 0 or 1; and 43% had Stage I or II disease. Of the 583 patients, 99% received the prescribed dose. In only 4 patients was any Grade 4-5 toxicity documented. The median survival from the start of RT was 16.2 months, and the 2-year survival rate of 34% was comparable to that reported in the original study. Conclusion: The results of this unselected series have confirmed that CHART is deliverable in routine clinical practice, with low levels of toxicity. Importantly, this series has demonstrated that the results of CHART reported from the randomized trial can be reproduced in routine clinical practice.

  18. Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

    SciTech Connect

    Canyilmaz, Emine; Yavuz, Melek Nur; Serdar, Lasif; Uslu, Gonca Hanedan; Zengin, Ahmet Yasar; Aynaci, Ozlem; Haciislamoglu, Emel; Bahat, Zumrut; Yoney, Adnan

    2014-11-01

    Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

  19. Phase III study of cisplatin with pemtrexed or vinorelbine plus concurrent late course accelerated hyperfractionated radiotherapy in patients with unresectable stage III non-small cell lung cancer

    PubMed Central

    Zhao, Qian; Wang, Zhongtang; Huang, Wei; Wang, Qiang; Yu, Shuzeng; Zhou, Tao; Han, Dan; Wu, Zhenying; Gong, Heyi; Sun, Hongfu; Zhang, Jian; Wei, Yumei; Li, Hongsheng; Zhang, Zicheng; Lin, Haiqun; Li, Baosheng

    2016-01-01

    Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy (LCAHRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to two regimens. The experimental (PP) arm included cisplatin, pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33%. The control (NP) arm used cisplatin, vinorelbine with the same radiotherapy protocol. The primary endpoint was overall survival. Median survival times were 26.0 months (95% CI 23.2 to 28.7 months) and 28.5 months (95% CI 17.1 to 39.9 months) for the NP and PP arms, respectively (P = 0.26). Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms (P = 0.07). In both arms of the study, there were no differences in overall survival between patients with squamous and nonsquamous NSCLC. The incidences of grade 3 or 4 toxicity were higher in NP than PP arm. With concurrent LCAHRT, pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin, but showed a more favorable toxicity profile. PMID:26761213

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

    SciTech Connect

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

    2011-11-01

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

  1. Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

    PubMed Central

    Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

    2006-01-01

    Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m2/d DDP + 750–1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Results Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. Conclusion The SCHARC protocol was effective in patients diagnosed with advanced head

  2. Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: Impact of chemotherapy schemes

    SciTech Connect

    Yau, T.K. . E-mail: tkokyau@gmail.com; Lee, Anne; Wong, Dominique; Pang, Ellie S.Y.; Ng, W.T.; Yeung, Rebecca; Soong, Inda S.

    2006-11-15

    Purpose: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. Methods and Materials: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. Results: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). Conclusions: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.

  3. Preventing radiation retinopathy with hyperfractionation

    SciTech Connect

    Monroe, Alan T.; Bhandare, Niranjan; Morris, Christopher G.; Mendenhall, William M. . E-mail: mendewil@shands.ufl.edu

    2005-03-01

    Purpose: The purpose of this study was to determine factors associated with the development of radiation retinopathy in a large series of patients with head-and-neck cancer. In particular, we addressed whether the use of hyperfractionated radiation therapy was effective in reducing the risk of retinopathy. Methods and materials: One hundred eighty-six patients received a significant dose to the retina as part of curative radiotherapy. Primary sites included: nasopharynx, 46; paranasal sinus, 64; nasal cavity, 69; and palate, 7. Prescription doses varied depending on primary site and histology. Hyperfractionated (twice-daily) radiation was delivered to 42% of the patients in this study, typically at 1.10 to 1.20 Gy per fraction. The remainder were treated once-daily. Retinal doses were determined from computerized dosimetry plans when available. For all other patients, retinal doses were retrospectively calculated using reconstructed off-axis dosimetry taken from contours through the center of the globes. Retinal dose was defined as the minimum dose received by at least 25% of the globe. The median retinal dose was 56.85 Gy. Patients were followed for a median of 7.6 years. Results: Thirty-one eyes in 30 patients developed radiation retinopathy, resulting in monocular blindness in 25, bilateral blindness in 1, and decreased visual acuity in 4. The median time to the diagnosis of retinopathy was 2.6 years (range, 11 months to 5.3 years). The actuarial incidence of developing radiation retinopathy was 20% at both 5 and 10 years. The incidence of developing ipsilateral blindness due to retinopathy was 16% at 5 years and 17% at 10 years. Site-specific incidences varied considerably, with ethmoid sinus (9 of 25, 36%), nasal cavity (13 of 69, 19%), and maxillary sinus (6 of 35, 17%) being the most common sites associated with radiation retinopathy. Three of 72 patients (4%) receiving retinal doses less than 50 Gy developed retinopathy. Higher retinal doses resulted in a

  4. Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

    SciTech Connect

    Budach, Volker; Stromberger, Carmen; Poettgen, Christoph; Baumann, Michael; Budach, Wilfried; Grabenbauer, Gerhard; Marnitz, Simone; Olze, Heidi; Wernecke, Klaus-Dieter; Ghadjar, Pirus

    2015-04-01

    Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.

  5. Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation

    SciTech Connect

    Lee, Anne W.M. . E-mail: awmlee@ha.org.hk; Yau, T.K.; Wong, Dominique H.M.; Chan, Elian W.K.; Yeung, Rebecca M.W.; Ng, W.T.; Tong, Macy; Soong, Inda S.; Sze, W.M.

    2005-12-01

    Purpose: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. Methods and Materials: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. Results: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. Conclusion: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

  6. Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Yalman, Deniz

    2015-01-01

    Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group of patients, and the optimal treatment is still controversial. The current standard of care is concurrent chemoradiotherapy. The prognosis is still poor, with high rates of local and distant failure despite multimodality treatment. One of the efforts to improve outcomes in these patients is to use neoadjuvant treatment to improve resectability, and downstaging the nodal disease, which has a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has been used historically without any survival benefit, but with increased toxicity. After the demonstrating a survival benefit by combining radiotherapy and chemotherapy, phase II studies were started to determine the neoadjuvant administration of these two modalities together. Although the results of these studies revealed a heterogeneous postinduction pathologic complete response, tumor and nodal down-staging can be achieved at the cost of a slightly higher morbidity and mortality. Subsequent phase III trials also failed to show a survival benefit to surgery, but indicated that there may be a subset of patients with locally advanced disease who can benefit from resection unless pneumonectomy is not provided. In order to increase the efficacy of radiotherapy, hyperfractionated-accelerated schedules have been used with promising complete pathologic response rates, which might improve prognosis. Recently, studies applying high radiotherapy doses in the neoadjuvant setting demonstrated the safety of resection after radiotherapy, with high nodal clearance rates and encouraging long-term survival results. In conclusion, neoadjuvant treatment of locally advanced NSCLC is one of the most challenging issues in the treatment of this disease, but it can be offered to appropriately selected patients, and should be done by a multidisciplinary team. Individual risk profiles, definite role of radiotherapy with optimal timing, and

  7. Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

    SciTech Connect

    Poettgen, Christoph; Eberhardt, Wilfried E.; Gauler, Thomas; Krbek, Thomas; Berkovic, Katharina; Abu Jawad, Jehad; Korfee, Soenke; Teschler, Helmut; Stamatis, Georgios; Stuschke, Martin

    2010-03-01

    Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision was made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing

  8. Outcome of hyperfractionated radiotherapy in chemotherapy-resistant non-Hodgkin's lymphoma

    SciTech Connect

    Martens, Chandra; Hodgson, David C.; Wells, Woodrow A.; Sun, Alex; Bezjak, Andrea; Pintilie, Melania; Crump, Michael; Gospodarowicz, Mary K.; Tsang, Richard . E-mail: Richard.Tsang@rmp.uhn.on.ca

    2006-03-15

    Purpose: Patients with chemotherapy-resistant lymphoma have rapidly progressive disease and a poor prognosis. Local symptoms are treated with radiotherapy (RT) for local control. We have reviewed local control and toxicity in patients treated with hyperfractionated accelerated RT. Methods and Materials: A total of 34 patients received hyperfractionated RT between 1997 and 2003. The radiation dose was 39.9-40.5 Gy in 30 fractions. The median treatment time was 22 days with twice-daily involved-field RT. The median follow-up was 4.4 years. Response was assessed <3 months after RT and was classified as a complete response, a complete response-unconfirmed, a partial response, or no response. Local control was defined as maintenance of local complete response, complete response-unconfirmed, or lack of local progression with a partial response. Recurrence or progression outside the RT volume was regarded as distant disease. Results: The median age was 53 years; 20 patients were men and 14 were women. The initial diagnosis was Stage I-II in 56% and Stage III-IV in 44%. The disease bulk was {>=}10 cm in 35% (n 12). The histologic features at diagnosis were follicular in 11 (Grade 1 in 4, Grade 2 in 3, and Grade 3 in 4), diffuse large B-cell in 14, peripheral T-cell lymphoma in 2, Burkitt-like in 1, mantle cell in 2, natural killer cell in 2, plasmacytoma/lymphoma in 1, and T-cell lymphoblastic in 1. The initial treatment was chemotherapy in 32 patients (94%); 71% were refractory to initial chemotherapy and 29% developed a relapse after an initial response. The RT response was complete in 24% (n = 8), complete, unconfirmed in 26% (n = 9), partial in 47% (n = 16), and none in 3% (n = 1). The local control rate was 73% at 1, 2, and 3 years. Grade 1 dermatitis was the most common side effect. Conclusion: Hyperfractionated RT provided good local control and was well tolerated. This encouraging result requires additional study with comparison to conventional fractionation

  9. Hyperfractionated Concomitant Boost Proton Beam Therapy for Esophageal Carcinoma

    SciTech Connect

    Mizumoto, Masashi; Sugahara, Shinji; Okumura, Toshiyuki; Hashimoto, Takayuki; Oshiro, Yoshiko; Fukumitsu, Nobuyoshi; Nakahara, Akira; Terashima, Hideo; Tsuboi, Koji; Sakurai, Hideyuki

    2011-11-15

    Purpose: To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. Methods and Materials: The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. Results: There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. Conclusions: The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.

  10. Reversible neurotoxicity following hyperfractionated radiation therapy of brain stem glioma

    SciTech Connect

    Griebel, M.; Friedman, H.S.; Halperin, E.C.; Wiener, M.D.; Marks, L.; Oakes, W.J.; Hoffman, J.M.; DeLong, G.R.; Schold, S.C.; Hockenberger, B. )

    1991-01-01

    Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. {sup 18}FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation-related neurotoxicity.

  11. Effects of chemoradiotherapy on voice and swallowing

    PubMed Central

    Lazarus, Cathy L.

    2009-01-01

    Purpose of review Chemotherapy has been found to result in comparable survival rates to surgery for head and neck cancer. However, toxicity can often be worse after chemoradiotherapy, with impairment in voice, swallowing, nutrition, and quality of life. Investigators are attempting to modify radiotherapy treatment regimens to spare organs that have an impact on swallowing. This review will highlight voice and swallowing impairment seen after chemoradiotherapy, as well as treatment for voice and swallowing disorders in this population. Results of newer radiotherapy regimens will also be highlighted. Recent findings Specific oropharyngeal swallowing motility disorders after chemoradiotherapy have been identified. Damage to specific structures has been correlated with specific pharyngeal phase swallow impairment. Swallowing function and quality of life have been examined over time, with improvement seen in both. Preventive/prophylactic swallow exercise programs have been encouraging. Chemoradiotherapy effects on voice have been identified in terms of acoustic, aerodynamic, and patient and clinician-rated perception of function. Improvement in voice has also been observed over time after chemoradiotherapy. Voice therapy has been found to have a positive impact on voice and perceptual measures in this population. Summary Current studies show some improvement in swallow function after swallow and voice therapy in patients treated with chemoradiotherapy. Further, there is a suggestion of improved swallow function with sparing of organs with specific radiotherapy protocols. Future research needs to focus on specific voice and swallow treatment regimens in the head and neck cancer patient treated with chemoradiotherapy, specifically, timing, frequency, duration, and specific treatment types. PMID:19337126

  12. Radiation-induced renal damage: the effects of hyperfractionation. [Mice

    SciTech Connect

    Stewart, F.A.; Soranson, J.A.; Alpen, E.L.; Williams, M.V.; Denekamp, J.

    1984-05-01

    The response of mouse kidneys to multifraction irradiation was assessed using three nondestructive functional end points. A series of schedules was investigated giving 1, 2, 4, 8, 16, 32, or 64 equal X-ray doses, using doses per fraction in the range of 0.9 to 16 Gy. The overall treatment time was kept constant at 3 weeks. Kidney function was assessed from 19 to 48 weeks after irradiation by measuring changes in isotope clearance, urine output, and hematocrit. All three assays yielded steep dose-effect curves from which the repair capacity of kidney could be estimated by comparing the isoeffective doses in different schedules. There was a marked influence of fractionation, with increasing dose being required to achieve the same level of damage for increasing fraction number, even between 32 and 64 fractions. The data are well fitted by a linear quadratic dose-response equation, and analysis of the data would suggest that hyperfractionation, using extremely small X-ray doses per fraction, would spare kidneys relative to tumors and acutely responding tissues.

  13. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  14. Amifostine (ETHYOL) protects rats from mucositis resulting from fractionated or hyperfractionated radiation exposure

    SciTech Connect

    Cassatt, David R.; McCarthy, Michael P. . E-mail: mccarthym@medimmune.com

    2005-03-01

    Purpose: The cytoprotective drug amifostine (Ethyol) protects rats from oral mucositis resulting from a single dose of {gamma}-irradiation. We expanded earlier studies to determine whether multiple doses of amifostine protect against fractionated or hyperfractionated radiation and whether the active metabolite of amifostine (WR-1065) accumulates in tissues upon repeated administration. Methods and materials: Rats received amifostine daily for 5 days in conjunction with a 1-week fractionated radiation schedule and were evaluated for oral mucositis. Rats also received amifostine before the am or pm exposure or b.i.d. in conjunction with hyperfractionated radiation. To determine the pharmacokinetics of WR-1065 after repeated dosing, amifostine was given 5 days a week for 1 or 3 weeks, and rat tissue and plasma were collected at intervals during and after treatment and analyzed for WR-1065. Results: Amifostine protected rats from mucositis resulting from fractionated or hyperfractionated radiation. When the number of days of amifostine administration was reduced, protection was diminished. A dose of 100 mg/kg given in the morning or 2 doses at 50 mg/kg provided the best protection against hyperfractionated radiation. WR-1065 did not accumulate in tissues or tumor upon repeated administration. Conclusions: Amifostine prevented radiation-induced mucositis in a rat model; protection was dose and schedule dependent.

  15. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  16. Prognosis of Esophageal Cancer Patients With Pathologic Complete Response After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    Park, Jae Won; Kim, Jong Hoon; Choi, Eun Kyung; Lee, Sang-wook; Yoon, Sang Min; Song, Si Yeol; Lee, Yu Sun; Kim, Sung Bae; Park, Seung il; Ahn, Seung Do

    2011-11-01

    Purpose: To define failure patterns and predictive factors in esophageal cancer patients who had a pathologic complete response (pCR) after preoperative concurrent chemoradiotherapy (PCRT). Methods and Materials: We performed a retrospective analysis of 61 esophageal cancer patients who were enrolled in prospective studies and showed pCR after PCRT. All of the patients had squamous cell carcinoma. Of the patients, 40 were treated with hyperfractionated radiotherapy (4,560 cGy in 28 fractions) with 5-fluorouracil (5-FU) and cisplatin (FP), and 21 patients received conventional fractionation radiotherapy with capecitabine and cisplatin (XP). Results: The median follow-up time was 45.2 months (range, 6.5-162.3 months). The 5-year overall survival (OS) and disease-free survival rates (DFS) were 60.2% and 80.4%, respectively. In univariate analysis, age and lymph node (LN) metastasis were poor prognostic factors for OS, and pretreatment weight loss (>2 kg) was a poor prognostic factor for DFS. In multivariate analysis, lymph node metastasis and pretreatment weight loss were independent prognostic factors for OS and DFS. Nine patients (15%) had disease recurrence. Of the nine patients, 5 patients had locoregional failure, 1 patients had distant metastasis, and 3 patients had distant and locoregional failure. In-field failure occurred in 5 patients; out-of-field failure occurred in 1 patient; both in-field and out-of-field failure occurred in 2 patients; and both marginal and out-of-field failure occurred in 1 patient. Conclusions: Even in pCR patients, the most common failure site was within the radiation field, which suggests that more efficient local treatment is needed. Tumor recurrence was more common in patients with older age and with pretreatment weight loss.

  17. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  18. Postoperative Chemoradiotherapy for Extrahepatic Bile Duct Cancer

    SciTech Connect

    Park, Jin-hong; Choi, Eun Kyung; Ahn, Seung Do; Lee, Sang-wook; Song, Si Yeol; Yoon, Sang Min; Kim, Young Seok; Lee, Yu Sun; Lee, Sung-Gyu; Hwang, Shin; Lee, Young-Joo; Park, Kwang-Min; Kim, Tae Won; Chang, Heung Moon; Lee, Jae-Lyun; Kim, Jong Hoon

    2011-03-01

    Purpose: To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with extrahepatic bile duct cancer. Methods and Materials: We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil. Results: The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p = .2779), progression-free survival (35% vs. 22%, p = .3107), or locoregional progression-free survival (75% vs. 63%, p = .2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival (p = .001) and progression-free survival (p = .033). A total of 3 patients developed Grade 3 or greater late toxicity. Conclusion: Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.

  19. Concurrent Chemoradiotherapy in Resected Extrahepatic Cholangiocarcinoma

    SciTech Connect

    Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.; Tyler, Douglas S.; Pappas, Theodore N.; Clary, Bryan M.; Hurwitz, Herbert I.; Bendell, Johanna C.; Morse, Michael A.; Clough, Robert W.; Czito, Brian G.

    2009-01-01

    Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic

  20. Intracranial Ependymomas in Children: Society of Pediatric Oncology Experience With Postoperative Hyperfractionated Local Radiotherapy

    SciTech Connect

    Conter, Cecile Carrie, Christian; Bernier, Valerie; Geoffray, Anne; Pagnier, Anne; Gentet, Jean-Claude; Lellouch-Tubiana, Arielle; Chabaud, Sylvie; Frappaz, Didier

    2009-08-01

    Purpose: To prospectively investigate the role of local hyperfractionated radiotherapy (RT) after surgical resection in the treatment of intracranial ependymomas in children. Patients and Methods: Postoperative local hyperfractionated RT was proposed for every child (>5 years old at diagnosis) with localized intracranial ependymoma. The planned dose was 60 Gy after complete resection (CR) and 66 Gy after partial resection, delivered in two daily fractions of 1 Gy, according to the early postoperative imaging findings. Results: Between November 1996 and December 2002, 24 children with infratentorial (n = 20) or supratentorial (n = 4) intracranial ependymoma were included. The median age was 8.6 years (range, 5-17). The World Health Organization grade was anaplastic in 10 of the 24 patients (not assessable in 1). After a retrospective central review, a CR was reported in 16 patients, partial resection in 4, and doubtful resection in 4. The radiation dose was 60 Gy in 18 cases (one partial resection), 66 Gy in 5 cases (one CR), and 54 Gy in 1 case (CR). The 5-year overall survival rate was 74.8%, and the progression-free survival rate was 54.2%. Of the 24 patients, 11 developed a relapse: 7 local only and 4 metastatic and local. The histological grade and extent of resection were not prognostic factors. More than 3 in 4 children had no sequelae of RT at a median follow-up of 7 years (95% confidence interval, 66.4-90.0 months). Conclusion: The results of our study have shown that hyperfractionated RT is safe but provides no outcome benefit compared with other strategies of RT such as standard fractionated regimens.

  1. Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial

    SciTech Connect

    Payne, D.G.; Simpson, W.J.; Keen, C.; Platts, M.E.

    1982-12-01

    A prospective randomized trial of 157 patients with malignant astrocytomas (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m/sup 2/) six weekly and hydroxyurea (HU, 3.5 gm/m/sup 2/ over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks). Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P<0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimes had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease.

  2. Analysis of late complications after rapid hyperfractionated radiotherapy in advanced head and neck cancers

    SciTech Connect

    Nguyen, T.D.; Panis, X.; Froissart, D.; Legros, M.; Coninx, P.; Loirette, M.

    1988-01-01

    Late effects were analyzed in a series of 39 patients with a 2-year minimal follow-up who were treated by rapid hyperfractionated radiotherapy. The total dose was 66-72 Gy delivered in two series of 33-36 Gy separated by a 2-4 week rest interval. The number of daily fractions ranged from 8 to 6 and the interval between each fraction was 2 hr. Late complications consisted of cervical fibrosis, mucosal necrosis, bone necrosis, trismus, and laryngeal edema. Seventy percent of patients experienced late complications, and in 54% of cases, these reactions were considered severe, causing death in 13% of patients. No relationship was found between field sizes, dosimetric data and type and frequency of late effects. It is therefore suggested that the interval between two daily sessions in any multifractionated protocol may be of critical importance.

  3. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

    SciTech Connect

    Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

    1985-04-01

    The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body.

  4. Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants

    SciTech Connect

    Shank, B.; Chu, F.C.H.; Dinsmore, R.; Kapoor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O'Reilly, R.J.

    1983-11-01

    From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as > 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

  5. Phase I/II Trial of Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme

    SciTech Connect

    Mizumoto, Masashi; Tsuboi, Koji; Igaki, Hiroshi; Yamamoto, Tetsuya; Takano, Shingo; Oshiro, Yoshiko; Hayashi, Yasutaka; Hashii, Haruko; Kanemoto, Ayae; Nakayama, Hidetsugu; Sugahara, Shinji; Sakurai, Hideyuki; Matsumura, Akira; Tokuuye, Koichi

    2010-05-01

    Purpose: To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM). Methods and Materials: Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of >=60; (2) the diameter of the enhanced area before radiotherapy was <=40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T{sub 2}-weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks. Results: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months. Conclusions: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences.

  6. Definitive Chemoradiotherapy ("Watch-and-Wait" Approach).

    PubMed

    Goodman, Karyn A

    2016-07-01

    Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision has been the standard of care for locally advanced patients with rectal cancer. Some patients achieve a pathologic complete response (pCR) to CRT and the oncologic outcomes are particularly favorable in this group. The role of surgery in patients with a pCR is now being questioned as radical rectal resection is associated with significant morbidity and long-term effects on quality of life. In an attempt to better tailor therapy, there is an interest in a "watch-and-wait" approach in patients who have a clinical complete response (cCR) after CRT with the goal of omitting surgery and allowing for organ preservation. However, a cCR does not always indicate a pCR, and improved clinical and imaging modalities are needed to better predict which patients have achieved a pCR and therefore can safely undergo a "watch-and-wait" approach. This article reviews the current data on nonoperative management and on-going controversies associated with this approach. PMID:27238472

  7. [Preoperative chemoradiotherapy for resectable lower rectal cancer].

