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Sample records for hyperfractionated accelerated chemoradiotherapy

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: Updated results of a randomized multicentric trial in advanced head-and-neck cancer

    SciTech Connect

    Semrau, Robert . E-mail: Robert.Semrau@uk-koeln.de; Mueller, Rolf-Peter; Stuetzer, Hartmut; Staar, Susanne; Schroeder, Ursula; Guntinas-Lichius, Orlando; Kocher, Martin; Eich, Hans Theodor; Dietz, Andreas; Flentje, Michael; Rudat, Volker; Volling, Peter; Schroeder, Michael; Eckel, Hans Edmund

    2006-04-01

    Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m{sup 2}/day) and carboplatin (70 mg/m{sup 2}/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

  16. HI-CHART: A Phase I/II Study on the Feasibility of High-Dose Continuous Hyperfractionated Accelerated Radiotherapy in Patients With Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Ruysscher, Dirk de Wanders, Rinus; Haren, Erik van; Hochstenbag, Monique; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Boersma, Liesbeth; Verschueren, Tom; Minken, Andre; Bentzen, Soren M.; Lambin, Philippe

    2008-05-01

    Purpose: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and Methods: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V{sub 20} <25%, V{sub 20} 25-37%, and V{sub 20} >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment {sup 18}F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. Results: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V{sub 20} <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V{sub 20} 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. Conclusions: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V{sub 20} up to 37% is feasible.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Pancreatic cancer chemoradiotherapy.

    PubMed

    Brunner, Thomas B; Seufferlein, Thomas

    2016-08-01

    Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery. PMID:27644909

  5. Rectal cancer: Neoadjuvant chemoradiotherapy.

    PubMed

    Rödel, Claus; Hofheinz, Ralf; Fokas, Emmanouil

    2016-08-01

    The monolithic approach to apply the same schedule of preoperative 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) to all patients with clinically staged TNM stage II/III rectal cancer need to be questioned. Five randomized trials have been completed to determine if the addition of oxaliplatin to preoperative 5-FU/capecitabine-based CRT offers an advantage compared with single-agent CRT. In contrast to the German CAO/ARO/AIO-04 trial, results from the ACCORD 12, STAR-01, PETACC-6 and NSAPB R-04 trials failed to demonstrate a significant improvement of early or late efficacy endpoints with the addition of oxaliplatin. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pCR; the combination of CRT with VEGF inhibition showed encouraging pCR rates but at the cost of increased surgical complications. Novel clinical trials currently address (1) the role of induction and consolidation chemotherapy before or after CRT, (2) minimal or omitted surgery following complete response to CRT, or (3) the omission of radiotherapy for selected patients with response to neoadjuvant chemotherapy. The notion of different multimodal treatment concepts according to tumor stage, location, mesorectal fascia margin status, molecular profiles, tumor response, and patients' preferences becomes increasingly popular and will render the multimodal treatment approach of rectal cancer more risk-adapted. PMID:27644910

  6. 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.

  7. 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

  8. 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.

  9. Factors Associated With Severe Acute Esophagitis From Hyperfractionated Radiotherapy With Concurrent Chemotherapy for Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Watkins, John M.; Wahlquist, Amy E. M.S.; Shirai, Keisuke; Garrett-Mayer, Elizabeth; Aguero, Eric G.; Fortney, John A.; Sherman, Carol A.; Sharma, Anand K.

    2009-07-15

    Purpose: To describe incidence and identify factors associated with development of severe acute esophagitis during hyperfractionated radiotherapy with concurrent chemotherapy (BID-CRT) in patients with limited-stage small-cell lung cancer (SCLC). Methods and Materials: Retrospective cohort analysis of patient-, tumor-, and treatment-related variables was performed to identify factors associated with Radiation Therapy Oncology Group (RTOG) Grade 3 acute esophagitis. Twice-daily chemoradiotherapy (BID-CRT) involved 45 Gy at 1.5 Gy per fraction, treated twice daily with concurrent platinum-based chemotherapy. Logistic regression analyses were used to identify factors associated with esophagitis. Results: Between June 1999 and June 2007, 48 patients underwent curative intent BID-CRT for SCLC and were included in the analysis. Median radiotherapy dose was 45 Gy (range, 42-51 Gy) delivered with a median 4 cycles of chemotherapy (range, 2-6). RTOG Grade 3 acute esophagitis developed in 11 patients. No patient developed Grade 4 or 5 esophagitis. Simple logistic regression analyses demonstrated a highly significant association between Grade 3 acute esophagitis and mean esophageal dose (p = 0.002) as well as relative volume dosimetric area under curve (RV-AUC; p = 0.004). Using multiple regression analysis, RV-AUC was identified as the only factor associated with Grade 3 esophagitis (p = 0.004). The most strongly associated dosimetric volume was the V15 (Grade 3 esophagitis rates of 15% vs. 64% for V15 <60% versus {>=}60%, respectively). Conclusions: RV-AUC is the factor most associated with development of Grade 3 acute esophagitis in limited stage SCLC patients receiving BID-CRT.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy.

    PubMed

    Boustani, J; Caubet, M; Bosset, J-F

    2016-02-01

    The aim of this overview was to investigate whether adjuvant chemotherapy has a favourable effect on the outcome of patients with rectal cancer who had preoperative (chemo)radiotherapy. A review of randomised clinical trials that allocated patients between fluorouracil-based and observation or between fluorouracil-based and oxaliplatin-based adjuvant chemotherapy after preoperative (chemo)radiotherapy was carried out, including their corresponding meta-analyses. None of the five randomised trials has shown a significant benefit of fluorouracil-based adjuvant chemotherapy for overall survival or disease-free survival. Also, the three corresponding meta-analyses failed to show a benefit of adjuvant treatment. Of three randomised trials - two phase III and one phase II with a 3-year disease-free survival end point - two showed a small benefit of adding oxaliplatin to fluorouracil, one failed. The corresponding meta-analyses showed that the pooled difference was not significant. In conclusion, the use of postoperative 5-fluorouracil-based chemotherapy with or without oxaliplatin in patients with rectal cancer after preoperative (chemo)radiotherapy is not scientifically proven.

  15. Nutritional status of patients undergoing chemoradiotherapy for lung cancer.

    PubMed

    Shintani, Yasushi; Ikeda, Naoki; Matsumoto, Tomoshige; Kadota, Yoshihisa; Okumura, Meinoshin; Ohno, Yuko; Ohta, Mitsunori

    2012-04-01

    Impaired nutrition is an important predictor of perioperative complications in lung cancer patients, and preoperative chemoradiotherapy increases the risk of such complications. The goal of this study was to assess the effect of an immune-enhancing diet on nutritional status in patients undergoing lung resection after chemoradiotherapy. We compared the preoperative nutritional status in 15 patients with lung cancer undergoing lung resection without chemoradiotherapy and 15 who had chemoradiotherapy. Body mass index and lymphocyte counts were lower in patients who had chemoradiotherapy. Although there was no difference in the rate of postoperative morbidity between groups, the chemoradiotherapy patients were more likely to have severe complications postoperatively. After chemoradiotherapy in 12 patients, 6 received oral Impact for 5 days, and 6 had a conventional diet before surgery. Oral intake of Impact for 5 days before surgery modified the decrease in transferrin and lymphocytes after the operation. Preoperative immunonutrition may improve the perioperative nutritional status after induction chemoradiotherapy in patients undergoing lung cancer surgery, and reduce the severity of postoperative complications. These potential benefits need to be confirmed in a randomized controlled trial.

  16. 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

  17. Laryngeal sensation and pharyngeal delay time after (chemo)radiotherapy.

    PubMed

    Maruo, Takashi; Fujimoto, Yasushi; Ozawa, Kikuko; Hiramatsu, Mariko; Suzuki, Atsushi; Nishio, Naoki; Nakashima, Tsutomu

    2014-08-01

    The objective of the study was to evaluate the association between changes in laryngeal sensation and initiation of swallowing reflex or swallowing function before and after (chemo)radiotherapy. A prospective study was conducted in a tertiary referral university hospital. Thirteen patients who received (chemo)radiotherapy for treatment of laryngeal or hypopharyngeal cancer were included. Laryngeal sensation was evaluated at the tip of the epiglottis before and 1, 3 months, and 1 year after (chemo)radiotherapy. Videofluoroscopy was performed at the same time. Quantitative determinations included changes in laryngeal sensation, computed analysis of pharyngeal delay time, the distance and velocity of hyoid bone movement during the phase of hyoid excursion, and pharyngeal residue rate (the proportion of the bolus that was left as residue in the pharynx at the first swallow). Laryngeal sensation significantly deteriorated 1 month after (chemo)radiotherapy, but there was a tendency to return to pretreatment levels 1 year after treatment. Neither pharyngeal delay time nor displacement of the hyoid bone changed significantly before and after (chemo)radiotherapy. In addition, there was no significant difference in the mean velocity of hyoid bone movement and the amount of stasis in the pharynx at the first swallow before and after (chemo)radiotherapy. After (chemo)radiotherapy, laryngeal sensation deteriorated. But, in this study, videofluoroscopy showed that swallowing reflex and function were maintained.

  18. Hyperfractionation decreases the deleterious effects of conventional radiation fractionation on vertebral growth in animals

    SciTech Connect

    Hartsell, W.F.; Hanson, W.R.; Conterato, D.J.; Hendrickson, F.R.

    1989-06-15

    Craniospinal axis irradiation in the treatment of pediatric tumors is associated with serious long-term sequelae including decreased bone growth (short sitting stature). In this study, an animal model was used to determine the effects of smaller incremental doses of radiation on bone growth. Sprague-Dawley weanling rats were given 25 Gy to the spine in 8 to 9 days, with fraction sizes ranging from 1.0 to 1.8 Gy. The animals receiving smaller doses per fraction (1.0 or 1.25 Gy) showed significantly more growth of the vertebral bodies in the treated fields than animals given larger incremental doses (1.5 or 1.8 Gy). These findings indicate a protective effect on bone growth for hyperfractionated irradiation of vertebral bodies.

  19. 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.

  20. Functional Outcomes after Chemoradiotherapy of Laryngeal and Pharyngeal Cancers

    PubMed Central

    Hutcheson, Katherine A.; Lewin, Jan S.

    2014-01-01

    Organ preservation regimens that combine chemotherapy and radiotherapy (chemoradiotherapy) are increasingly used as the primary treatment of laryngeal and pharyngeal cancers. Meta-analytic data show a survival benefit with combined modality therapy, but the functional sequelae can be significant. Dysphagia is recognized as a common and often devastating late effect of chemoradiotherapy. This review examines functional outcomes after chemoradiotherapy for laryngeal and pharyngeal cancers, with a particular emphasis on dysphagia. Topics examined include the burden of dysphagia after chemoradiation, pathophysiology of dysphagia, baseline functioning, recommendations to improve long-term function, and voice outcomes. PMID:22249533

  1. 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.

  2. Anal cancer - What is the optimum chemoradiotherapy?

    PubMed

    Vinayan, A; Glynne-Jones, R

    2016-08-01

    Radical concurrent chemoradiotherapy with 5FU and Mitomycin C is the standard-of-care for squamous-cell carcinoma of the anus (SCCA). Phase III trials combined radiation doses of 50-60 Gy with concurrent Fluoropyrimidines, Mitomycin C and Cisplatin in various doses and schedules. CRT is highly successful for early T1/T2 cancers, but results in appreciable late morbidities and still fails to control larger and node-positive tumours. Compliance to chemotherapy is important for local control. Modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy (IGRT) have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. These advances offer the potential for integrating higher doses of radiation, escalation of the currently used drugs and the safe use of other more novel agents with acceptable toxicity. In this chapter potential novel approaches are discussed in the context of SCCA. PMID:27644911

  3. 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.

  4. [Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy].

    PubMed

    Nakagawa, Kei; Katayose, Yu; Ishida, Kazuyuki; Hayashi, Hiroki; Morikawa, Takanori; Yoshida, Hiroshi; Motoi, Fuyuhiko; Naitoh, Takeshi; Kubo, Shoji; Unno, Michiaki

    2015-07-01

    A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma.

  5. Chemoradiotherapy response in recurrent rectal cancer

    PubMed Central

    Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

    2014-01-01

    The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan–Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. PMID:24403010

  6. Role of Adjuvant Chemoradiotherapy for Ampulla of Vater Cancer

    SciTech Connect

    Kim, Kyubo; Chie, Eui Kyu Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2009-10-01

    Purpose: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Methods and Materials: Between January 1991 and December 2002, 118 patients with ampulla of Vater cancer underwent en bloc resection. Forty-one patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-) group]. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a planned 2-week rest period halfway through the treatment period. Intravenous 5-fluorouracil (500 mg/m{sup 2}/day) was given on Days 1 to 3 of each split course. The median follow-up was 65 months. Results: The 5-year overall survival rate in the RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9% and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were incorporated into the Cox proportional hazard model, there was an improvement in the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a longer overall survival (p = 0.0762) associated with the use of adjuvant chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional relapse-free survival (p = 0.0095) were also evident in patients with nodal metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not result in longer survival in patients with locally advanced disease (p = 0.4544). Conclusions: Adjuvant chemoradiotherapy may enhance locoregional control and overall survival in patients with ampulla of Vater cancer after curative resection, especially in those with nodal involvement.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. Radiobiological modeling of interplay between accelerated repopulation and altered fractionation schedules in head and neck cancer.

    PubMed

    Marcu, Loredana G; Bezak, Eva

    2009-10-01

    Head and neck cancer represents a challenge for radiation oncologists due to accelerated repopulation of cancer cells during treatment. This study aims to simulate, using Monte Carlo methods, the response of a virtual head and neck tumor to both conventional and altered fractionation schedules in radiotherapy when accelerated repopulation is considered. Although clinical trials are indispensable for evaluation of novel therapeutic techniques, they are time-consuming processes which involve many complex and variable factors for success. Models can overcome some of the limitations encountered by trials as they are able to simulate in less complex environment tumor cell kinetics and dynamics, interaction processes between cells and ionizing radiation and their outcome. Conventional, hyperfractionated and accelerated treatment schedules have been implemented in a previously developed tumor growth model which also incorporates tumor repopulation during treatment. This study focuses on the influence of three main treatment-related parameters, dose per fraction, inter fraction interval and length of treatment gap and gap timing based on RTOG trial data on head and neck cancer, on tumor control. The model has shown that conventionally fractionated radiotherapy is not able to eradicate the stem population of the tumor. Therefore, new techniques such as hyperfractionated/ accelerated radiotherapy schedules should be employed. Furthermore, the correct selection of schedule-related parameters (dose per fraction, time between fractions, treatment gap scheduling) is crucial in overcoming accelerated repopulation. Modeling of treatment regimens and their input parameters can offer better understanding of the radiobiological interactions and also treatment outcome.

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

    PubMed

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

    2013-09-17

    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.

  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. Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients

    PubMed Central

    Zaboli, David; Tan, Marietta; Gogineni, Hrishikesh; Lake, Spencer; Fan, Katherine; Zahurak, Marianna L.; Messing, Barbara; Ulmer, Karen; Zinreich, Eva S.; Levine, Marshall A.; Tang, Mei; Pai, Sara I.; Blanco, Ray G.; Saunders, John R.; Best, Simon R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h) daily for five days and 5-fluorouracil (600 mg/m2/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events. PMID:22778748

  15. Diffuse alveolar hemorrhage after erlotinib combined with concurrent chemoradiotherapy in a patient with esophageal carcinoma.

    PubMed

    Zhao, Chuan-Hua; Liu, Rong-Rui; Lin, Li; Liu, Jian-Zhi; Ge, Fei-Jiao; Li, Shan-Shan; Ye, Chen-Yang; Chen, Yu-Ling; Wang, Yan; Xu, Jian-Ming

    2014-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to combination therapy of chemoradiotherapy and erlotinib. As to know, DAH following chemoradiotherapy was only reported among hematopoietic stem cell transplant recipients with hematologic malignancies till now. DAH associated with chemoradiotherapy for oesophageal carcinoma has not been reported. This is the first DAH report on erlotinib-combined chemoradiotherapy for esophageal cancer. The authors believe epidermal growth factor receptor tyrosine kinase inhibitor erlotinib increased the lung injury. Molecular targeted drugs are gradually applied to be combined with chemoradiation, whether this combination will cause the increase of serious adverse reactions need further study. This case can provide certain reference for erlotinib in the treatment. Meanwhile, after long term hormone therapy for DAH, the patient was diagnosed with pneumocystis carinii pneumonia. It reminds us to attach importance to the immunosuppressive diseases after long-term hormone treatment.

  16. 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

  17. MRI of anal cancer: assessing response to definitive chemoradiotherapy.

    PubMed

    Gourtsoyianni, S; Goh, V

    2014-02-01

    Anal cancer is an uncommon malignancy of the gastrointestinal tract but has a relatively good prognosis with an 80% 5-year overall survival. In this article, we review the role of MRI for assessing treatment response in anal cancer after completion of definitive chemoradiotherapy. New generation MRI scanners with optimal-phased array body coils, resulting in better signal to noise and improved contrast and spatial resolution, have contributed to high-resolution imaging in clinical practice enabling visualization of relevant anatomy including the sphincter complex, adjacent structures, mesorectal and pelvic lymph nodes with a diameter down to 2 mm. Multiplanar, high-resolution T2-weighted and diffusion-weighted sequences have a role in initial locoregional staging of anal SCC, assisting radiotherapy planning, as well as in assessing response to treatment and treatment-related complications. PMID:24072381

  18. Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer.

    PubMed

    Parikh, Falguni; Duluc, Dorothée; Imai, Naoko; Clark, Amelia; Misiukiewicz, Krzys; Bonomi, Marcello; Gupta, Vishal; Patsias, Alexis; Parides, Michael; Demicco, Elizabeth G; Zhang, David Y; Kim-Schulze, Seunghee; Kao, Johnny; Gnjatic, Sacha; Oh, Sangkon; Posner, Marshall R; Sikora, Andrew G

    2014-12-15

    While viral antigens in human papillomavirus (HPV)-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from patients with stage III-IV oropharyngeal cancer undergoing concomitant chemoradiotherapy with or without induction chemotherapy. Circulating immunocytes including CD4(+) and CD8(+) T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry. Antigen-specific T-cell responses were measured in response to HPV16 E6 and E7 peptide pools. The role of PD-1 signaling in treatment-related immunosuppression was functionally defined by performing HPV-specific T-cell assays in the presence of blocking antibody. While HPV-specific T-cell responses were present in 13 of 18 patients before treatment, 10 of 13 patients lost these responses within 3 months after chemoradiotherapy. Chemoradiotherapy decreased circulating T cells and markedly elevated MDSCs. PD-1 expression on CD4(+) T cells increased by nearly 2.5-fold after chemoradiotherapy, and ex vivo culture with PD-1-blocking antibody enhanced HPV-specific T-cell responses in 8 of 18 samples tested. Chemoradiotherapy suppresses circulating immune responses in patients with HPVOPC by unfavorably altering effector:suppressor immunocyte ratios and upregulating PD-1 expression on CD4(+) T cells. These data strongly support testing of PD-1-blocking agents in combination with standard-of-care chemoradiotherapy for HPVOPC.

  19. Sensitivity value of hematological markers in patients receiving chemoradiotherapy for esophageal squamous cell carcinoma

    PubMed Central

    Zhu, Shan; Miao, Chuan-Wang; Wang, Zhong-Tang; Peng, Li; Li, Baosheng

    2016-01-01

    Background Hematological markers of the systemic inflammatory response (SIR) including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and the combination of NLR with PLR (CNP) are associated with prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, their value in predicting the sensitivity to chemoradiotherapy in patients with ESCC is unclear. The aim of this study was to investigate whether these markers can be used as sensitivity predictors for chemoradiotherapy in patients with ESCC. Patients and methods A total of 114 patients with newly diagnosed ESCC were retrospectively evaluated. They were treated with curative intent by primary radiotherapy only or concurrent chemoradiotherapy. These patients were grouped for further analysis according to the optimum cutoff values of NLR, PLR, and CNP. A univariate analysis was conducted to compare the ability of each of the hematological markers of SIR and clinicopathological characteristics. Multivariate analysis was performed to identify whether the markers were associated with the sensitivity to chemoradiotherapy. The relationship between clinicopathological characteristics and hematological markers was assessed. Results NLR, CNP, T stage, M stage, and clinical stage were significantly associated with the sensitivity to chemoradiotherapy. In multivariate analysis, CNP and clinical stage were the independent risk factors predicting a poorer sensitivity. Conclusion This study validated novel, easy-to-use hematological markers and found that CNP, an SIR score, is an independent hematological marker of poor sensitivity to chemoradiotherapy in patients with ESCC. This may help guide the planning of follow-up regimens. PMID:27789959

  20. Hyperfractionation versus single dose irradiation in human acute lymphocytic leukemia cells: application to TBI for marrow transplantation.

    PubMed

    Shank, B

    1993-04-01

    A major purpose of total body irradiation (TBI) for bone marrow transplantation in leukemia patients is to help eradicate all leukemia cells; the ideal regimen has not yet been determined. To answer basic questions regarding leukemic cell survival kinetics, a human acute lymphoblastic leukemia (ALL) cell line (Reh), with the common ALL antigen (CALLA-positive), has been used to assess in vitro the efficacy of one widely used hyperfractionated TBI (HTBI) regimen versus single dose TBI (SDTBI). The regimen studied in this model was 1.2-1.25 Gy/fraction, 3 fractions/day, 5 h apart each day, for 5 days (11-12 fractions) for a total dose of 13.2-15.0 Gy. It was found that: (i) cell survival was consistent with the linear-quadratic model for early responding tissues (alpha/beta = 7.0 Gy). (ii) The change in shape of the 'effective' cell survival curve for three fractions/day was consistent with the hypothesis that there was complete repair between fractions. (iii) Cell regrowth between fractions was minimal (< or = 5%). (iv) Division delay between fractions (2.9 h/Gy) could explain the small contribution to the survival curve of regrowth between fractions. (v) For a full HTBI course to 15 Gy, cell survival was predicted to be approximately 5 x 10(-5), compared with approximately 10(-3) for a low dose rate (0.04-0.07 Gy/min) SDTBI to 10 Gy; the latter projected from the initial slope of the high dose rate, single dose survival curve. PMID:8327730

  1. 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.

  2. 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.

  3. Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma.

    PubMed

    Yi, Yan; Li, Baosheng; Sun, Hongfu; Zhang, Zicheng; Gong, Heyi; Li, Hongsheng; Huang, Wei; Wang, Zhongtang

    2010-08-01

    The purpose of this study was to investigate clinical-biological factors which could predict the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). One hundred eighty-one patients with stages I-IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), albumin (A) as well as hemoglobin (HB) concentration were measured before the initiation of chemoradiotherapy (CRT). The cutoff values of CYFRA21-1, CEA, and A were defined as 3.4 ng/ml, 3.3 ng/ml, 3.5 g/dl, respectively. HB was divided into three levels: <12.0, 12.0-14.0, and >14.0 g/dl. Clinical factors such as sex, age, tumor location, primary cancer length, and tumor-node-metastasis stage were also evaluated. The effective rate (complete response + partial response) of the primary tumor estimated by computed tomography was 60.71% (17 out of 28) in patients with CEA high group while 92.54% (62 out of 67) in patients with CEA low group (P = 0.000) and 62.50% (20 out of 32) in patients with CYFRA21-1 high group while 92.98% (53 out of 57) in patients with CYFRA21-1 low group (P = 0.000). HB levels before and during CRT were also associated with the effectiveness (P = 0.005, 0.033, respectively). HB levels before CRT at 12.0-14.0 g/dl were associated with the best effectiveness, followed by >14.0 and <12.0 g/dl (effective rates 88.89% vs. 83.75%, 62.07%, respectively, P = 0.005). HB levels during CRT also showed similar results (effective rates 87.80% vs. 85.41%, 70.59%, respectively, P = 0.033). Furthermore, according to numbers of the above risk factors, the sensitivity of CRT was higher in patients with zero to one risk factors than those with two to four risk factors (P = 0.023). CYFRA21-1 and CEA as well as HB and their combination may be helpful in predicting the sensitivity to CRT of ESCC. However, the results should be further confirmed in larger, more homogeneous studies.

  4. Incidence, Natural History, and Patterns of Locoregional Recurrence in Gastric Cancer Patients Treated With Preoperative Chemoradiotherapy

    SciTech Connect

    Reed, Valerie K.; Krishnan, Sunil; Mansfield, Paul F.; Bhosale, Priya R.; Kim, Michelle; Das, Prajnan; Janjan, Nora A.; Delclos, Marc E.; Lowy, Andrew M.; Feig, Barry W.; Pisters, Peter W.T.; Ajani, Jaffer A.; Crane, Christopher H.

    2008-07-01

    Purpose: To retrospectively determine the incidence and patterns (in-field, marginal, or out-of-field) of locoregional gastric cancer recurrence in patients who received preoperative chemoradiotherapy and to determine the outcome in these patients. Methods and Materials: Between 1994 and 2004, 149 patients with gastric carcinoma were treated according to institutional protocols with preoperative chemoradiotherapy. Ultimately, 105 patients had an R0 resection. Of these 105 patients, 65 received preoperative chemotherapy followed by chemoradiotherapy and 40 received preoperative chemoradiotherapy. Most (96%) of these patients received 5-fluorouracil-based chemotherapy during radiotherapy, and the median radiation dose was 45 Gy. We retrospectively identified and classified the patterns of locoregional recurrence. Results: The 3-year actuarial incidence of locoregional recurrence was 13%, with locoregional disease recurring as any part of the failure pattern in 14 patients. Most (64%) of the evaluable locoregional recurrences were in-field. Of the 4 patients with a marginal recurrence, 2 had had inadequate coverage of the regional nodal volumes on their oblique fields. The pathologic complete response rate was 23%. A pathologic complete response was the only statistically significant predictor of locoregional control. Conclusion: Patients with gastric cancer who received preoperative chemoradiotherapy had low rates of locoregional recurrence. This strategy merits prospective multi-institutional and randomized evaluation.

  5. [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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Acute phlegmonous esophagitis as a rare but threatening complication of chemoradiotherapy: report of a case.

    PubMed

    Karimata, Hiroyuki; Nishimaki, Tadashi; Oshita, Akehiro; Nagahama, Masayoshi; Shimoji, Hideaki; Inamine, Morihiko; Kinjyo, Tadatsugu

    2014-06-01

    Phlegmonous infection involving the digestive tract has been reported to have a poor prognosis. However, the pathogenesis and clinical features of acute phlegmonous esophagitis have remained unclear due to the rarity of the disease. We herein report a case of acute phlegmonous esophagitis that showed a fulminant course during chemoradiotherapy for uterine cancer. The patient developed septic shock 10 h after postprandial nausea and vomiting, and a computed tomographic scan showed diffuse thickening of the esophageal wall. Severe leukopenia that was refractory to the administration of granulocyte colony-stimulating factor persisted during the first few days. The patient fortunately survived after intensive treatment. The acute phlegmonous esophagitis of the present case might have been evoked and worsened by chemoradiotherapy due to its emetic and myelosuppressive adverse effects, respectively. Although its incidence is extremely rare, acute phlegmonous esophagitis may occur as a life-threatening complication of chemoradiotherapy.

  11. 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.

  12. Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

    PubMed Central

    Mihmanlı, Mehmet; Kabul Gürbulak, Esin; Akgün, İsmail Ethem; Celayir, Mustafa Fevzi; Yazıcı, Pınar; Tunçel, Deniz; Bek, Tuba Tülin; Öz, Ayhan; Ömeroğlu, Sinan

    2016-01-01

    AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response. PMID:27672428

  13. [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

  14. 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.

  15. Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

    PubMed Central

    Mihmanlı, Mehmet; Kabul Gürbulak, Esin; Akgün, İsmail Ethem; Celayir, Mustafa Fevzi; Yazıcı, Pınar; Tunçel, Deniz; Bek, Tuba Tülin; Öz, Ayhan; Ömeroğlu, Sinan

    2016-01-01

    AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Neurocognitive function after (chemo)-radiotherapy for head and neck cancer.

    PubMed

    Welsh, L C; Dunlop, A W; McGovern, T; McQuaid, D; Dean, J A; Gulliford, S L; Bhide, S A; Harrington, K J; Nutting, C M; Newbold, K L

    2014-12-01

    Radical radiotherapy has a pivotal role in the treatment of head and neck cancer (HNC) and cures a significant proportion of patients while simultaneously sparing critical normal organs. Some patients treated with radical radiotherapy for HNC receive significant radiation doses to large volumes of brain tissue. In fact, intensity-modulated radiotherapy techniques for HNC have been associated with a net increase in irradiated brain volumes. The increasing use of chemoradiotherapy for HNC has additionally exposed this patient population to potential neurotoxicity due to cytotoxic drugs. Patients with HNC may be particularly at risk for adverse late brain effects after (chemo)-radiotherapy, such as impaired neurocognitive function (NCF), as risk factors for the development of HNC, such as smoking, excess alcohol consumption and poor diet, are also associated with impaired NCF. The relatively good survival rates with modern treatment for HNC, and exposure to multiple potentially neurotoxic factors, means that it is important to understand the impact of (chemo)-radiotherapy for HNC on NCF, and to consider what measures can be taken to minimise treatment-related neurotoxicity. Here, we review evidence relating to the late neurotoxicity of radical (chemo)-radiotherapy for HNC, with a focus on studies of NCF in this patient population.

  1. Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy

    PubMed Central

    Yamaguchi, Motoko; Takata, Katsuyoshi; Yoshino, Tadashi; Ishizuka, Naoki; Oguchi, Masahiko; Kobayashi, Yukio; Isobe, Yasushi; Ishizawa, Kenichi; Kubota, Nobuko; Itoh, Kuniaki; Usui, Noriko; Miyazaki, Kana; Wasada, Izumi; Nakamura, Shigeo; Matsuno, Yoshihiro; Oshimi, Kazuo; Kinoshita, Tomohiro; Tsukasaki, Kunihiro; Tobinai, Kensei

    2014-01-01

    Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61–94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057–1.013; 80% CI, 0.093–0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αβ T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy. PMID:25181936

  2. 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

  3. 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

  4. 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.

  5. Can Accelerators Accelerate Learning?

    SciTech Connect

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

    2009-03-10

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis.

    PubMed

    Ueno, Hideki; Shinto, Eiji; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Kajiwara, Yoshiki; Sueyama, Takahiro; Yamamoto, Junji; Hase, Kazuo

    2015-06-01

    Although the essential contribution of the desmoplastic reaction (DR) to aggressive tumor behavior is increasingly recognized, its prognostic value has not been investigated in rectal cancer after preoperative chemoradiotherapy. We retrospectively analyzed 101 consecutive patients with rectal cancer treated with short-course chemoradiotherapy followed by surgery (2001-2007). The DR in the resected primary tumor was pathologically classified into three patterns on the basis of products of cancer-associated fibroblasts (CAFs): mature (multilayered fibrotic), intermediate (keloid-like hyalinized), and immature (mostly myxoid). We classified 46 tumors as mature, 30 as intermediate, and 25 as immature DR. In addition, immunostaining of CD8(+) and FoxP3(+) cells was performed to characterize the immune response accompanying DR. Mature DR correlated with higher density of CD8(+) and FoxP3(+) cells in both resected surgical and pretreatment biopsy specimens. A significant association with DR category was observed for T stage, lymphatic invasion, and venous invasion (P ≤ 0.0001-0.0006). Mature DR was significantly associated with higher grade of pathological response (P = 0.0350). The 5-year disease-free survival (DFS) rates were 82, 72, and 47 % for mature, intermediate, and immature DR, respectively (P = 0.0055). On multivariate analysis, DR category and ypN were independently predictive of DFS. The pattern of the DR in rectal cancers after chemoradiotherapy treatment might have a prognostic value, as it likely reflects pretreatment desmoplastic environment.

  12. TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

    PubMed Central

    Piro, G; Giacopuzzi, S; Bencivenga, M; Carbone, C; Verlato, G; Frizziero, M; Zanotto, M; Mina, M M; Merz, V; Santoro, R; Zanoni, A; De Manzoni, G; Tortora, G; Melisi, D

    2015-01-01

    Background: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. Methods: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. Results: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). Conclusions: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy. PMID:26291056

  13. 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.

  14. Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

    PubMed Central

    McCallion, K; Moorehead, RJ; McAllister, I; Mulholland, K; Gilliland, R; Campbell, WJ

    2016-01-01

    Background In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management.1 The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. Methods A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System® (NIPACS) and Electronic Care Record® (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. Results Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to

  15. Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

    PubMed Central

    McCallion, K; Moorehead, RJ; McAllister, I; Mulholland, K; Gilliland, R; Campbell, WJ

    2016-01-01

    Background In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management.1 The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. Methods A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System® (NIPACS) and Electronic Care Record® (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. Results Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to

  16. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  17. Usefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre-operative radiotherapy

    PubMed Central

    Liszka, Łukasz; Zielińska-Pająk, Ewa; Pająk, Jacek; Gołka, Dariusz; Starzewski, Jacek; Lorenc, Zbigniew

    2007-01-01

    AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between “T-downstaging” versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN. RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. “T-downstaging” was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between “T-downstaging” and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRG5. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG. CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patients with rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between “T-downstaging” and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement. PMID:17278216

  18. '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.

  19. 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.

  20. 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.

  1. [A Case of Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy with Carboplatin plus Etoposide in a Hemodialysis Patient].

    PubMed

    Terashima, Takeshi; Iwami, Eri; Chubachi, Shotaro; Ikemura, Shinnosuke; Nakajima, Takahiro; Matsuzaki, Tatsu; Aoyagi, Hiroshi

    2016-01-01

    In recent years, many patients have had to undergo hemodialysis due to chronic renal failure. In addition, the number of hemodialysis patients in whom lung cancer is discovered is increasing. However, a standard chemoradiotherapy regimen for limited-disease small-cell lung cancer patients undergoing maintenance hemodialysis has not yet been established. We administered concurrent chemoradiotherapy using carboplatin 300 mg/m2 (day 1) plus etoposide 50 mg/m2 (day 1, 3). A partial response was achieved after 4 courses of chemotherapy and 68 Gy of radiotherapy. The major toxicities were hematological toxicities; they included grade 4 thrombocytopenia, grade 3 anemia, and neutropenia. PMID:26809534

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Radical chemoradiotherapy for urethral squamous cell carcinoma: two case reports and a review of the literature.

    PubMed

    Coop, H; Pettit, L; Boon, C; Ramachandra, P

    2013-01-01

    Primary urethral squamous cell carcinoma is rare. Its management is particularly challenging owing to the paucity of evidence from randomised trials to inform practice. We report two male and female cases of squamous cell carcinoma of the urethra, which were treated with concomitant cisplatin and radiotherapy. These cases add to the body of case reports that have shown benefit for concomitant chemoradiotherapy in urethral squamous cell carcinoma. They also illustrate that single agent chemotherapy, namely, cisplatin, may be used successfully with limited toxicities. PMID:23738187

  7. 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

  8. 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

  9. 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

  10. Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

    PubMed

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2015-06-01

    Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes.

  11. Effect of chemoradiotherapy on nutrition status of patients with nasopharyngeal cancer.

    PubMed

    Hong, Jin-Sheng; Wu, Li-Hong; Su, Li; Zhang, Hai-Rong; Lv, Wen-Long; Zhang, Wei-Jian; Tian, Jun

    2016-01-01

    We aimed to assess the effect of chemoradiotherapy on the nutritional status of patients with nasopharyngeal cancer (NPC) and to detect the risk factors for poor nutrition status in NPC patients after radiotherapy. A total of 104 NPC patients participated in this clinical observational study. Psychological distress and nutritional indicators were measured prior to chemoradiotherapy. During the course of radiation therapy, side effect symptoms were assessed weekly. At the end of radiotherapy, nutritional indicators were measured again. Logistic regression was used to identify the risk factors for poor nutritional status after radiotherapy. The values of the 9 nutritional indicators were significantly lower after radiotherapy (P < 0.001) than the initial values before treatment. After radiotherapy, 20.19% of patients had more than 10% weight loss. At a significance level of α = 0.05, the risk factors for poor nutritional status were old age (P = 0.042), female gender (P < 0.001), late stage of the disease (P = 0.013), depression (P = 0.024), high side effect score (P = 0.007), and moderate nutritional status before radiotherapy (P = 0.015). Radiotherapy affects the nutritional status of NPC patients. To prevent malnutrition during radiotherapy, nutritional assessment and intervention should be an integral part of treatment. PMID:26709739

  12. Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer

    PubMed Central

    Teng, Feifei; Mu, Dianbin; Meng, Xiangjiao; Kong, Li; Zhu, Hui; Liu, Sujing; Zhang, Jianbo; Yu, Jinming

    2015-01-01

    Backgrounds: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. Methods: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. Results: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). Conclusions: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis. PMID:26269765

  13. Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis

    PubMed Central

    Zhou, Yu-juan; Yang, Wen-juan; Qiu, Yan-fang; Wang, Hui

    2016-01-01

    Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated. PMID:27016412

  14. [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

  15. Improving Cancer Chemoradiotherapy Treatment by Dual Controlled Release of Wortmannin and Docetaxel in Polymeric Nanoparticles.

    PubMed

    Au, Kin Man; Min, Yuanzeng; Tian, Xi; Zhang, Longzhen; Perello, Virginia; Caster, Joseph M; Wang, Andrew Z

    2015-09-22

    Combining molecularly targeted agents and chemotherapeutics is an emerging strategy in cancer treatment. We engineered sub-50 nm diameter diblock copolymer nanoparticles (NPs) that can sequentially release wortmannin (Wtmn, a cell signaling inhibitor) and docetaxel (Dtxl, genotoxic anticancer agent) to cancer cells. These NPs were studied in chemoradiotherapy, an important cancer treatment paradigm, in the preclinical setting. We demonstrated that Wtmn enhanced the therapeutic efficacy of Dtxl and increased the efficiency of radiotherapy (XRT) in H460 lung cancer and PC3 prostate cells in culture. Importantly, we showed that NPs containing both Wtmn and Dtxl release the drugs in a desirable sequential fashion to maximize therapeutic efficacy in comparison to administering each drug alone. An in vivo toxicity study in a murine model validated that NPs containing both Dtxl and Wtmn do not have a high toxicity profile. Lastly, we demonstrated that Dtxl/Wtmn-coencapsulated NPs are more efficient than each single-drug-loaded NPs or a combination of both single-drug-loaded NPs in chemoradiotherapy using xenograft models. Histopathological studies and correlative studies support that the improved therapeutic efficacy is through changes in signaling pathways and increased tumor cell apoptosis. Our findings suggest that our nanoparticle system led to a dynamic rewiring of cellular apoptotic pathways and thus improve the therapeutic efficiency.