    PubMed

    Takase, Shiro; Kamigaki, Takashi; Yamashita, Kimihiro; Nakamura, Tetsu; Nishimura, Hideki; Sasaki, Ryohei

    2009-11-01

    To suppress local recurrence and preserve sphincter function, we performed preoperative chemoradiotherapy( CRT) of rectal cancer. Sixteen patients with lower advanced rectal cancer received tegafur/uracil/calcium folinate+RT followed by curative resection with lateral lymph node dissection 2-8 weeks later. The male/female ratio was found to be 11:5 (41-75 years old) and the CRT was feasible for all patients. There were 11-PR and 5-SD according to RECIST criteria, and lower isotope accumulation was observed for all primary tumors in FDG-PET study. After CRT, all patients received R0 curative resection (11 APR, 2 LAR, 1 Hartmann and 1 ISR). On pathological study, 3 patients showed complete response. Surgical complications including pelvic infection, delayed a wound healing and deep venous thrombosis, etc. In conclusion, preoperative CRT of advanced rectal cancer could potentially be useful for local control and sphincter saving, however, it is necessary to manage specific surgical complications due to radiation. PMID:20037306

  8. Hyperfractionated radiotherapy in advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Nguyen, T.D.; Panis, X.; Legros, M.; Froissart, D.

    1983-03-01

    From January, 1976 to January, 1980, 141 patients (135 males and 6 females) with Stage III and IV squamous cell carcinoma of the head and neck received a split course of hyperfractionated radiotherapy (HFR). In the first group, involving 91 patients, the therapeutic schedule was as follows: first and fourth week, 7.2 Gy per day in 8 sessions of .9 Gy from Monday to Friday, the second and third week no irradiation was given. Thus, patients were given 72 Gy total dose, fractionated into 80 sessions. Mucosal necrosis and severe hemorrhage were responsible for the death of 26 patients (28%). Therefore the therapeutic protocol was altered for the 50 patients of the second group: during the first and sixth week 6.6 Gy per day in 6 sessions of 1.1 Gy from Monday to Friday. The total dose was thus reduced to 66 Gy fractionated into 60 sessions, resulting in the decrease of toxicity. Regardless of the therapeutic protocol and site of primary, 114 patients (80%) achieved a complete remission and 8 showed a partial remission (>50%), whereas no change was seen for the 19 remainders. Local recurrence appeared in 60 patients (48%). Acute mucositis and laryngeal edema regularly occurred a week after every course of HFR and were considered severe in 40 patients. In spite of toxicity, the median survival is 14 months and 22 patients are still alive in November 1981: 19 without disease, and 8 of these patients have a survival time of at least 3 years.

  9. Phase I Trial of Gross Total Resection, Permanent Iodine-125 Brachytherapy, and Hyperfractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Chen, Allen M.; Chang, Susan; Pouliot, Jean; Sneed, Penny K.; Prados, Michael D.; Lamborn, Kathleen R.; Malec, Mary K.; McDermott, Michael W.; Berger, Mitchell S.; Larson, David A.

    2007-11-01

    Purpose: To evaluate the feasibility of gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy for patients with newly diagnosed glioblastoma. Methods and Materials: From April 1999 to May 2002, 21 patients with glioblastoma multiforme were enrolled on a Phase I protocol investigating planned gross total resection and immediate placement of permanent I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively. Toxicity was assessed according to Radiation Therapy Oncology Group criteria. Results: Eighteen patients completed treatment according to protocol. The median preoperative tumor volume on magnetic resonance imaging was 18.6 cm{sup 3} (range, 4.4-41.2 cm{sup 3}). The median brachytherapy dose measured 5 mm radially outward from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent 12 reoperations, with 11 of 12 reoperations demonstrating necrosis without evidence of tumor. Because of high toxicity, the study was terminated early. Median progression-free survival and overall survival were 57 and 114 weeks, respectively, but not significantly improved compared with historical patients treated at University of California, San Francisco, with gross total resection and radiotherapy without brachytherapy. Conclusions: Treatment with gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy as performed in this study results in high toxicity and reoperation rates, without demonstrated improvement in survival.

  10. Response of adenocarcinoma of the uterine cervix to chemoradiotherapy

    PubMed Central

    KAIDAR-PERSON, ORIT; YOSEFIA, SAWSAN; ABDAH-BORTNYAK, ROXOLYANA

    2015-01-01

    The aim of the current retrospective study was to investigate the response of advanced cervical adenocarcinoma (AC) to definitive chemoradiotherapy. Uterine cervical cancer is one of the most common cancer types among females, with squamous cell carcinoma (SQCC) being the most prevalent histological type. The incidence of cervical AC and its variants has markedly increased in recent decades. The current understanding with regard to the treatment of cervical cancer has been established through studies in which the majority of the patients suffered from SQCC, while only a limited number of studies have focused on the treatment of AC. Therefore, the optimal treatment for uterine cervical AC remains unclear. In the present study, data were collected from the medical files of patients who were diagnosed with advanced uterine cervical AC and treated with chemoradiotherapy between 1998 and 2013. Data were also collected from a group of patients with SQCC for comparison with AC patients in terms of response and survival. A total of 68 uterine cervical cancer cases were included, including 29 AC patients and 39 SQCC patients. Compared with the SQCC subgroup, a higher number of AC patients required surgery following chemoradiotherapy due to a lack of response to the initial treatment (5% vs. 31%, respectively; P=0.0065). After a median follow-up period of 10 years, patients with AC exhibited shorter overall survival (7.4 years vs. 11 years for AC and SQCC groups, respectively; P=0.01). Differences in recurrence (40.7% vs. 34.4%; P=0.79) and disease-free interval (1.2 years vs. 2 years; P=0.11) were not statistically significant. The results indicated that cervical AC is less responsive to chemoradiotherapy compared with SQCC. PMID:26137148

  11. Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

    SciTech Connect

    Welz, Stefan Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

    2007-12-01

    Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m{sup 2}), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m{sup 2}/24 h). A dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m{sup 2} in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m{sup 2} administered before and after simultaneous 5-FU and radiotherapy.

  12. [Current Status and Perspective of Chemoradiotherapy for Uterine Cervical Cancer].

    PubMed

    Toita, Takafumi; Ariga, Takuro; Kasuya, Goro; Hashimoto, Seiji; Maemoto, Hitoshi; Heianna, Joichi; Kakinohana, Yasumasa; Murayama, Sadayuki

    2015-10-01

    Fifteen years has passed since the NCI announced the clinical importance of concurrent chemoradiotherapy (CCRT) in radiotherapy for patients with locoregionally advanced uterine cervical cancer. Numerous clinical trials have been performed to further improve the outcomes of CCRT. In addition to investigations of chemotherapeutic regimens and schedules, adaptation of novel radiotherapy methods such as image-guided brachytherapy (IGBT) and intensity-modulated radiotherapy (IMRT) is encouraged in CCRT for cervical cancer. PMID:26489545

  13. A patient with Loeys-Dietz syndrome treated with chemoradiotherapy for an oropharyngeal carcinoma.

    PubMed

    Chan, Andrew K; Teoh, Daren; Matthews, Paul; Fresco, Lydia

    2013-01-01

    We present the first published case of a patient with Loeys-Dietz syndrome (LDS) who was treated with radical chemoradiotherapy for an oropharyngeal carcinoma. In view of this newly recognised connective tissue disease, the uncertainty of severe toxicity from chemoradiotherapy to treat a potentially curative cancer posed a management challenge. The patient was treated with chemoradiotherapy and remains well with no evidence of recurrence at 3 years. Furthermore, we have observed minimal late effects secondary to chemoradiotherapy at 3 years following the completion of treatment suggesting that the underlying pathogenesis of LDS may provide an interesting human model to further elucidate the complex interactions of transforming growth factor β1 (TGF-β1) and tissue fibrosis secondary to chemoradiotherapy. A review of LDS as well as the association of TGF-β1 expression and tissue fibrosis is presented. PMID:24045763

  14. Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

    SciTech Connect

    Trotti, Andy; Zhang, Qiang; Bentzen, Søren M.; Emami, Bahman; Hammond, M. Elizabeth; Jones, Christopher U.; Morrison, William H.; Sagar, Stephen M.; Ridge, John A.; Fu, Karen K.; Ang, K. Kian

    2014-08-01

    Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239 patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.

  15. Unresectable pancreatic adenocarcinoma with complete clinical response following chemoradiotherapy.

    PubMed

    Aksoy, Erol; Ulaş, Murat; Çolakoğlu, Muhammet Kadri; Özer, İlter; Bostancı, Erdal Birol; Akoğlu, Musa

    2015-01-01

    Locally advanced or metastatic disease is present in 2/3s of patients with pancreatic cancer. Pancreatic cancer patients are assessed as resectable, potentially resectable (borderline) and unresectable according to pre-operative examinations. The chance for operability may be enhanced by using adjuvant-neoadjuvant systemic chemotherapy, radiotherapy or both. The rates of R0 resection may be increased by means of treatment delivered this way. This case report presents a pancreatic adenocarcinoma case that was assessed to be resectable but was identified to be unresectable during surgical exploration, thus received adjuvant chemoradiotherapy. The patient was then re-evaluated, identified as resectable and received pancreaticoduodenectomy. PMID:25931951

  16. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  17. Hyperfractionated Low-Dose (21 Gy) Radiotherapy for Cranial Skeletal Metastases in Patients With High-Risk Neuroblastoma

    SciTech Connect

    Kushner, Brian H.; Cheung, Nai-Kong V.; Barker, Christopher A.; Kramer, Kim; Modak, Shakeel; Yataghene, Karima; Wolden, Suzanne L.

    2009-11-15

    Purpose: To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common. Methods and Materials: High-risk NB patients with measurable cranial disease at diagnosis or residual cranial disease after induction therapy had those sites irradiated with hyperfractionated 21 Gy; a brain-sparing technique was used for an extensive field. The patients were grouped according to the response to systemic therapy. Thus, when irradiated, Group 1 patients were in complete remission and Group 2 patients had primary refractory disease. Follow-up was from the start of cranial RT. Results: At 3 years, the 39 Group 1 patients had a progression-free survival rate of 51%; control of cranial disease was 79%. Two relapses involved irradiated cranial sites. Two other patients relapsed in the irradiated cranial sites 6 and 12 months after a systemic relapse. At 3 years, the 34 Group 2 patients had a progression-free survival rate of 33%; control of cranial disease was 52%. Group 2 included 19 patients who had residual cranial (with or without extracranial) disease. The cranial sites showed major (n = 13), minor (n = 2), or no response (n = 4) to RT. Five patients had progression in the cranial RT field at 10-27 months. Group 2 also included 15 patients who had persistent NB in extracranial, but not cranial, sites. Of these 15 patients, 2 relapsed in the irradiated cranial sites and elsewhere at 8 and 14 months. Cranial RT was well tolerated, with no Grade 2 or greater toxicity. Conclusion: Hyperfractionated 21-Gy cranial RT might help control NB and is feasible without significant toxicity in children.

  18. Phase II Trial of Hyperfractionated IMRT and Concurrent Weekly Cisplatin for Stage III and IVa Head and Neck Cancer

    PubMed Central

    Maguire, Patrick D.; Papagikos, Michael; Hamann, Sue; Neal, Charles; Meyerson, Martin; Hayes, Neil; Ungaro, Peter; Kotz, Kenneth; Couch, Marion; Pollock, Hoke; Tepper, Joel

    2010-01-01

    Purpose Investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). Patients and Methods Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25 Gy fractions bid to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07 and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m2/week was started week 1. Patients completed the Quality of Life Radiation Therapy Instrument prior to (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results Thirty of 39 patients (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE versus 3.9 EOT. By month 1, H&N QOL returned near baseline: mean 6.2 (sd=1.7). Most common acute grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%) and leukopenia (26%). Conclusions Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol. PMID:20378262

  19. Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

    SciTech Connect

    Kennedy, Colin; Bull, Kim; Chevignard, Mathilde; Culliford, David; Dörr, Helmuth G.; Doz, François; Kortmann, Rolf-Dieter; Lannering, Birgitta; Massimino, Maura; Navajas Gutiérrez, Aurora; Rutkowski, Stefan; Spoudeas, Helen A.; Calaminus, Gabriele

    2014-02-01

    Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.

  20. Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-Up of a Randomized Phase III Trial (SAKK 10/94)

    SciTech Connect

    Ghadjar, Pirus; Simcock, Mathew; Studer, Gabriela; Allal, Abdelkarim S.; Ozsahin, Mahmut; Bernier, Jacques; Toepfer, Michael; Zimmermann, Frank; Betz, Michael; Glanzmann, Christoph; Aebersold, Daniel M.

    2012-02-01

    Purpose: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer. Methods and Materials: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m{sup 2} for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria. Results: Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval {l_brace}CI{r_brace}, 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1; p = 0.02]), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.02]), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5; p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]). Conclusions: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity.

  1. STAT3: A Novel Molecular Mediator of Resistance to Chemoradiotherapy

    PubMed Central

    Spitzner, Melanie; Ebner, Reinhard; Wolff, Hendrik A.; Ghadimi, B. Michael; Wienands, Jürgen; Grade, Marian

    2014-01-01

    Chemoradiotherapy (CRT) represents a standard treatment for many human cancers, frequently combined with radical surgical resection. However, a considerable percentage of primary cancers are at least partially resistant to CRT, which represents a substantial clinical problem, because it exposes cancer patients to the potential side effects of both irradiation and chemotherapy. It is therefore exceedingly important to determine the molecular characteristics underlying CRT-resistance and to identify novel molecular targets that can be manipulated to re-sensitize resistant tumors to CRT. In this review, we highlight much of the recent evidence suggesting that the signal transducer and activator of transcription 3 (STAT3) plays a prominent role in mediating CRT-resistance, and we outline why inhibition of STAT3 holds great promise for future multimodal treatment concepts in oncology. PMID:25268165

  2. Concurrent Hyperfractionated Radiation Therapy and Chemotherapy in Locally Advanced (Stage III) Non-Small-Cell Lung Cancer: Single Institution Experience With 600 Patients

    SciTech Connect

    Jeremic, Branislav; Milicic, Biljana; Milisavljevic, Slobodan

    2012-03-01

    Purpose: Our institutional experience with the use of hyperfractionated radiation therapy (RT) alone or concurrently with chemotherapy (RT-CHT) in Stage III non-small-cell lung cancer was reviewed. Methods and Materials: Three phase III and two phase II studies included a total of 600 patients. Hyperfractionated RT alone was given to 127 patients, and hyperfractionated RT-CHT was given to 473 patients. RT doses were 64.8 Gy and 69.6 Gy (using 1.2 Gy twice daily) and 67.6 Gy (using 1.3 Gy twice daily). CHT consisted of concurrent administration of carboplatin and etoposide to 409 patients and concurrent administration of carboplatin and paclitaxel to 64 patients. Results: The median survival times were 19 months, 21 months, and 12 months for all, RT-CHT, and RT-only patients, respectively. The survival difference between the RT-CHT and RT group was significant (p < 0.0001). Four-year rates of local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) were 29% and 35%, respectively, for the entire group. The RT-CHT group had significantly better LPFS rates than the RT group (31% for the RT-CHT group vs. 16% for the RT group; p = 0.0015) but not DMFS rates (36% for the RT-CHT group vs. 36% for the RT group, p = 0.0571). Acute high-grade esophagitis, pneumonitis, and hematological toxicities were seen most frequently and in 11%, 9%, and 12% of patients, respectively. Late high-grade esophageal and bronchopulmonary toxicity were each seen in 6% of patients. Conclusions: Compared to the majority of existing phase II and III studies, this study reconfirmed the excellent results achieved with concurrent RT-CHT, including low toxicity. Concurrent RT-CHT results in survival benefit primarily by increasing LPFS, not DMFS.

  3. Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

    PubMed

    Qian, Haili; Wang, Haijuan; Guan, Xiuwen; Yi, Zongbi; Ma, Fei

    2016-06-01

    The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, P<0.001], but not 2-year progression-free survival (OR=1.81, 95% CI: 0.61-5.36, P=0.284). Specifically, early (OR=3.32, 95% CI: 1.38-7.95, P<0.01) but not advanced (OR=3.75, 95% CI: 0.96-14.68, P=0.057) NSCLC patients were likely to gain a large benefit from the adoptive immunotherapy. Most of the adoptive immunotherapy-induced adverse effects were self-limited, mainly including fever, shiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID:26872311

  4. [Jinlong capsule combined with chemoradiotherapy for NSCLC: a Meta-analysis].

    PubMed

    Lu, Qiang; Luo, Jing-bin; Feng, Yi-fan; She, Qin; Shi, Zhong-feng

    2015-11-01

    The purpose of this study was to evaluate the effect and safety of Jinlong capsule combined with chemotherapy or radio-therapy for non-small cell lung cancer (NSCLS) using Meta-analysis. PubMed, Embase, CNKI and Wanfang databases were all searched without language restriction, and searching time was from January 1990 to July 2015. All eligible published studies were included in this study for quality assessment and data extraction. All the data were analyzed using Revman 5.3. A total of ten studies including 736 subjects (370 in Jinlong capsule plus chemoradiotherapy and 366 in chemoradiotherapy only) were finally included in this Meta-analysis. The result of Meta analysis showed that compared with pure chemoradiotherapy group, Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the patients' curative effect (OR = 1.77, 95% CI: 1.29-2.43, P < 0.05), clinical benefit rate (OR = 1.89, 95% CI: 1.22-2.91, P < 0.05), life quality improvement rate (OR = 2. 56, 95% CI: 1.61-4.05, P < 0.05), and decrease leucopenia incidence rate (OR = 0.35, 95% CI: 0. 22-0.56, P < 0.05) and gastrointestinal reaction rate (OR = 0.67, 95% CI: 0.40-1.11, P < 0.05). The pooled results showed that Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the curative effect and life quality, and decrease the adverse reaction of patients. PMID:27097429

  5. Alternating chemo-radiotherapy in bladder cancer: A conservative approach

    SciTech Connect

    Orsatti, M.; Franzone, P.; Giudici, S.

    1995-08-30

    The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy. 34 refs., 4 figs., 5 tabs.

  6. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae Lee, Woo Jin; Woo, Sang Myung; Moon, Sung Ho; Yoo, Tae; Kim, Sang Soo; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  7. Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

    PubMed Central

    Henríquez Hernández, Luis Alberto; Lara, Pedro Carlos; Pinar, Beatriz; Bordón, Elisa; Gallego, Carlos Rodríguez; Bilbao, Cristina; Pérez, Leandro Fernández; Morales, Amílcar Flores

    2009-01-01

    Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results. PMID:19497124

  8. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    SciTech Connect

    Gupta, Tejpal; Jalali, Rakesh; Goswami, Savita; Nair, Vimoj; Moiyadi, Aliasgar; Epari, Sridhar; Sarin, Rajiv

    2012-08-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children {>=}5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  9. Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer

    PubMed Central

    Zhang, Jin-Liang; Wang, Hui-Yun; Yang, Qing; Lin, Shi-Yong; Luo, Guang-Yu; Zhang, Rong; Xu, Guo-Liang

    2015-01-01

    AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC. PMID:25892874

  10. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    SciTech Connect

    Jeremic, Branislav . E-mail: b.jeremic@iaea.org; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-07-15

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.

  11. Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: Results of the French M-SFOP 98 protocol

    SciTech Connect

    Carrie, Christian . E-mail: carrie@lyon.fnclcc.fr; Muracciole, Xavier; Gomez, Frederic

    2005-11-01

    Purpose: Between December 1998 and October 2001, patients <19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Societe Francaise d'Oncologie Pediatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start. Results: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years. Conclusion: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

  12. [Research hotspot and progress of preoperative chemoradiotherapy for rectal cancer].

    PubMed

    Peng, Jianhong; Pan, Zhizhong

    2016-06-01

    Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy. PMID:27353093

  13. Late Toxicity After Definitive Concurrent Chemoradiotherapy for Thoracic Esophageal Carcinoma

    SciTech Connect

    Morota, Madoka Gomi, Kotaro; Kozuka, Takuyo; Chin, Keisho; Matsuura, Masaaki; Oguchi, Masahiko; Ito, Hisao; Yamashita, Takashi

    2009-09-01

    Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

  14. Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

    SciTech Connect

    Yang, Gary Y.; May, Kilian Salerno; Iyer, Renuka V.; Chandrasekhar, Rameela M.A.; Wilding, Gregory E.; McCloskey, Susan A.; Khushalani, Nikhil I.; Yendamuri, Saikrishna S.; Gibbs, John F.; Fakih, Marwan; Thomas, Charles R.

    2010-10-01

    Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

  15. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    PubMed Central

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2013-01-01

    Purpose To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p <.01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors. PMID:21658855

  16. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  17. Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

    SciTech Connect

    Weiler, Markus; Hartmann, Christian; Wiewrodt, Dorothee; Herrlinger, Ulrich

    2010-07-01

    Purpose: To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. Patients and Methods: A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m{sup 2} (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m{sup 2}), maintenance TMZ starting at 150 mg/m{sup 2} using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). Results: The median follow-up interval was 21.7 months. Grade 4 hematologic toxicity was observed in 15 patients (36.6%). Treatment-related nonhematologic Grade 4-5 toxicity was reported for 2 patients (4.9%). The median progression-free survival was 7.6 months (95% confidence interval, 6.2-10.4). The 1-year survival rate was 73.2% (95% confidence interval, 56.8-84.2%). The presence of O{sup 6}-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was associated with significantly superior progression-free survival. Conclusion: The dose-dense regimen of TMZ administered in a 1-week on/1-week off schedule resulted in acceptable nonhematologic toxicity. Compared with data from the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981-22981/CE.3, patients with an unmethylated MGMT gene promoter appeared not to benefit from intensifying the TMZ schedule regarding the median progression-free survival and overall survival. In contrast, data are promising for patients with a methylated MGMT promoter.