  16. Small cell carcinoma of the pyriform sinus successfully treated with concurrent chemo-radiotherapy

    PubMed Central

    Lee, Joon Hyung; Jeong, Jae Seok; Kim, So Ri; Lee, Yong Chul

    2016-01-01

    Abstract Background: Primary small cell carcinomas (SCCs) are uncommon in extrapulmonary sites and account for only 2.5% to 5.0% of all SCCs. SCCs in the pyriform sinus are rare and there is little information regarding this disease, especially on therapeutics. Herein, we present a case of successfully treated SCC in the right pyriform sinus that occurred in a patient with small cell lung carcinoma (SCLC) that completely resolved 4 years prior. Methods: A 1.5 × 1.5-cm mass in the right pyriform sinus was detected on imaging studies in a 71-year-old male at a regular check-up visit after being in remission from SCLC. Results: Based on histologic examination and immunohistochemistry, the tumor in the right pyriform sinus was diagnosed as an extrapulmonary SCC. Chemo-radiotherapy was applied to the SCC of the pyriform sinus with a regimen of etoposide and cisplatin. The patient exhibited complete response to treatment and has been disease free for 11 months. Conclusion: This interesting case shows that chemotherapy with concurrent radiation may be an effective therapeutic modality for localized extrapulmonary SCC similar to localized SCLC, which is treated with concurrent chemo-radiotherapy as the standard therapeutic option. PMID:27603375

  17. Development of a Preclinical Therapeutic Model of Human Brain Metastasis with Chemoradiotherapy

    PubMed Central

    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

  18. [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

  19. Chemo-radiotherapy induced oral mucositis during IMRT for head and neck cancer - An assessment

    PubMed Central

    2015-01-01

    Background This study is conducted mainly to evaluate the changes in quality and quantity of oral epithelial cells during the course of IMRT. Material and Methods 30 Patients undergoing chemo-radiotherapy were followed through course of treatment. They were compared with a group of age- and sex-matched healthy individuals. The procedure involved WHO clinical scoring, collection of oral washings and preparation of buccal smears from both study group and control group. The changes occurred were recorded as a way of assessing the severity of oral mucositis. Results Revealed a significant occurrence of oral mucositis in almost all patients during weekly follow up. There was a significant increase in percentage of viable buccal epithelial cells in study group when compared to normal controls (P<0.005) during and at the end of chemo-radiotherapy. Conclusions Quantification of oral mucositis can be done at cellular level by determining the oral mucosal cell viability and their maturation during IMRT. Key words:Oral mucositis, in vitro assay, quantification, radiotherapy, chemotherapy, viable cells. PMID:25662542

  20. [Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

    PubMed

    Yamashiro, Keita; Heianna, Joichi; Azama, Kimei; Iraha, Yuko; Yamashiro, Tsuneo; Kinoshita, Ryo; Toita, Takafumi; Toyama, Masatomo; Agena, Shinya; Maeda, Hiroyuki; Suzuki, Mikio; Murayama, Sadayuki

    2016-02-01

    We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.

  1. 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

  2. Wakefield accelerators

    SciTech Connect

    Simpson, J.D.

    1990-01-01

    The search for new methods to accelerate particle beams to high energy using high gradients has resulted in a number of candidate schemes. One of these, wakefield acceleration, has been the subject of considerable R D in recent years. This effort has resulted in successful proof of principle experiments and in increased understanding of many of the practical aspects of the technique. Some wakefield basics plus the status of existing and proposed experimental work is discussed, along with speculations on the future of wake field acceleration. 10 refs., 6 figs.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. The impact of early percutaneous endoscopic gastrostomy placement on treatment completeness and nutritional status in locally advanced head and neck cancer patients receiving chemoradiotherapy.

    PubMed

    Atasoy, Beste M; Yonal, Oya; Demirel, Birsen; Dane, Faysal; Yilmaz, Yusuf; Kalayci, Cem; Abacioglu, Ufuk; Imeryuz, Nese

    2012-01-01

    To investigate the impact of early insertion of percutaneous endoscopic gastrostomy-tube on nutritional status and completeness of concurrent chemotherapy in locally advanced head and neck cancer patients treated with chemoradiotherapy. Twenty-three patients were enrolled into this prospective study. Gastrostomy-tube was inserted in patients before the initiation of chemoradiotherapy. There was not any significant change in nutritional parameters of patients that used their tube during treatment. Despite the grade 3 mucositis, the planned concurrent chemotherapy could be given in 70% of the patients. However, nine patients had weak compliance and their body weight (P = 0.01) and body mass index (P = 0.01) deteriorated in the first 4 weeks of chemoradiotherapy. The completeness of concurrent chemo-rate was 44% in these patients. Toxicity, requiring aggressive supportive care, may limit the chemotherapy part of curative concomitant chemoradiotherapy. By providing adequate enteral nutrition the insertion of gastrostomy-tube can increase the completeness rate of concurrent chemotherapy.

  10. Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis

    PubMed Central

    Zhang, Lijuan; Jiang, Nan; Shi, Yuexian; Li, Shipeng; Wang, Peiguo; Zhao, Yue

    2015-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). Whether induction chemotherapy (IC) with CCRT will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens for LA-SCCHN. Literature searches were carried out in PubMed, Embase, Cochrane Library and Chinese Biology Medicine from inception to November 2014. Five prospective randomized controlled trials (RCTs) with 922 patients were included in meta-analysis. Results were expressed as hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). Compared with CCRT, IC with CCRT showed no statistically significant differences in overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or locoregional recurrence rate (LRR), but could increase risks of grade 3–4 febrile neutropenia (P = 0.0009) and leukopenia (P = 0.04). In contrast, distant metastasis rate (DMR) decreased (P = 0.006) and complete response rate (CR) improved (P = 0.010) for IC with CCRT. In conclusion, the current studies do not support the use of IC with CCRT over CCRT, and the further positioning of IC with CCRT as standard treatment for LA-SCCHN will come from more RCTs directly comparing IC followed by CCRT with CCRT. PMID:26041604

  11. Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: a direct and adjusted indirect comparison meta-analysis.

    PubMed

    Kumagai, K; Rouvelas, I; Tsai, J A; Mariosa, D; Lind, P A; Lindblad, M; Ye, W; Lundell, L; Schuhmacher, C; Mauer, M; Burmeister, B H; Thomas, J M; Stahl, M; Nilsson, M

    2015-03-01

    Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.

  12. 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.

  13. Malnutrition and cachexia in patients with head and neck cancer treated with (chemo)radiotherapy

    PubMed Central

    Gorenc, Mojca; Kozjek, Nada Rotovnik; Strojan, Primož

    2015-01-01

    Aim To highlight the problems associated with nutrition that occur in patients with squamous cell carcinoma of the head and neck (SCCHN). Background SCCHN is associated with weight loss before, during and after radiotherapy or concurrent chemoradiotherapy. Because of serious consequences of malnutrition and cachexia on treatment outcome, mortality, morbidity, and quality of life, it is important to identify SCCHN patients with increased risk for the development of malnutrition and cachexia. Materials and methods Critical review of the literature. Results This review describes pathogenesis, diagnosis and treatment of malnutrition and cancer cachexia. Treatment of malnutrition and cancer cachexia includes nutritional interventions and pharmacological therapy. Advantages and disadvantages of different nutritional interventions and their effect on the nutritional status, quality of life and specific oncological treatment are presented. Conclusions Nutritional management is an essential part of care of these patients, including early screening, assessment of nutritional status and appropriate intervention. PMID:26109912

  14. [Efficacy of concurrent chemoradiotherapy in cases with cervical lymph node metastasis from oropharyngeal or hypopharyngeal cancer].

    PubMed

    Shimane, Toshikazu; Ikeda, Kenichiro; Akiyama, Rio; Uzuki, Aya; Sugimoto, Akane; Ikenoya, Youichi; Hayashi, Takeshi; Egawa, Shunya; Kobayashi, Sei; Sanbe, Takeyuki; Suzaki, Harumi

    2011-04-01

    We reported the efficacy of concurrent chemoradiotherapy(CCRT)for cervical lymph node metastasis in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma. The subjects were 17 patients with oropharyngeal or hypopharyngeal cancer with cervical lymph node metastasis, who underwent CCRT treatment between January 2005 and December 2009. The proportion of patients showing a complete response(CR)was 64. 7%; however, if patients without any residual viable cancer cells in the specimens obtained by neck dissection were also defined as CR, then, 82. 4% achieved CR. Thus, CCRT showed good efficacy without the need for planned neck dissection(PND). The limited recurrence cases and absence of serious complications associated with neck dissection after CCRT suggested that PND is not necessarily required. However, since assessment of cervical lymph nodes after CCRT is difficult, it would be desirable to develop a reliable examination and to study the most suitable examination for detecting the presence/absence of cervical lymph node metastasis.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-03-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving {>=}10 and 20 Gy (V{sub 10} and V{sub 20}) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V{sub 10} (regression coefficient ({beta}) = -0.060, p = 0.009) and V{sub 20} ({beta} = -0.044, p = 0.010). In the combined cohort, the (adjusted) {beta} estimates for log (white blood cell) vs. V{sub 10} and V{sub 20} were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V{sub 10} {>=} 95% were more likely to experience Grade {>=}3 leukopenia (68.8% vs. 24.6%, p < 0.001) than were patients with V{sub 20} > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V{sub 10} < 95% and V{sub 20} < 76% may reduce HT.

  1. 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.

  2. CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients.

    PubMed

    Li, Cong; Wang, Zhimin; Liu, Fangqi; Zhu, Ji; Yang, Li; Cai, Guoxiang; Zhang, Zhen; Huang, Wei; Cai, Sanjun; Xu, Ye

    2014-10-01

    Chemoradiotherapy has been commonly used as neoadjuvant therapy for rectal cancer to allow for less aggressive surgical approaches and to improve quality of life. In cancer, it has been reported that CXCL10 has an anti-tumor function. However, the association between CXCL10 and chemoradiosensitivity has not been fully investigated. We performed this study to investigate the relationship between CXCL10 expression and chemoradiosensitivity in rectal cancer patients. Ninety-five patients with rectal cancer who received neoadjuvant chemoradiotherapy (NCRT) were included. Clinical parameters were compared with the outcome of NCRT and CXCL10 messenger RNA (mRNA) expression between the pathological complete response (pCR) group and non-pathological complete response (npCR) group. CXCL10 mRNA and protein expressions between groups were analyzed using the Student's t test and chi-square test. The mean mRNA level of CXCL10 in the pCR group was significantly higher than that in the npCR group (p = 0.010). In the pCR group, 73.7 % of the patients had high CXCL10 mRNA expression, and 61.4 % of the patients in the npCR group had low CXCL10 mRNA expression. Subjects with high CXCL10 mRNA expression demonstrated a higher sensitivity to NCRT (p = 0.011). The receiver operating characteristic curve showed that the diagnostic performance of CXCL10 mRNA expression had an area under the curve of 0.720 (95 % confidence interval, 0.573-0.867). There were no differences between the pCR and npCR groups in CXCL10 protein expression (p > 0.05). High CXCL10 mRNA expression is associated with a better tumor response to NCRT in rectal cancer patients and may predict the outcome of NCRT in this malignancy.

  3. Pre-operative Neutrophils/Lymphocyte Ratio in Rectal Cancer Patients with Preoperative Chemoradiotherapy

    PubMed Central

    Lino-Silva, Leonardo S.; Salcedo-Hernández, Rosa A.; Ruiz-García, Erika B.; García-Pérez, Leticia; Herrera-Gómez, Ángel

    2016-01-01

    Background: Several studies have reported that an elevation in neutrophils/lymphocyte ratio (NLR) is correlated with poor survival in patients with colorectal cancer, but in rectal cancer (RC), it has been reported only in a few studies. It is necessary to separate colon cancer and rectal cancer to clarify the prognostic significance of NLR, especially in patients who received chemoradiotherapy. Methods: It is a comparative, observational retrospective study of a cohort of 175 patients. We grouped the patients into two based on their NLR (0-3 vs. > 3) to correlate with disease-specific survival (DSS) and pathologic complete response (pCR). Results: The average NLR was 2.65 + 1.32 (range 0.58-6.89), and 144 (82.3%) patients had an NLR of 0-3. The median follow-up was 33.53 months. There were no differences in pCR between the two groups. The 5-year DSS was 78.8%. NLR did not correlate with survival. Mesorectal quality, pT3-4 tumors, lymph node metastasis, lymphovascular invasion, perineural invasion, positive margins and recurrence were statistically significant predictors of increased mortality in univariate analysis. In multivariate analysis, only overall recurrence correlated with poor survival. The analysis of the association of NLR with outcomes with different cut points (2.0, 2.5, 4 and 5) did not show differences in DSS and pCR. Conclusion: In our cohort, the NLR did not serve as a prognostic marker in patients with locally advanced rectal cancer and who received chemoradiotherapy and did not correlate with pCR as well. PMID:27703284

  4. 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

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. 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.

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

    PubMed

    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.

  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. 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.

  13. Arterial Chemoradiotherapy for Locally Advanced Tongue Cancer: Analysis of Retrospective Study of Therapeutic Results in 88 Patients

    SciTech Connect

    Fuwa, Nobukazu Kodaira, Takesi; Furutani, Kazuhisa; Tachibana, Hiroyuki; Nakamura, Tatsuya; Nakahara, Rie; Tomoda, Takuya; Inokuti, Haruo; Daimon, Takashi

    2008-11-15

    Purpose: To retrospectively investigate the therapeutic results of arterial injection therapy by way of the superficial temporal artery for 88 cases of Stage III and IV (M0) tongue cancer and to clarify the factors that affected the therapeutic results. Methods and Materials: We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 39 patients between January 1993 and July 2002. Systemic concurrent chemotherapy was given to 19 of these patients. We administered intra-arterial chemoradiotherapy with cisplatin with sodium thiosulfate to 49 patients between October 2002 and December 2006. Concurrent systemic chemotherapy was given to 38 of these patients. Results: The 3-year local control rate was 72% (T2-T3, 80%; and T4, 48%), and the 3-year survival rate was 57% (Stage III, 67%; Stage IV, 43%). On univariate analysis, age, T stage, N stage, overall stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and performance status had a significant effect on survival. On multivariate analysis, N stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and artery selected had a significant effect on survival. Conclusions: The therapeutic results of intra-arterial chemoradiotherapy using the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy using cisplatin with sodium thiosulfate were excellent, and we believe it will be a new therapy for advanced tongue cancer.

  14. 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).

  15. 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].

  16. 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

  17. 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

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  3. [A Case of Locally Advanced Rectal Cancer with a Pathological Complete Response to Preoperative Chemoradiotherapy].

    PubMed

    Akahoshi, Shin-ichi; Iizaka, Masayoshi; Murakami, Seiichi; Nimura, Satoshi; Takeguchi, Touichirou

    2015-11-01

    A 61-year-old woman presented with the chief complaint of melena. She was diagnosed with rectal cancer via colonoscopy. Computed tomography (CT) revealed a rectal cancer with wall thickening, accompanied by several regional lymph node metastases with no distant metastasis. The tumor stage was cT3, cN2a, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative chemoradiotherapy (CRT) (UFT 400 mg/day tegafur-uracil and 75 mg/day Leucovorin; 1.8 Gy in 25 fractions, total 45 Gy) was administered. Eight weeks after CRT, laparoscopy-assisted low anterior resection was performed. A pathological examination revealed that both the primary site and regional lymph nodes had no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 4 years since the operation. We report a case of rectal cancer that was successfully treated via preoperative CRT. This case may aid the development of a standard therapy for advanced rectal cancer.

  4. 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

  5. The provision of enteral nutritional support during definitive chemoradiotherapy in head and neck cancer patients.

    PubMed

    Bishop, Sarah; Reed, Warren Michael

    2015-12-01

    Combination chemoradiation is the gold standard of management for locally advanced squamous cell carcinomas of the head and neck. One of the most significant advantages of this approach to treatment is organ preservation which may not be possible with radical surgery. Unfortunately, few treatments are without side-effects and the toxicity associated with combined modality treatment causes meaningful morbidity. Patients with head and neck cancer (HNC) may have difficulties meeting their nutritional requirements as a consequence of tumour location or size or because of the acute toxicity associated with treatment. In particular, severe mucositis, xerostomia, dysgeusia and nausea and vomiting limit intake. In addition to this, dysphagia is often present at diagnosis, with many patients experiencing silent aspiration. As such, many patients will require enteral nutrition in order to complete chemoradiotherapy (CRT). Feeding occurs via catheters placed transnasally (nasogastric tubes) or directly into the stomach through the anterior abdominal wall (percutaneous gastrostomy tubes). In the absence of clear evidence concerning the superiority of one method over another, the choice of feeding tube tends to be dependent on clinician and patient preference. This review examines key issues associated with the provision of enteral nutritional support during definitive CRT in HNC patients, including feeding methods, patient outcomes and timing of tube insertion and use. PMID:27512573

  6. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  7. 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.

  8. Primary signet ring cell carcinoma of the prostate treated by radical cystoprostatectomy and chemoradiotherapy

    PubMed Central

    Kim, Sun Wook; Kim, Woohyun; Cho, Yong-Hyun; Kim, Tae-Jung; Woo, Insuk; Sohn, Dong Wan

    2016-01-01

    Primary signet ring cell carcinoma (SRCC) of the prostate is very rare. Although SRCC is primarily found in the stomach and colon, it can also be found in the pancreas, breast, thyroid, bladder, and prostate. We recently diagnosed and treated a case of primary SRCC of the prostate. A 56-year-old Korean man was referred to our institution for evaluation of a one-month history of hematuria and recently identified bladder mass. Transurethral resection of the bladder tumour was performed and histological and immunohistochemical evaluation revealed a diagnosis of SRCC with tumour invading into the outer half of the deep muscularis propria. After three weeks, the patient had radical cystoprostatectomy with ileal conduit. Tumour involved both prostate and bladder, but the centre of the tumour was located in the prostate. Duodenoscopy and colon fibroscopy both indicated no evidence of tumour origin in the gastrointestinal (GI) tract. Overall, this tumour was regarded as primary SRCC of the prostate. Concurrent chemoradiotherapy (CCRT) using leucovorin and fluorouracil was initiated two months later. The patient eventually developed bone and liver metastases and died of hepatopathy.

  9. A clinical trial of neoadjuvant concurrent chemoradiotherapy followed by resection for esophageal carcinoma

    PubMed Central

    Anvari, Kazem; Aledavood, Seyed Amir; Toussi, Mehdi Seilanian; Forghani, Mohammad Naser; Mohtashami, Samira; Rajabi, Mohammad Taghi; Shandiz, Fatemeh Homaee; Nosrati, Fatemeh; Nowferesti, Gholamhossein; Salek, Roham

    2015-01-01

    Background: Esophageal carcinoma is a common malignancy in the North East of Iran. Combined modality treatments have been adopted to improve survival in patients with esophageal carcinoma. In this trial, we evaluated the efficacy and toxicity of a preoperative concurrent chemoradiotherapy protocol in the patients with locally advanced esophageal carcinoma. Materials and Methods: Between 2006 and 2011, eligible patients with locally advanced esophageal carcinoma underwent concurrent radiotherapy and chemotherapy and 3-4 weeks later, esophagectomy. Pathologic response, overall survival rate, toxicity, and feasibility were evaluated. Results: One hundred ninety-seven patients with a median age of 59 (range: 27-70) entered the protocol. One hundred ninety-four cases (98.5%) had esophageal squamous cell carcinoma. Grades 3-4 of toxicity in patients undergoing neoadjuvant chemoradotherapy were as follows: Neutropenia in 21% and esophagitis in 2.5% of cases. There were 11 (5.6%) early death probably due to the treatment-related toxicities. One hundred twenty-seven patients underwent surgery with postsurgical mortality of 11%. In these cases, the complete pathological response was shown in 38 cases (29.9%) with a 5-year overall survival rates of 48.2% and median overall survival of 44 months (95% confidence interval, 24.46-63.54). Conclusion: The pathological response rate and the overall survival rate are promising in patients who completed the protocol as receiving at least one cycle of chemotherapy. However, the treatment toxicities were relatively high. PMID:26664422

  10. 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.

  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. 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.

  13. 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.

  14. 18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

    PubMed Central

    Anderegg, Maarten C. J.; de Groof, Elisabeth J.; Gisbertz, Suzanne S.; Bennink, Roel J.; Lagarde, Sjoerd M.; Klinkenbijl, Jean H. G.; Dijkgraaf, Marcel G. W.; Bergman, Jacques J. G. H. M.; Hulshof, Maarten C. C. M.; van Laarhoven, Hanneke W. M.; van Berge Henegouwen, Mark I.

    2015-01-01

    Background Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. Methods From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. Results 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). Conclusion In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery. PMID:26529313

  15. Is Duodenal Invasion a Relevant Prognosticator in Patients Undergoing Adjuvant Chemoradiotherapy for Distal Common Bile Duct Cancer?

    SciTech Connect

    Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe

    2010-07-15

    Purpose: To analyze the outcome of adjuvant chemoradiotherapy for patients with distal common bile duct (CBD) cancer who underwent curative surgery, and to identify the prognostic factors for these patients. Methods and Materials: Between January 1991 and December 2002, 38 patients with adenocarcinoma of the distal CBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 27 men and 11 women, and the median age was 60 years (range, 34-73). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500mg/m{sup 2}/day) was given on day 1 to day 3 of each split course. The median follow-up period was 39 months. Results: The 5-year overall survival rate of all patients was 49.1%. On univariate analysis, only histologic differentiation (p = 0.0005) was associated with overall survival. Tumor size ({<=}2cm vs. >2cm) had a marginally significant impact on the treatment outcome (p = 0.0624). However, there was no difference in overall survival rates between T3 and T4 tumors (p = 0.6189), for which the main determinants were pancreatic and duodenal invasion, respectively. On multivariate analysis, histologic differentiation (p = 0.0092) and tumor size (p = 0.0046) were independent risk factors for overall survival. Conclusions: Long-term survival can be expected in patients with distal CBD cancer undergoing curative surgery and adjuvant chemoradiotherapy. Histologic differentiation and tumor size were significant prognostic factors predicting overall survival, whereas duodenal invasion was not. This finding suggests the need for further refinement in tumor staging.

  16. 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

  17. Unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy: a case report with review of literature.

    PubMed

    Joshi, Nikhil P; Haresh, Kunhi Parambath; Das, Prasenjit; Kumar, Rajender; Prabhakar, Ramachandran; Sharma, Daya Nand; Heera, Puthiyeduthu; Julka, Pramod Kumar; Rath, Goura Kishor

    2010-01-01

    Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma of the trachea. We describe the case of an unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy up to a dose of 60 Gy in 33 fractions with weekly paclitaxel and carboplatin. The pathological recognition of basaloid squamous cell carcinoma and its distinction from adenoid cystic carcinoma of the trachea is important for its management. Combining systemic chemotherapy with locoregional radiation is a logical approach to treatment, especially for the basaloid squamous cell carcinoma of the trachea, given its tendency to metastasize early after definitive therapy. PMID:21119264

  18. Changes in Immunohistochemical Protein Levels in Anaplastic Lymphoma Kinase-positive Lung Adenocarcinoma Possibly due to Chemo-radiotherapy.

    PubMed

    Taniguchi, Hirokazu; Ikeda, Takaya; Soda, Hiroshi; Fukuda, Yuichi; Kitazaki, Takeshi; Nakamura, Yoichi; Kohno, Shigeru

    2016-01-01

    To detect the anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the standard methods. However, there are discrepancies between them. We herein report a 40-year-old woman with ALK fusion-positive adenocarcinoma that changed from positive to negative in IHC due to chemo-radiotherapy. Recurrence of the disease restored the IHC expression, whereas FISH was positive throughout the entire clinical course. Our experience suggests that we should therefore carefully evaluate samples after chemotherapy and radiotherapy. PMID:27374682

  19. 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

  20. CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy.

    PubMed

    Barker, Holly E; Patel, Radhika; McLaughlin, Martin; Schick, Ulrike; Zaidi, Shane; Nutting, Christopher M; Newbold, Katie L; Bhide, Shreerang; Harrington, Kevin J

    2016-09-01

    Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit. CCT244747 abrogated radiation-induced G2 arrest in the p53-deficient HNSCC cell lines, HN4 and HN5, causing cells to enter mitosis with unrepaired DNA damage. The addition of paclitaxel further increased cell kill and significantly reduced tumor growth in an HN5 xenograft model. Importantly, a lower dose of paclitaxel could be used when CCT244747 was included, therefore potentially limiting toxicity. Triple therapy reduced the expression of several markers of radioresistance. Moreover, the more radioresistant HN5 cell line exhibited greater radiation-mediated CHK1 activation and was more sensitive to triple therapy than HN4 cells. We analyzed CHK1 expression in a panel of head and neck tumors and observed that primary tumors from HPV(+) patients, who went on to recur postradiotherapy, exhibited significantly stronger expression of total, and activated CHK1. CHK1 may serve as a biomarker for identifying tumors likely to recur and, therefore, patients who may benefit from concomitant treatment with a CHK1 inhibitor and paclitaxel during radiotherapy. Clinical translation of this strategy is under development. Mol Cancer Ther; 15(9); 2042-54. ©2016 AACR.

  1. 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.

  2. 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.

  3. Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma.

    PubMed

    Wang, J; Myles, B; Wei, C; Chang, J Y; Hofstetter, W L; Ajani, J A; Swisher, S G; Cox, J D; Komaki, R; Liao, Z; Lin, S H

    2014-01-01

    Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m(2) ) or nonobese (BMI < 25 kg/m(2) ). Progression-free survival and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis-free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy- and radiotherapy-related treatment toxicities.

  4. Obesity and Outcomes in Patients Treated with Chemoradiotherapy for Esophageal Carcinoma

    PubMed Central

    Wang, Jingya; Myles, Bevan; Wei, Caimiao; Chang, Joe Y.; Hofstetter, Wayne L.; Ajani, Jaffer A.; Swisher, Stephen G.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing; Lin, Steven H.

    2013-01-01

    Background Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. We hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). Methods From March 2002 to April 2010, we retrospectively analyzed 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center, treated with either definitive or neoadjuvant CRT. Patients were categorized as either obese (BMI ≥ 25 kg/m2) or non-obese (BMI < 25 kg/m2). Progression-free survival (PFS) and overall survival (OS) times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results One hundred fifteen (28.4%) patients were classified as non-obese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (p < 0.001), adenocarcinoma located distally (p < 0.001), and have undergone surgery (p = 0.004). Obesity was not associated with either worse operative morbidity/mortality (p > 0.05) or worse positron emission tomography (PET) tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (pCR) (P = 0.98) on multivariate analysis. There was also no difference in OS, locoregional control, or metastasis-free survival between obese and non-obese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). Conclusions In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, our data suggest it may be associated with decreased risk of acute chemotherapy and radiotherapy-related treatment toxicities. PMID:23621168

  5. 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.

  6. NSE can predict the sensitivity to definitive chemoradiotherapy of small cell carcinoma of esophagus.

    PubMed

    Yan, Hongjiang; Wang, Renben; Jiang, Shumei; Zhu, Kunli; Feng, Rui; Xu, Xiaoqing; Meng, Xiangjiao

    2014-01-01

    Patients with esophageal small cell carcinoma undergoing definitive chemoradiotherapy (CRT) seem to have disparity in tumor response. The identification of CRT sensitivity-related tumor markers would be helpful for selecting patients most likely to benefit from CRT. The aim of this study was to examine the predictive value of biological markers in small cell carcinoma of the esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays, while the tumor responses were evaluated according to the World Health Organization response criteria. The relationships between pretreatment expression of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The effective rates (complete response + partial response) in NSE high and low groups were 10.80 % (9/82) and 37.98 % (31/82), respectively (P = 0.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (P = 0.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (P = 0.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (P = 0.003). The result showed a promising predictive value of NSE regarding to the sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT efficacy in patients with SCEC.

  7. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    PubMed

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  8. Quantification of Organ Motion During Chemoradiotherapy of Rectal Cancer Using Cone-Beam Computed Tomography

    SciTech Connect

    Chong, Irene; Hawkins, Maria; Hansen, Vibeke; Thomas, Karen; McNair, Helen; O'Neill, Brian; Aitken, Alexandra; Tait, Diana

    2011-11-15

    Purpose: There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic ({Sigma}) and random ({sigma}) setup errors. Methods and Materials: CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCT images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic ({Sigma}) and random ({sigma}) setup errors. Results: A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. Conclusions: In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.

  9. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  10. Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma

    PubMed Central

    Chan, Ellie; Duckworth, Lizette Vila; Alkhasawneh, Ahmad; Toro, Tania Zuluaga; Lu, Xiaomin; Ben-David, Kfir; Hughes, Steven J.; Rossidis, Georgios; Zlotecki, Robert; Lightsey, Judith; Daily, Karen C.; Dang, Long; Allegra, Carmen J.; King, Brent

    2016-01-01

    Background Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery. Methods All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+). Results Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival. Conclusions Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease. PMID:27034783

  11. Concurrent chemoradiotherapy with nedaplatin in patients with stage IIA to IVA cervical carcinoma.

    PubMed

    Fujioka, Toru; Yasuoka, Toshiaki; Koizumi, Masae; Tanaka, Hiroki; Hashimoto, Hisashi; Nabeta, Motoo; Koizumi, Koji; Matsubara, Yuko; Hamada, Katsuyuki; Matsubara, Keiichi; Katayama, Tomihiro; Nawa, Akihiro

    2013-01-01

    The present study aimed to evaluate the efficacy and toxicities of nadaplatin-based concurrent chemoradiotherapy (CCRT) in patients with stage IIA to IVA cervical carcinoma. Patients with an International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA cervical carcinoma were treated with nadaplatin-based CCRT, using high-dose rate intracavitary brachytherapy (HDR-ICBT) or radiotherapy (RT) alone, in patients with FIGO stage IIA to IVA cervical carcinoma. CCRT with nedaplatin (80 mg/m(2)) was administered on Days 1 and 29. The records of 17 women treated either with nadaplatin-based CCRT using HSR-ICBT (n=8) or RT alone (n=9), for stage IIA to IVA cervical carcinoma were retrospectively reviewed. The activity and toxicity were compared in the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. The 5-year overall survival rates in the CCRT and RT groups were 68.6 and 77.8%, respectively. The median OS of the CCRT and RT groups was 38.5 and 27.3 months, respectively. There was no significant difference in either PFS (P=0.618) or OS (P= 0.231). The most common grade 3-4 or higher toxicities in the CCRT groups were leuko-/neutropenia (37.5%). The frequency of acute grade 3-4 toxicity was higher in the CCRT compared to the RT group. However, no statistically significant difference was observed. Nedaplatin-based CCRT was safely performed. Although the prognosis of patients with FIGO stage IIA to IVA cervical carcinoma was not significantly improved, fewer distant relapses were observed in this treatment. Consequently, nedaplatin-based CCRT may be considered as a potential alternative to cisplatin-based CCRT in this patient population.

  12. CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy.

    PubMed

    Barker, Holly E; Patel, Radhika; McLaughlin, Martin; Schick, Ulrike; Zaidi, Shane; Nutting, Christopher M; Newbold, Katie L; Bhide, Shreerang; Harrington, Kevin J

    2016-09-01

    Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit. CCT244747 abrogated radiation-induced G2 arrest in the p53-deficient HNSCC cell lines, HN4 and HN5, causing cells to enter mitosis with unrepaired DNA damage. The addition of paclitaxel further increased cell kill and significantly reduced tumor growth in an HN5 xenograft model. Importantly, a lower dose of paclitaxel could be used when CCT244747 was included, therefore potentially limiting toxicity. Triple therapy reduced the expression of several markers of radioresistance. Moreover, the more radioresistant HN5 cell line exhibited greater radiation-mediated CHK1 activation and was more sensitive to triple therapy than HN4 cells. We analyzed CHK1 expression in a panel of head and neck tumors and observed that primary tumors from HPV(+) patients, who went on to recur postradiotherapy, exhibited significantly stronger expression of total, and activated CHK1. CHK1 may serve as a biomarker for identifying tumors likely to recur and, therefore, patients who may benefit from concomitant treatment with a CHK1 inhibitor and paclitaxel during radiotherapy. Clinical translation of this strategy is under development. Mol Cancer Ther; 15(9); 2042-54. ©2016 AACR. PMID:27422809

  13. Low thrombospondin 2 expression is predictive of low tumor regression after neoadjuvant chemoradiotherapy in rectal cancer

    PubMed Central

    Lin, Cheng-Yi; Lin, Ching-Yih; Chang, I-Wei; Sheu, Ming-Jen; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Lee, Ying-En; He, Hong-Lin

    2015-01-01

    Background: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. Methods: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. Results: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). Conclusion: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer. PMID:26807188

  14. Tumour volume changes assessed with high-quality KVCT in lung cancer patients undergoing concurrent chemoradiotherapy

    PubMed Central

    Lee, Y H; Lee, H C; Lee, S W; Kang, Y N; Kang, J H; Hong, S H; Kim, S J; Ahn, M I; Han, D H; Yoo, I R; Park, J G; Sung, S W; Lee, K Y

    2015-01-01

    Objective: We evaluated tumour volume changes in patients with lung cancer undergoing concurrent chemoradiotherapy using image-guided radiotherapy (RT). Methods: The kilovoltage image was obtained using CT on rail at every five fractions. The gross tumour volumes (GTVs), including the primary tumour and lymph nodes (LNs), were contoured to analyse the time and degree of tumour regression. Results: 46 patients [32, non-small-cell lung cancer (NSCLC), and 14, small-cell lung cancer (SCLC)] were included in this study. In total, 281 CT scans and 82 sites of GTVs were evaluated. Significant volume changes occurred in both the NSCLC and SCLC groups (p < 0.001 and 0.002), and the average GTV change compared with baseline was 49.85 ± 3.65 [standard error (SE)]% and 65.95 ± 4.60 (SE)% for the NSCLC and SCLC groups, respectively. A significant difference in the degree of volume reduction between the primary tumour and LNs was observed in only the NSCLC group (p < 0.0001) but not in the SCLC group (p = 0.735). The greatest volume regression compared with the volume before the five fractions occurred between the 15 and 20 fractions in the NSCLC group and between the 5 and 10 fractions in the SCLC group. Conclusion: Both primary tumour and LNs were well defined using CT on rail. Significant volume changes occurred during RT, and there was a difference in volume reduction between the NSCLC and SCLC groups, regarding the degree and timing of the tumour reduction in the primary tumour and LNs. Advances in knowledge: NSCLC and SCLC groups showed differences in the degree and timing of volume reduction. The primary tumour and LNs in NSCLC regressed differently. PMID:26055505

  15. 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

  16. 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.

  17. Analysis of simultaneous modulated accelerated radiotherapy (SMART) for nasopharyngeal carcinomas

    PubMed Central

    Tang, Jian Min; Ma, Xiu Mei; Hou, Yan Li; Dai, Li Yan; Cao, Hong Bin; Ye, Ming; Bai, Yong Rui

    2014-01-01

    The purpose of this study was to analyze the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) in patients with nasopharyngeal carcinoma (NPC). A total of 97 patients who underwent SMART for NPC between August 2005 and November 2011 were evaluated. The prescribed dose was 69.9 Gy/30 fractions at 2.33 Gy/fraction to the primary gross tumor volume (PGTV) including the nasopharynx gross target volume and the positive neck lymph nodes, and 60 Gy/30 fraction at 2.0 Gy/fraction to the PCTV1; 54 Gy/30 fractions at 1.8 Gy/fraction was given to the PCTV2. Among 59 patients with local advanced disease, 31 patients received concurrent chemoradiotherapy (chemo-RT) with a regimen consisting of 135 mg/m2 paclitaxel on Day 1 and 25 mg/m2 cisplatin on Days 1–3. The median follow-up period was 42 months. The local control rate (LCR), distant metastases-free survival (DMFS) and overall survival (OS) rates were 93.3%, 90.3% and 91.6% at 3 years, and 87.6%, 87.9% and 85.7% at 5 years, respectively. There was no significant difference in outcome with respect to these three indicators for Stage III and IV disease treated with/without concurrent chemoradiotherapy (P > 0.05). Acute toxicities included Grade 3 mucositis, skin desquamation, and leucopenia, which occurred in 78 (80.4%), 8 (8.2%), and 45 (46.4%) patients, respectively. No patient had a Grade 3–4 late toxicity. SMART was associated with a favorable outcome for NPC with acceptable toxicity. The local-regional control was excellent but distant metastasis remains the main risk. The combination of SMART and chemotherapy needs to be optimized through further studies to enhance outcomes for locally advanced diseases. PMID:24614820

  18. Pathological Assessment of Rectal Cancer after Neoadjuvant Chemoradiotherapy: Distribution of Residual Cancer Cells and Accuracy of Biopsy

    PubMed Central

    Xiao, Lin; Yu, Xin; Deng, Wenjing; Feng, Huixia; Chang, Hui; Xiao, Weiwei; Zhang, Huizhong; Xi, Shaoyan; Liu, Mengzhong; Zhu, Yujia; Gao, Yuanhong

    2016-01-01

    We investigated the distribution of residual cancer cells (RCCs) within different layers of the bowel wall in surgical specimens and the value of biopsies of primary rectal lesion after preoperative volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients with rectal cancer. Between April 2011 and April 2013, 178 patients with rectal cancer who received preoperative VMAT, concurrent chemotherapy, and surgery were evaluated; 79 of the patients received a biopsy of the primary lesion after chemoradiotherapy and prior to surgery. The distribution of RCCs in the surgical specimens and the sensitivity and specificity of the biopsy of primary rectal lesions for pathological response were evaluated. Fifty-two patients had a complete pathological response in the bowel wall. Of the 120 patients with ypT2-4, the rate of detection of RCCs in the mucosa, submucosa, and muscularis propria was 20%, 36.7%, 69.2%, respectively. The sensitivity and specificity of biopsies of primary rectal lesions was 12.9% and 94.1%, respectively. After chemoradiotherapy, the RCCs were primarily located in the deeper layers of the bowel wall, and the biopsy results for primary rectal lesions were unreliable due to poor sensitivity. PMID:27721486

  19. 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

  20. [Effectiveness of chemoradiotherapy for a patient with local recurrence of advanced gastric cancer followed by curable gastrectomy].