  18. Efficacy of Neo-Adjuvant Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma

    PubMed Central

    Liu, Wei; Fu, Xue-Liang; Yang, Jian-Yu; Liu, De-Jun; Li, Jiao; Zhang, Jun-Feng; Huo, Yan-Miao; Yang, Min-Wei; Hua, Rong; Sun, Yong-Wei

    2016-01-01

    Abstract We have conducted a meta-analysis and systematic review to determine the overall survival, mortality rate, and complete resection rate of neo-adjuvant chemoradiotherapy (CRT) compared with pancreaticoduodenectomy alone in patients with pancreatic adenocarcinoma. Whether neo-adjuvant CRT is beneficial in the treatment of resectable pancreatic cancer or not, it is still a controversial issue. Medline and Cochrane were searched with relevant terms. Eight studies with a total of 833 participants were selected. The meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The analysis revealed neo-adjuvant group may have a benefit in the overall survival, as compared with the resection group, although it did not reach statistical significance (pooled hazard ratio = 0.87, 95% confidence interval [CI] = 0.75–1.00, P = 0.051). We found no difference in the in-hospital mortality rate (pooled odds ratio [OR] = 1.27, 95% CI = 0.35–4.58, P = 0.710). The complete resection rate was significantly higher in the neo-adjuvant group than in the resection group (pooled OR = 2.39, 95% CI = 1.21–4.74, P = 0.012). This meta-analysis found that there was no significant difference in the overall survival between patients treated with neo-adjuvant CRT or pancreaticduodenectomy. PMID:27082545

  19. Concurrent Chemoradiotherapy for Esophageal Cancer With Malignant Fistula

    SciTech Connect

    Koike, Ryuta; Nishimura, Yasumasa Nakamatsu, Kiyoshi; Kanamori, Shuichi; Shibata, Toru

    2008-04-01

    Background: We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. Methods and Materials: The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m{sup 2} x 14 days) and cisplatin (7 mg/m{sup 2} x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. Results: The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. Conclusion: Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

  20. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  1. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  2. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  3. [Complete Response in Far-Advanced Esophageal Cancer Treated with Induction Chemotherapy Followed by Definitive Chemoradiotherapy].

    PubMed

    Kaburagi, Takuji; Harada, Hiroki; Koizumi, Wataru; Aga, Kenichiro; Watanabe, Hajime; Seki, Hiroaki; Yasui, Nobutaka; Sakata, Michio; Matsumoto, Hidetoshi; Shimada, Akihiko

    2015-09-01

    We report a case of far-advanced esophageal cancer in which induction chemotherapy followed by chemoradiotherapy achieved complete remission. A 61-year-old female presented to our hospital with dyspnea and hoarseness. CT revealed a tumor at the cervical esophagus invading and narrowing the trachea, a bulky metastasis at the right paraesophageal node, and nodal metastases at levels II and III of the left neck. No finding indicated other distant metastases. According to findings of CT and endoscopy, she was diagnosed with unresectable cancer at the cervical esophagus(cT4bN1M1[LYM], according to UICC-TNM 7 th). After 2 courses of induction chemotherapy(DTX, CDDP, and 5-FU), the tumor's volume was remarkably reduced. Thereafter, chemoradiotherapy with CDDP, 5-FU, and 60 Gy/30 Fr was administered. After 7 months of systemic chemotherapy with paclitaxel following chemoradiotherapy, the patient was judged to have complete remission based on CT and endoscopic findings. After additional administration of S-1 for 5 months, systemic chemotherapy was ceased. The patient has survived without disease progression for 22 months following initiation of treatment. It is thought that induction chemotherapy followed by chemoradiotherapy might improve local control and survival of patients with far-advanced esophageal cancers, such as our patient. PMID:26469169

  4. Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer

    SciTech Connect

    Jansen, Edwin; Boot, Henk; Cats, Annemieke

    2007-03-01

    Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc{sup 99m}-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V{sub 20} (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V{sub 20} (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 {mu}mol/L before treatment to 86.1 {mu}mol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months, one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored.

  5. Disparities in receipt of modern concurrent chemoradiotherapy in glioblastoma.

    PubMed

    Rhome, Ryan; Fisher, Rebecca; Hormigo, Adília; Parikh, Rahul R

    2016-06-01

    Temozolomide given concurrently with radiation after resection/biopsy improves survival in glioblastoma (GBM). The disparities in receipt of adjuvant single-agent chemotherapy and their association with outcome have not been well established. Observational study of a prospectively collected database, the National Cancer Database (NCDB), from 1998 to 2012 with median follow-up 12.4 months. Among the 114,979 patients in the NCDB with GBM, 44,531 patients were analyzed for disparities, and 28,279 patients were analyzed for overall survival (OS). Associations were assessed in a multivariable Cox proportional hazards regression model. Survival was estimated using the Kaplan-Meier method. Median age was 58 years. Chemotherapy use was associated with male gender, white race, younger age (≤50), higher performance status (≥70), more extensive surgery, insurance status, higher income/education, and treatment at academic centers (all p < 0.05). We found improved OS associated with type of insurance (private insurance HR 0.91, 95 % CI 0.85-0.96 and Medicare HR 1.24, 95 % CI 1.16-1.33, both p < 0.01 compared to uninsured) and treatment at academic programs (HR 0.86; p < 0.01). MGMT methylation status predicted improved OS (HR 0.54; 95 % CI 0.41-0.70, p < 0.01). 1-year OS for patients receiving chemotherapy was 55.9 % versus 35.3 % for those without (p < 0.0001). After adjustment for confounders, chemotherapy use remained associated with improved OS (HR 0.64, 95 % CI 0.63-0.66, p < 0.01). Chemotherapy utilization increased from 26.9 to 93.3 % during the study period. We have identified specific disparities in the use of chemotherapy that may be targeted to improve patient access to care. Widespread adoption of adjuvant chemoradiotherapy after resection or biopsy for GBM appears to improve OS. PMID:26970981

  6. Prediction of concurrent chemoradiotherapy outcome in advanced oropharyngeal cancer

    PubMed Central

    HASEGAWA, MASAHIRO; MAEDA, HIROYUKI; DENG, ZEYI; KIYUNA, ASANORI; GANAHA, AKIRA; YAMASHITA, YUKASHI; MATAYOSHI, SEN; AGENA, SHINYA; TOITA, TAKAFUMI; UEHARA, TAKAYUKI; SUZUKI, MIKIO

    2014-01-01

    The aim of this study was to investigate human papillomavirus (HPV) infection as a predictor of concurrent chemoradiotherapy (CCRT) response and indicator of planned neck dissection (PND) for patients with advanced oropharyngeal squamous cell carcinoma (OPSCC; stage III/IV). Overall, 39 OPSCC patients (32 men, 7 women; median age 61 years, range 39–79 years) were enrolled. The primary lesion and whole neck were irradiated up to 50.4 Gy, and subsequently the primary site and metastatic lymph nodes were boosted with a further 16.2 Gy. Although several chemotherapy regimens were employed, 82.1% of OPSCC patients received the combination of nedaplatin and 5-fluorouracil. HPV-related OPSCC (16 cases) was defined as both HPV DNA-positive status by polymerase chain reaction and p16INK4a overexpression by immunohistochemistry. Patients with N2 and N3 disease received PND 2–3 months after CCRT completion. Compared to non-responders, CCRT responders showed significantly lower nodal stage (N0 to N2b) and HPV-positive status in univariate analysis. Patients with HPV-related OPSCC had longer time to treatment failure (TTF) than those with HPV-unrelated OPSCC (p=0.040). Three-year TTF was 81.3 and 47.8% in the HPV-related and HPV-unrelated groups, respectively. There were also significant differences in disease-free survival (DFS) between the two OPSCC patient groups (p=0.042). Three-year DFS was 93.8 and 66.7% in patients with HPV-related and HPV-unrelated OPSCC, respectively. Multivariate logistic analysis showed a lower risk of TTF event occurrence in HPV-related OPSCC (p=0.041) than in HPV-unrelated OPSCC. Thus, HPV testing in addition to nodal stage was useful for predicting CCRT response, especially in advanced OPSCC. Because patients who received PND showed moderate locoregional control, PND is an effective surgical procedure for controlling neck lesions in patients with advanced HPV-unrelated disease. PMID:24969413

  7. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  8. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  9. Phase II Trial of Hyperfractionated Intensity-Modulated Radiation Therapy and Concurrent Weekly Cisplatin for Stage III and IVa Head-and-Neck Cancer

    SciTech Connect

    Maguire, Patrick D.; Papagikos, Michael; Hamann, Sue; Neal, Charles; Meyerson, Martin; Hayes, Neil; Ungaro, Peter; Kotz, Kenneth; Couch, Marion; Pollock, Hoke; Tepper, Joel

    2011-03-15

    Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m{sup 2}/week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results: Of 39 patients, 30 (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE vs. 3.9 EOT. By month 1, H and N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%). Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.

  10. [Untoward side effects of chemoradiotherapy in children with malignant brain tumors].

    PubMed

    Morozova, S K; Begun, I V; Spivak, L V; Radiuk, K A; Papkevich, I I; Savich, T V; Pershaĭ, E B; Vashkevich, T I; Aleĭnikova, O V

    2002-01-01

    Untoward side-effects of chemoradiotherapy were compared in 48 children treated for brain tumors and those in remission lasting from less than 12 months to 11 years. The investigation concerned disturbances in the neurologic, endocrine, cardiovascular, urinary, hepatobiliary and psychic systems; neurologic ones proved the most frequent. No cases of heart failure were reported among patients with brain tumors during remission. Hormonal study revealed inhibited thyroid function in brain tumor sufferers. PMID:12455363

  11. A Phase I-II Study of Postoperative Capecitabine-Based Chemoradiotherapy in Gastric Cancer

    SciTech Connect

    Jansen, Edwin; Crosby, Tom D.L.; Dubbelman, Ria; Bartelink, Harry; Verheij, Marcel

    2007-12-01

    Background: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine. Patients and Methods: After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m{sup 2} twice daily for 2 weeks. After a 1-week treatment-free interval, patients received capecitabine (650-1,000 mg/m{sup 2} orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes. Results: Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m{sup 2} twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation. Conclusions: This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.

  12. Prognostic factors for salvage endoscopic resection for esophageal squamous cell carcinoma after chemoradiotherapy or radiotherapy alone

    PubMed Central

    Kondo, Shinya; Tajika, Masahiro; Tanaka, Tsutomu; Kodaira, Takeshi; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Imaoka, Hiroshi; Goto, Hidemi; Yamao, Kenji; Niwa, Yasumasa

    2016-01-01

    Background and study aims: Endoscopic resection is one treatment option for residual or locally recurrent esophageal cancer after definitive chemoradiotherapy or radiotherapy alone. However, little is known about the clinical benefit of salvage endoscopic resection for these lesions. Therefore, the effectiveness and prognostic factors of salvage endoscopic resection were investigated. Patients and methods: A total of 37 patients with esophageal squamous cell carcinoma (SCC) who underwent salvage endoscopic resection after definitive chemoradiotherapy or radiotherapy alone were reviewed. The method of salvage endoscopic resection was endoscopic mucosal resection using a cap (EMR-C), strip biopsy, or endoscopic submucosal dissection. The effectiveness and prognostic factors of salvage endoscopic resection were retrospectively analyzed. Results: A total of 37 patients with 49 lesions underwent salvage endoscopic resection. Baseline clinical stages were I in 23 patients, II in 3 patients, III in 9 patients, and IV in 2 patients. The number of locoregional recurrences and residual lesions were 35 and 14, respectively. The curative en bloc resection rate was 53.1 % (26/49). The total incidence of complications was 18.9 % (7/37); all were successfully managed conservatively. The 3-year and 5-year overall survival rates were 72.9 % and 53.3 %, respectively, with a median follow-up period of 54 months. Baseline clinical T1 – 2 and N0 were significant factors for good prognosis in terms of overall survival on univariate analysis. Conclusions: Salvage endoscopic resection, especially EMR-C, is a safe and feasible procedure to control residual or recurrent superficial esophageal SCC after definitive chemoradiotherapy or radiotherapy alone. The present results showed that baseline clinical T1 – 2 and N0 before chemoradiotherapy or radiotherapy were significant prognostic factors. PMID:27540571

  13. Secondary osteosarcoma developing 10 years after chemoradiotherapy for non-small-cell lung cancer.

    PubMed

    Yagishita, Shigehiro; Horinouchi, Hidehito; Yorozu, Takashi; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Mori, Taisuke; Tsuta, Koji; Sumi, Minako; Tamura, Tomohide

    2014-02-01

    A 53-year-old female patient was admitted with pain and a progressively enlarging mass in the right upper chest. Chest computed tomography revealed a mass lesion in the region of the right upper ribs. Ten years prior to this admission, the patient had undergone right lobectomy for lung adenocarcinoma. One year after the surgery, follow-up computed tomography had revealed tumor recurrence in the mediastinal and supraclavicular lymph nodes, and the patient had been treated by chemoradiotherapy. Thereafter, regular follow-up had revealed no evidence of recurrence of the non-small-cell lung cancer. Histopathological findings revealed proliferation of spindle-shaped malignant tumor cells in a background of osteoid, consistent with the diagnosis of osteosarcoma. The location of the tumor was consistent with the radiation field. Based on the clinicopathological findings, the patient was diagnosed as having secondary osteosarcoma occurring as a result of the chemoradiotherapy administered previously for the recurrent non-small-cell lung cancer. Unfortunately, the patient died of rapid progression of the osteosarcoma within a week of admission to the hospital. The autopsy revealed contiguous invasion by the tumor of the heart, with massive thrombus formation. The peripheral pulmonary arteries were diffusely occluded by metastatic tumors. Our case serves to highlight the risk of development of secondary sarcoma as a life-threatening late complication after chemoradiotherapy for locally advanced non-small-cell lung cancer, even after complete cure of the primary tumor. PMID:24338556

  14. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer

    PubMed Central

    Conroy, T; Yataghène, Y; Etienne, P L; Michel, P; Senellart, H; Raoul, J L; Mineur, L; Rives, M; Mirabel, X; Lamezec, B; Rio, E; Le Prisé, E; Peiffert, D; Adenis, A

    2010-01-01

    Background: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. Methods: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. Results: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82% arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. Conclusion: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial. PMID:20940718

  15. Primary anorectal malignant melanoma treated with neoadjuvant chemoradiotherapy and sphincter-sparing surgery: A case report

    PubMed Central

    SU, MENG; ZHU, LUCHENG; LUO, WENHUA; WEI, HANGPING; ZOU, CHANGLIN

    2014-01-01

    Primary anorectal (PA) malignant melanoma (MM) is a rare disease associated with a high mortality rate. The most appropriate treatment strategy for PAMM remains controversial. A 55-year-old female patient, who was misdiagnosed with locally advanced rectal carcinoma, was treated with preoperative radiotherapy and concurrent oral capecitabine. During the therapy, grade 1 leukopenia occurred, however, there was no interruption to treatment. Following chemoradiotherapy, a computer tomography scan identified that the tumor had shrunk significantly and the original enlarged lymph nodes had disappeared. Eight weeks after completion of chemoradiotherapy, sphincter-sparing surgery was performed on the patient and based on the postoperative pathological result, MM was diagnosed. At the time of writing, the patient has survived disease-free for 15 months and at the most recent follow-up examination the Karnofsky Performance Scale score was 100. The therapeutic regimen of neoadjuvant concurrent chemoradiotherapy together with sphincter-sparing surgery is considered to be an optimal choice for patients with PAMM. However, further studies are required to evaluate the efficacy and clinical utility of this therapeutic regimen. PMID:24765186

  16. Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

    PubMed

    Crotti, Sara; Enzo, Maria Vittoria; Bedin, Chiara; Pucciarelli, Salvatore; Maretto, Isacco; Del Bianco, Paola; Traldi, Pietro; Tasciotti, Ennio; Ferrari, Mauro; Rizzolio, Flavio; Toffoli, Giuseppe; Giordano, Antonio; Nitti, Donato; Agostini, Marco

    2015-08-01

    Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy. PMID:25522009

  17. Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience

    PubMed Central

    Duignan, Sophie; Maguire, Donal; Ravichand, Chamarajanagar S; Geoghegan, Justin; Hoti, Emir; Fennelly, David; Armstrong, John; Rock, Kathy; Mohan, Helen; Traynor, Oscar

    2014-01-01

    Background Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. Materials and methods Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). Results Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10–58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18–76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. Discussion In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens. PMID:23600750

  18. Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

    SciTech Connect

    Gondi, Vinai; Bentzen, Soren M.; Sklenar, Kathryn L.; Dunn, Emily F.; Petereit, Daniel G.; Tannehill, Scott P.; Straub, Margaret; Bradley, Kristin A.

    2012-11-15

    Purpose: To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. Methods and Materials: Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade {>=}3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring {>=}6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. Results: At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. Conclusion: Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

  19. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  20. 125I particle implantation combined with chemoradiotherapy to treat advanced pancreatic cancer

    PubMed Central

    Guo, J-M; Jiang, H-T; Di, X-Y; Zhu, Y

    2014-01-01

    Objective: To evaluate the therapy effects of 125I implantation combined with chemoradiotherapy on pancreatic cancer patients. Methods: 30 patients with Stage III or IV pancreatic cancer were equally divided into two groups (control and treatment group). The patients in the treatment group (nine males, six females) received chemotherapy in the first week and 125I implantation in the third week, followed by combined chemoradiotherapy in the fifth week. The patients in the control group (10 males, 5 females) received the same treatment except 125I implantation. The therapy in the control group and treatment group was repeated every 4 weeks. Results: The median conformal radiotherapy dose in the treatment group (30.62 Gy) was significantly lower than that in the control group (47.86 Gy). The total radiation dose was 88.71 ± 27.39 Gy, and the surface activity was 0.6 mCi in the treatment group. After treatment, the average tumour size decreased both in the treatment group [9.17 cm2, 95% confidence interval (CI): 5.60–12.74, p < 0.001] and in the control group (4.54 cm2, 95% CI: 2.74–6.35, p < 0.001). The median survival time in the treatment group was 14 months (95% CI: 12.215–14.785) and in the control group was 12 months (95% CI: 10.884–13.116). There was no statistical significance in survival rates between the two groups (χ2 = 0.908, p = 0.341). Conclusion: 125I implanted into tumour combined with chemoradiotherapy has higher local control rate of advanced pancreatic cancer than chemoradiotherapy. Advances in knowledge: We combined chemoradiotherapy with 125I implantation to treat advanced pancreatic cancer and obtained a higher local control rate and better quality of life than when using chemoradiatherapy alone. PMID:24625042

  1. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study

    SciTech Connect

    Valentini, Vincenzo . E-mail: vvalentini@rm.unicatt.it; Morganti, Alessio G.; Gambacorta, M. Antonietta; Mohiuddin, Mohammed; Doglietto, G. Battista; Coco, Claudio; De Paoli, Antonino; Rossi, Carlo; Di Russo, Annamaria; Valvo, Francesca; Bolzicco, Giampaolo; Dalla Palma, Maurizio

    2006-03-15

    Purpose: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Methods and Materials: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses {<=}55 Gy; age {>=}18 years; performance status (PS) (Karnofsky) {>=}60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m{sup 2}/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F

  2. Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

    SciTech Connect

    Gerber, Nicolas U.; Hoff, Katja von; Resch, Anika; Ottensmeier, Holger; Kwiecien, Robert; Faldum, Andreas; Matuschek, Christiane; Hornung, Dagmar; Bremer, Michael; Benesch, Martin; Pietsch, Torsten; Warmuth-Metz, Monika; Kuehl, Joachim; Rutkowski, Stefan; Kortmann, Rolf D.

    2014-07-15

    Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

  3. 'Pharyngocise': Randomized Controlled Trial of Preventative Exercises to Maintain Muscle Structure and Swallowing Function During Head-and-Neck Chemoradiotherapy

    SciTech Connect

    Carnaby-Mann, Giselle; Crary, Michael A.; Schmalfuss, Ilona

    2012-05-01

    Purpose: Dysphagia after chemoradiotherapy is common. The present randomized clinical trial studied the effectiveness of preventative behavioral intervention for dysphagia compared with the 'usual care.' Methods and Materials: A total of 58 head-and-neck cancer patients treated with chemoradiotherapy were randomly assigned to usual care, sham swallowing intervention, or active swallowing exercises (pharyngocise). The intervention arms were treated daily during chemoradiotherapy. The primary outcome measure was muscle size and composition (determined by T{sub 2}-weighted magnetic resonance imaging). The secondary outcomes included functional swallowing ability, dietary intake, chemosensory function, salivation, nutritional status, and the occurrence of dysphagia-related complications. Results: The swallowing musculature (genioglossus, hyoglossuss, and mylohyoid) demonstrated less structural deterioration in the active treatment arm. The functional swallowing, mouth opening, chemosensory acuity, and salivation rate deteriorated less in the pharyngocise group. Conclusion: Patients completing a program of swallowing exercises during cancer treatment demonstrated superior muscle maintenance and functional swallowing ability.

  4. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Bertolini, Federica . E-mail: bertolini.federica@policlinico.mo.it; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

    2007-08-01

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.

  5. Electroglottographic Comparison of Voice Outcomes in Patients With Advanced Laryngopharyngeal Cancer Treated by Chemoradiotherapy or Total Laryngectomy

    SciTech Connect

    Kazi, Rehan; Venkitaraman, Ramachandran; Johnson, Catherine; Prasad, Vyas; Clarke, Peter; Rhys-Evans, Peter; Nutting, Christopher M.; Harrington, Kevin J.

    2008-02-01

    Purpose: To conduct prospective electroglottographic analyses of voice outcomes after radical chemoradiotherapy for locally advanced laryngopharyngeal cancers and to compare them with patients who have undergone total laryngectomy (TL). Patients and Methods: Twenty-one patients (19 male, 2 female, median age [range] 65 [50-85] years) with Stage III/IV laryngopharyngeal cancer received induction chemotherapy followed by radical chemoradiotherapy. Electroglottography, using the sustained vowel /i/ and connected speech, was performed before treatment and 1, 6, and 12 months after treatment. In addition, single voice recordings were taken from 21 patients (16 male, 5 female, aged 65 [50-84] years) who had undergone TL and surgical voice restoration and from 21 normal controls (18 male, 3 female, aged 65 [33-80] years). Results: Before treatment the vocal measures for the chemoradiotherapy patients were significantly different from normal controls in jitter (p = 0.02), maximum phonation time (MPT) (p = 0.001), and words per minute (WPM) (p = 0.01). At 12 months after treatment MPT and WPM had normalized, but jitter and normalized noise energy were significantly worse than in normal controls. Comparison of voice outcomes at 12 months for chemoradiotherapy patients revealed superiority over the TL group in all parameters except MPT (18.2 s vs. 10.4 s, p = 0.06). Analysis of the recovery of voice up to 12 months after treatment revealed progressive improvement in most electroglottographic measures. Conclusions: This prospective study demonstrates significantly better outcome for patients treated with chemoradiotherapy as compared with TL. Progressive normalization of many voice parameters occurs over the 12 months following chemoradiotherapy.