    PubMed

    Natsume, Soichiro; Iwasaki, Yoshiaki; Yajima, Kazuhito; Yuu, Ken; Oohinata, Ryouki; Ishiyama, Satoshi; Takahashi, Keiichi; Maeda, Yoshiharu

    2014-11-01

    We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

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

    PubMed

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

    2015-08-01

    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/m(2) per 24 h on days 1-5) and cisplatin (100 mg/m(2) 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.

  2. 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

  3. 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

  4. 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

  5. Basic Fibroblast Growth Factor-2/beta3 Integrin Expression Profile: Signature of Local Progression After Chemoradiotherapy for Patients With Locally Advanced Non-Small-Cell Lung Cancer

    SciTech Connect

    Massabeau, Carole; Rouquette, Isabelle; Lauwers-Cances, Valerie; Mazieres, Julien; Bachaud, Jean-Marc; Armand, Jean-Pierre; Delisle, Marie-Bernadette; Favre, Gilles; Toulas, Christine; Cohen-Jonathan-Moyal, Elizabeth

    2009-11-01

    Purpose: No biologic signature of chemoradiotherapy sensitivity has been reported for patients with locally advanced non-small-cell lung cancer (NSCLC). We have previously demonstrated that basic fibroblast growth factor (FGF-2) and alphavbeta3 integrin pathways control tumor radioresistance. We investigated whether the expression of the proteins involved in these pathways might be associated with the response to treatment and, therefore, the clinical outcome. Methods and Materials: FGF-2, beta3 integrin, angiopoietin-2, and syndecan-1 expression was studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemoradiotherapy for locally advanced NSCLC. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria using computed tomography at least 6 weeks after the end of the chemoradiotherapy. Local progression-free survival, metastasis-free survival, and disease-free survival were studied using the log-rank test and Cox proportional hazard analysis. Results: Among this NSCLC biopsy population, 43.7% overexpressed beta3 integrin (beta3{sup +}), 43% FGF-2 (FGF-2{sup +}), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our results showed a strong association between FGF-2 and beta3 integrin expression (p = .001). The adjusted hazard ratio of local recurrence for FGF-2{sup +}/beta3{sup +} tumors compared with FGF-2{sup -}/beta3{sup -} tumors was 6.1 (95% confidence interval, 2.6-14.6, p = .005). However, the risk of local recurrence was not increased when tumors overexpressed beta3 integrin or FGF-2 alone. Moreover, the co-expression of these two proteins was marginally associated with the response to chemoradiotherapy and metastasis-free survival. Conclusion: The results of this study have identified the combined profile FGF-2/beta3 integrin expression as a signature of local control in patients treated with chemoradiotherapy for locally advanced

  6. Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy

    PubMed Central

    Kasahara, Norimitsu; Imai, Hisao; Kaira, Kyoichi; Mori, Keita; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Harada, Hideyuki; Naito, Tateaki; Murakami, Haruyasu; Endo, Masahiro; Nakajima, Takashi; Yamada, Masanobu; Takahashi, Toshiaki

    2015-01-01

    Background The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients. Patients and methods. We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0–2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS. Results OS is more strongly correlated with PPS (Spearman’s r = 0.86, R2 = 0.72, p < 0.05) than PFS (Spearman’s r = 0.46, R2 = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS. Conclusions PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings. PMID:26834529

  7. 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.

  8. The Effect of Chemoradiotherapy with SRC Tyrosine Kinase Inhibitor, PP2 and Temozolomide on Malignant Glioma Cells In Vitro and In Vivo

    PubMed Central

    Eom, Keun-Yong; Cho, Bong Jun; Choi, Eun Jung; Kim, Jin-Ho; Chie, Eui Kyu; Wu, Hong-Gyun; Kim, Il Han; Paek, Sun Ha; Kim, Jae-Sung; Kim, In Ah

    2016-01-01

    Purpose We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays and in vivo brain tumor model. Materials and Methods The effect of PP2 on radiosensitivity of U251 and T98G cells was investigated using clonogenic assays. The expression of E-cadherin, matrix metalloproteinases 2 (MMP2), Ephrin type-A receptor 2 (EphA2), and vascular endothelial growth factor (VEGF) was measured by Western blotting and an accumulation of γH2AX foci 6 hours after radiotherapy was measured after PP2 treatment. The effect of PP2 on migration, invasion, and vasculogenic mimicry formation (VMF) of U251 cells was evaluated. In an orthotopical brain tumor model with U251 cells, PP2 was injected intraperitoneally with or without oral TMZ before, during and after whole brain radiotherapy. Bioluminescence images were taken to visualize in vivo tumors and immunohistochemical staining of VEGF, CD31, EphA2, and hypoxia-inducible factor 1a was performed. Results PP2 increased radiosensitivity of U251 and T98G cells without decreasing survival of normal human astrocytes. Chemoradiotherapy with PP2 and TMZ resulted in increased accumulation of γH2AX foci. PP2 induced overexpression of E-cadherin and suppression of MMP2, VEGF, and EphA2. PP2 also compromised invasion, migration, and VMF of U251 cells. In brain tumors, chemoradiotherapy with PP2 and TMZ decreased tumor volume best, but not statistically significantly compared with chemoradiotherapy with TMZ. The expression of VEGF and CD31 was suppressed in PP2-treated tumors. Conclusion PP2 enhances radiosensitivity of malignant glioma cells and suppresses invasion and migration of U251 cells. Chemoradiotherapy with PP2 and TMZ resulted in non-significant tumor volume decrease. PMID:26044161

  9. 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

  10. 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

  11. 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

  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. Salvage chemoradiotherapy after primary chemotherapy for locally advanced pancreatic cancer: a single-institution retrospective analysis

    PubMed Central

    2012-01-01

    Background There is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC. Methods Thirty patients who underwent salvage CRT, after the failure of primary chemotherapy for LAPC, were retrospectively enrolled from 2004 to 2011 at the authors’ institution. All the patients had histologically confirmed pancreatic adenocarcinoma. Results Primary chemotherapy was continued until progression or emergence of unacceptable toxicity. Eventually, 26 patients (87%) discontinued primary chemotherapy because of local tumor progression, whereas four patients (13%) discontinued chemotherapy because of interstitial pneumonitis caused by gemcitabine. After a median period of 7.9 months from starting chemotherapy, 30 patients underwent salvage CRT combined with either S-1 or 5-FU. Toxicities were generally mild and self-limiting. Median survival time (MST) from the start of salvage CRT was 8.8 months. The 6 month, 1-year and 2-year survival rates from the start of CRT were 77%, 33% and 26%, respectively. Multivariate analysis revealed that a lower pre-CRT serum CA 19–9 level (≤ 1000 U/ml; p = 0.009) and a single regimen of primary chemotherapy (p = 0.004) were independent prognostic factors for survival after salvage CRT. The MST for the entire patient population from the start of primary chemotherapy was 17.8 months, with 2- and 3-year overall survival rates of 39% and 22%, respectively. Conclusions CRT had moderate anti-tumor activity and an acceptable toxicity profile in patients with LAPC, even after failure of gemcitabine-based primary chemotherapy. If there are any signs of failure of primary chemotherapy without distant metastasis

  15. 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

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

    SciTech Connect

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

    2008-04-01

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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Long-term eradication of locally recurrent invasive follicular thyroid carcinoma after taxane-based concomitant chemoradiotherapy.

    PubMed

    Tulloch-Reid, Marshall; Skarulis, Monica C; Sherman, Steven I; Sarlis, Nicholas J; Santarpia, Libero

    2009-11-01

    A 46-year-old woman with history of radioiodine-refractory follicular thyroid carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease. She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT), which was well tolerated, resulting in complete remission and freedom from residual or recurrent FTC for longer than 5 years until her last follow-up at age 52. This case highlights the possibility of combining taxane-based chemotherapy with definitive radiotherapy (as CRT) for the management of locally aggressive recurrences in poorly differentiated thyroid carcinoma, thereby resulting in rapid and persistent disease eradication. Even in the light of recent data on the potential benefit of novel targeted therapy agents in poorly differentiated thyroid carcinoma, this approach in similar clinical settings deserves future investigation. PMID:20032418

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. RLIP76 Regulates PI3K/Akt Signaling and Chemo-Radiotherapy Resistance in Pancreatic Cancer

    PubMed Central

    Leake, Kathryn; Singhal, Jyotsana; Nagaprashantha, Lokesh Dalasanur; Awasthi, Sanjay; Singhal, Sharad S.

    2012-01-01

    Purpose Pancreatic cancer is an aggressive malignancy with characteristic metastatic course of disease and resistance to conventional chemo-radiotherapy. RLIP76 is a multi-functional cell membrane protein that functions as a major mercapturic acid pathway transporter as well as key regulator of receptor-ligand complexes. In this regard, we investigated the significance of targeting RLIP76 on PI3K/Akt pathway and mechanisms regulating response to chemo-radiotherapy. Research Design and Methods Cell survival was assessed by MTT and colony forming assays. Cellular levels of proteins and phosphorylation was determined by Western blot analyses. The impact on apoptosis was determined by TUNEL assay. The anti-cancer effects of RLIP76 targeted interventions in vivo were determined using mice xenograft model of the pancreatic cancer. The regulation of doxorubicin transport and radiation sensitivity were determined by transport studies and colony forming assays, respectively. Results Our current studies reveal an encompassing model for the role of RLIP76 in regulating the levels of fundamental proteins like PI3K, Akt, E-cadherin, CDK4, Bcl2 and PCNA which are of specific importance in the signal transduction from critical upstream signaling cascades that determine the proliferation, apoptosis and differentiation of pancreatic cancer cells. RLIP76 depletion also caused marked and sustained regression of established human BxPC-3 pancreatic cancer tumors in nude mouse xenograft model. RLIP76 turned out to be a major regulator of drug transport along with contributing to the radiation resistance in pancreatic cancer. Conclusions/Significance RLIP76 represents a mechanistically significant target for developing effective interventions in aggressive and refractory pancreatic cancers. PMID:22509328

  7. 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.

  8. Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: A matched-pair analysis

    SciTech Connect

    Das, Prajnan . E-mail: PrajDas@mdanderson.org; Lin, Edward H.; Bhatia, Sumita; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Hoff, Paulo M.; Eng, Cathy; Wolff, Robert A.; Delclos, Marc E.; Krishnan, Sunil; Janjan, Nora A.; Crane, Christopher H.

    2006-12-01

    Purpose: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU). Methods: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002. Results: In each group, 5 patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively. Conclusion: Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.

  9. 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.

  10. Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma—a pilot study

    PubMed Central

    Orditura, M.; Galizia, G.; Di Martino, N.; Ancona, E.; Castoro, C.; Pacelli, R.; Morgillo, F.; Rossetti, S.; Gambardella, V.; Farella, A.; Laterza, M.M.; Ruol, A.; Fabozzi, A.; Napolitano, V.; Iovino, F.; Lieto, E.; Fei, L.; Conzo, G.; Ciardiello, F.; De Vita, F.

    2014-01-01

    Background To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. Methods We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin–5-fluorouracil–oxaliplatin) for 4 cycles, and concurrent computed tomography–based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. Results All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. Conclusions In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response. PMID:24940093

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Management of the neck after chemoradiotherapy for head and neck cancers in Asia: consensus statement from the Asian Oncology Summit 2009.

    PubMed

    Wee, Joseph T; Anderson, Benjamin O; Corry, June; D'Cruz, Anil; Soo, Khee C; Qian, Chao-Nan; Chua, Daniel T; Hicks, Rodney J; Goh, Christopher H K; Khoo, James B; Ong, Seng C; Forastiere, Arlene A; Chan, Anthony T

    2009-11-01

    The addition of a planned neck dissection after radiotherapy has traditionally been considered standard of care for patients with positive neck-nodal disease. With the acceptance of chemoradiotherapy as the new primary treatment for patients with locally advanced squamous-cell head and neck cancers, and the increasing numbers of patients who achieve a complete response, the role of planned neck dissection is now being questioned. The accuracy and availability of a physical examination or of different imaging modalities to identify true complete responses adds controversy to this issue. This consensus statement will address some of the controversies surrounding the role of neck dissection following chemoradiotherapy for squamous-cell carcinomas of the head and neck, with particular reference to patients in Asia.

  17. 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.

  18. 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

  19. 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.

  20. Accelerator Technology Division

    NASA Astrophysics Data System (ADS)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  1. Linear accelerator: A concept

    NASA Technical Reports Server (NTRS)

    Mutzberg, J.

    1972-01-01

    Design is proposed for inexpensive accelerometer which would work by applying pressure to fluid during acceleration. Pressure is used to move shuttle, and shuttle movement is sensed and calibrated to give acceleration readings.

  2. 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.

  3. MEQALAC rf accelerating structure

    SciTech Connect

    Keane, J.; Brodowski, J.

    1981-01-01

    A prototype MEQALAC capable of replacing the Cockcroft Walton pre-injector at BNL is being fabricated. Ten milliamperes of H/sup -/ beam supplied from a source sitting at a potential of -40 kilovolt is to be accelerated to 750 keV. This energy gain is provided by a 200 Megahertz accelerating system rather than the normal dc acceleration. Substantial size and cost reduction would be realized by such a system over conventional pre-accelerator systems.

  4. Chemoradiotherapy versus radiotherapy alone in elderly patients with stage III non-small cell lung cancer: A systematic review and meta-analysis.

    PubMed

    Dawe, David E; Christiansen, David; Swaminath, Anand; Ellis, Peter M; Rothney, Janet; Rabbani, Rasheda; Abou-Setta, Ahmed M; Zarychanski, Ryan; Mahmud, Salaheddin M

    2016-09-01

    In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care. PMID:27565937

  5. Preoperative chemoradiotherapy with 5-fluorouracil and oxaliplatin for locally advanced rectal cancer: long-term results of a phase II trial.

    PubMed

    Liu, Luying; Cao, Caineng; Zhu, Yuan; Li, Dechuan; Feng, Haiyang; Luo, Jialin; Tang, Zhongzhu; Liu, Peng; Lu, Ke; Ju, Haixing; Zhang, Na

    2015-03-01

    The aim of this study was to report long-term results of patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy with fluorouracil, leucovorin, and oxaliplatin. From February 2002 to November 2006, a total of 58 patients with locally advanced rectal cancer were recruited. Secondary endpoints included the cumulative incidence of local and distant recurrences, disease-free survival, and overall survival. The median follow-up time was 138 months (109-151 months). The cumulative incidence of local recurrence at 10 years was 12.1%. The cumulative incidence of distant recurrence at 10 years was 53.4%. The overall survival in the intention-to-treat population was 39.5% at 10 years. Disease-free survival in the intention-to-treat population was 41.8% at 10 years. Univariate analysis revealed that pathologic complete response was associated with local recurrence, distant recurrence, disease-free survival, and overall survival (p < .05). Distant recurrence remains the predominant pattern of failure for patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision. Pathologic complete response is an independent prognostic factor for locally advanced rectal cancer after preoperative chemoradiotherapy.

  6. 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.

  7. Acceleration: It's Elementary

    ERIC Educational Resources Information Center

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  8. Far field acceleration

    SciTech Connect

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail.

  9. Angular Acceleration without Torque?

    ERIC Educational Resources Information Center

    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.

  10. Compact Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E.

    2004-01-01

    A plasma accelerator has been conceived for both material-processing and spacecraft-propulsion applications. This accelerator generates and accelerates ions within a very small volume. Because of its compactness, this accelerator could be nearly ideal for primary or station-keeping propulsion for spacecraft having masses between 1 and 20 kg. Because this accelerator is designed to generate beams of ions having energies between 50 and 200 eV, it could also be used for surface modification or activation of thin films.

  11. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

    PubMed Central

    Sebag-Montefiore, David; Stephens, Richard J; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Quirke, Phil; Couture, Jean; de Metz, Catherine; Myint, Arthur Sun; Bessell, Eric; Griffiths, Gareth; Thompson, Lindsay C; Parmar, Mahesh

    2009-01-01

    Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. Methods We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. Findings At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI

  12. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  13. Fiber Accelerating Structures

    SciTech Connect

    Hammond, Andrew P.; /Reed Coll. /SLAC

    2010-08-25

    One of the options for future particle accelerators are photonic band gap (PBG) fiber accelerators. PBG fibers are specially designed optical fibers that use lasers to excite an electric field that is used to accelerate electrons. To improve PBG accelerators, the basic parameters of the fiber were tested to maximize defect size and acceleration. Using the program CUDOS, several accelerating modes were found that maximized these parameters for several wavelengths. The design of multiple defects, similar to having closely bound fibers, was studied to find possible coupling or the change of modes. The amount of coupling was found to be dependent on distance separated. For certain distances accelerating coupled modes were found and examined. In addition, several non-periodic fiber structures were examined using CUDOS. The non-periodic fibers produced several interesting results and promised more modes given time to study them in more detail.

  14. Acceleration in astrophysics

    SciTech Connect

    Colgate, S.A.

    1993-12-31

    The origin of cosmic rays and applicable laboratory experiments are discussed. Some of the problems of shock acceleration for the production of cosmic rays are discussed in the context of astrophysical conditions. These are: The presumed unique explanation of the power law spectrum is shown instead to be a universal property of all lossy accelerators; the extraordinary isotropy of cosmic rays and the limited diffusion distances implied by supernova induced shock acceleration requires a more frequent and space-filling source than supernovae; the near perfect adiabaticity of strong hydromagnetic turbulence necessary for reflecting the accelerated particles each doubling in energy roughly 10{sup 5} to {sup 6} scatterings with negligible energy loss seems most unlikely; the evidence for acceleration due to quasi-parallel heliosphere shocks is weak. There is small evidence for the expected strong hydromagnetic turbulence, and instead, only a small number of particles accelerate after only a few shock traversals; the acceleration of electrons in the same collisionless shock that accelerates ions is difficult to reconcile with the theoretical picture of strong hydromagnetic turbulence that reflects the ions. The hydromagnetic turbulence will appear adiabatic to the electrons at their much higher Larmor frequency and so the electrons should not be scattered incoherently as they must be for acceleration. Therefore the electrons must be accelerated by a different mechanism. This is unsatisfactory, because wherever electrons are accelerated these sites, observed in radio emission, may accelerate ions more favorably. The acceleration is coherent provided the reconnection is coherent, in which case the total flux, as for example of collimated radio sources, predicts single charge accelerated energies much greater than observed.

  15. Intensity-Modulated Chemoradiotherapy Aiming to Reduce Dysphagia in Patients With Oropharyngeal Cancer: Clinical and Functional Results

    PubMed Central

    Feng, Felix Y.; Kim, Hyungjin M.; Lyden, Teresa H.; Haxer, Marc J.; Worden, Francis P.; Feng, Mary; Moyer, Jeffrey S.; Prince, Mark E.; Carey, Thomas E.; Wolf, Gregory T.; Bradford, Carol R.; Chepeha, Douglas B.; Eisbruch, Avraham

    2010-01-01

    Purpose To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia. Patients and Methods This was a prospective study of weekly chemotherapy (carboplatin dosed at one times the area under the curve [AUC, AUC 1] and paclitaxel 30 mg/m2) concurrent with IMRT aiming to spare noninvolved parts of the swallowing structures: pharyngeal constrictors, glottic and supraglottic larynx, and esophagus as well as the oral cavity and major salivary glands. Swallowing was assessed by patient-reported Swallowing and Eating Domain scores, observer-rated scores, and videofluoroscopy (VF) before therapy and periodically after therapy through 2 years. Results Overall, 73 patients with stages III to IV OPC participated. At a median follow-up of 36 months, 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. All measures of dysphagia worsened soon after therapy; observer-rated and patient-reported scores recovered over time, but VF scores did not. At 1 year after therapy, observer-rated dysphagia was absent or minimal (scores 0 to 1) in all patients except four: one who was feeding-tube dependent and three who required soft diet. From pretherapy to 12 months post-therapy, the Swallowing and Eating Domain scores worsened on average (± standard deviation) by 10 ± 21 and 13 ± 19, respectively (on scales of 0 to 100), and VF scores (on scale of 1 to 7) worsened from 2.9 ± 1.5 (mild dysphagia) to 4.1 ± 0.9 (mild/moderate dysphagia). Conclusion Chemoradiotherapy with IMRT aiming to reduce dysphagia can be performed safely for OPC and has high locoregional tumor control rates. On average, long-term patient-reported, observer-rated, and objective measures of swallowing were only slightly worse than pretherapy measures, representing potential improvement compared with previous studies

  16. The Dielectric Wall Accelerator

    SciTech Connect

    Caporaso, George J.; Chen, Yu-Jiuan; Sampayan, Stephen E.