  6. Treatment of limited-stage small cell lung cancer in the elderly, chemotherapy vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy: that’s the question

    PubMed Central

    Casaluce, Francesca; Sgambato, Assunta; Monaco, Fabio; Guida, Cesare

    2016-01-01

    Chemotherapy is the mainstay of the treatment in limited disease (LD) and extended disease (ED) small cell lung cancer (SCLC) patients, while concurrent chemoradiotherapy (CRT) is the standard of care in healthy patients with LD. However, this intensive treatment is associated with significantly more toxicity in the subset of patients aged 70 years or more. To date, most of available data concerning CRT in elderly derived from retrospective analyzes, usually conducted on small samples of patients, poorly representative of this population. Modern CRT appears to confer a survival benefit compared to chemotherapy alone in a recent retrospective analysis conducted on elderly patients with LD-SCLC. Age alone should not be a contraindication for multimodality treatment in this subset of patients. PMID:27186510

  7. Mitomycin-C- or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

    SciTech Connect

    Olivatto, Luis O.; Cabral, Vania; Rosa, Arthur; Bezerra, Marcos; Santarem, Erick; Fassizoli, Ana; Castro, Leonaldson; Simoes, Jose Humberto; Small, Isabele A.; Ferreira, Carlos Gil

    2011-02-01

    Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m{sup 2} 120-hour infusion or 1,000 mg/m{sup 2} 96-hour infusion) plus CP (100 mg/m{sup 2}) on the first day of each cycle or MMC (10-15 mg/m{sup 2}) on the first day of Cycle 1 was administered concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.

  8. Phase II study of concomitant chemoradiotherapy in bulky refractory or chemoresistant relapsed lymphomas

    SciTech Connect

    Girinsky, Theodore . E-mail: girinsky@igr.fr; Lapusan, Simona; Ribrag, Vincent; Koscielny, Serge; Ferme, Christophe; Carde, Patrice

    2005-02-01

    Purpose: To evaluate the local efficacy of concomitant chemoradiotherapy in patients with mostly refractory lymphoma. Methods and materials: Patients with refractory or chemoresistant-relapsed lymphoma and bulky life-threatening masses were included in this study. A split course of concomitant radiotherapy and chemotherapy (mostly cisplatin and etoposide) was delivered during a 6-week period. Weekly blood tests and a clinical examination using the Radiation Therapy Oncology Group guidelines were performed to assess acute toxicity. The tumor response was evaluated 1-3 months after treatment and at regular follow-up visits. Results: We enrolled 21 patients in the study between January 1998 and April 2003. Of the 21 patients, 60% had disseminated disease with bulky tumor masses and 85% had refractory lymphoma, of which most had been treated with at least two different chemotherapy regimens before concomitant chemoradiotherapy. Seventy-five percent received regimens containing cisplatinum and etoposide. The median radiation dose was 40 Gy (range, 12-62.5 Gy). Grade 3-4 hematologic toxicity and mucositis was observed in 70% and 30% of cases respectively, without any deaths. The overall response and complete remission rate was 70% and 20%, respectively. The 1-year overall survival and local progression-free survival rate was 20.4% and 54%, respectively. Three patients with localized disease were still alive 16, 33, and 48 months after treatment. Conclusion: Concomitant chemoradiotherapy for refractory or chemoresistant-relapsed lymphoma induced high hematologic toxicity, but seemed adequate for controlling local bulky tumor masses. No toxicity-related death was observed.

  9. Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy.

    PubMed

    Li, Tingting; Zhang, Mingfu; Wang, Jianzhen; Wang, Tianqi; Yao, Yao; Zhang, Xiaomei; Zhang, Cai; Zhang, Na

    2016-01-01

    Chemoradiotherapy, as a well-established paradigm to treat various cancers, still calls for novel strategies. Recently, gold nanoparticles (AuNPs) have been shown to play an important role as a radiosensitizer in cancer radiotherapy. The aim of this study was to evaluate the combination of polyethylene glycol (PEG) modified AuNPs and doxorubicin (DOX) to improve cancer chemoradiotherapy, in which the AuNPs was the radiosensitizer and the DOX was the model chemotherapeutic. A Pluronic® F127-based thermosensitive hydrogel (Au-DOX-Gel) loading AuNPs and DOX was developed by "cold method" for intratumoral injection. The formulation was optimized at a F127 concentration of 22% for Au-DOX-Gel. The release profiles compared to a control group were assessed in vitro and in vivo. Au-DOX-Gel showed sustained release of AuNPs and DOX. The cell viability and surviving fraction of mouse melanoma (B16) and Human hepatocellular liver carcinoma (HepG2) cells were significantly inhibited by the combination treatment of DOX and AuNPs under radiation. Tumor sizes of mice were significantly decreased by Au-DOX-Gel compared to controls. Interestingly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki-67 staining results showed that tumor cell growth and proliferation were inhibited by AuNPs combined with DOX under radiation, suggesting that the radiosensitization activity and combination effects might be caused by inhibition of tumor cell growth and proliferation. Furthermore, the results of skin safety tests, histological observation of organs, and the body weight changes indicated in vivo safety of Au-DOX-Gel. In conclusion, the Au-DOX-Gel developed in this study could represent a promising strategy for improved cancer chemoradiotherapy. PMID:26381779

  10. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    SciTech Connect

    Alexander, Brian M.; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-05-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  11. New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect

    PubMed Central

    Altundal, Yucel; Cifter, Gizem; Detappe, Alexandre; Sajo, Erno; Tsiamas, Panagiotis; Zygmanski, Piotr; Berbeco, Ross; Cormack, Robert A.; Makrigiorgos, Mike; Ngwa, Wilfred

    2015-01-01

    We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles. PMID:25492359

  12. Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV.

    PubMed

    Sugimoto, Aya; Nakazuru, Shoichi; Sakakibara, Yuko; Nishio, Kumiko; Yamada, Takuya; Ishida, Hisashi; Yajima, Keishiro; Uehira, Tomoko; Mori, Kiyoshi; Mita, Eiji

    2016-01-01

    Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/μl before chemoradiotherapy to 138 cells/μl after 3 months, but increased to 210 cells/μl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years

  13. New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect.

    PubMed

    Altundal, Yucel; Cifter, Gizem; Detappe, Alexandre; Sajo, Erno; Tsiamas, Panagiotis; Zygmanski, Piotr; Berbeco, Ross; Cormack, Robert A; Makrigiorgos, Mike; Ngwa, Wilfred

    2015-02-01

    We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles. PMID:25492359

  14. Prolonged Survival of a Patient With Pelvic Recurrence of Ovarian Malignant Mixed Mullerian Tumor After Chemoradiotherapy

    PubMed Central

    Homaei Shandiz, Fatemeh; Kadkhodayan, Sima; Hsanzade Mofrad, Malihe; Yousefi Roodsari, Zohre; Sharifi Sistani, Noorieh; Nabizadeh Marvast, Majid; Sadeghei, Mahbobe

    2014-01-01

    Introduction: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor, accounting for less than 1% of all ovarian cancers. Case Presentation: We present a 64-year-old woman with stage III MMMT of ovary that was treated with platinum-based chemotherapy after optimal cytoreductive surgery. After 25 months of being disease free, she had a pelvic recurrence and a good response to chemoradiotherapy. Conclusions: Optimal cytoreductive surgery and chemotherapy may be the best treatment in MMMT but more discussion and experiences are needed regarding the effectiveness of radiotherapy. PMID:25593719

  15. Mucinous Adenocarcinoma Arising in Chronic Perianal Fistula: Good Results with Neoadjuvant Chemoradiotherapy Followed by Surgery

    PubMed Central

    Santos, Marisa D.; Nogueira, Carlos; Lopes, Carlos

    2014-01-01

    Chronic perianal fistulas are a common clinical condition. However, their evolution to adenocarcinoma is rare. We report the case of a 48-year-old man with perianal chronic fistulas, who developed two perianal ulcerated lesions near the external orifices of the fistulas, which extended proximally as a pararectal tumor. No intestinal lesion was seen at endoscopic examination. Histopathological biopsy indicated mucinous adenocarcinoma. Staging was performed by pelvic magnetic resonance imaging (MRI) and thoracoabdominal CT scan. The patient underwent a laparoscopic colostomy followed by neoadjuvant chemoradiotherapy and then laparoscopic abdominoperineal resection followed by adjuvant therapy. We have seen a favorable outcome with no recurrence at 3 years of follow-up. PMID:25506029

  16. Chemoradiotherapy for locally advanced pancreatic cancer patients: is it still an open question?

    PubMed Central

    Sawicka, Emilia; Mirończuk, Anna; Wojtukiewicz, Marek Z.

    2016-01-01

    Operable pancreatic cancer is characterized by a high risk of recurrence. Efforts are made to incorporate new therapies. Throughout the world there is a lack of uniform recommendations concerning the adjuvant treatment of pancreatic cancer patients, due to confusing evidence-based data. The patients recruited to clinical trials differ from the population of patients treated in everyday practice. These differences have an influence on tolerance of treatment, toxicity and results of therapy. The decision on administration of adjuvant treatment is made individually and differs from center to center. A review of the literature concerning both results and tolerance of postoperative chemoradiotherapy of pancreatic cancer patients is presented. PMID:27358587

  17. Accelerated Reader.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Accelerated Reader, a system of computerized testing and record-keeping that supplements the regular classroom reading program. Accelerated Reader's primary goal is to increase literature-based reading practice. The program offers a computer-aided reading comprehension and management program intended to motivate…

  18. A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer

    PubMed Central

    Nikas, Jason B; Lee, Janet T; Maring, Elizabeth D; Washechek-Aletto, Jill; Felmlee-Devine, Donna; Johnson, Ruth A; Smyrk, Thomas C; Tawadros, Patrick S; Boardman, Lisa A; Steer, Clifford J

    2015-01-01

    An important determinant of the pathogenesis and prognosis of various diseases is inherited genetic variation. Single-nucleotide polymorphisms (SNPs), variations at a single base position, have been identified in both protein-coding and noncoding DNA sequences, but the vast majority of millions of those variants are far from being functionally understood. Here we show that a common variant in the gene MTHFR [rs1801133 (C>T)] not only influences response to neoadjuvant chemoradiotherapy in patients with rectal cancer, but it also influences recurrence of the disease itself. More specifically, patients with the homozygous ancestral (wild type) genotype (C/C) were 2.91 times more likely (291% increased benefit) to respond to neoadjuvant chemoradiotherapy {95% CI: [1.23, 6.89]; P=0.0150} and 3.25 times more likely (325% increased benefit) not to experience recurrence of the disease {95% CI: [1.37, 7.72]; P=0.0079} than patients with either the heterozygous (C/T) or the homozygous mutation (T/T) genotype. These results identify MTHFR as an important genetic marker and open up new, pharmacogenomic strategies in the treatment and management of rectal cancer. PMID:26693073

  19. [A Case of Locally Advanced Rectal Cancer Curatively Resected Following Chemoradiotherapy].

    PubMed

    Kawahara, Yohei; Terada, Itsuro; Terai, Shiro; Yamamoto, Seiichi; Kaji, Masahide; Maeda, Kiichi; Shimizu, Koichi

    2015-11-01

    A man in his 70s was referred to our hospital with anorexia, weight loss, and constipation. After examination by computed tomography (CT), magnetic resonance imaging (MRI), and colonoscopy, he was diagnosed as having a locally advanced rectal cancer with abscess formation. Because CT and MRI indicated that the tumor had invaded the seminal vesicle, prostate, and sacrum, we diagnosed it as an unresectable tumor. We treated the abscesses around the tumor by sigmoid colostomy with administration of antibiotics. After control of the infection, the patient received systemic chemotherapy with capecitabine/oxaliplatin (XELOX) plus bevacizumab (BV). After the 5th courses of XELOX plus BV, the primary tumor showed a tendency to shrink, but invasion to the neighboring organs was still seen. Therefore, we treated him with chemoradiotherapy (CRT) using S-1. After completion of CRT with no significant adverse effects, the tumor invasion to the neighboring organs disappeared, and we performed a low anterior resection 9 weeks later. Pathological findings revealed that the tumor had shrunk remarkably and it was resected curatively, although a few tumor cells remained in the subserosal layer of the ulcerative scar caused by the CRT. His postoperative course was uneventful, and he underwent adjuvant chemotherapy with S-1 for 3 months after discharge. To date, no disease recurrence has been detected. We report a case of locally advanced rectal cancer, which was curatively resected following chemoradiotherapy, along with a short literature review. PMID:26805354

  20. [Sequential Chemoradiotherapy for Advanced Head and Neck Cancer: A Clinical Study with 33 Cases].

    PubMed

    Takahashi, Katsumasa; Nakajima, Kyoko; Murata, Takaaki; Shino, Masato; Nikkuni, Osamu; Toyoda, Minoru; Takayasu, Yukihiro; Chikamatsu, Kazuaki

    2016-05-01

    A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival. PMID:27459819

  1. Development of a preclinical therapeutic model of human brain metastasis with chemoradiotherapy.

    PubMed

    Martínez-Aranda, Antonio; Hernández, Vanessa; Picón, Cristina; Modolell, Ignasi; Sierra, Angels

    2013-01-01

    Currently, survival of breast cancer patients with brain metastasis ranges from 2 to 16 months. In experimental brain metastasis studies, only 10% of lesions with the highest permeability exhibited cytotoxic responses to paclitaxel or doxorubicin. Therefore, radiation is the most frequently used treatment, and sensitizing agents, which synergize with radiation, can improve the efficacy of the therapy. In this study we used 435-Br1 cells containing the fluorescent protein (eGFP) gene and the photinus luciferase (PLuc) gene to develop a new brain metastatic cell model in mice through five in vivo/in vitro rounds. BR-eGFP-CMV/Luc-V5 brain metastatic cells induce parenchymal brain metastasis within 60.8 ± 13.8 days of intracarotid injection in all mice. We used this model to standardize a preclinical chemoradiotherapy protocol comprising three 5.5 Gy fractions delivered on consecutive days (overall dose of 16.5 Gy) which improved survival with regard to controls (60.29 ± 8.65 vs. 47.20 ± 11.14). Moreover, the combination of radiotherapy with temozolomide, 60 mg/Kg/day orally for five consecutive days doubled survival time of the mice 121.56 ± 52.53 days (Kaplan-Meier Curve, p < 0.001). This new preclinical chemoradiotherapy protocol proved useful for the study of radiation response/resistance in brain metastasis, either alone or in combination with new sensitizing agents. PMID:23591844

  2. [A Case Report of a Pathological Complete Response of Rectal Cancer to Preoperative Chemoradiotherapy with Tegafur].

    PubMed

    Morikawa, Tatsuya; Teraishi, Fuminori; Shima, Yasuo; Iwata, Jun

    2016-03-01

    We report the case of a patient with advanced rectal cancer who achieved a pathological complete response to preoperative chemoradiotherapy (CRT). A 65-year-old man was diagnosed as having a two-thirds circumferential well-to moderately differentiated tumor (Rb-P, type 2). To control local recurrence, we treated the patient with CRT. Radiotherapy was administered in fractions of 2 Gy/day (total, 40 Gy). Concurrently, S-1 was administered orally at a fixed daily dose of 80 mg/m2 for 20 days. Withdrawal and/or dose reduction of S-1 was not necessary in spite of Grade 1 or 2 toxic effects, including diarrhea and periproctitis, occurring on day 7. Laparoscopic abdominoperineal resection was performed 6 weeks after the final dose of chemotherapy was administered. The histopathological regression grade was Grade 3. No recurrence was detected on enhanced CT more than 5 years after surgery. This case suggests that the regimen was both effective and tolerated, and that preoperative chemoradiotherapy may be effective for tumor suppression to prevent local recurrence. PMID:27067861

  3. Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

    PubMed Central

    Gondi, Vinai; Bentzen, Søren M.; Sklenar, Kathryn L.; Dunn, Emily F.; Petereit, Daniel G.; Tannehill, Scott P.; Straub, Margaret; Bradley, Kristin A.

    2013-01-01

    Purpose To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. Methods and Materials Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade ≥3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring ≥6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. Results At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7–5.2, P<001), and skeletal (HR 7.0, 95% CI 1.4–34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0–6.5, P<.001) and poor (HR 8.5, 95% CI 4.3–16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1–3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2–27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. Conclusion Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities

  4. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  5. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  6. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  7. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  8. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  9. Adjuvant versus neoadjuvant chemoradiotherapy in distal rectal cancer: Comparison of two decades in a single center

    PubMed Central

    Zengel, Baha; Uslu, Adam; Adıbelli, Zehra; Yetiş, Halit; Cengiz, Fevzi; Aykas, Ahmet; Şimşek, Cenk; Akpınar, Göksever; Eliyatkın, Nuket; Duran, Ali

    2015-01-01

    Objective: Standard surgery alone was not able to decrease local recurrence (LR) rate below 20% in rectal cancer treatment. Thus, many centers administered neoadjuvant radiotherapy (preopRTx) with or without concomitant chemotherapy for the prevention of LR. In this study, the results of 164 consecutive patients with mid- and distal rectal cancer who received surgery and adjuvant chemoradiotherapy (Group A) or neoadjuvant chemoradiotherapy (Group NA) followed by surgery are presented. Material and Methods: The staging system used in this study is that of the American Joint Committee on Cancer (AJCC), also known as the TNM system. Eligible patients were required to have radiologically assessed stage 1 (only T2N0M0) to stage 3C (T4bN1-2M0) tumor with pathologically confirmed R0 resection. The surgical method was total mesorectal excision (TME). Radiotherapy was applied with daily 180 cGy fractions for 28 consecutive days. Chemo-therapy comprised 5-fluorouracil (450 mg/m2/d) and leucovorin (20 mg/m2/d) bolus at days 1–5 and 29–33. Results: Nine patients (13%) in Group NA achieved pathologic complete response (pCR). In Group NA and Group A, locoregional recurrence (LRR) rates were 6.7% and 30.8%, (p<0.001), the mean LR-free survival was 190.0±7.3 months and 148.0±11.7 months (p=0.002) and the mean overall survival (OS) was 119.2±15.3 months and 103.0±9.4 months (p=0.23), respectively. A significant difference with regard to LR has been obtained with a statistical power of 0.92. Secondary outcome measures (DFS and OS) have not been met. Conclusion: Neoadjuvant chemoradiotherapy with TME is an efficient treatment protocol, particularly for the treatment of magnetic resonance imaging-staged 2A to 3C patients with two or three distal rectal adenocarcinomas. Given that a considerable proportion of patients with cT2N0M0 would develop pCR, this method of treatment can be considered for further studies. PMID:26668530

  10. Outcomes of Chemoradiotherapy in Cervical Cancer-The Western Australian Experience

    SciTech Connect

    Lim, Adeline; Sia, Serena

    2012-03-15

    Purpose: A retrospective review of patients with Stage IB1-IVA cervical cancer treated with combined chemoradiotherapy in Western Australia was conducted with the aim of assessing outcomes and patterns of recurrence. Multivariate analysis was performed to identify potential prognostic factors. Methods and Materials: Patients treated with radical chemoradiotherapy for cervical cancer in Western Australia between June 2005 and November 2008 were analyzed. Treatment consisted of external-beam radiotherapy with concurrent weekly cisplatin (40 mg/m{sup 2}), followed by high-dose-rate brachytherapy. The Kaplan-Meier method was used to determine overall survival and disease-free survival, and Cox regression analysis was used to identify potential prognostic factors. Results: Sixty-nine patients were included in the analysis. All patients completed external-beam radiotherapy; however, only 43.5% of patients completed the planned course of brachytherapy. At a median follow-up of 27 months, 24- and 48-month overall survival were 68.8% and 61.1%, respectively. Disease-free survival at 24 and 48 months was 59.4% and 56.7%, respectively. The 2-year local control rate was 70.1%. Nodal involvement resulted in increased risk of disease recurrence (hazard ratio [HR] 6.26, p = 0.002) and death (HR 5.15, p = 0.013). Pretreatment hemoglobin <120 g/L was a negative prognostic factor for disease recurrence (HR 4.20, p = 0.031) and death (HR 8.19, p = 0.020). Completion of brachytherapy improved overall survival (p = 0.039), with a trend to reducing disease recurrence (p = 0.052). The risk of relapse increased with treatment time over 8 weeks (HR 8.18, p = 0.019), however treatment time did not affect the risk of death (p = 0.245). Conclusion: The overall survival outcomes in this group of women with locally advanced cervical carcinomas treated with chemoradiotherapy are comparable to worldwide data. Despite the use of modern treatment protocols, a significant proportion of women

  11. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives.

    PubMed

    Biondi, Alberto; Lirosi, Maria C; D'Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando Cm; Persiani, Roberto

    2015-12-15

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  12. Chemoradiotherapy as initial management in patients with squamous cell carcinoma of the head and neck

    SciTech Connect

    Adelstein, D.J.; Sharan, V.M.; Earle, A.S.; Shah, A.C.; Vlastou, C.; Haria, C.D.; Carter, S.G.; Damm, C.; Hines, J.D.

    1986-06-01

    Thirty-nine previously untreated or minimally treated patients with squamous cell carcinoma of the head and neck were entered onto a chemoradiotherapy protocol employing multiple courses of simultaneous radiation therapy, cisplatin, and a 4-day 5-FU infusion. Thirty-eight patients were evaluable for response and toxicity. Twenty-three patients underwent surgical resection midway through this therapy and 11 (48%) were pathologically free of disease. Thirty-five of the 38 patients (92%) were ultimately rendered disease-free by this combined modality protocol. Thirty-one patients remain disease-free, with a projected 2-year disease-free survival of 74%. Although the treatment-associated mucositis and myelo-suppression were significant, this chemoradiotherapeutic approach is promising and merits further study.

  13. Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma.

    PubMed

    Setua, Sonali; Ouberai, Myriam; Piccirillo, Sara G; Watts, Colin; Welland, Mark

    2014-09-21

    Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies. PMID:25117686

  14. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  15. Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma

    NASA Astrophysics Data System (ADS)

    Setua, Sonali; Ouberai, Myriam; Piccirillo, Sara G.; Watts, Colin; Welland, Mark

    2014-08-01

    Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies.Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies. Electronic supplementary information (ESI) available: Additional figures. See DOI: 10.1039/c

  16. Involved-Field, Low-Dose Chemoradiotherapy for Early-Stage Anal Carcinoma

    SciTech Connect

    Hatfield, Paul; Cooper, Rachel; Sebag-Montefiore, David

    2008-02-01

    Purpose: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. Methods and Materials: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m{sup 2} on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m{sup 2}/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. Results: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. Conclusion: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.

  17. Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

    SciTech Connect

    Fu Shen; Lu Jiade; Zhang Qing Yang Zhe; Peng Lihua; Xiong, Fei

    2008-12-01

    Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate.

  18. The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer

    PubMed Central

    2013-01-01

    Background Adequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters. Methods A total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation. Results One-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 – 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0–39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006). Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes. Conclusion In TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression. PMID:24246069

  19. Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy

    SciTech Connect

    De Ruyck, Kim; Sabbe, Nick; Oberije, Cary; Vandecasteele, Katrien; Thas, Olivier; De Ruysscher, Dirk; Lambin, Phillipe; Van Meerbeeck, Jan; De Neve, Wilfried; Thierens, Hubert

    2011-10-01

    Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

  20. Cognitive Functioning After Radiotherapy or Chemoradiotherapy for Head-and-Neck Cancer

    SciTech Connect

    Gan, Hui K.; Bernstein, Lori J.; Brown, Jennifer; Ringash, Jolie; Vakilha, Mehrdad; Wang, Lisa; Goldstein, David; Kim, John; Hope, Andrew; O'Sullivan, Brian; Waldron, John; Abdul Razak, Albiruni R.; Chen, Eric X.; Siu, Lillian L.

    2011-09-01

    Purpose: To perform a comprehensive cognitive function (CF) assessment in patients who were relapse free after curative intent radiotherapy (RT) or chemoradiotherapy for squamous cell carcinoma of the head and neck. Methods and Materials: Patients underwent neuropsychological tests to assess their objective CF; completed questionnaires to assess subjective CF, quality of life, and affect; and underwent blood tests to assess hematologic, biochemical, endocrine, and cytokine status. Retrospectively, the dosimetry of incidental radiation to the brain was determined for all patients, and the dose intensity of cisplatin was determined in those who had undergone chemoradiotherapy. Results: A total of 10 patients were enrolled (5 treated with radiotherapy only and 5 with radiotherapy and cisplatin). The mean time from the end of treatment was 20 months (range, 9-41). All patients were able to complete the assessment protocol. Of the 10 patients, 9 had impaired objective CF, with memory the most severely affected. The severity of memory impairment correlated significantly with the radiation dose to the temporal lobes, and impaired dexterity correlated significantly with the radiation dose to the cerebellum, suggesting that these deficits might be treatment related. Patients receiving cisplatin appeared to have poorer objective CF than patients receiving only RT, although this difference did not achieve statistical significance, likely owing to the small sample size. Consistent with the published data, objective CF did not correlate with subjective CF or quality of life. No association was found between objective CF and patients' affect, hematologic, biochemical, endocrine, and cytokine status. Conclusion: Neuropsychological testing is feasible in squamous cell carcinoma of the head-and-neck survivors. The findings were suggestive of treatment-related cognitive dysfunction. These results warrant additional investigation.

  1. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  2. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  3. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  4. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  5. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  6. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  7. Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

    PubMed

    Molinari, Chiara; Matteucci, Federica; Caroli, Paola; Passardi, Alessandro

    2015-12-01

    Standard treatment of patients with locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Tumor regression after NCRT varies substantially among individuals and pathological complete response is a known prognostic factor for LARC. The identification of a predictive model for response to chemoradiotherapy would help clinicians to identify patients who would probably benefit from multimodal treatment and to perform an early assessment of individual prognosis. Carcinoembryonic antigen has proven to be a good predictor of response in several clinical trials. Other widely studied predictive models in LARC include molecular biomarkers, analyzed at various levels and by different techniques, and molecular imaging, in particular magnetic resonance imaging and positron emission tomography/computed tomography. Although none of the studied markers have been approved in clinical practice, their evaluation in larger, prospective trials and in combined predictive models could be of use to define tailored therapeutic strategies. PMID:26170142

  8. Stents in patients with esophageal cancer before chemoradiotherapy: high risk of complications and no impact on the nutritional status.

    PubMed

    Mão-de-Ferro, S; Serrano, M; Ferreira, S; Rosa, I; Lage, P; Alexandre, D P; Freire, J; Mirones, L; Casaca, R; Bettencourt, A; Pereira, A D

    2016-03-01

    Preoperative chemoradiotherapy is the standard of care for locally advanced esophageal cancer, causing persistent deterioration in the nutritional status. We performed a prospective study to evaluate the safety and efficacy of esophageal double-covered self-expandable metal stents in patients with esophageal cancer before chemoradiotherapy. The nutritional status and dysphagia were prospectively recorded. Eleven patients were included: eight were moderate and three were severely malnourished. After stent placement, dysphagia improved in all patients. With regard to complications, one patient developed an esophageal perforation that required urgent esophagectomy. Four patients presented stent migration. Three of these patients required enteral nutrition and none was submitted to surgery because of poor nutritional status. Of the other six patients, only four were operated upon. Stent placement presented a high complication rate and did not prevent weight loss or malnutrition. Other alternatives, including naso-gastric tube placement or endoscopic percutaneous gastrostomy or jejunostomy, should be considered. PMID:26669568

  9. Consolidation chwemotherapy after concurrent chemoradiotherapy vs. chemoradiotherapy alone for locally advanced unresectable stage III non-small-cell lung cancer: A meta-analysis

    PubMed Central

    Chang, Xiu-Jun; Wang, Zi-Tong; Yang, Lei

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced unresectable stage III non-small-cell lung cancer (LA-NSCLC). Whether consolidation chemotherapy (CCT) following CCRT is able to further improve the clinical outcome remains unclear. We therefore undertook a meta-analysis to compare the two regimens for LA-NSCLC. A literature search was performed through PubMed, Embase, Cochrane Library and Chinese Biology Medicine, from their inception to November, 2015. Irrelevant studies were excluded using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Our primary endpoint was overall survival (OS), which was defined as the time from randomisation until death from any cause; the secondary endpoint was progression-free survival (PFS). All analyses were by intention-to-treat. Five phase III randomized controlled trials with 958 patients were included in the present meta-analysis. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Compared with CCRT, CCT after CCRT was not associated with statistically significant differences in OS (OR=1.24; 95% CI: 0.89–1.72; P=0.21) or PFS (OR=1.16; 95% CI: 0.74–1.83; P=0.53), but increased the risk of toxicity, including infection (P=0.02), pneumonitis (P=0.003) and treatment-related death (P=0.04). There were no significant differences in terms of benefit according to particular patient characteristics, such as age, gender, performance status, tumor histology or clinical stage. Thus, the present study failed to support the use of CCT after CCRT over CCRT alone, as there was no significant OS and PFS benefit for LA-NSCLC patients, but the use of CCT after CCRT resulted in increased toxicity. PMID:27446563

  10. Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

    SciTech Connect

    Câmara-Costa, Hugo; Resch, Anika; Kieffer, Virginie; Lalande, Clémence; Poggi, Geraldina; Kennedy, Colin; Bull, Kim; Calaminus, Gabriele; Grill, Jacques; Doz, François; Rutkowski, Stefan; Massimino, Maura; Kortmann, Rolf-Dieter; Lannering, Birgitta; Dellatolas, Georges; Chevignard, Mathilde

    2015-08-01

    Purpose: In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8 years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms. Methods and Materials: Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's Progressive Matrices, we estimated full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ), performance IQ (PIQ), working memory index (WMI), and processing speed index (PSI). Results: Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5% males), mean (±SD) ages at diagnosis and assessment respectively were 9.3 (±3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (±4.3) years of age. Mean (±SD) FSIQ was 88 (±19), and mean intergroup difference was 3.88 (95% confidence interval: −2.66 to 10.42, P=.24). No significant differences were found in children >8 years of age at diagnosis. In children <8 years of age at diagnosis, a marginally significant trend toward higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI, or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67; P=.02]; 3.77 for PIQ [95% CI: −5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: −2.07 to 12.47; P>.10]; 10.90 for PSI [95% CI: −1.54 to 23.36; P=.08]; and 5.28 for FSIQ [95% CI: −4.23 to 14.79; P>.10]). Conclusions: HFRT was associated with marginally

  11. Accelerated radiotherapy and concurrent chemotherapy for patients with contralateral central or mediastinal lung cancer relapse after pneumonectomy

    PubMed Central

    Abu Jawad, Jehad; Gkika, Eleni; Freitag, Lutz; Lübcke, Wolfgang; Welter, Stefan; Gauler, Thomas; Schuler, Martin; Eberhardt, Wilfried Ernst Erich; Stamatis, Georgios; Stuschke, Martin

    2015-01-01

    Background Treatment options are very limited for patients with lung cancer who experience contralateral central or mediastinal relapse following pneumonectomy. We present results of an accelerated salvage chemoradiotherapy regimen. Methods Patients with localized contralateral central intrapulmonary or mediastinal relapse after pneumonectomy were offered combined chemoradiotherapy including concurrent weekly cisplatin (25 mg/m2) and accelerated radiotherapy [accelerated fractionated (AF), 60 Gy, 8×2 Gy per week] to reduce time for repopulation. Based on 4D-CT-planning, patients were irradiated using multifield intensity-modulated radiotherapy (IMRT) or helical tomotherapy. Results Between 10/2011 and 12/2012, seven patients were treated. Initial stages were IIB/IIIA/IIIB: 3/1/3; histopathological subtypes scc/adeno/large cell: 4/1/2. Tumour relapses were located in mediastinal nodal stations in five patients with endobronchial tumour in three patients. The remaining patients had contralateral central tumour relapses. All patients received 60 Gy (AF), six patients received concurrent chemotherapy. Median dose to the remaining contralateral lung, esophagus, and spinal cord was 6.8 (3.3-11.4), 8.0 (5.1-15.5), and 7.6 (2.8-31.2) Gy, respectively. With a median follow-up of 29 [17-32] months, no esophageal or pulmonary toxicity exceeding grade 2 [Common terminology criteria for adverse events (CTC-AE) v. 3] was observed. Median survival was 17.2 months, local in-field control at 12 months 80%. Only two local recurrences were observed, both in combination with out-field metastases. Conclusions This intensified accelerated chemoradiotherapy schedule was safely applicable and offers a curative chance in these pretreated frail lung cancer patients. PMID:25922702

  12. Role of Adaptive Radiotherapy During Concomitant Chemoradiotherapy for Lung Cancer: Analysis of Data From a Prospective Clinical Trial

    SciTech Connect

    Spoelstra, Femke; Pantarotto, Jason R.; Soernsen de Koste, John R. van; Slotman, Ben J.; Senan, Suresh

    2009-11-15

    Purpose: Respiratory-gated radiotherapy allows for the reduction of the toxicity associated with concomitant chemoradiotherapy, but the smaller fields used could increase the risk of missing the target. A prospective study was performed to evaluate the dosimetric consequences of time-trend changes in patients with lung cancer who were treated with concomitant chemoradiotherapy. Methods and Materials: A total of 24 lung cancer patients eligible for chemoradiotherapy and gated delivery underwent four-dimensional computed tomography (4D-CT) after 15 fractions. This scan was co-registered with the initial planning 4D-CT and a new planning target volume (PTV) was generated on the basis of the tumor visualized after 15 fractions. Coverage of the repeat PTV was evaluated by applying the original plan to the second scan and recalculating the dose. Plan modification was triggered by a 5% reduction in the PTV included within the 95% isodose volume or an unacceptable increase in the critical organ dose. Results: Of the 21 evaluable patients, 15 had an average reduction in the PTV of 8% after 30 Gy. The PTV increased in the remaining 6 patients, but the increase was >20% in only 1 patient. In the latter patient, disease progression was observed, and repeat planning was required. The plans created using the new PTV were acceptable in all the other patients. Conclusion: The role of adaptive radiotherapy appears limited when respiratory-gated radiotherapy is used to reduce the toxicity related to concomitant chemoradiotherapy. The use of more conformal treatment techniques might provide the rationale for repeat imaging as a method to identify patients at risk of dosimetric miss.

  13. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

    SciTech Connect

    Unsal, Diclehan . E-mail: diclehan@yahoo.com; Uner, Aytug; Akyurek, Nalan; Erpolat, Petek; Dursun, Ayse; Pak, Yucel

    2007-01-01

    Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

  14. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients

    PubMed Central

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer. PMID:26023803

  15. [Extranodal natural killer/T-cell lymphoma, nasal type developing central nervous system and epididymis involvement immediately after concurrent chemoradiotherapy].

    PubMed

    Sasaki, Yuya; Yonezawa, Akihito; Kinoshita, Yoshihiro; Kitagawa, Tomoya; Mori, Minako; Onaka, Takashi; Imada, Kazunori

    2015-12-01

    A 66-year-old man showed central nervous system (CNS) and epididymis involvement after concurrent chemoradiotherapy for extranodal natural killer/T-cell lymphoma, nasal type (ENKL). The patient experienced continuous nasal obstruction. CT revealed a mass in the nasal cavity and paranasal sinuses. Biopsy of the nasal cavity mass showed it to be ENKL. Based on bone marrow biopsy and 18F-FDG PET/CT findings, the clinical stage was suspected to be IIE. The sites involved were the nasal cavity, paranasal sinuses, and cervical lymph nodes. We performed concurrent chemoradiotherapy consisting of a 67% dose of DeVIC and involved field radiation therapy towards his head and neck. Head and neck CT confirmed a therapeutic response. After receiving concurrent chemoradiotherapy, the patient complained of perineal discomfort. Ultrasonography revealed swelling of the left epididymis. Left epididymis biopsy showed ENKL involvement and lumbar puncture revealed CNS involvement. The findings of this case suggest that evaluation of CNS involvement might be an essential part of the initial workup for some ENKL patients. PMID:26725358

  16. Expression of Excision Repair Cross-Complementation Group 1 as Predictive Marker for Nasopharyngeal Cancer Treated With Concurrent Chemoradiotherapy

    SciTech Connect

    Sun, Jong-Mu; Ahn, Myung-Ju; Park, Min Jae; Lee, Hui-Young; Ahn, Jin Seok; Lee, Seungkoo; Kang, Gu; Han, Joungho; Son, Young-Ik; Baek, Chung-Hwan; Ahn, Yong Chan; Park, Keunchil

    2011-07-01

    Purpose: Cisplatin-based concurrent chemoradiotherapy is the standard treatment of nasopharyngeal cancer. The expression of excision repair cross-complementation group 1 (ERCC1) has been reported to be associated with resistance to platinum-based chemotherapy. We evaluated whether ERCC1 expression could predict the treatment response and survival outcome of patients with locally advanced nasopharyngeal cancer who were treated with cisplatin-based concurrent chemoradiotherapy. Methods and Materials: Immunohistochemistry was used to examine the expression of ERCC1 in nasopharyngeal tumor tissue. Patients were categorized into either a resistant or sensitive group depending on their treatment response outcome. A total of 77 patients were assessed in the present study. Results: The resistant and sensitive groups included 25 and 52 patients, respectively. ERCC1 expression was positive in the tumor tissue for 39 of the 77 patients (51%). Significantly more ERCC1-negative tumors were in the sensitive group than in the resistant group (p = .035). In terms of survival outcome, univariate analysis determined that patients with ERCC1-negative tumors had longer disease-free survival (p = .076) and overall survival (p = .013) than patients with ERCC1-positive tumors. Multivariate analysis determined that negative ERCC expression in tumors was an independent predictor for prolonged overall survival (hazard ratio, 0.14; 95% confidence interval, 0.03-0.71). Conclusion: These results suggest that ERCC1 expression might be a useful predictive marker in patients with locally advanced nasopharyngeal cancer who are under consideration for cisplatin-based concurrent chemoradiotherapy.

  17. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

    SciTech Connect

    Kim, Jun-Sang . E-mail: k423j@cnu.ac.kr; Kim, Jin-Man; Li, Shengjin; Yoon, Wan-Hee; Song, Kyu-Sang; Kim, Ki-Hwan; Yeo, Seung-Gu; Nam, Ji Sook; Cho, Moon-June

    2006-09-01

    Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

  18. Study of Functional Infrared Imaging for Early Detection of Mucositis in Locally Advanced Head and Neck Cancer Treated With Chemoradiotherapy

    PubMed Central

    Cohen, Ezra E.W.; Ahmed, Omar; Kocherginsky, Masha; Shustakova, Galyna; Kistner-Griffin, Emily; Salama, Joseph K.; Yefremenko, Volodymyr; Novosad, Valentyn

    2013-01-01

    Background and Purpose Chemoradiotherapy (CRT) has led to improved efficacy in treating locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) but has led to almost universal in-field mucositis. Patients treated with the same regimen often have differences in mucositis occurrence and severity. Mucositis induced via radiation is known to represent an intense inflammatory response histologically. We hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy than identically treated counterparts. This will allow identification of patients that will require more intensive supportive care using thermal imaging technology. Materials and Methods Subjects with LA-SCCHN (oral cavity or oropharynx) being treated with the identical chemoradiotherapy regimen underwent baseline and weekly thermal imaging. Changes in skin temperature caused by mucositis and dermatitis compared with a reference area (T were calculated and correlated to grade of mucositis based on NCI-CTCAE 3.0. Results Thirty-four subjects were enrolled. Grade 3 mucositis and dermatitis was observed in 53% and 21%, respectively. We observed a statistically significant positive association between an early rise in T and mucositis grade (p value=0.03). Conclusions Thermal imaging is able to detect small and early changes in skin surface temperature that may be associated with development of mucositis in patients being treated with chemoradiotherapy. PMID:23988569

  19. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  20. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  1. Completion pneumonectomy and chemoradiotherapy as treatment options in local recurrence of non-small-cell lung cancer

    PubMed Central

    Sławiński, Grzegorz; Musik, Martyna; Marciniak, Łukasz; Dyszkiewicz, Wojciech; Piwkowski, Cezary; Gałęcki, Bartłomiej

    2015-01-01

    Introduction The selection of treatment for local recurrence in patients with non-small-cell lung cancer (NSCLC) depends on the possibility of performing a radical tumor resection, the patient's performance status, and cardiopulmonary efficiency. Compared with chemoradiotherapy, surgical treatment offers a greater chance of long-term survival, but results in completion pneumonectomy and is associated with a relatively high rate of complications. Aim of the study Aim of the study was to evaluate early and long-term results of surgery and conservative treatment (chemoradiotherapy) in patients with local NSCLC recurrence. Material and methods Between 1998 and 2011, 1697 NSCLC patients underwent lobectomy or bilobectomy at the Department of Thoracic Surgery in Poznań. Among them, 137 patients (8.1%) were diagnosed with cancer recurrence; chemotherapy or chemoradiotherapy was provided to 116 patients; 21 patients (15.3%) were treated with completion pneumonectomy. The median time from primary surgery to recurrence was 13.4 months. No metastases to N2 lymph nodes were observed among the patients undergoing surgery; in 7 patients N1 lymph node metastases were confirmed. Results The rate of complications after surgery was significantly higher in comparison with conservative therapy (80.9% vs. 48.3%). Patients treated with surgery were most likely to suffer from complications associated with the circulatory system (80.9%), while hematologic complications were dominant in the group undergoing oncological treatment (41.4%). There were no perioperative deaths after completion pneumonectomy. The age of the patients was the only factor which significantly influenced the incidence of complications in both groups of patients. Analysis of the survival curves demonstrated statistically significant differences in survival between the groups treated with surgery, chemoradiotherapy, and chemotherapy (p = 0.00001). Five-year survival probability was significantly higher among patients

  2. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option

    PubMed Central

    Meulendijks, D; Dewit, L; Tomasoa, N B; van Tinteren, H; Beijnen, J H; Schellens, J H M; Cats, A

    2014-01-01

    Background: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC. Methods: One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m−2) on days 1–5 and 29–33, mitomycin C (MMC, 10 mg m−2) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m−2 b.i.d. on weekdays), MMC (10 mg m−2) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity. Results: Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3–4) toxicity. Conclusions: Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC. PMID:25167226

  3. Clinical experience with chronomodulated infusional 5-fluorouracil chemoradiotherapy for pancreatic adenocarcinoma

    SciTech Connect

    Keene, Kimberly S. . E-mail: Kimberlykeene@earthlink.net; Rich, Tyvin A.; Penberthy, David R.; Shepard, Robert C.; Adams, Reid; Jones, R. Scott

    2005-05-01

    Purpose: To evaluate retrospectively the efficacy and chronic toxicities of concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in patients with pancreatic adenocarcinoma. Methods and Materials: Twenty-eight patients with pancreatic adenocarcinoma were treated between January 1997 and May 2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of chemotherapy was chosen on the basis of a lower toxicity profile in the treatment of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men and 16 were women. Eight patients had unresectable disease and 20 were treated after pancreatic resection. The median radiation dose was 50.4 Gy given in 28 fractions. The median field length and width was 10.6 cm and 10.9 cm, respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a median total dose of 8.4 g/m{sup 2} (300 mg/m{sup 2}/d). Chronomodulated 5-FU delivery consisted of a low basal infusion for 16 h followed by an 8-h escalating-deescalating infusion peaking at 10 PM. Survival and recurrence data were evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using the Radiation Therapy Oncology Group grading system. Results: The median follow-up for all patients was 26 months (range, 4-68 months). The median overall survival for the 20 patients treated postoperatively was 34 months, with a 3- and 5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients with carcinoma of the ampulla were removed from the data set, the mean overall survival in the resected patients was 34 months, with a 3-year and 5-year actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients had a median overall survival of 14 months, and none lived past 2 years. No patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five patients had nausea and dehydration requiring i.v. fluids; only one (4%) was hospitalized. Four patients required a dose

  4. Adjuvant Pelvic Radiotherapy vs. Sequential Chemoradiotherapy for High-Risk Stage I-II Endometrial Carcinoma

    PubMed Central

    El-Hadaad, Hend Ahmed; Wahba, Hanan Ahmed; Gamal, Anas Mohamed; Dawod, Tamer

    2012-01-01

    Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135−175 mg/m2) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45−50 Gy (1.8 Gy/day × 5 days/week). Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma. PMID:23691474

  5. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  6. Accelerators and the Accelerator Community

    SciTech Connect

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  7. A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

    SciTech Connect

    Allen, Jeffrey Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C.; Rorke, Lucy B.; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, K.-W.

    2009-07-15

    Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm{sup 2} postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% {+-} 5% and 52% {+-} 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.

  8. Tumor Volume Is a Prognostic Factor in Non-Small-Cell Lung Cancer Treated With Chemoradiotherapy

    SciTech Connect

    Alexander, Brian M.; Othus, Megan; Caglar, Hale B.

    2011-04-01

    Purpose: To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. Methods and Materials: A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. Results: For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09; p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. Conclusions: In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.