    2009-01-01

    The Dielectric Wall Accelerator (DWA), a class of induction accelerators, employs a novel insulating beam tube to impress a longitudinal electric field on a bunch of charged particles. The surface flashover characteristics of this tube may permit the attainment of accelerating gradients on the order of 100 MV/m for accelerating pulses on the order of a nanosecond in duration. A virtual traveling wave of excitation along the tube is produced at any desired speed by controlling the timing of pulse generating modules that supply a tangential electric field to the tube wall. Because of the ability to control the speed of this virtual wave, the accelerator is capable of handling any charge to mass ratio particle; hence it can be used for electrons, protons and any ion. The accelerator architectures, key technologies and development challenges will be described.

  17. Switched matrix accelerator

    SciTech Connect

    Whittum, David H.; Tantawi, Sami G.

    2001-01-01

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We also provide an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392 GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  18. Switched Matrix Accelerator

    SciTech Connect

    Whittum, David H

    2000-10-04

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  19. Outcomes for Patients Who Fail High Dose Chemoradiotherapy and Autologous Stem Cell Rescue for Relapsed and Primary Refractory Hodgkin Lymphoma

    PubMed Central

    Moskowitz, Alison J; Perales, Miguel-Angel; Kewalramani, Tarun; Yahalom, Joachim; Castro-Malaspina, Hugo; Zhang, Zhigang; Vanak, Jill; Zelenetz, Andrew D; Moskowitz, Craig H

    2012-01-01

    Most patients with Hodgkin lymphoma (HL) are cured with first and second-line treatment; however for those who fail high dose chemoradiotherapy with autologous stem cell transplant (HDT-ASCT), outcome is unknown. This report is an analysis of patients with relapsed and primary refractory HL who were treated with HDT-ASCT and failed due to progression of disease (POD). Two hundred and two patients received HDT-ASCT at Memorial Sloan Kettering Cancer Center for relapsed or refractory HL between December 1994 and December 2005 and 71 failed due to POD. The median survival following HDT-ASCT failure was 25 months. Only 16 (23%) of the 71 patients are currently alive, 9 of whom are in remission. Multivariate analysis revealed two factors associated with poor outcome: relapse within 6 months of HDT-ASCT and primary refractory disease. The only factor associated with improved survival was the ability to receive a second transplant, in particular, reduced intensity allogeneic transplant (RIT). Novel therapies are needed for patients who fail HDT-ASCT, particularly those with primary refractory disease and those who relapse within 6 months of HDT-ASCT. Future studies should focus on prospectively evaluating RIT following HDT-ASCT failure in patients with remission duration from HDT-ASCT of greater than 6 months. PMID:19438504

  20. Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

    PubMed Central

    HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

    2016-01-01

    An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

  1. Interplay Between Oncoproteins and Antioxidant Enzymes in Esophageal Carcinoma Treated Without and With Chemoradiotherapy: A Prospective Study

    SciTech Connect

    Kaur, Tranum; Gupta, Rajesh; Vaiphei, Kim; Kapoor, Rakesh; Gupta, N.M.; Khanduja, K.L.

    2008-02-01

    Purpose: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. Methods and Materials: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. Results: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue of Group 2 patients showed similar pattern levels (high and low) as that of superoxide dismutase/catalase. The association of cyclooxygenase-2 and p53 with various antioxidant enzymes showed a significant positive correlation between cyclooxygenase-2 expression and catalase activity and an inverse trend between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given neoadjuvant therapy. In addition, patients with overexpressed p53 protein levels had lower glutathione peroxidase enzyme levels and vice versa in the tumor tissue of patients who had undergone surgery as their main mode of treatment. Conclusion: The results of this study broaden the insight into the relationships shared among oncoproteins and the antioxidant defense system, and this could be helpful in the clinical management of esophageal carcinoma.

  2. Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

    PubMed Central

    Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

    2016-01-01

    Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

  3. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  4. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  5. Dysphagia After Chemoradiotherapy for Head-and-Neck Squamous Cell Carcinoma: Dose-Effect Relationships for the Swallowing Structures

    SciTech Connect

    Dirix, Piet Abbeel, Sarah; Vanstraelen, Bianca; Hermans, Robert; Nuyts, Sandra

    2009-10-01

    Purpose: To evaluate late dysphagia after chemoradiotherapy for locally advanced head-and-neck squamous cell carcinoma, and to examine its correlation with clinical and dosimetric parameters. Methods and Materials: Consecutive patients, treated with radiotherapy (70-72 Gy) and concomitant chemotherapy (cisplatinum 100 mg/m{sup 2} every 3 weeks) between 2004 and 2007, were examined. Swallowing was evaluated by four quality-of-life questionnaires: EORTC C30 and H and N35, the Performance Status Scale of List, and the MD Anderson Dysphagia Inventory. Clinical and dosimetric parameters were correlated with late dysphagia. Results: A total of 53 disease-free patients were evaluated; mean follow-up was 20.4 months (range, 6-45 months). The volume of the middle pharyngeal constrictor muscle receiving {>=}50 Gy (p = 0.04), the mean dose to this structure (p = 0.02) and to the supraglottic larynx (p = 0.04) were significantly associated with late swallowing problems at univariate analysis, along with tumor localization (p = 0.008), T-classification (p = 0.02), and pretreatment swallowing problems (p = 0.01). Only this last factor significantly correlated with late dysphagia at multivariate analysis. Conclusion: These findings motivate further efforts to reduce the dose to the swallowing structures, especially to the pharyngeal constrictor muscles and the larynx. However, clinical parameters are also important and should be included in future prospective trials.

  6. Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

    PubMed Central

    Solanki, Abhishek A; Chang, Daniel T; Liauw, Stanley L

    2013-01-01

    Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive) disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT), followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision). Approximately 15% of patients can have a pathologic complete response (pCR) at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT. PMID:23983475

  7. Wake field accelerators

    SciTech Connect

    Wilson, P.B.

    1986-02-01

    In a wake field accelerator a high current driving bunch injected into a structure or plasma produces intense induced fields, which are in turn used to accelerate a trailing charge or bunch. The basic concepts of wake field acceleration are described. Wake potentials for closed cavities and periodic structures are derived, as are wake potentials on a collinear path with a charge distribution. Cylindrically symmetric structures excited by a beam in the form of a ring are considered. (LEW)

  8. ACCELERATION RESPONSIVE SWITCH

    DOEpatents

    Chabrek, A.F.; Maxwell, R.L.

    1963-07-01

    An acceleration-responsive device with dual channel capabilities whereby a first circuit is actuated upon attainment of a predetermined maximum acceleration level and when the acceleration drops to a predetermined minimum acceleriltion level another circuit is actuated is described. A fluid-damped sensing mass slidably mounted in a relatively frictionless manner on a shaft through the intermediation of a ball bushing and biased by an adjustable compression spring provides inertially operated means for actuating the circuits. (AEC)

  9. Optically pulsed electron accelerator

    DOEpatents

    Fraser, John S.; Sheffield, Richard L.

    1987-01-01

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radio frequency powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  10. Optically pulsed electron accelerator

    DOEpatents

    Fraser, J.S.; Sheffield, R.L.

    1985-05-20

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radiofrequency-powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  11. Acceleration of polarized protons in circular accelerators

    SciTech Connect

    Courant, E.D.; Ruth, R.D.

    1980-09-12

    The theory of depolarization in circular accelerators is presented. The spin equation is first expressed in terms of the particle orbit and then converted to the equivalent spinor equation. The spinor equation is then solved for three different situations: (1) a beam on a flat top near a resonance, (2) uniform acceleration through an isolated resonance, and (3) a model of a fast resonance jump. Finally, the depolarization coefficient, epsilon, is calculated in terms of properties of the particle orbit and the results are applied to a calculation of depolarization in the AGS.

  12. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-01-01

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  13. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  14. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

  15. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases. PMID:24365468

  16. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-09-02

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  17. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  18. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  19. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph

    2010-07-29

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?.

  20. Accelerators (4/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  1. Induction linear accelerators

    NASA Astrophysics Data System (ADS)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typically<10) structures and very large beam pipes. This combination increases the beam breakup limited maximum currents to of order kiloamperes. The micropulse lengths of these machines are measured in 10's of nanoseconds and duty factors as high as 10-4 have been achieved. Until recently the major problem with these machines has been associated with the pulse power drive. Beam currents of kiloamperes and accelerating potentials of megavolts require peak power drives of gigawatts since no energy is stored in the structure. The marriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  2. Accelerators (3/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  3. Accelerators (5/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  4. Accelerators (5/5)

    SciTech Connect

    2009-07-09

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  5. Accelerators (4/5)

    SciTech Connect

    2009-07-08

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  6. Accelerators (3/5)

    SciTech Connect

    2009-07-07

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  7. Ion Induction Accelerators

    NASA Astrophysics Data System (ADS)

    Barnard, John J.; Horioka, Kazuhiko

    The description of beams in RF and induction accelerators share many common features. Likewise, there is considerable commonality between electron induction accelerators (see Chap. 7) and ion induction accelerators. However, in contrast to electron induction accelerators, there are fewer ion induction accelerators that have been operated as application-driven user facilities. Ion induction accelerators are envisioned for applications (see Chap. 10) such as Heavy Ion Fusion (HIF), High Energy Density Physics (HEDP), and spallation neutron sources. Most ion induction accelerators constructed to date have been limited scale facilities built for feasibility studies for HIF and HEDP where a large numbers of ions are required on target in short pulses. Because ions are typically non-relativistic or weakly relativistic in much of the machine, space-charge effects can be of crucial importance. This contrasts the situation with electron machines, which are usually strongly relativistic leading to weaker transverse space-charge effects and simplified longitudinal dynamics. Similarly, the bunch structure of ion induction accelerators relative to RF machines results in significant differences in the longitudinal physics.

  8. Particle Acceleration in Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi

    2005-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., active galactic nuclei (AGNs), gamma ray burst (GRBs), and Galactic microquasar systems usually have power-law emission spectra. Fermi acceleration is the mechanism usually assumed for the acceleration of particles in astrophysical environments.

  9. Microscale acceleration history discriminators

    DOEpatents

    Polosky, Marc A.; Plummer, David W.

    2002-01-01

    A new class of micromechanical acceleration history discriminators is claimed. These discriminators allow the precise differentiation of a wide range of acceleration-time histories, thereby allowing adaptive events to be triggered in response to the severity (or lack thereof) of an external environment. Such devices have applications in airbag activation, and other safety and surety applications.

  10. Diagnostics for induction accelerators

    SciTech Connect

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960`s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore`s Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail.

  11. KEK digital accelerator

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  12. Controllable Laser Ion Acceleration

    NASA Astrophysics Data System (ADS)

    Kawata, S.; Kamiyama, D.; Ohtake, Y.; Takano, M.; Barada, D.; Kong, Q.; Wang, P. X.; Gu, Y. J.; Wang, W. M.; Limpouch, J.; Andreev, A.; Bulanov, S. V.; Sheng, Z. M.; Klimo, O.; Psikal, J.; Ma, Y. Y.; Li, X. F.; Yu, Q. S.

    2016-02-01

    In this paper a future laser ion accelerator is discussed to make the laser-based ion accelerator compact and controllable. Especially a collimation device is focused in this paper. The future laser ion accelerator should have an ion source, ion collimators, ion beam bunchers, and ion post acceleration devices [Laser Therapy 22, 103(2013)]: the ion particle energy and the ion energy spectrum are controlled to meet requirements for a future compact laser ion accelerator for ion cancer therapy or for other purposes. The energy efficiency from the laser to ions is improved by using a solid target with a fine sub-wavelength structure or a near-critical density gas plasma. The ion beam collimation is performed by holes behind the solid target or a multi-layered solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching would be successfully realized by a multistage laser-target interaction.

  13. Cascaded radiation pressure acceleration

    SciTech Connect

    Pei, Zhikun; Shen, Baifei E-mail: zhxm@siom.ac.cn; Zhang, Xiaomei E-mail: zhxm@siom.ac.cn; Wang, Wenpeng; Zhang, Lingang; Yi, Longqing; Shi, Yin; Xu, Zhizhan

    2015-07-15

    A cascaded radiation-pressure acceleration scheme is proposed. When an energetic proton beam is injected into an electrostatic field moving at light speed in a foil accelerated by light pressure, protons can be re-accelerated to much higher energy. An initial 3-GeV proton beam can be re-accelerated to 7 GeV while its energy spread is narrowed significantly, indicating a 4-GeV energy gain for one acceleration stage, as shown in one-dimensional simulations and analytical results. The validity of the method is further confirmed by two-dimensional simulations. This scheme provides a way to scale proton energy at the GeV level linearly with laser energy and is promising to obtain proton bunches at tens of gigaelectron-volts.

  14. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    SciTech Connect

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  15. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in stage III-IVb nasopharyngeal carcinoma patients with Epstein-Barr virus DNA ≥4000 copies/ml: a matched study

    PubMed Central

    Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Guo, Ling; Mo, Hao-Yuan; Luo, Dong-Hua; Huang, Pei-Yu; Xiang, Yan-Qun; Sun, Rui; Chen, Ming-Yuan; Wang, Lin; Lv, Xing; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan; Zeng, Mu-Shen; Bei, Jin-Xin; Hong, Ming-Huang; Shao, Jian-Yong; Sun, Ying; Ma, Jun; Mai, Hai-Qiang

    2016-01-01

    Background The effects of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in high-risk (stage III-IVb with EBV DNA≥4000 copies/ml) nasopharyngeal carcinoma (NPC) patients are unclear. Methods A total of 325 high-risk NPC patients treated with IC+CCRT or CCRT alone who were treated with intensity-modulated radiation therapy (IMRT) between March 2007 and March 2013 were included. For each patient in the IC+CCRT group, a matched pair in the CCRT group was matching for: gender, age, T stage, N stage, clinical stage and WHO (World Health Organization) type. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Results There were no significant differences in OS, PFS, DMFS, and LRFS between the IC+CCRT (148 patients) and CCRT (177 patients) groups. After matching, 103 paired patients were analyzed, and there were no differences between the IC+CCRT and CCRT groups regarding clinical outcomes. Based on the subgroup analysis of 156 very-high-risk patients (stage N2-3 with EBV DNA ≥4000 copies/ml), the 5-year OS of the IC+CCRT and CCRT groups was 84.3% and 67.5% (P =0.033), respectively. Based on our multivariate analysis, the treatment group was significantly associated with OS (P=0.034; HR0.451, 95%CI 0.216-0.941). Conclusions IC+CCRT did not improve the clinical outcomes of high-risk NPC patients compared to CCRT alone. However, in very-high-risk patients, IC+CCRT treatment led to increased OS compared to patients received CCRT treatment alone. PMID:27105538

  16. Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway.

    PubMed

    Yu, Zhiqi; Zhang, Chang; Wang, Hao; Xing, Junjie; Gong, Haifeng; Yu, Enda; Zhang, Wei; Zhang, Xiaoqing; Cao, Guangwen; Fu, Chuangang

    2014-10-28

    This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II-III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade ≤ 2 vs. ≥3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094-2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041-2.200, p = 0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.

  17. Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

    PubMed

    Wen, Shu Wen; Everitt, Sarah J; Bedő, Justin; Chabrot, Marine; Ball, David L; Solomon, Benjamin; MacManus, Michael; Hicks, Rodney J; Möller, Andreas; Leimgruber, Antoine

    2015-01-01

    There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60 Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (p<0.001) and 19.3% for Ci/E (p<0.001) patients. By Week 4, spleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.

  18. Use of Concept of Chemotherapy-Equivalent Biologically Effective Dose to Provide Quantitative Evaluation of Contribution of Chemotherapy to Local Tumor Control in Chemoradiotherapy Cervical Cancer Trials

    SciTech Connect

    Plataniotis, George A. Dale, Roger G.

    2008-12-01

    Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell kill as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.

  19. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  20. Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy Before Surgery

    PubMed Central

    Giorgetti, Assuero; Pallabazzer, Giovanni; Ripoli, Andrea; Solito, Biagio; Genovesi, Dario; Lencioni, Monica; Fabrini, Maria Grazia; D’Imporzano, Simone; Pieraccini, Laura; Marzullo, Paolo; Santi, Stefano

    2016-01-01

    Abstract To investigate the prognostic value of tumor metabolism measurements on serial 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography scans in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiotherapy. Forty-five patients (63 ± 7 years, 6 female) treated with concomitant chemoradiotherapy before surgery were followed up for 24 ± 18 months (range 4–71). Positron emission tomography and computed tomography scans were obtained within 1 week before the start (PET1) and 1 month after the completion of the treatment (PET2). Total body tumor metabolic activity was measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass, and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters between PET1 and PET2 were calculated and expressed as percentage of PET1 results. At the time of the analysis, 27 patients were dead and 18 were alive. There was no difference between the 2 groups in terms of age, sex, site of the disease, histology, and the presence/absence of linfonodal metastases (P = NS). Survival random forest analysis (20,000 trees) resulted in an estimate of error rate of 36%. The nonparametric approach identified ΔTLG40 as the most predictive factor of survival (relative importance 100%). Moreover, T (17%), N (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the end of chemioradioterapy, and ΔTLG50–70 (17%–5%) were positively associated with patient outcome. The nonparametric analysis confirmed the prognostic importance of some clinical parameters, such as TNM stage and cancer histology. Moreover, ΔTLG resulted to be the most important factor in predicting outcome and should be considered in risk stratification of patients treated with neoadjuvant chemoradiotherapy. PMID:27043676

  1. Pretreatment Apparent Diffusion Coefficient of the Primary Lesion Correlates With Local Failure in Head-and-Neck Cancer Treated With Chemoradiotherapy or Radiotherapy

    SciTech Connect

    Hatakenaka, Masamitsu; Nakamura, Katsumasa; Yabuuchi, Hidetake; Shioyama, Yoshiyuki; Matsuo, Yoshio; Ohnishi, Kayoko; Sunami, Shunya; Kamitani, Takeshi; Setoguchi, Taro; Yoshiura, Takashi; Nakashima, Torahiko; Nishikawa, Kei; Honda, Hiroshi

    2011-10-01

    Purpose: This study was performed to evaluate whether the apparent diffusion coefficient (ADC) of a primary lesion correlates with local failure in primary head-and-neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy or radiotherapy. Methods and Materials: We retrospectively studied 38 patients with primary HNSCC (12 oropharynx, 20 hypopharynx, 4 larynx, 2 oral cavity) treated with chemoradiotherapy or radiotherapy with radiation dose to gross tumor volume equal to or over 60 Gy and who underwent pretreatment magnetic resonance imaging, including diffusion-weighted imaging. Ten patients developed local failure during follow-up periods of 2.0 to 9.3 months, and the remaining 28 showed local control during follow-up periods of 10.5 to 31.7 months. The variables that could affect local failure (age, tumor volume, ADC, T stage, N stage, dose, treatment method, tumor location, and overall treatment time) were analyzed using logistic regression analyses for all 38 patients and for 17 patients with Stage T3 or T4 disease. Results: In univariate logistic analysis for all 38 cases, tumor volume, ADC, T stage, and treatment method showed significant (p < 0.05) associations with local failure. In multivariate analysis, ADC and T stage revealed significance (p < 0.01). In univariate logistic analysis for the 17 patients with Stage T3 or T4 disease, ADC and dose showed significant (p < 0.01) associations with local failure. In multivariate analysis, ADC alone showed significance (p < 0.05). Conclusions: The results suggest that pretreatment ADC, along with T stage, is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy.