  9. The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

    PubMed Central

    Yildiz, Ramazan; Can, Mehmet Fatih; Yagci, Gokhan; Ozgurtas, Taner; Guden, Metin; Gamsizkan, Mehmet; Ozturk, Erkan; Cetiner, Sadettin

    2013-01-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen therapy (HBOT) on colon anastomosis after chemoradiotherapy (CRT). Sixty female Wistar-Albino rats were divided into 5 groups and underwent left colon resection and end-to-end anastomosis. CRT simulation was performed on 2 sham groups before the anastomosis, and 1 of these groups was administered additional postoperative HBOT. Two groups were administered CRT before the anastomosis, and 1 of them received additional postoperative HBOT. On postoperative day 5, all groups underwent relaparotomy; burst pressure was measured and samples were obtained for histopathologic and biochemical analysis. There was a significant weight loss in the CRT groups and postoperative HBOT had an improving effect. Significantly decreased burst pressure values increased up to the levels of the controls after HBOT. Hydroxyproline levels were elevated in all groups compared to the control group. Hydroxyproline levels decreased with HBOT after CRT. No significant difference was observed between the groups regarding fibrosis formation at the anastomosis site. However, regression was observed in fibrosis in the group receiving HBOT after CRT. Preoperative CRT affected anastomosis and wound healing unfavorably. These unfavorable effects were alleviated by postoperative HBOT. HBOT improved the mechanical and biochemical parameters of colon anastomosis in rats. PMID:23438274

  10. Usefulness of Prophylactic Percutaneous Gastrostomy Placement in Patients with Head and Neck Cancer Treated with Chemoradiotherapy.

    PubMed

    Moleiro, Joana; Faias, Sandra; Fidalgo, Catarina; Serrano, Miguel; Pereira, A Dias

    2016-02-01

    Chemoradiotherapy (CRT) has evolved as the preferred organ preservation strategy in the treatment of locally advanced head and neck cancer (HNC). This approach increases malnutrition, and thus, establishing a direct enteral feeding route is essential. To evaluate the usefulness of prophylactic percutaneous endoscopic gastrostomy (PEG) in HNC patients receiving definitive CRT, we performed a prospective evaluation of HNC patients over a 6-month period. Patients and tumor characteristics, nutritional status 30 days after PEG insertion and technique complications were evaluated. We also assessed the long-term PEG usage. Forty-seven PEGs were placed and only 2 patients did not use it. The mean time of PEG use was 131 days (4-255) and mean duration of exclusive utilization was 71 days (4-180). On 30th day after procedure, 34/45 (76 %) patients had lost weight, but only 10/45 (22 %) patients had lost more than 10 % of their initial weight. The most frequent complications were minor peristomal infections, which were correlated with proton-pump inhibitor use before PEG placement (OR 3.91, 95 % CI 1.01-15.2, and p = 0.049). One year later, 19 % of patients in remission continue needing PEG. Enteric nutritional support is essential during and after CRT in HNC patients. Most patients lost weight even with PEG. One-fifth of patients in remission required long-term PEG utilization. PMID:26487063

  11. Recursive Partitioning Analysis for New Classification of Patients With Esophageal Cancer Treated by Chemoradiotherapy

    SciTech Connect

    Nomura, Motoo; Shitara, Kohei; Kodaira, Takeshi; Kondoh, Chihiro; Takahari, Daisuke; Ura, Takashi; Kojima, Hiroyuki; Kamata, Minoru; Muro, Kei; Sawada, Satoshi

    2012-11-01

    Background: The 7th edition of the American Joint Committee on Cancer staging system does not include lymph node size in the guidelines for staging patients with esophageal cancer. The objectives of this study were to determine the prognostic impact of the maximum metastatic lymph node diameter (ND) on survival and to develop and validate a new staging system for patients with esophageal squamous cell cancer who were treated with definitive chemoradiotherapy (CRT). Methods: Information on 402 patients with esophageal cancer undergoing CRT at two institutions was reviewed. Univariate and multivariate analyses of data from one institution were used to assess the impact of clinical factors on survival, and recursive partitioning analysis was performed to develop the new staging classification. To assess its clinical utility, the new classification was validated using data from the second institution. Results: By multivariate analysis, gender, T, N, and ND stages were independently and significantly associated with survival (p < 0.05). The resulting new staging classification was based on the T and ND. The four new stages led to good separation of survival curves in both the developmental and validation datasets (p < 0.05). Conclusions: Our results showed that lymph node size is a strong independent prognostic factor and that the new staging system, which incorporated lymph node size, provided good prognostic power, and discriminated effectively for patients with esophageal cancer undergoing CRT.

  12. Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

    SciTech Connect

    Bentzen, Anne Gry; Guren, Marianne G.; Wanderas, Eva H.; Frykholm, Gunilla; Tveit, Kjell M.; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

    2012-06-01

    Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

  13. Motor and cognitive testing of bone marrow transplant patients after chemoradiotherapy

    NASA Technical Reports Server (NTRS)

    Parth, P.; Dunlap, W. P.; Kennedy, R. S.; Ordy, J. M.; Lane, N. E.

    1989-01-01

    Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.

  14. Postoperative chemoradiotherapy versus radiotherapy alone for cervical cancer: A systematic review and meta-analysis.

    PubMed

    Yang, Jialin; Yin, Jun; Yan, Gaoshu; Huang, Dandan; Wang, Jichuan

    2016-07-01

    The aim of this study was to compare the treatment outcomes of postoperative chemoradiotherapy (CRT) with radiotherapy (RT) alone in patients with cervical cancer. Based on articles published up to December 2014 a literature search in PubMed and EMBASE was conducted to identify eligible studies. Risk ratio (RR) and its 95% confidence interval (CI) were used as pooled statistics. A total of 4 articles consisting of 461 patients were selected for the meta-analysis. Results revealed that there were a significant overall survival improvements (RR = 1.35, 95% CI: 1.15-1.60, p = 0.0003), a significant reduction of local recurrence (RR = 0.26, 95% CI: 0.14-0.51, p < 0001) and distant recurrence (RR = 0.41, 95% CI: 0.26-0.63, p < 0.0001) in the patients who received postoperative CRT, comparing with the patients who received RT alone. In conclusion, the results suggest a significant benefit of CRT for patients with cervical cancer, comparing with RT alone treatment. PMID:26821995

  15. Clinical Parameters Predicting Pathologic Tumor Response After Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yoon, Sang Min; Kim, Dae Yong Kim, Tae Hyun; Jung, Kyung Hae; Chang, Hee Jin; Koom, Woong Sub; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-11-15

    Purpose: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. Methods and Materials: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). Conclusions: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

  16. Complete response of giant desmoplastic small round cell tumor treated with chemoradiotherapy: A case report

    PubMed Central

    ZHANG, SHUO; ZHANG, YONG; YU, YONG-HUA; LI, JIA

    2016-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare tumor that mainly affects adolescents, and typically involves the abdominal and pelvic peritoneum. The present study reports one case of giant DSRCT, treated with concurrent chemoradiotherapy, and reviews the available medical literature. A 38-year-old man presented with a 3-month history of pain in the left lower abdomen and nausea, associated with decreased appetite and weight loss. Computed tomography (CT) showed a 12.3×7.9 cm confluent solid mass in the lower abdomen and pelvic cavity. The patient underwent exploratory laparotomy and the final pathological diagnosis was DSRCT. Following laparotomy, the patient was treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 40 Gy plus a 20 Gy boost to the residual disease. The results indicated that synchronous chemotherapy with cyclophosphamide, adriamycin and cisplatin combined with radiotherapy significantly improved locoregional control of DSRCT and a complete response, as measured by CT assessment 2 months subsequent to radiotherapy. In conclusion, DSRCT is a rare malignancy requiring multidisciplinary treatment, including surgery, chemotherapy and radiotherapy. The results of the present study confirm that radiotherapy has a significant role in the treatment of advanced abdominal DSRCT and may contribute to durable remission. PMID:26893693

  17. Preoperative chemoradiotherapy followed by transanal local excision for T3 distal rectal cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2016-01-01

    Local excision (LE) for rectal cancer is currently indicated for selected T1 stage tumors. However, preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves local disease control, but also leads to a decrease in the stage and size of the primary mural tumor, along with a decrease in the risk of regional lymphadenopathy. The present study reports the outcome of a patient with T3N0M0 rectal cancer who was treated with LE following preoperative CRT. The distal pole of the tumor was located 2 cm from the anal verge. Preoperative pelvic radiotherapy of 50.4 Gy was administered in 28 fractions. Chemotherapy using 5-fluorouracil and leucovorin was administered during the first and last weeks of radiotherapy. The tumor response to CRT, was found to be marked at 7 weeks after CRT completion, and a complete response was presumed clinically. Transanal full-thickness LE was performed, and pathological examination revealed the absence of residual cancer cells. After 30 months of close follow-up, the patient was alive with no evidence of disease, and treatment-associated severe toxicities were not observed. Although a longer follow-up period is required, this case report suggests that LE may also be a feasible alternative treatment for T3 rectal cancer, which exhibits a marked response to preoperative CRT, particularly in elderly and comorbid patients contraindicated for radical surgery, or patients who are reluctant to undergo sphincter-ablation surgery. PMID:27073466

  18. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  19. Attention's Accelerator.

    PubMed

    Reinhart, Robert M G; McClenahan, Laura J; Woodman, Geoffrey F

    2016-06-01

    How do people get attention to operate at peak efficiency in high-pressure situations? We tested the hypothesis that the general mechanism that allows this is the maintenance of multiple target representations in working and long-term memory. We recorded subjects' event-related potentials (ERPs) indexing the working memory and long-term memory representations used to control attention while performing visual search. We found that subjects used both types of memories to control attention when they performed the visual search task with a large reward at stake, or when they were cued to respond as fast as possible. However, under normal circumstances, one type of target memory was sufficient for slower task performance. The use of multiple types of memory representations appears to provide converging top-down control of attention, allowing people to step on the attentional accelerator in a variety of high-pressure situations. PMID:27056975

  20. Induction chemoradiotherapy is superior to induction chemotherapy for the survival of non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis

    PubMed Central

    Toyooka, Shinichi; Kiura, Katsuyuki; Shien, Kazuhiko; Katsui, Kuniaki; Hotta, Katsuyuki; Kanazawa, Susumu; Date, Hiroshi; Miyoshi, Shinichiro

    2012-01-01

    OBJECTIVES The purpose of this study was to compare the clinical outcomes of induction chemoradiotherapy and chemotherapy and to identify the prognostic factors for non-small-cell lung cancer patients with mediastinal lymph node metastasis who were treated with induction therapy. METHODS Between August 1995 and December 2010, 50 non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis were scheduled to receive induction therapy followed by surgery. Irinotecan plus cisplatin was used for induction chemotherapy from June 1995 to April 1999, and docetaxel plus cisplatin with concurrent radiation at a dose of 40–46 Gy has been used for induction chemoradiotherapy since May 1999. RESULTS Thirty-five patients were treated with induction chemoradiotherapy and 15 were treated with induction chemotherapy. For the entire population, the 3-year and 5-year overall survival rates were 64.1 and 53.9%, respectively, and the 1-year and 2-year disease-free survival rates were 70.0 and 53.1%, respectively. Among the clinicopathological factors, the chemoradiotherapy group exhibited longer overall survival and disease-free survival than the chemotherapy group (overall survival, P = 0.0020; disease-free survival, P = 0.015). Pathological downstaging was also significantly associated with favorable overall survival (P = 0.0042) and disease-free survival (P = 0.021). A multivariate analysis showed that chemoradiotherapy (P = 0.0099) and pathological downstaging (P = 0.039) were independent prognostic factors. CONCLUSIONS Our results indicated that induction chemoradiotherapy was superior to induction chemotherapy with regard to the outcome of non-small-cell lung cancer patients with mediastinal lymph node metastasis. PMID:22976995

  1. Pros: concurrent chemo-radiotherapy remains the ideal treatment in fit patients with large volume unresectable stage III non-small cell lung cancer

    PubMed Central

    Rabatic, Bryan M.

    2016-01-01

    The debate of treating stage III, large volume non-small cell lung cancer (NSCLC) with definitive chemo-radiotherapy continues to be waged. A physically fit patient, having large volume and unresectable disease is the ideal candidate for this treatment approach. The ability of this patient population to successfully complete, and thereby benefit from an aggressive, combined treatment to improve local control and survival, drives the recommendation of treating oncologists for this approach. Until a phase III trial proves otherwise, concurrent chemo-radiotherapy will remain the ideal treatment for fit patients having large volume unresectable stage III NSCLC. PMID:27186513

  2. Study to Determine Adequate Margins in Radiotherapy Planning for Esophageal Carcinoma by Detailing Patterns of Recurrence After Definitive Chemoradiotherapy

    SciTech Connect

    Button, Michael R. Morgan, Carys A.; Croydon, Elizabeth S.; Roberts, S. Ashley; Crosby, Thomas D.L.

    2009-03-01

    Purpose: To ascertain the adequacy of radiotherapy (RT) margins by studying the relapse patterns after definitive chemoradiotherapy for carcinoma of the esophagus. Methods and Materials: We performed a retrospective study assessing the first site of disease relapse after definitive chemoradiotherapy that included four 3-weekly cycles of cisplatin and continuous infusion 5-fluorouracil, with conformal RT (50 Gy in 25 fractions) concurrent with Cycles 3 and 4. The RT planning target volume was the endoscopic ultrasonography/computed tomography-defined gross tumor volume with 1.5-cm lateral and 3-cm superoinferior margins. Results: A total of 145 patients were included. Their average age was 65.4 years, 45% had adenocarcinoma, 61% had lower third esophageal tumors, and 75% had Stage III-IVA disease. After RT, of 142 patients, 85 (60%) had evidence of relapse at a median follow-up of 18 months. The relapse was local (within the RT field) in 55; distant (metastatic) in 13, and a combination of local and distant in 14. The local relapse rates were not influenced by tumor stage, lymph node status, or disease length. Three patients developed a relapse in regions adjacent to the RT fields; however, it is unlikely that larger field margins would have been clinically acceptable or effective in these cases. The median overall survival was 15 months. Conclusion: The gross tumor volume-planning target volume margins in this study appeared adequate. Future efforts to improve outcomes using definitive chemoradiotherapy should be directed toward reducing the high rates of in-field and distant relapses.

  3. Evaluating the Role of Prophylactic Gastrostomy Tube Placement Prior to Definitive Chemoradiotherapy for Head and Neck Cancer

    SciTech Connect

    Chen, Allen M.; Li Baoqing; Lau, Derick H.; Farwell, D. Gregory; Luu, Quang; Stuart, Kerri; Newman, Kathleen; Purdy, James A.; Vijayakumar, Srinivasan M.D.

    2010-11-15

    Purpose: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. Methods and Materials: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. Results: Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). Conclusions: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.

  4. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy

    PubMed Central

    Song, Yong-xi; Sun, Jing-xu; Chen, Xiao-wan; Zhao, Jun-hua; Ma, Bin; Wang, Jun; Wang, Zhen-ning

    2016-01-01

    Background Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992–2009. We enrolled patients with yp stages I–III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan–Meier survival analysis with propensity score-matching and Cox proportional hazards models. Results Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN− patients, and oxaliplatin did not significantly improve OS, regardless of age. Conclusions In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN− patients. PMID:26910371

  5. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  6. Acute Cardiac Impairment Associated With Concurrent Chemoradiotherapy for Esophageal Cancer: Magnetic Resonance Evaluation

    SciTech Connect

    Hatakenaka, Masamitsu; Yonezawa, Masato; Nonoshita, Takeshi; Nakamura, Katsumasa; Yabuuchi, Hidetake; Shioyama, Yoshiyuki; Nagao, Michinobu; Matsuo, Yoshio; Kamitani, Takeshi; Higo, Taiki; Nishikawa, Kei; Setoguchi, Taro; Honda, Hiroshi

    2012-05-01

    Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference

  7. Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

    SciTech Connect

    Folkvord, Sigurd; Flatmark, Kjersti; Dueland, Svein

    2010-10-01

    Purpose: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Methods and Materials: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. Results: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Conclusions: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

  8. Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer

    PubMed Central

    INOUE, YASUHIRO; SAIGUSA, SUSUMU; HIRO, JUNICHIRO; TOIYAMA, YUJI; ARAKI, TOSHIMITSU; TANAKA, KOJI; MOHRI, YAUSHIKO; KUSUNOKI, MASATO

    2016-01-01

    Preoperative chemoradiotherapy (CRT) with total mesorectal excision (TME) is the widely accepted treatment for rectal cancer (RC) in Western countries. However, there remains controversy as to whether preoperative CRT is useful in tumors that extend beyond the mesorectum, including metastasis to the lateral pelvic lymph nodes (LPLN). The aim of this study was to assess the prognostic significance of LPLN enlargement in patients with RC who receive preoperative CRT followed by TME without LPLN dissection. We evaluated the prognostic effect of radiographic LPLN enlargement before and after CRT, as well as the patients' clinicopathological and genetic profiles. Of the 104 patients investigated, pretreatment imaging identified 19 (18%) as LPLN-positive (>7 mm in diameter). Of these 19 patients, 7 (37%) exhibited LPLN downsizing to <7 mm following CRT. The median follow-up period was 52 months. The 5-year cancer-specific survival (CSS) or relapse-free survival (RFS) did not differ significantly between patients who did and those who did not have positive LPLN on pretreatment imaging. However, LPLN that remained positive after CRT were significantly associated with poorer 5-year CSS (73 vs. 84%, respectively; P=0.0052) and RFS (32 vs. 78%, respectively; P=0.0264). None of the patients whose LPLN were downsized to <7 mm following CRT developed recurrence; however, those with positive LPLN after CRT had a 55% higher recurrence rate, characterized by delayed local recurrence, a pattern that may be affected by certain chemokines. In conclusion, changes in initially positive LPLN (>7 mm) may predict the prognosis of patients with RC who receive preoperative CRT-TME. LPLN positivity after CRT was associated with shorter CSS and RFS. Strategies to improve patient survival may include selective LPLN dissection or more aggressive multimodality therapy. PMID:27313860

  9. Involved-field irradiation in definitive chemoradiotherapy for T4 squamous cell carcinoma of the esophagus

    PubMed Central

    Li, M.; Zhao, F.; Zhang, X.; Shi, F.; Zhu, H.; Han, A.; Zhang, Y.; Kong, L.; Yu, J.

    2016-01-01

    Objectives Definitive concurrent chemoradiotherapy (ccrt) is currently a therapeutic option for locally advanced esophageal cancer. However, clinical practice differs with respect to the target volume for irradiation. The purpose of the present study was to analyze failure patterns and survival, and to determine the feasibility of using involved-field irradiation (ifi) with concurrent chemotherapy for T4 squamous cell carcinoma (scc) of the esophagus. Methods Between January 2003 and January 2013, 56 patients with clinical T4M0 scc of the esophagus received ccrt using ifi. The radiation field included the primary tumour and clinically involved lymph nodes. Target volumes and sites of failure were analyzed, as were treatment-related toxicity and survival time. Results In this 56-patient cohort, 13 patients (23.2%) achieved a complete response, and 21 (37.5%) achieved a partial response, for a total response rate of 60.7%. The major toxicities experienced were leucocytopenia and esophagitis, with 14 patients (25.0%) experiencing grade 3 toxicities. At a median follow-up of 34 months, 48 patients (85.7%) had experienced failure: 39 (69.6%) in-field, 7 (12.5%) elective nodal, and 19 (33.9%) distant. Only 1 patient (1.8%) experienced isolated elective nodal failure. The 1-, 2-, and 3-year survival rates were 39.3%, 21.4%, and 12.5% respectively. Conclusions For patients with T4M0 scc of the esophagus, definitive ccrt using ifi resulted in an acceptable rate of isolated elective nodal failure and an overall survival comparable to that achieved with elective nodal irradiation. A limited radiation therapy target volume, including only clinically involved lesions, would therefore be a feasible choice for this patient subgroup. PMID:27122981

  10. Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy

    PubMed Central

    Crvenkova, Simonida

    2015-01-01

    BACKGROUND: According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer. AIM: To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy. MATERIAL AND METHODS: In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT. RESULTS: From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05. CONCLUSION: In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated

  11. Cost-effectiveness of para-aortic lymphadenectomy before chemoradiotherapy in locally advanced cervical cancer

    PubMed Central

    Lee, Jung-Yun; Kim, Younhee; Lee, Tae-Jin; Jeon, Yong Woo; Kim, Kidong; Chung, Hyun Hoon; Park, Sang Min; Kim, Jae-Weon

    2015-01-01

    Objective To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). Methods A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. Results We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was $19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of $60,000/QALY. Conclusion Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines. PMID:25925292

  12. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  13. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

    SciTech Connect

    Kim, Dae Yong; Jung, Kyung Hae . E-mail: khjung@ncc.re.kr; Kim, Tae Hyun; Kim, Duck-Woo; Chang, Hee Jin; Jeong, Jun Yong; Kim, Young Hoon; Son, Seok-Hyun; Yun, Tak; Hong, Chang Won; Sohn, Dae Kyung; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-02-01

    Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% {+-} 20.5% in the FL group and 68.3% {+-} 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

  14. What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy?

    PubMed Central

    Kim, Soo Hee; Chang, Hee Jin; Kim, Dae Yong; Park, Ji Won; Baek, Ji Yeon; Kim, Sun Young; Park, Sung Chan; Oh, Jae Hwan; Yu, Ami; Nam, Byung-Ho

    2016-01-01

    Purpose Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. Materials and Methods This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. Results All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. Conclusion The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone. PMID:26511803

  15. Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study

    PubMed Central

    Choi, Younak; Oh, Do-Youn; Kim, Kyubo; Chie, Eui Kyu; Kim, Tae-Yong; Lee, Kyung-Hun; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Ha, Sung Whan; Bang, Yung-Jue

    2016-01-01

    Purpose The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively. Results Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone. PMID:26511805

  16. Survival implications of pretreatment pelvic CT in rectal cancer patients after neoadjuvant chemoradiotherapy and surgery

    PubMed Central

    Cui, Chunyan; Zhang, Min; Tian, Li; Jiang, Wu; Zeng, Zhifang; Li, Li

    2015-01-01

    Purpose: To determine the correlation between pretreatment computed tomography (CT) data and survival duration after neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. Materials and methods: 122 consecutive patients with advanced rectal cancer were assessed retrospectively. Pretreatment imaging and postoperative data were evaluated through Kaplan-Meier and Cox proportional hazard regression analyses. Results: Pretreatment CT identified 557 metastatic lymph nodes (mean, 4.55 per patient; median 4). Survival durations were measured during the period between the application of CT and death or the last follow-up examination. Univariate analysis showed that the following factors had a significant impact on survival: maximum tumor diameter (P = 0.019), distance from inferior tumor margin to anorectal ring (P <0.0001), number of lymph nodes involved in patients with short-axis, lymph node diameter ≥8 mm (P <0.0001) in pretreatment CT, distance from the anorectal ring (P = 0.027), ypN stage (P = 0.0008), ypM stage (P = 0.046) and number of metastatic lymph nodes (P <0.0001) in clinical assessment. Multivariate analysis showed that the following factors were significant: number of lymph nodes in patients with short-axis lymph node diameter ≥5 mm but <8 mm (P = 0.044) and in those with this diameter ≥8 mm (P = 0.028; pretreatment CT) and number of metastatic lymph nodes (assessed in histopathological examination). Conclusion: Pretreatment lymph node size and number can predict survival duration after treatment for locally advanced rectal cancer. For patients with lymph nodes >8 mm (short-axis diameter) and/or >1, such lymph nodes tend to have a poor performance for prognosis. PMID:26550194

  17. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: a single center experience

    PubMed Central

    Choi, Euncheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results. PMID:27306776

  18. Treatment results of chemoradiotherapy for clinical stage I (Taman) esophageal carcinoma

    SciTech Connect

    Yamada, Kazunari . E-mail: kyamada-rad@umin.ac.jp; Murakami, Masao; Okamoto, Yoshiaki; Okuno, Yoshishige; Nakajima, Toshifumi; Kusumi, Fusako; Takakuwa, Hiroshi; Matsusue, Satoru

    2006-03-15

    Purpose: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (Crt) for clinical Stage I (Taman) esophageal cancer. Patients and Methods: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T 1a) in 23 and submucosal cancer (T 1b) in 40. Crt consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. Results: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T 1a and T 1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T 1a and T 1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G: 1; G: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. Conclusion: We confirmed that patients with Taman esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive Crt, and the survival rates were equivalent to those of previous reports of surgery.

  19. Is Adjuvant Chemoradiotherapy Overtreatment in Cervical Cancer Patients With Intermediate Risk Factors?

    SciTech Connect

    Ryu, Sang-Young; Park, Sang-Il; Nam, Byung-Ho; Cho, Chul-Koo; Kim, Kidong; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Lee, Eui-Don; Lee, Kyoung-Hee

    2011-03-01

    Purpose: To determine whether adjuvant chemoradiotherapy (CRT) improves the outcome of cervical cancer patients with intermediate risk factors. Methods and Materials: Between January 2000 and June 2006, the medical records of 735 patients who had undergone radical surgery for Stage IB-IIA cervical cancer were reviewed retrospectively. Of the 735 patients, 172 with two or more intermediate risk factors (i.e., lymphovascular space involvement, deep stromal invasion, and tumor size {>=}2 cm) were grouped as follows according to the adjuvant treatment received: 34 patients, no further treatment; 49 patients, RT; and 89 patients, CRT. The significance of the clinical parameters and recurrence-free survival of each group were analyzed. Results: Of the 172 patients with any of the intermediate risk factors, 137 (79.6%) had two or more intermediate risk factors. Of the 172 patients, 12 developed recurrences (6.4%)->(7.0%), with 6 in the pelvis and 6 in distant sites. All 12 recurrences occurred in those who had two or more intermediate risk factors (sensitivity, 100%); however, only six recurrences were detected in patients who met the Gynecologic Oncology Group criteria for the intermediate-risk group (sensitivity, 50%; Z test, p < .05). A statistically significant difference was found in the 3-year recurrence-free survival rate among the no further treatment, RT, and CRT groups (67.5%, 90.5%, and 97.5%, respectively; p < .05). The incidence of Grade 3-4 hematologic and gastrointestinal toxicities was not significantly different statistically between the RT and CRT groups (6.1% and 13.4%, respectively; p > .05). Conclusion: Postoperative adjuvant CRT can improve the outcome of cervical cancer patients with intermediate risk factors, with low increase in toxicity.

  20. Hearing and tinnitus in head and neck cancer patients after chemoradiotherapy.

    PubMed

    Niemensivu, Riina; Saarilahti, K; Ylikoski, J; Aarnisalo, A; Mäkitie, A A

    2016-09-01

    Head and neck cancer patients treated with high-dose cisplatin and radiotherapy will suffer from hearing deficits. The current low-dose regimen seldom causes hearing threshold decrease. Tinnitus in this patient population has not been investigated earlier. We aimed to evaluate the possible ototoxicity of low-dose (40 mg/m(2)) weekly administered cisplatin with concomitant radiotherapy. Twenty-two patients with locally advanced head and neck cancer were prospectively recruited to participate the study after treatment recommendation for chemoradiotherapy with low-dose cisplatin and intensity-modulated radiotherapy. They filled in a Tinnitus Handicap Inventory and undertook audiologic evaluations before and after treatment. Ototoxicity was determined by >10 dB threshold shift at frequencies 4 and 8 kHz or in pure tone average. A historical cohort of nine patients treated with high-dose (100 mg/m(2)) cisplatin and radiotherapy was used for comparison. After treatment, study patients demonstrated no significant changes in their hearing over frequencies 0.5-4 kHz, and the threshold shifts were minor at 4 and 8 kHz. More than 50 % of patients reported no tinnitus after treatment and the remainder only had slight to moderate tinnitus causing no interference with their daily activities. In contrast, five of the nine patients having received high-dose cisplatin reported disturbing tinnitus. Further, changes in pure tone averages were exhibited in three of these patients and six had significant threshold shifts at 4 and 8 kHz. Head and neck cancer patients treated with concomitant intensity-modulated radiotherapy and low-dose cisplatin seem to experience only minor audiological sequelae and therefore, these patients appear to require no routine audiological monitoring. Such evaluation could be performed only when needed. PMID:26685859

  1. Progress on plasma accelerators

    SciTech Connect

    Chen, P.

    1986-05-01

    Several plasma accelerator concepts are reviewed, with emphasis on the Plasma Beat Wave Accelerator (PBWA) and the Plasma Wake Field Accelerator (PWFA). Various accelerator physics issues regarding these schemes are discussed, and numerical examples on laboratory scale experiments are given. The efficiency of plasma accelerators is then revealed with suggestions on improvements. Sources that cause emittance growth are discussed briefly.

  2. Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy.

    PubMed

    Sato, Atsushi; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Minegishi, Masayoshi; Iinuma, Kazuie; Imaizumi, Masue

    2006-12-01

    Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n = 12) or single prophylaxis (n = 5), or left untreated (n = 7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. PMID:17146197

  3. Role of nutritional status and intervention in oesophageal cancer treated with definitive chemoradiotherapy: outcomes from SCOPE1

    PubMed Central

    Cox, S; Powell, C; Carter, B; Hurt, C; Mukherjee, Somnath; Crosby, Thomas David Lewis

    2016-01-01

    Background: Malnutrition is common in oesophageal cancer. We aimed to identify nutritional prognostic factors and survival outcomes associated with nutritional intervention in the SCOPE1 (Study of Chemoradiotherapy in OesoPhageal Cancer with or without Erbitux) trial. Methods: Two hundred and fifty eight patients were randomly allocated to definitive chemoradiotherapy (dCRT) +/− cetuximab. Nutritional Risk Index (NRI) scores were calculated; NRI<100 identified patients at risk of malnutrition. Nutritional intervention included dietary advice, oral supplementation or major intervention (enteral feeding/tube placement). Univariable and multivariable analyses using Cox proportional hazard modelling were conducted. Results: At baseline NRI<100 strongly predicted for reduced overall survival (hazard ratio (HR) 12.45, 95% CI 5.24–29.57; P<0.001). Nutritional intervention improved survival if provided at baseline (dietary advice (HR 0.12, P=0.004), oral supplementation (HR 0.13, P<0.001) or major intervention (HR 0.13, P=0.003)), but not if provided later in the treatment course. Cetuximab patients receiving major nutritional intervention had worse outcomes compared with controls (13 vs 28 months, P=0.003). Conclusions: Pre-treatment assessment and correction of malnutrition may improve survival outcomes in oesophageal cancer patients treated with dCRT. Nutritional Risk Index is a simple and objective screening tool to identify patients at risk of malnutrition. PMID:27328311

  4. The Long-Term Outcomes of Induction Chemoradiotherapy Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Uramoto, Hidetaka; Akiyama, Hirohiko; Nakajima, Yuki; Kinoshita, Hiroyasu; Inoue, Takuya; Kurimoto, Futoshi; Nishimura, Yu; Saito, Yoshihiro; Sakai, Hiroshi; Kobayashi, Kunihiko

    2014-01-01

    Background Although the concept of induction therapy followed by surgical resection for locally advanced non-small cell lung cancer (LA-NSCLC) has found general acceptance, the appropriate indications and the strategy for this treatment are still controversial. Methods From 2000 through 2008, 36 patients received concurrent chemoradiotherapy followed by surgery. We retrospectively reviewed these cases, analyzed the outcomes and examined the prognosis. Results The median radiation dose given was 60 Gy. Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered to 9 cases, and a carboplatin-based chemotherapy regimen was administered to 27. A complete resection was performed in 94% of the patients. Seventeen (47.2%) patients exhibited a complete pathological response, and downstaging was induced in 26 (72%) cases. The morbidity and 30-day mortality rates were 11.1 and 0%, respectively. The 5-year overall survival rate in the patients with complete resection (n = 33) was 83.3%. Conclusions Induction chemoradiotherapy followed by surgery for LA-NSCLC provided a favorable prognosis for selected patients. A complete pathological response was found in about half of cases. This strategy is feasible and was associated with low morbidity and high resectability rates, suggesting that it contributed to improving the treatment results. PMID:25493083

  5. Successful Chemo-Radiotherapy for Primary Anaplastic Large Cell Lymphoma of the Lung: A Case Report and Literature Review

    PubMed Central

    Zhao, Qian; Liu, Yongmei; Chen, Huijiao; Zhang, Yan; Du, Zedong; Wang, Jin; Wang, Yongsheng

    2016-01-01

    Patient: Male, 39 Final Diagnosis: Primary anaplastic large cell lymphoma of the lung Symptoms: Hemoptysis • palpitation • shortness of breath Medication: Cyclophosphamide • Doxorubicin • Vincristine • Prednisone Clinical Procedure: Chemoradiotherapy Specialty: Oncology Objective: Rare disease Background: Primary anaplastic large cell lymphoma (ALCL) of the lung is an extremely rare disease. This disease is a great challenge for pneumologists due to its nonspecific clinical presentations and radiological findings. Appropriate invasive biopsy and immunohistochemistry are important for diagnosis. There is currently no standard treatment. Case Report: We report a very rare case of primary pulmonary ALCL in a 39-year-old man. The clinical features, imaging, pathological findings, treatment outcomes, and prognosis, are described. Successful treatment outcomes were achieved after 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed by involved field radiotherapy of 54Gy/27f. The patient was disease-free after follow-up for 65 months. Conclusions: Our study found that chemotherapy (such as CHOP) is recognized as the first-line regimen for primary ALCL of the lung. For patients with dyspnea caused by a mass blocking the main bronchus, chemoradiotherapy may be a reasonable therapeutic option. The prognosis is better for patients with positive ALK staining. CD56(+), age older than 60 years, Ann Arbor stage III or IV, survivin expression, PS>2, and high serum LDH level and IPI scores are the poor prognostic factors of ALCL. PMID:26852792

  6. The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study

    PubMed Central

    Fuwa, Nobukazu; Kodaira, Takeshi; Daimon, Takashi; Yoshizaki, Tomokazu

    2015-01-01

    To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0–2, 18–70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m2 per 24 h on days 1–5) and cisplatin (100 mg/m2 per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1∼87.0%), and 68.74% (95% CI: 58.8∼78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC. PMID:25991077

  7. The Effect of Topical Application of Royal Jelly on Chemoradiotherapy-Induced Mucositis in Head and Neck Cancer: A Preliminary Study

    PubMed Central

    Kogashiwa, Yasunao; Moro, Yorihisa; Kohno, Naoyuki

    2014-01-01

    Purpose. One of the common side effects experienced by head and neck cancer patients on chemoradiotherapy is mucositis. Severe mucositis may be controllable by limiting cancer therapy, but it has resulted in decreasing the completion rate of chemoradiotherapy. The efficacy of royal jelly (RJ) as prophylaxis against chemoradiotherapy-induced mucositis was evaluated through clinical scoring of oral and pharyngeal mucositis. Methods. In this randomized, single-blind (physician-blind), clinical trial, 13 patients with head and neck cancer requiring chemoradiation were randomly assigned to two groups. Seven patients assigned to the study group received RJ, and 6 patients were assigned to the control group. RJ group patients took RJ three times per day during treatment. The patients in both groups were evaluated twice a week for the development of mucositis using Common Terminology Criteria for Adverse Events version 3.0. Results. A significant reduction in mucositis was seen among RJ-treated patients compared with controls (P < 0.001). Conclusion. This study demonstrated that prophylactic use of RJ was effective in reducing mucositis induced by chemoradiotherapy in head and neck cancer patients. However, further studies are needed because of the small sample size and the absence of double blinding. PMID:25400667

  8. An observational study of extending FOLFOX chemotherapy, lengthening the interval between radiotherapy and surgery, and enhancing pathological complete response rates in rectal cancer patients following preoperative chemoradiotherapy

    PubMed Central

    Huang, Chun-Ming; Huang, Ming-Yii; Tsai, Hsiang-Lin; Huang, Ching-Wen; Ma, Cheng-Jen; Yeh, Yung-Sung; Juo, Suh-Hang; Huang, Chih-Jen; Wang, Jaw-Yuan

    2016-01-01

    Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients. Methods: A total of 78 patients with rectal cancer were enrolled. Patients were administered chemoradiotherapy, which comprised radiotherapy and chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Surgery was performed 10–12 weeks after radiotherapy completion. Tumor regression, adverse events, surgical complications, and short-term clinical outcomes were recorded. Results: Two patients were excluded because of incomplete radiotherapy treatment or refusal of surgery. Eventually, 76 patients underwent total mesorectal excision and no perioperative mortality was observed. Of these, 20 patients (25.6%) developed grade 3 or 4 toxicity during concurrent chemoradiotherapy. Among the 76 patients who underwent surgery, 24 (31.6%) patients achieved a pathologic complete response. The sphincter preservation rate was 96.1% (73/76) in all patients and 92.2% (39/42) in patients with tumors located less than 5 cm from the anal verge. The 2-year overall and disease-free survivals were 94% and 87.4%, respectively. Conclusion: The intensified multimodality therapy was well tolerated in our cohort and resulted in a considerably high pathologic complete response rate. Regardless of favorable short-term clinical outcomes, long-term oncologic outcomes will be closely monitored among the patients with a pathologic complete response. PMID:27582883

  9. A Randomized, Double-Blind Pilot Trial of Hydrolyzed Rice Bran versus Placebo for Radioprotective Effect on Acute Gastroenteritis Secondary to Chemoradiotherapy in Patients with Cervical Cancer

    PubMed Central

    Itoh, Yoshiyuki; Mizuno, Mika; Ikeda, Mitsuru; Nakahara, Rie; Kubota, Seiji; Ito, Junji; Okada, Tohru; Kawamura, Mariko; Kikkawa, Fumitaka; Naganawa, Shinji

    2015-01-01

    We aimed to evaluate the radioprotective effect of hydrolyzed rice bran (HRB) on acute gastroenteritis due to chemoradiotherapy for treatment of cervical cancer. This placebo-controlled, double-blind study was conducted as an exploratory investigation of the colitis-inhibiting effects of HRB in alleviating acute-phase gastrointestinal side effects of chemoradiotherapy. The study involved 20 patients (10 in the HRB group, 10 in the control group). The patients in the control group underwent the same chemoradiotherapy regimen as those in the HRB group, but they received a placebo instead of HRB. The diarrheal side effect assessment score was lower in the HRB than control group, and a trend toward a reduction in diarrhea symptoms was observed with the oral intake of HRB. Additionally, no significant difference was observed in the administration of intestinal regulators and antidiarrheal agents, but again the assessment score was lower in the HRB than control group, and diarrhea symptoms were alleviated with the oral intake of HRB. A trend toward no need for strong antidiarrheal agents was seen. Although this study was an exploratory clinical trial, the results suggest that HRB may relieve diarrhea, an acute-phase gastrointestinal side effect of chemoradiotherapy. PMID:26693248

  10. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-02-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m{sup 2}]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade >=3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  11. Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer

    PubMed Central

    Corso, Christopher D.; Rutter, Charles E.; Park, Henry S.; Lester-Coll, Nataniel H.; Kim, Anthony W.; Wilson, Lynn D.; Husain, Zain A.; Lilenbaum, Rogerio C.; Yu, James B.; Decker, Roy H.

    2015-01-01

    Purpose To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database. Patients and Methods Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching. Results A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01). Conclusion In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach. PMID:26481366

  12. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402

    PubMed Central

    Cairncross, Gregory; Wang, Meihua; Shaw, Edward; Jenkins, Robert; Brachman, David; Buckner, Jan; Fink, Karen; Souhami, Luis; Laperriere, Normand; Curran, Walter; Mehta, Minesh

    2013-01-01

    Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis. PMID:23071247

  13. PET/CT with Fluorodeoxyglucose During Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    Travaini, Laura L; Zampino, Maria G; Colandrea, Marzia; Ferrari, Mahila E; Gilardi, Laura; Leonardi, Maria C; Santoro, Luigi; Orecchia, Roberto; Grana, Chiara M

    2016-01-01

    Objective The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. Patients and methods Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. Results Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and posttreatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). Conclusions [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant

  14. Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M.; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

    2012-06-01

    Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T{sub 2}- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm{sup 2}/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs (<1.0 Multiplication-Sign 10{sup -3}mm{sup 2}/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC {>=}1.4 Multiplication-Sign 10{sup -3}mm{sup 2}/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising

  15. Is Preoperative Chemoradiotherapy Beneficial for Sphincter Preservation in Low-Lying Rectal Cancer Patients?

    PubMed Central

    Park, In Ja; Yu, Chang Sik; Lim, Seok-Byung; Lee, Jong Lyul; Kim, Chan Wook; Yoon, Yong Sik; Park, Seong Ho; Kim, Jin Cheon

    2016-01-01

    Abstract The present study explored the benefit of preoperative chemoradiotherapy (PCRT) for sphincter preservation in locally advanced low-lying rectal cancer patients who underwent stapled anastomosis, especially in those with deep and narrow pelvises determined by magnetic resonance imaging. Patients with locally advanced low-lying rectal cancer (≤5 cm from the anal verge) who underwent stapled anastomosis were included. Patients were categorized into two groups (PCRT+ vs. PCRT–) according to PCRT application. Patients in the PCRT+ group were matched to those in the PCRT– group according to potential confounding factors (age, gender, clinical stage, and body mass index) for sphincter preservation. Sphincter preservation, permanent stoma, and anastomosis-related complications were compared between the groups. Pelvic magnetic resonance imaging was used to measure 12 dimensions representing pelvic cavity depth and width with which deep and narrow pelvis was defined. The impact of PCRT on sphincter preservation and permanent stoma in pelvic dimensions defined as deep and narrow pelvis was evaluated, and factors associated with sphincter preservation and permanent stoma were analyzed. One hundred sixty-six patients were one-to-one matched between the PCRT+ and PCRT− groups. Overall, sphincter-saving surgery was performed in 66.3% and the rates were not different between the 2 groups. Anastomotic complications and permanent stoma occurred nonsignificantly more frequently in the PCRT+ group. PCRT was not associated with higher rate of sphincter preservation in all pelvic dimensions defined as deep and narrow pelvis, while PCRT was related to higher rate of permanent stoma in shorter transverse diameter and interspinous distance. On logistic regression analysis, PCRT was not shown to influence both sphincter preservation and permanent stoma, while longer transverse diameter and interspinous distance were associated with lower rate of permanent stoma. PCRT had

  16. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  17. Perioperative outcomes associated with robotic Ivor Lewis esophagectomy in patient’s undergoing neoadjuvant chemoradiotherapy

    PubMed Central

    Abbott, Andrea M.; Doepker, Matthew; Hoffe, Sarah E.; Almhanna, Khaldoun; Meredith, Kenneth L.

    2016-01-01

    Background Neoadjuvant chemoradiotherapy (NCR) for the treatment of esophageal cancer has been associated with increased perioperative morbidity and mortality. Minimally invasive procedures utilizing robotic techniques have been shown to reduce perioperative complications and length of hospitalization (LOH). The purpose of this study is to compare perioperative outcomes between patients undergoing NCR and robotic-assisted Ivor Lewis esophagectomy (RAIL) versus upfront RAIL. Methods A database of esophagectomy patients was queried to identify RAIL patients. Differences in perioperative outcomes were analyzed between NCR and non NCR patients. Results Eighty-nine patients were identified who underwent RAIL Seventy-seven patients (87%) had NCR and 22 patients did not (13%). The median age was 66 (range, 44-83). The median age of the patients treated with NCR was younger {69 [44-83] vs. 64 [46-81] years respectively, P=0.05}. The patients who underwent NCR had a higher BMI then those who went straight to esophagectomy (31 vs. 27; P=0.001). There were no conversions to open laparotomy or thoracotomy in either group. There were no statistically significant differences in the mean operative times and estimated blood loss (EBL) between both groups. Complications occurred in 17 (19.1%) patients. There were no statistically significant differences in the rates of any complications between patients receiving NCR and those that did not receive NCR (P=0.11). There were no deaths in either group. The total number of days in hospital and total number of intensive care unit (ICU) days were also similar in both groups (P=0.25). There was no statistically significant difference in the mean number of lymph nodes harvested in the patients treated with NCR compared with those treated without NCR. Conclusions We have demonstrated that RAIL is a safe and feasible option for patients with esophageal cancer. The administration of NCR to RAIL did not result in an increase in perioperative

  18. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2006-04-18

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  19. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2005-06-14

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  20. Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

    SciTech Connect

    Yoon, Dok Hyun; Jang, Geundoo; Kim, Jong Hoon; Kim, Yong-Hee; Kim, Ji Youn; Kim, Hyeong Ryul; Jung, Hwoon-Yong; Lee, Gin-Hyug; Song, Ho Young; Cho, Kyung-Ja; Ryu, Jin-Sook; Kim, Sung-Bae

    2015-03-01

    Purpose: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m{sup 2} on day 1 and S1 at 40 mg/m{sup 2} twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m{sup 2} on days 1 and 21 and S1 30 mg/m{sup 2} twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

  1. Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

    PubMed Central

    2014-01-01

    Background To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy. Methods Seventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE. Results Seventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, OR = 1.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; OR = 9.686) and V50 (p<0.001; OR = 1.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (p = 0.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC. Conclusions Concomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to

  2. Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study

    PubMed Central

    Haslett, Kate; Franks, Kevin; Harden, Susan; Hatton, Matthew; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil

    2016-01-01

    Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. Trial registration number NCT01836692; Pre-results. PMID:27084277

  3. Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series

    PubMed Central

    Yamashina, Takeshi; Takada, Ryoji; Uedo, Noriya; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ioka, Tatsuya; Ishihara, Ryu; Teshima, Teruki; Nishiyama, Kinji; Iishi, Hiroyasu

    2016-01-01

    In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries. PMID:27366048

  4. Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2015-01-01

    The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer. PMID:25692418

  5. Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series.