  2. Combined chemoradiotherapy with local microwave hyperthermia for treatment of T3N0 laryngeal carcinoma: a retrospective study with long-term follow-up.

    PubMed

    Kouloulias, V; Triantopoulou, S; Vrouvas, J; Gennatas, K; Ouzounoglou, N; Kouvaris, J; Karaiskos, P; Aggelakis, P; Antypas, C; Zygogianni, A; Papavasiliou, K; Platoni, K; Kelekis, N

    2014-06-01

    The purpose of our study was to test the efficacy and toxicity of hyperthermia in conjunction with chemoradiotherapy for T3N0 laryngeal cancer. From 1997-2006, 25 patients diagnosed with T3N0 laryngeal carcinoma who denied laryngectomy were selected for this retrospective study. Patients received a total dose of 70 Gy (2 Gy per fraction, 5 days per week) in combination with 6 weekly sessions of hyperthermia, in addition to weekly cisplatin chemotherapy. The hyperthermia device was operated as a 433 MHz microwave heating with water loaded and water-cooled waveguides. The temperature was monitored subcutaneously in the skin under the aperture of the waveguide. The median follow-up was 60 months, while 23 of 25 patients (92%) presented complete response to treatment. The two patients that did not respond to thermoradiotherapy underwent total laryngectomy, and during follow-up were alive and free of disease. According to EORTC/RTOG criteria, toxicity was mild: three patients (12%) presented grade III, eight (32%) presented grade II and 14 (56%) presented grade I acute skin toxicity. Grade III laryngeal late toxicity (vocal cord malfunction due to severe oedema) was noted in two patients (8%) at 6-8 months post-thermo-chemoradiotherapy. Tmin was correlated (Spearman rho, p < 0.05) with response to treatment as well as with acute skin toxicity and laryngeal function. When a patient with T3N0 laryngeal carcinoma denies laryngectomy, an alternative treatment is combined thermo-chemoradiotherapy which seems to be effective and generally tolerable with radiation-induced skin toxicity and/or late side effects. A larger patient cohort is needed to confirm these results.

  3. Large electrostatic accelerators

    SciTech Connect

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  4. Analyzing radial acceleration with a smartphone acceleration sensor

    NASA Astrophysics Data System (ADS)

    Vogt, Patrik; Kuhn, Jochen

    2013-03-01

    This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

  5. An Interdisciplinary Nutrition Support Team Improves Clinical and Hospitalized Outcomes of Esophageal Cancer Patients with Concurrent Chemoradiotherapy

    PubMed Central

    Cong, Ming-Hua; Li, Shu-Luan; Cheng, Guo-Wei; Liu, Jin-Ying; Song, Chen-Xin; Deng, Ying-Bing; Shang, Wei-Hu; Yang, Di; Liu, Xue-Hui; Liu, Wei-Wei; Lu, Shi-Yan; Yu, Lei

    2015-01-01

    Background: The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT). Methods: Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups. Results: At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group. Conclusions: A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs. PMID:26608978

  6. Prospective Comparison of Surgery Alone and Chemoradiotherapy With Selective Surgery in Resectable Squamous Cell Carcinoma of the Esophagus

    SciTech Connect

    Ariga, Hisanori Nemoto, Kenji; Miyazaki, Shukichi; Yoshioka, Takashi; Ogawa, Yohishiro; Sakayauchi, Toru; Jingu, Keiichi; Miyata, Go; Onodera, Ko; Ichikawa, Hirofumi; Kamei, Takashi; Kato, Shunsuke; Ishioka, Chikashi; Satomi, Susumu; Yamada, Shogo

    2009-10-01

    Purpose: Esophagectomy remains the mainstay treatment for esophageal cancer, although retrospective studies have suggested that chemoradiotherapy (CRT) is as effective as surgery. To determine whether CRT can substitute for surgery as the primary treatment modality, we performed a prospective direct comparison of outcomes after treatment in patients with resectable esophageal cancer who had received CRT and those who had undergone surgery. Methods and Materials: Eligible patients had resectable T1-3N0-1M0 thoracic esophageal cancer. After the surgeon explained the treatments in detail, the patients selected either CRT (CRT group) or surgery (OP group). The CRT course consisted of two cycles of cisplatin and fluorouracil with split-course concurrent radiotherapy of 60Gy in 30 fractions. Patients with progressive disease during CRT and/or with persistent or recurrent disease after CRT underwent salvage resection. Results: Of 99 eligible patients with squamous cell carcinoma registered between January 2001 and December 2005, 51 selected CRT and 48 selected surgery. Of the patients in the CRT group, 13 (25.5%) underwent esophagectomy as salvage therapy. The 3- and 5-year survival rates were 78.3% and 75.7%, respectively, in the CRT group compared with 56.9% and 50.9%, respectively, in the OP group (p = 0.0169). Patients in the OP group had significantly more metastatic recurrence than those in the CRT group. Conclusions: Treatment outcomes among patients with resectable thoracic esophageal squamous cell carcinoma were comparable or superior after CRT (with salvage therapy if needed) to outcomes after surgery alone.

  7. Treatment Outcome and Recursive Partitioning Analysis-Based Prognostic Factors in Patients With Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Kim, Sung- Bae Ahn, Jin Hee; Kim, Yong Hee; Kim, Jong Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho-Young; Shin, Ji Hoon; Cho, Kyung-Ja; Ryu, Jin-Sook; Park, Seung-Il

    2008-07-01

    Purpose: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). Methods and Materials: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. Results: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). Conclusion: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated.

  8. Curative Chemoradiotherapy in Patients With Stage IVB Cervical Cancer Presenting With Paraortic and Left Supraclavicular Lymph Node Metastases

    SciTech Connect

    Kim, Ji-Yoon; Kim, Joo-Young; Kim, Jin Hee; Yoon, Mee Sun; Kim, Juree; Kim, Young Seok

    2012-11-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group II received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity.

  9. A Retrospective Comparison of Taxane and Fluorouracil-based Chemoradiotherapy in Patients with Inoperable Esophageal Squamous Cell Carcinoma

    PubMed Central

    Sun, Xiaojiang; Han, Shuiyun; Gu, Feiying; Lin, Gang; Wang, Zhun; Wang, Yuezhen; Xu, Yaping

    2016-01-01

    Purpose: To retrospectively compare taxane-based with fluorouracil-based chemoradiotherapy in terms of toxicity profiles, efficacy and survival in patients with inoperable esophageal cancer. Methods and Materials: We analyzed retrospectively 179 consecutive patients who were unresectable or medically unfit for surgery between March 2009 and November 2014. Eight-three patients were included in the taxane group and 96 cases were in the fluorouracil group. Results: The overall response rate (ORR) in the taxane group was higher than fluorouracil group, but was not significantly different (71.6% vs. 63.5%, respectively, P=0.255). In total, 53.0% (44/83) of the patients in the taxane group had progressive disease versus 54.2% (52/96) in the fluorouracil group (not significantly different (P=0.758)). There was no significant difference in overall response rate, progression free survival and overall survival, as well as treatment-related death. In terms of non-hematological toxicity, patients in the taxane group experienced a lower incidence of ≥ grade 3 esophageal perforation or fistula (4.8% vs. 13.5%, P=0.047) and pneumonia (4.8% vs. 9.7%, P=0.242). Regarding hematological toxicity, thrombocytopenia in the taxane group was significantly lower (4.8% vs. 13.5%, P=0.047), but there was a trend towards a higher rate of ≥ grade 3 leukopenia (34.9% vs.26.0%, P=0.196). Conclusions: Chemoradiation with taxane-based regimens is well tolerated, with potentially promising efficacy, and could become a good alternative treatment in a first line setting for patients with inoperable esophageal squamous cell carcinoma. PMID:27326249

  10. Prospective Pilot Study of Consolidation Chemotherapy With Docetaxel and Cisplatin After Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer

    SciTech Connect

    Lee, Kyun Chan; Lee, Seok Ho; Lee, Yuna; Park, Se Hoon Park, Jinny; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon; Kim, Dong Young; Kim, Seon Tae

    2008-05-01

    Purpose: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. Methods and Materials: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m{sup 2}, on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m{sup 2}, and cisplatin, 75 mg/m{sup 2}, every 3 weeks. Results: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. Conclusion: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.

  11. Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

    2010-09-01

    Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% {+-} 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p <.05). When the TVRR was categorized into three groups (<60%, 60-80%, and >80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of {>=}60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

  12. The Value of Restaging With Chest and Abdominal CT/MRI Scan After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Liu, Guo-Chen; Zhang, Xu; Xie, E.; An, Xin; Cai, Pei-Qiang; Zhu, Ying; Tang, Jing-Hua; Kong, Ling-Heng; Lin, Jun-Zhong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2015-01-01

    Abstract Little was known with regard to the value of preoperative systemic restaging for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). This study was designed to evaluate the role of chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) on preoperative restaging in LARC after neoadjuvant CRT and to assess the impact on treatment strategy. Between January 2007 and April 2013, 386 newly diagnosed consecutive patients with LARC who underwent neoadjuvant CRT and received restaging with chest and abdominal CT/MRI scan were included. Imaging results before and after CRT were analyzed. Twelve patients (3.1%) (6 liver lesions, 2 peritoneal lesions, 2 distant lymph node lesions, 1 lung lesions, 1 liver and lung lesions) were diagnosed as suspicious metastases on the restaging scan after radiotherapy. Seven patients (1.8%) were confirmed as metastases by pathology or long-term follow-up. The treatment strategy was changed in 5 of the 12 patients as a result of restaging CT/MRI findings. Another 10 patients (2.6%) who present with normal restaging imaging findings were diagnosed as metastases intra-operatively. The sensitivity, specificity accuracy, negative predictive value, and positive predictive values of restaging CT/MRI was 41.4%, 98.6%, 58.3%, and 97.3%, respectively. The low incidence of metastases and minimal consequences for the treatment plan question the clinical value of routine restaging of chest and abdomen after neoadjuvant CRT. Based on this study, a routine restaging CT/MRI of chest and abdomen in patients with rectal cancer after neoadjuvant CRT is not advocated, carcino-embryonic antigen (CEA) -guided CT/MRI restaging might be an alternative. PMID:26632714

  13. Complications After Sphincter-Saving Resection in Rectal Cancer Patients According to Whether Chemoradiotherapy Is Performed Before or After Surgery

    SciTech Connect

    Kim, Chan Wook; Kim, Jong Hoon; Yu, Chang Sik; Shin, Ui Sup; Park, Jin Seok; Jung, Kwang Yong; Kim, Tae Won; Yoon, Sang Nam; Lim, Seok-Byung; Kim, Jin Cheon

    2010-09-01

    Purpose: The aim of the present study was to compare the influence of preoperative chemoradiotherapy (CRT) with postoperative CRT on the incidence and types of postoperative complications in rectal cancer patients who underwent sphincter-saving resection. Patients and Methods: We reviewed 285 patients who received preoperative CRT and 418 patients who received postoperative CRT between January 2000 and December 2006. Results: There was no between-group difference in age, gender, or cancer stage. In the pre-CRT group, the mean level of anastomosis from the anal verge was lower (3.5 {+-} 1.4 cm vs. 4.3 {+-} 1.7 cm, p < 0.001) and the rate of T4 lesion and temporary diverting ileostomy was higher than in the post-CRT group. Delayed anastomotic leakage and rectovaginal fistulae developed more frequently in the pre-CRT group than in the post-CRT group (3.9% vs. 1.2%, p = 0.020, 6.5% vs. 1.3%, p = 0.027, respectively). Small bowel obstruction (arising from radiation enteritis) requiring surgical intervention was more frequent in the post-CRT group (0% in the pre-CRT group vs. 1.4% in the post-CRT group, p = 0.042). Multivariate analysis identified preoperative CRT as an independent risk factor for fistulous complications (delayed anastomotic leakage, rectovaginal fistula, rectovesical fistula), and postoperative CRT as a risk factor for obstructive complications (anastomotic stricture, small bowel obstruction). The stoma-free rates were significantly lower in the pre-CRT group than in the post-CRT group (5-year stoma-free rates: 92.8% vs. 97.0%, p = 0.008). Conclusion: The overall postoperative complication rates were similar between the pre-CRT and the Post-CRT groups. However, the pattern of postoperative complications seen after sphincter- saving resection differed with reference to the timing of CRT.

  14. Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas

    SciTech Connect

    Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.; Winter, Jordan; Hruban, Ralph H.; Guler, Mehmet; Schulick, Richard D.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.; Herman, Joseph M.

    2010-03-01

    Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.

  15. Dose-Volume Histogram Parameters and Clinical Factors Associated With Pleural Effusion After Chemoradiotherapy in Esophageal Cancer Patients

    SciTech Connect

    Shirai, Katsuyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi; Murata, Kazutoshi; Satoh, Yumi; Higuchi, Keiko; Nonaka, Tetsuo; Ishikawa, Hitoshi; Katoh, Hiroyuki; Takahashi, Takeo; Nakano, Takashi

    2011-07-15

    Purpose: To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose {>=}50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving {>=}10-60 Gy (Heart-V{sub 10} to V{sub 60} and Lung-V{sub 10} to V{sub 60}, respectively) were analyzed in relation to pleural effusion. Results: The median follow-up time was 26.9 months (range, 6.7-70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V{sub 10} to V{sub 60}, and Lung-V{sub 50} to V{sub 60} were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age {>=}65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V{sub 50} as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V{sub 50} <20%, 20%{<=} Heart-V{sub 50} <40%, and Heart-V{sub 50} {>=}40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01). Conclusion: Heart-V{sub 50} is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion.

  16. Outcomes of Chemoradiotherapy With 5-Fluorouracil and Mitomycin C for Anal Cancer in Immunocompetent Versus Immunodeficient Patients

    SciTech Connect

    Seo, Yuji; Kinsella, Michael T.; Reynolds, Harry L.; Chipman, Gregory; Remick, Scot C.; Kinsella, Timothy J.

    2009-09-01

    Purpose: Information is limited as to how we should treat invasive anal squamous cell carcinoma (SCC) in patients with chronic immunosuppression, since the majority of clinical studies to date have excluded such patients. The objective of this study is to compare treatment outcomes in immunocompetent (IC) versus immunodeficient (ID) patients with invasive anal SCC treated similarly with combined modality therapy. Methods and Materials: Between January 1999 and March 2007, a total of 36 consecutive IC and ID patients received concurrent chemoradiotherapy using three-dimensional conformal radiotherapy with infusional 5-fluorouracil and mitomycin C. The IC and ID groups consisted of 19 and 17 patients, respectively, with 14 human immunodeficiency virus-positive (HIV+) and 3 post-solid organ transplant ID patients. There were no significant differences in tumor size, T stage, N stage, chemotherapy doses, or radiation doses between the two groups. Results: With a median follow-up of 3.1 years, no differences were found in overall survival, disease-specific survival, and colostomy-free survival. Three-year overall survival was 83.6% (95% CI = 68.2-100) and 91.7% (95% CI = 77.3-100) in the IC and ID groups, respectively. In addition, there were no differences in acute and late toxicity profiles between the two groups. In the human immunodeficiency virus-positive patients, Cox modeling showed no difference in overall survival by pretreatment CD4 counts (hazard ratio = 0.994, 95% CI = 0.98-1.01). No correlation was found between CD4 counts and the degree of acute toxicities. Conclusion: Our data suggest that standard combined modality therapy with three-dimensional conformal radiotherapy and 5-fluorouracil plus mitomycin C is as safe and effective for ID patients as for IC patients.

  17. The Cumulative Cisplatin Dose Affects the Long-Term Survival Outcomes of Patients with Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Mao, Yan-Ping; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of the cumulative cisplatin dose (CCD) remains controversial for patients with nasopharyngeal carcinoma (NPC) receiving only concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 549 consecutive patients with non-metastatic, histologically-proven NPC treated using intensity-modulated radiotherapy (IMRT) at Sun Yat-sen university cancer center. Patient survival between different CCD groups were compared. The cut-off value of pre-treatment plasma EBV DNA (pre-DNA) and CCD based on disease-free survival (DFS) were 1460 copies/ml (AUC, 0.691; sensitivity, 0.717; specificity, 0.635) and 240 mg/m2 (AUC, 0.506; sensitivity, 0.526; specificity, 0.538), respectively. Of the entire cohort, 92/549 (16.8%) patients received a CCD ≥ 240 mg/m2 and 457 (83.2%) patients, <240 mg/m2. For CCD ≥ 240 mg/m2 vs. < 240 mg/m2, the estimated 4-year DFS, overall survival (OS), locoregional-free survival (LRFFS) and distant metastasis-free survival (DMFS) rates were 89.1% vs. 81.3% (P = 0.097), 92.4% vs. 90.0% (P = 0.369), 95.6% vs. 91.2% (P = 0.156), and 91.3% vs. 88.4% (P = 0.375), respectively. For the whole cohort, multivariate analysis identified the CCD was an independent prognostic factor for DFS (HR, 0.515; 95% CI, 0.267–0.995; P = 0.048). However, CCD (≥240 mg/m2) had no prognostic value in subgroup analysis with stratification by the cut-off value of pre-DNA (P > 0.05 for all rates). PMID:27071833

  18. Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.; Simon, Michael A.; Luu, Hue H.; Haydon, Rex C.; Montag, Anthony G.; Undevia, Samir D.