    PubMed

    Yamashina, Takeshi; Takada, Ryoji; Uedo, Noriya; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ioka, Tatsuya; Ishihara, Ryu; Teshima, Teruki; Nishiyama, Kinji; Iishi, Hiroyasu

    2016-01-01

    In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries. PMID:27366048

  6. Esophageal complications from combined chemoradiotherapy (cyclophosphamide + adriamycin + cisplatin + XRT) in the treatment of non-small cell lung cancer

    SciTech Connect

    Umsawasdi, T.; Valdivieso, M.; Barkley, H.T. Jr.; Booser, D.J.; Chiuten, D.F.; Murphy, W.K.; Dhingra, H.M.; Dixon, C.L.; Farha, P.; Spitzer, G.

    1985-03-01

    Esophageal complications from combined chemoradiotherapy (CCRT) were analyzed in 55 patients with limited non-small cell lung cancer. CCRT consisted of chemotherapy (cyclophosphamide, doxorubicin (Adriamycin), and cisplatin: CAP) and chest irradiation (5000 rad in 25 fractions/5 weeks). Forty-five patients received two courses of CAP, followed by five weekly courses of low dose CAP and irradiation followed by maintenance courses of CAP (Group 1). Ten patients received concomitant CCRT from the onset of treatment (Group 2). Esophagitis occurred in 80% of all patients. Severe esophagitis occurred in 27% of patients of Group 1 and 40% of patients of Group 2. Esophageal stricture or fistula developed in 1 of 45 (2%) patients in Group 1, and 3 of 10 (30%) patients in Group 2. The duration between onset of chemotherapy either before or after R should be greater than one week.

  7. Alterations of ghrelin with weights and correlation among ghrelin, cytokine and survival in patients receiving chemoradiotherapy for gastrointestinal cancers

    PubMed Central

    Karaca, Feryal; Afsar, Cigdem Usul; Gunaldi, Meral; Erkurt, Erkut; Ercolak, Vehbi; Sertdemir, Yasar; Paydas, Semra

    2015-01-01

    Aim: This study involved 30 patients (16 had gastric, 9 pancreatic and 5 gall bladder cancer) who had received concomitant chemoradiotherapy (CRT). Blood ghrelin and IL-6 values were compared before, in the last week of, and 3 months after CRT. Meanwhile, changes in body weight of patients were also investigated with changes in ghrelin and IL-6 levels before, in the last week of, and after radiotherapy (RT). Methods: Informed consent of the patients and the ethical committee approval from Cukurova University Medical Faculty were taken. Blood ghrelin and IL-6 levels were measured by using the ELISA method. Survival analysis was performed by the Kaplan Maier method, and data were evaluated by using the SPSS 19.0 package. Categorical measurements were calculated as numbers and percentages, whereas numerical data were summarized as mean and standard deviation. Results: The correlation between ghrelin and IL-6 values at the baseline of RT and overall survival rates at the end of the 30-month follow up was analyzed. Accordingly, ghrelin values were also changed in line with changes in patients’ weights (P < 0.001). Patients with ghrelin values above 35 pg/ml before RT had longer survival rates at the end of the 30-month follow up (P = 0.001). Overall survival rates in patients with IL-6 value at or below 3.9 pg/ml before RT were longer than patients with IL-6 value above 3.9 pg/ml (P = 0.021). Conclusion: Therefore, the initiation of ghrelin analogue prophylactically in patients receiving chemoradiotherapy with gastrointestinal system malignancies can both prevent weight loss by increasing appetite and decrease severity of inflammation, thereby increasing survival. PMID:25785069

  8. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy.

    PubMed

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-11-01

    Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  9. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Abstract Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process. We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients. We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04. Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  10. A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy.

    PubMed

    Huang, Jiayi; Campian, Jian L; Gujar, Amit D; Tran, David D; Lockhart, A Craig; DeWees, Todd A; Tsien, Christina I; Kim, Albert H

    2016-06-01

    Disulfiram, a generic alcohol aversion drug, has promising preclinical activity against glioblastoma (GBM). This phase I study aims to evaluate its safety, maximum tolerated dose (MTD), pharmacodynamic effect, and preliminary efficacy when combined with adjuvant temozolomide in GBM patients after standard chemoradiotherapy. Patients received disulfiram 500-1000 mg once daily, in combination with 150-200 mg/m(2) temozolomide. A modified 3 + 3 dose-escalation design was used to determine the MTD. The pharmacodynamic effect of proteasome inhibition was assessed using fluorometric 20S proteasome assay on peripheral blood cells. The MTD was determined based on the dose-limiting toxicities (DLTs) within the first month of therapy. Twelve patients were enrolled to two dose levels: 500 and 1000 mg. Two DLTs of grade 3 delirium occurred after 15 days of administration at 1000 mg per day. Other possible grade 2-3 DSF-related toxicities included fatigue, ataxia, dizziness, and peripheral neuropathy. The toxicities were self-limiting or resolved after discontinuing DSF. The MTD was determined to be 500 mg per day. Limited proteasome inhibition was observed at week 4 and showed an increased trend with escalated disulfiram. Median progression-free survival with 500 mg of DSF was 5.4 months from the start of disulfiram and 8.1 months from the start of chemoradiotherapy. Disulfiram can be safely combined with temozolomide but can cause reversible neurological toxicities. The MTD of disulfiram with adjuvant temozolomide appears to produce limited proteasome inhibition on peripheral blood cells. PMID:26966095

  11. Phase II Study of Chemoradiotherapy With S-1 and Low-Dose Cisplatin for Inoperable Advanced Gastric Cancer

    SciTech Connect

    Saikawa, Yoshiro Kubota, Tetsuro; Kumagai, Koshi; Nakamura, Rieko; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki; Kitagawa, Yuko

    2008-05-01

    Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.

  12. Oxaliplatin and Capecitabine-Based Chemoradiotherapy for Gastric Cancer-An Extended Phase I MARGIT and AIO Trial

    SciTech Connect

    Hofheinz, Ralf-Dieter Wenz, Frederik; Lukan, Nadine; Mai, Sabine; Kripp, Melanie; Staiger, Wilko; Schwarzbach, Matthias; Willeke, Frank; Moehler, Markus; Post, Stefan; Hochhaus, Andreas

    2009-01-01

    Purpose: Adjuvant 5-fluorouracil-based chemoradiotherapy has been shown to improve the prognosis of gastric cancer. To optimize these results, in the present study oxaliplatin and capecitabine were used instead of 5-fluorouracil. We sought to determine the maximum tolerated dose and the dose-limiting toxicities (DLT) of these drugs in combination with intensity-modulated radiotherapy. Methods and Materials: Patients with resected adenocarcinoma of the stomach or the gastroesophageal junction were included. They received two cycles of induction chemotherapy (oxaliplatin and capecitabine [XelOx] regimen). Using standard Phase I methodology, patients received 45 Gy in 1.8-Gy fractions either in combination with capecitabine 825 mg m{sup -1} twice a day (Dose Level [DL] I) or capecitabine in combination with weekly oxaliplatin 40 or 50 mg m{sup -1} (DL II and III). After the completion of chemoradiation, two additional cycles of XelOx were scheduled. Results: A total of 32 patients were recruited. Only 1 of 6 patients evaluable on DL I had DLT. Of the first 6 patients on DL II, 1 patient experienced DLT, and 3 of the remaining patients had Grade 3 toxicity. Therefore, DL II was defined as the maximum tolerated dose and a total of 20 patients were treated at this DL. The most frequently observed toxicities (Common Toxicity Criteria Grades 1, 2 and 3) were, respectively, leukocytopenia in 5, 5, and 4 patients; nausea in 3, 7, and 3; and diarrhea in 4, 0, and 1. Conclusions: In summary, capecitabine 825 mg m{sup -1} twice a day (Days 1-33) and weekly oxaliplatin 40 mg m{sup -1} was safe and tolerable in combination with intensity-modulated radiotherapy. Furthermore, four cycles of XelOx could be applied before and after chemoradiotherapy in two thirds of the patients.

  13. Posttreatment FDG-PET Uptake in the Supraglottic and Glottic Larynx Correlates With Decreased Quality of Life After Chemoradiotherapy

    SciTech Connect

    Dornfeld, Ken Hopkins, Shane; Simmons, Joel; Spitz, Douglas R.; Menda, Yusuf; Graham, Michael; Smith, Russell; Funk, Gerry; Karnell, Lucy; Karnell, Michael; Dornfeld, Maude; Yao Min; Buatti, John

    2008-06-01

    Purpose: Inflammation and increased metabolic activity associated with oxidative stress in irradiated normal tissues may contribute to both complications following radiotherapy and increased glucose uptake as detected by posttherapy fluorodeoxyglucose (FDG)-PET imaging. We sought to determine whether increased glucose uptake in normal tissues after chemoradiotherapy is associated with increased toxicity. Methods and Materials: Consecutive patients with locoregionally advanced head and neck cancers treated with intensity-modulated radiation therapy and free of recurrence at 1 year were studied. FDG-PET imaging was obtained at 3 and 12 months posttreatment. Standardized uptake value (SUV) levels were determined at various head and neck regions. Functional outcome was measured using a quality of life questionnaire and weight loss and type of diet tolerated 1 year after therapy. A one-tailed Pearson correlation test was used to examine associations between SUV levels and functional outcome measures. Results: Standardized uptake value levels in the supraglottic and glottic larynx from FDG-PET imaging obtained 12 months posttreatment were inversely associated with quality of life measures and were correlated with a more restricted diet 1 year after therapy. SUV levels at 3 months after therapy did not correlate with functional outcome. Increases in SUV levels in normal tissues between 3 and 12 months were commonly found in the absence of recurrence. Conclusion: Altered metabolism in irradiated tissues persists 1 year after therapy. FDG-PET scans may be used to assess normal tissue damage following chemoradiotherapy. These data support investigating hypermetabolic conditions associated with either inflammation, oxidative stress, or both, as causal agents for radiation-induced normal tissue damage.

  14. A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara; Ubezio, Paolo; Marchini, Sergio; De Stefano, Alfonso; Singh, Vijay Kumar; D'Incalci, Maurizio; De Placido, Sabino; Pepe, Stefano

    2012-07-15

    Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

  15. Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy

    SciTech Connect

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng; Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh; Lee, Steve P.; Hong, Ji-Hong

    2012-10-01

    Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.

  16. Phenylbutyrate Mouthwash Mitigates Oral Mucositis During Radiotherapy or Chemoradiotherapy in Patients With Head-and-Neck Cancer

    SciTech Connect

    Yen, Sang-Hue; Wang, Ling-Wei; Lin, Yi-Hsien; Jen, Yee-Min; Chung, Yih-Lin

    2012-03-15

    Purpose: Deleterious oral mucositis (OM) develops during radiotherapy (RT) or chemoradiotherapy for head-and-neck cancer (HNC) patients. There are currently no effective cytoprotective treatments for OM without a potential risk of tumor protection. This randomized, double-blind, placebo-controlled pilot study aimed to determine the therapeutic safety and efficacy of phenylbutyrate (an antitumor histone deacetylase inhibitor and chemical chaperone) 5% mouthwash for treating OM caused by cancer therapy. Methods and Materials: Between September 2005 and June 2006, 36 HNC patients were randomized to standard oral care plus 5 mL of either phenylbutyrate 5% mouthwash (n = 17) or placebo (mouthwash vehicle, n = 19) taken four times daily (swish and spit). Treatment began when mild mucositis (Radiation Therapy Oncology Group Grade 1) occurred, and ended 4 weeks after RT completion. Safety and efficacy were based on adverse events, physical examination, laboratory determinations, vital signs, Oral Mucosa Assessment Scale (OMAS) and World Health Organization scores, the ability to eat, body weight change, local control, and survival. Results: We found no severe drug-related side effect. At RT doses of 5500-7500 cGy, phenylbutyrate significantly mitigated the severity of mucositis compared with placebo, based on both the WHO score (severity {>=} 3; p = 0.0262) and the OMAS scale (ulceration score {>=} 2; p = 0.0049). The Kaplan-Meier estimates for 2- and 3-year local control, and overall survival were 100% and 80.8%, and 78.6% and 64.3%, respectively, in the phenylbutyrate group and 74.2% and 74.2%, and 57.4% and 50.2%, respectively, in the placebo group. Conclusions: This pilot trial suggested that phenylbutyrate mouthwash significantly decreased the impact of OM in HNC patients receiving RT or chemoradiotherapy and did not confront the tumor control. Larger Phase II randomized trials are needed to confirm these results.

  17. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

    SciTech Connect

    Tho, Lye Mun . E-mail: l.tho@beatson.gla.ac.uk; Glegg, Martin; Paterson, Jennifer; Yap, Christina; MacLeod, Alice; McCabe, Marie; McDonald, Alexander C.

    2006-10-01

    Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further

  18. Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

    SciTech Connect

    Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S.

    2011-07-15

    Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

  19. Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial

    SciTech Connect

    Bujko, Krzysztof . E-mail: bujko@coi.waw.pl; Michalski, Wojciech M.S.; Kepka, Lucyna; Nowacki, Marek P.; Nasierowska-Guttmejer, Anna; Tokar, Piotr; Dymecki, Dariusz; Pawlak, Mariusz; Lesniak, Tadeusz; Richter, Piotr; Wojnar, Andrzej; Chmielik, Ewa

    2007-02-01

    Purpose: To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups. Methods: The Cox model was used to evaluate the prognostic value of ypTN ('yp' denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients. Results: Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48). Conclusion: N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.

  20. Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced gastric cancer

    PubMed Central

    Kim, Mi Sun; Lim, Joon Seok; Hyung, Woo Jin; Lee, Yong Chan; Rha, Sun Young; Keum, Ki Chang; Koom, Woong Sub

    2015-01-01

    AIM: To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectability of locally advanced gastric cancer (LAGC). METHODS: Between November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study. Resectability was evaluated with radiologic and endoscopic exams before and after NACRT. Using three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume. Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection. The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria. Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and progression-free survival (PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test. RESULTS: All patients were assessed as unresectable cases. Twenty-four patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%) with vague invasion or abutment to an adjacent organ underwent diagnostic laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case, underwent an “open and closure” after the tumor was found to be unresectable. Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29) of patients had a resectable tumor. Of the 20 patients with a resectable tumor, 18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4% and two patients (2/18; 11

  1. Apparent Diffusion Coefficient Predicts Pathology Complete Response of Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

    PubMed Central

    Chen, Yuan-Gui; Chen, Ming-Qiu; Guo, Yu-Yan; Li, Si-Cong; Wu, Jun-Xin; Xu, Ben-Hua

    2016-01-01

    Objective To evaluate the predictive value of the apparent diffusion coefficient (ADC) for pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer. Methods A total of 265 patients with rectal adenocarcinoma, whole Diffusion-Weighted MRI (DWI-MRI) images, clinically stage II to III (cT3-4 and/or cN+) and treated with NCRT followed by TME were screened. Fifty patients with pCR and another 50 patients without pCR with similar clinical charcacters and treatment regimens were selected for statistical analysis. All the patients’ pre-CRT and post-CRT average ADC values were calculated from the coefficient maps created by DWI-MRI and recorded independently. The difference in the ADC values between the pCR and non-pCR was analyzed by the Mann-Whitney U test. The cut-off ADC value of the receiver operating characteristic (ROC) curve with pCR was then established. Results The mean pre- and post-ADC values in all patients, and in pCR patients and non-pCR patients were 0.879±0.06 and 1.383±0.11, 0.859±0.04 and 1.440±0.10, 0.899±0.07 and 1.325±0.09 (×10-3mm2/s), respectively. The difference between the pre- and post-ADC values in all patients, pCR patients, and non-pCR patients were considered to be statistically significant. The pre-ADC value was significantly lower in the pCR patients than in the non-pCR patients (p = 0.003), whereas the post-ADC values were significantly higher in the pCR patients than in the non-pCR patients. The percentage increase of the ADC value (ΔADC%) in the pCR and non-pCR patients were 68% and 48% respectively (p<0.001). The ROC curves of the cut-off value of the pre-CRT patient ADC value was 0.866×10-3mm2/s. The AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing pCR were 0.670 (95% CI 0.563–0.777), 0.600, 0.640, 60%, 60%, and 60%, respectively. The cut-off value of ΔADC% was 58%. The corresponding AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing p

  2. The direction of acceleration

    NASA Astrophysics Data System (ADS)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  3. TURBULENT SHEAR ACCELERATION

    SciTech Connect

    Ohira, Yutaka

    2013-04-10

    We consider particle acceleration by large-scale incompressible turbulence with a length scale larger than the particle mean free path. We derive an ensemble-averaged transport equation of energetic charged particles from an extended transport equation that contains the shear acceleration. The ensemble-averaged transport equation describes particle acceleration by incompressible turbulence (turbulent shear acceleration). We find that for Kolmogorov turbulence, the turbulent shear acceleration becomes important on small scales. Moreover, using Monte Carlo simulations, we confirm that the ensemble-averaged transport equation describes the turbulent shear acceleration.

  4. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  5. Improved plasma accelerator

    NASA Technical Reports Server (NTRS)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  6. Organ Preservation With Daily Concurrent Chemoradiotherapy Using Superselective Intra-Arterial Infusion via a Superficial Temporal Artery for T3 and T4 Head and Neck Cancer

    SciTech Connect

    Mitsudo, Kenji; Shigetomi, Toshio; Fujimoto, Yasushi; Nishiguchi, Hiroaki; Yamamoto, Noriyuki; Furue, Hiroki; Ueda, Minoru; Itoh, Yoshiyuki; Fuwa, Nobukazu; Tohnai, Iwai

    2011-04-01

    Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with advanced head and neck cancer treated with superselective intra-arterial chemotherapy via a superficial temporal artery and daily concurrent radiotherapy. Methods and Materials: Between April 2002 and March 2006, 30 patients with T3 or T4a squamous cell carcinoma of the head and neck underwent intra-arterial chemoradiotherapy. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m{sup 2}; cisplatin, total 150 mg/m{sup 2}) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. Results: The median follow-up for all patients was 46.2 months (range, 10-90 months). The median follow-up for living patients was 49.7 months (range, 36-90 months). After intra-arterial chemoradiotherapy was administered, primary site complete response was achieved in 30 (100%) of 30 cases. Seven patients (23.3%) died. Using the Kaplan-Meier method, 1-year, 3-year, and 5-year survival rates were 96.7%, 83.1%, and 70.2%, respectively, while 1-year, 3-year, and 5-year local control rates were 83.3%, 79.7%, and 73.0%, respectively. Grade 3 or 4 mucositis occurred in 20 cases (66.7%). Grade 3 toxicities included dysphagia in 20 cases (66.7%), dermatitis in 6 cases (20%), nausea/vomiting in 2 cases (6.7%), and neutropenia and thrombocytopenia in 1 case (3.3%). No osteoradionecrosis of mandible and maxillary bones developed during follow-up. Conclusions: Intra-arterial chemoradiotherapy using a superficial temporal artery provided good overall survival and local control rates. This combination chemoradiotherapy approach can preserve organs and minimize functional disturbance, thus contributing to patients' quality of life.

  7. Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

    PubMed

    Homma, A; Furuta, Y; Oridate, N; Nakano, Y; Kohashi, G; Yagi, K; Nagahashi, T; Yagi, K; Nagahashi, T; Fukuda, S; Inoue, K; Inuyama, Y

    1999-04-01

    Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS. PMID:10213215

  8. The Influence of Metastatic Lymph Node Ratio on the Treatment Outcomes in the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) Trial: A Phase III Trial

    PubMed Central

    Kim, Youjin; Kim, Kyoung-Mee; Choi, Min Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Lee, Su Jin; Kim, Seung Tae; Lee, Jeeyun; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki

    2016-01-01

    Purpose In the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial, we investigated whether chemoradiotherapy after D2 gastrectomy reduces the rate of recurrence. Recently, the ratio of metastatic lymph nodes to examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC). The aim of this study was to investigate the relationship between the metastatic N ratio and prognosis of GC after curative D2 surgery. Materials and Methods We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy (XP, n=228) or chemoradiotherapy (XPRT, n=230). The disease-free survival (DFS) rates of patients were used to evaluate the influence of N ratio on the treatment outcome. To achieve this, 4 different N ratio categories (0%, 1%~9%, 10%~25%, and >25%) were compared on the basis of their influence on the treatment outcome. Results On multivariate analysis, the N ratio remained an independent prognostic factor for DFS. The hazard ratios (HRs) for the N ratio categories of 0%, 1%~9%, 10%~25%, and >25% were 1, 1.061, 1.202, and 3.571, respectively. In patients having N ratio >25%, the 5-year DFS rates were 55% and 28% for the XPRT and XP arms, respectively (HR, 0.527; 95% confidence interval, 0.307~0.904; P=0.020). Conclusions In patients with curatively resected GC, the N ratio was independently associated with DFS. Although this finding warrants further investigation in future prospective studies, the benefit of chemoradiotherapy for D2 resected GC appears to be more beneficial in cancers having N ratios >25%. PMID:27433396

  9. Acceleration gradient of a plasma wakefield accelerator

    SciTech Connect

    Uhm, Han S.

    2008-02-25

    The phase velocity of the wakefield waves is identical to the electron beam velocity. A theoretical analysis indicates that the acceleration gradient of the wakefield accelerator normalized by the wave breaking amplitude is K{sub 0}({xi})/K{sub 1}({xi}), where K{sub 0}({xi}) and K{sub 1}({xi}) are the modified Bessel functions of the second kind of order zero and one, respectively and {xi} is the beam parameter representing the beam intensity. It is also shown that the beam density must be considerably higher than the diffuse plasma density for the large radial velocity of plasma electrons that are required for a high acceleration gradient.

  10. Angular Acceleration Without Torque?

    NASA Astrophysics Data System (ADS)

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.2