    2010-03-15

    Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

  19. Assessment of Anxiety and Depression in Oral Mucositis Patients Undergoing Cancer Chemoradiotherapy: A Randomized Cross-sectional Study

    PubMed Central

    Chaitanya, Nallan CSK; Garlapati, Komali; Priyanka, Danam Reshma; Soma, Sravani; Suskandla, Ujwala; Boinepally, Niharika Harsha

    2016-01-01

    Introduction: Oral mucositis is an unavoidable complication occurring during the treatment of cancer by radiotherapy, concurrent chemoradiotherapy (CCRT), or chemotherapy. This is a painful sequelae, significantly affecting the nutritional intake and quality of life. Materials and Methods: A multicentric cross-sectional study was done at four cancer centers in Hyderabad. About 455 subjects of both genders between 20 and 80 years undergoing cancer treatment such as chemotherapy (Group I), CCRT (Group II), radiotherapy within 14 days of initiation (Group III), and radiotherapy after 14 days of initiation of therapy (Group IV) who had oral mucositis were included in the study. A self-addressed Hospital Anxiety and Depression Scale questionnaire was used to assess the anxiety/depression in cancer therapy-induced oral mucositis patients. Results: Group III had established anxiety (58.82%) followed by Group IV (47.5%) of patients showing severe oral mucositis. In Group I, 47.17% and in Group II, 40% patients with borderline anxiety had mild mucositis, which was statistically significant (P = 0.01). Group III had established depression in 56.36%, followed by Group IV with 39.62% patients showed severe oral mucositis. Group I and II had mild to moderate mucositis, which was associated with established depression at statistically significant result (P = 0.02). Conclusion: Group IV had maximum participants with anxiety and depression, closely followed by Group II, Group III, and least in Group I. Thus appropriate intervention in the form of nonpharmacological and pharmacological treatment is warranted. PMID:27803567

  20. Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck

    SciTech Connect

    Sher, David J.; Balboni, Tracy A.; Haddad, Robert I.; Norris, Charles M.; Posner, Marshall R.; Wirth, Lori J.; Goguen, Laura A.; Annino, Donald; Tishler, Roy B.

    2011-08-01

    Purpose: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. Patients and Materials: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpoint was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. Results: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. Conclusion: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.

  1. Prognostic Factors for Survival and Resection in Patients With Initial Nonresectable Locally Advanced Pancreatic Cancer Treated With Chemoradiotherapy

    SciTech Connect

    Bjerregaard, Jon K.; Mortensen, Michael B.; Jensen, Helle A.; Nielsen, Morten; Pfeiffer, Per

    2012-07-01

    Background and Purpose: Controversies regarding the optimal therapy for patients with locally advanced pancreatic cancer (LAPC) exist. Although the prognosis as a whole remains dismal, subgroups are known to benefit from intensive therapy, including chemoradiotherapy (CRT). We describe the results in 178 patients treated from 2001 to 2010 and have developed a prognostic model for both survival and the possibility of a subsequent resection in these patients. Methods and Materials: From 2001 until 2010, 178 consecutive patients with LAPC were treated and included in the present study, with CRT consisting of 50 Gy in 27 fractions combined with tegafur-uracil(UFT)/folinic acid(FA). Results: The median survival from diagnosis was 11.5 months. Adverse events of Grade 3 or above were seen in 36% of the patients. Ninety-three percent of the patients completed all fractions. A Cox regression model for survival demonstrated resection (hazard ratio [HR] 0.12; 95% confidence interval [CI], 0.1-0.3) and pre-CRT gemcitabine-based therapy (HR 0.57; 95% CI, 0.4-0.9) as being associated with a favorable outcome, increasing gross tumor volume (HR 1.14; 95% CI, 1.0-1.3) was associated with shorter survival. A logistic regression model showed Stage III disease (odds ratio [OR] 0.16; 95% CI, 0.0-1.1) and abnormal hemoglobin (OR 0.26; 95% CI, 0.0-1.2) as being associated with lower odds of resection. Conclusion: This study confirms the favorable prognosis for patients receiving gemcitabine therapy before CRT and the poor prognosis associated with increasing tumor volume. In addition, CRT in patients with abnormal hemoglobin and Stage III disease rarely induced tumor shrinkage allowing subsequent resection.

  2. Can IMRT or Brachytherapy Reduce Dysphagia Associated With Chemoradiotherapy of Head and Neck Cancer? The Michigan and Rotterdam Experiences

    SciTech Connect

    Eisbruch, Avraham Levendag, Peter C.; Feng, Felix Y.; Teguh, David; Lyden, Teresa M.A.; Schmitz, Paul I.M.; Haxer, Marc; Noever, Inge; Chepeha, Douglas B.; Heijmen, Ben J.

    2007-10-01

    Purpose: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. Patients and Methods: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. Results: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. Conclusion: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia.

  3. A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer

    PubMed Central

    Homma, Akihiro; Hatakeyama, Hiromitsu; Mizumachi, Takatsugu; Kano, Satoshi; Sakashita, Tomohiro; Kuramoto, Rinnosuke; Nakamaru, Yuji; Onimaru, Rikiya; Tsuchiya, Kazuhiko; Yoshida, Daisuke; Yasuda, Koichi; Shirato, Hiroki; Fukuda, Satoshi

    2016-01-01

    Objective Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7–42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. Methods We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. Results At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). Conclusions The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT. PMID:27556279

  4. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

    PubMed Central

    Kim, Hwan-Ik; Noh, O Kyu; Oh, Young-Taek; Chun, Mison; Kim, Sang-Won; Cho, Oyeon; Heo, Jaesung

    2016-01-01

    Purpose Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. Materials and Methods From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Results Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). Conclusion CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy. PMID:27730801

  5. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

    SciTech Connect

    Kubicek, Gregory J.; Axelrod, Rita S.; Machtay, Mitchell; Ahn, Peter H.; Anne, Pramila R.; Fogh, Shannon; Cognetti, David; Myers, Thomas J.; Curran, Walter J.; Dicker, Adam P.

    2012-07-15

    Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m{sup 2} per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 2}. Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 2} (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m{sup 2} in patients previously treated for HNC and 1.3 mg/m{sup 2} in radiation-naive patients.

  6. Impact of dexamethasone, etoposide, ifosfamide and carboplatin as concurrent chemoradiotherapy agents for nasal natural killer/T-cell lymphoma.

    PubMed

    Hatayama, Yoshiomi; Aoki, Masahiko; Kawaguchi, Hideo; Narita, Yuichiro; Hirose, Katsumi; Sato, Mariko; Takai, Yoshihiro

    2013-07-01

    The nasal type of extranodal natural killer (NK)/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. The reported 5-year overall survival for patients with localized nasal NKTCL treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) is <50%. Dexamethasone, etoposide, ifosfamide and carboplatin (DeVIC) chemotherapy was designed as a salvage chemotherapeutic regimen for aggressive lymphoma, comprising multidrug resistance (MDR) non-related agents and etoposide, which is considered to be effective against nasal NKTCL. An experimental chemoradiotherapy (CRT) is currently being designed using DeVIC as the concurrent chemotherapeutic regimen for nasal NKTCL. The aim of this study was to examine the initial outcome of this treatment and evaluate its effectiveness and feasibility. Six patients (age range, 29-82 years; median age, 68 years) were treated with CRT using DeVIC between April, 2004 and February, 2010. The median follow-up was 56 months (range, 11-80 months). All patients were administered 3-6 cycles of full-dose DeVIC regimen. The chemotherapy was administered concurrently with radiotherapy (RT) and was repeated every 3 weeks. RT was performed using 4-MV X-ray and the prescription dose was 46-50 Gy/23-25 fx (median, 50 Gy). After treatment, all patients were followed up at our hospital. A complete remission was achieved in 5 patients (83%) at 1 month after treatment. The 5-year overall survival and disease-free survival rates were 100%. No severe adverse effect (grade ≥3) was reported. In conclusion, the initial results of the experimental CRT with DeVIC for this type of aggressive lymphoma were very encouraging. Further investigation is required on concurrent CRT with 50 Gy/25 fx and 3 cycles of DeVIC comprising non-MDR agents and etoposide for nasal NKTCL. PMID:24649228

  7. Impact of treatment time-related factors on prognoses and radiation proctitis after definitive chemoradiotherapy for cervical cancer.

    PubMed

    Huang, Eng-Yen; Lin, Hao; Wang, Chong-Jong; Chanchien, Chan-Chao; Ou, Yu-Che

    2016-09-01

    This study aimed to investigate the impact of treatment time-related factors on outcomes and radiation proctitis in patients undergoing concurrent chemoradiotherapy (CCRT) for cervical cancer. From September 2001 to December 2012, 146 patients with stage IIB cervical squamous cell carcinoma treated with CCRT were reviewed from a prospective cohort. Patients who received the same dose (45 Gy) of external beam radiation therapy (EBRT) were included in the analysis (n = 125). The same equivalent dose of 2 Gy (EQD2) of high-dose-rate intracavitary brachytherapy (HDR-ICBT) was delivered at either 4 fractions of 6 Gy or 6 fractions of 4.5 Gy. The effects of the overall treatment time (OTT) and interval between EBRT and HDR-ICBT on the cancer-specific survival (CSS), local recurrence (LR), and incidence of proctitis were compared. The treatment time-related factors did not adversely affect the CSS and LR rates. The multivariate analyses did not identify the OTT as an independent factor of CSS (P = 0.839) and LR (P = 0.856). However, OTT ≤56 days (P = 0.026) was identified as the only independent factor of overall proctitis. The 5-year Grade 2 or greater proctitis rates were 14.9% and 0% (P = 0.001) in patients with the EBRT to ICBT interval ≤5 days and >5 days, respectively. To reduce rectal damage without compromising prognosis, the gap between EBRT and HDR-ICBT should exceed 5 days in cervical cancer patients undergoing CCRT. Strictly limiting the OTT to 56 days may result in radiation proctitis without improvements in prognosis.

  8. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  9. Confronting Twin Paradox Acceleration

    NASA Astrophysics Data System (ADS)

    Murphy, Thomas W.

    2016-05-01

    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  10. Twisted waveguide accelerating structure.

    SciTech Connect

    Kang, Y. W.

    2000-08-15

    A hollow waveguide with a uniform cross section may be used for accelerating charged particles if the phase velocity of an accelerating mode is equal to or less than the free space speed of light. Regular straight hollow waveguides have phase velocities of propagating electromagnetic waves greater than the free-space speed of light. if the waveguide is twisted, the phase velocities of the waveguide modes become slower. The twisted waveguide structure has been modeled and computer simulated in 3-D electromagnetic solvers to show the slow-wave properties for the accelerating mode.

  11. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, Graeme (Inventor)

    1984-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids (16, 18) with multiple pairs of aligned holes positioned to direct a group of beamlets (20) along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam (14). An accelerator electrode device (22) downstream from the extraction grids, is at a much lower potential than the grids to accelerate the combined beam.

  12. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, G. (Inventor)

    1981-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids with multiple pairs of aligned holes positioned to direct a group of beamlets along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam. An accelerator electrode device downstream from the extraction grids is at a much lower potential than the grids to accelerate the combined beam. The application of the system to ion implantation is mentioned.

  13. Accelerator on a Chip

    ScienceCinema

    England, Joel

    2016-07-12

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  14. Charged particle accelerator grating

    DOEpatents

    Palmer, R.B.

    1985-09-09

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator is described. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams onto the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  15. Non-accelerator experiments

    SciTech Connect

    Goldhaber, M.

    1986-01-01

    This report discusses several topics which can be investigated without the use of accelerators. Topics covered are: (1) proton decay, (2) atmospheric neutrinos, (3) neutrino detection, (4) muons from Cygnus X-3, and (5) the double-beta decay.

  16. Dielectric assist accelerating structure

    NASA Astrophysics Data System (ADS)

    Satoh, D.; Yoshida, M.; Hayashizaki, N.

    2016-01-01

    A higher-order TM02 n mode accelerating structure is proposed based on a novel concept of dielectric loaded rf cavities. This accelerating structure consists of ultralow-loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure. Unlike conventional dielectric loaded accelerating structures, most of the rf power is stored in the vacuum space near the beam axis, leading to a significant reduction of the wall loss, much lower than that of conventional normal-conducting linac structures. This allows us to realize an extremely high quality factor and a very high shunt impedance at room temperature. A simulation of a 5 cell prototype design with an existing alumina ceramic indicates an unloaded quality factor of the accelerating mode over 120 000 and a shunt impedance exceeding 650 M Ω /m at room temperature.

  17. CLASHING BEAM PARTICLE ACCELERATOR

    DOEpatents

    Burleigh, R.J.

    1961-04-11

    A charged-particle accelerator of the proton synchrotron class having means for simultaneously accelerating two separate contra-rotating particle beams within a single annular magnet structure is reported. The magnet provides two concentric circular field regions of opposite magnetic polarity with one field region being of slightly less diameter than the other. The accelerator includes a deflector means straddling the two particle orbits and acting to collide the two particle beams after each has been accelerated to a desired energy. The deflector has the further property of returning particles which do not undergo collision to the regular orbits whereby the particles recirculate with the possibility of colliding upon subsequent passages through the deflector.

  18. Rare Isotope Accelerators

    NASA Astrophysics Data System (ADS)

    Savard, Guy

    2002-04-01

    The next frontier for low-energy nuclear physics involves experimentation with accelerated beams of short-lived radioactive isotopes. A new facility, the Rare Isotope Accelerator (RIA), is proposed to produce large amount of these rare isotopes and post-accelerate them to energies relevant for studies in nuclear physics, astrophysics and the study of fundamental interactions at low energy. The basic science motivation for this facility will be introduced. The general facility layout, from the 400 kW heavy-ion superconducting linac used for production of the required isotopes to the novel production and extraction schemes and the highly efficient post-accelerator, will be presented. Special emphasis will be put on a number of technical breakthroughs and recent R&D results that enable this new facility.

  19. Accelerator on a Chip

    SciTech Connect

    England, Joel

    2014-06-30

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  20. HEAVY ION LINEAR ACCELERATOR

    DOEpatents

    Van Atta, C.M.; Beringer, R.; Smith, L.

    1959-01-01

    A linear accelerator of heavy ions is described. The basic contributions of the invention consist of a method and apparatus for obtaining high energy particles of an element with an increased charge-to-mass ratio. The method comprises the steps of ionizing the atoms of an element, accelerating the resultant ions to an energy substantially equal to one Mev per nucleon, stripping orbital electrons from the accelerated ions by passing the ions through a curtain of elemental vapor disposed transversely of the path of the ions to provide a second charge-to-mass ratio, and finally accelerating the resultant stripped ions to a final energy of at least ten Mev per nucleon.

  1. Wake field acceleration experiments

    SciTech Connect

    Simpson, J.D.

    1988-01-01

    Where and how will wake field acceleration devices find use for other than, possibly, accelerators for high energy physics. I don't know that this can be responsibly answered at this time. What I can do is describe some recent results from an ongoing experimental program at Argonne which support the idea that wake field techniques and devices are potentially important for future accelerators. Perhaps this will spawn expanded interest and even new ideas for the use of this new technology. The Argonne program, and in particular the Advanced Accelerator Test Facility (AATF), has been reported in several fairly recent papers and reports. But because this is a substantially new audience for the subject, I will include a brief review of the program and the facility before describing experiments. 10 refs., 7 figs.

  2. Vibration control in accelerators

    SciTech Connect

    Montag, C.

    2011-01-01

    In the vast majority of accelerator applications, ground vibration amplitudes are well below tolerable magnet jitter amplitudes. In these cases, it is necessary and sufficient to design a rigid magnet support structure that does not amplify ground vibration. Since accelerator beam lines are typically installed at an elevation of 1-2m above ground level, special care has to be taken in order to avoid designing a support structure that acts like an inverted pendulum with a low resonance frequency, resulting in untolerable lateral vibration amplitudes of the accelerator components when excited by either ambient ground motion or vibration sources within the accelerator itself, such as cooling water pumps or helium flow in superconducting magnets. In cases where ground motion amplitudes already exceed the required jiter tolerances, for instance in future linear colliders, passive vibration damping or active stabilization may be considered.

  3. Breakthrough: Fermilab Accelerator Technology

    ScienceCinema

    None

    2016-07-12

    There are more than 30,000 particle accelerators in operation around the world. At Fermilab, scientists are collaborating with other laboratories and industry to optimize the manufacturing processes for a new type of powerful accelerator that uses superconducting niobium cavities. Experimenting with unique polishing materials, a Fermilab team has now developed an efficient and environmentally friendly way of creating cavities that can propel particles with more than 30 million volts per meter.

  4. Collective field accelerator

    DOEpatents

    Luce, John S.

    1978-01-01

    A collective field accelerator which operates with a vacuum diode and utilizes a grooved cathode and a dielectric anode that operates with a relativistic electron beam with a .nu./.gamma. of .about. 1, and a plurality of dielectric lenses having an axial magnetic field thereabout to focus the collectively accelerated electrons and ions which are ejected from the anode. The anode and lenses operate as unoptimized r-f cavities which modulate and focus the beam.

  5. Rolamite acceleration sensor

    DOEpatents

    Abbin, Joseph P.; Briner, Clifton F.; Martin, Samuel B.

    1993-01-01

    A rolamite acceleration sensor which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently.

  6. Microgravity Acceleration Measurement System

    NASA Technical Reports Server (NTRS)

    Foster, William

    2009-01-01

    Microgravity Acceleration Measurement System (MAMS) is an ongoing study of the small forces (vibrations and accelerations) on the ISS that result from the operation of hardware, crew activities, as well as dockings and maneuvering. Results will be used to generalize the types of vibrations affecting vibration-sensitive experiments. Investigators seek to better understand the vibration environment on the space station to enable future research.

  7. Rolamite acceleration sensor

    DOEpatents

    Abbin, J.P.; Briner, C.F.; Martin, S.B.

    1993-12-21

    A rolamite acceleration sensor is described which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently. 6 figures.

  8. Microwave inverse Cerenkov accelerator

    NASA Astrophysics Data System (ADS)

    Zhang, T. B.; Marshall, T. C.; LaPointe, M. A.; Hirshfield, J. L.

    1997-03-01

    A Microwave Inverse Cerenkov Accelerator (MICA) is currently under construction at the Yale Beam Physics Laboratory. The accelerating structure in MICA consists of an axisymmetric dielectrically lined waveguide. For the injection of 6 MeV microbunches from a 2.856 GHz RF gun, and subsequent acceleration by the TM01 fields, particle simulation studies predict that an acceleration gradient of 6.3 MV/m can be achieved with a traveling-wave power of 15 MW applied to the structure. Synchronous injection into a narrow phase window is shown to allow trapping of all injected particles. The RF fields of the accelerating structure are shown to provide radial focusing, so that longitudinal and transverse emittance growth during acceleration is small, and that no external magnetic fields are required for focusing. For 0.16 nC, 5 psec microbunches, the normalized emittance of the accelerated beam is predicted to be less than 5πmm-mrad. Experiments on sample alumina tubes have been conducted that verify the theoretical dispersion relation for the TM01 mode over a two-to-one range in frequency. No excitation of axisymmetric or non-axisymmetric competing waveguide modes was observed. High power tests showed that tangential electric fields at the inner surface of an uncoated sample of alumina pipe could be sustained up to at least 8.4 MV/m without breakdown. These considerations suggest that a MICA test accelerator can be built to examine these predictions using an available RF power source, 6 MeV RF gun and associated beam line.

  9. Amps particle accelerator definition study

    NASA Technical Reports Server (NTRS)

    Sellen, J. M., Jr.

    1975-01-01

    The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

  10. Laser Plasma Accelerators

    NASA Astrophysics Data System (ADS)

    Malka, Victor

    The continuing development of powerful laser systems has permitted to extend the interaction of laser beams with matter far into the relativistic domain, and to demonstrate new approaches for producing energetic particle beams. The extremely large electric fields, with amplitudes exceeding the TV/m level, that are produced in plasma medium are of relevance particle acceleration. Since the value of this longitudinal electric field, 10,000 times larger than those produced in conventional radio-frequency cavities, plasma accelerators appear to be very promising for the development of compact accelerators. The incredible progresses in the understanding of laser plasma interaction physic, allows an excellent control of electron injection and acceleration. Thanks to these recent achievements, laser plasma accelerators deliver today high quality beams of energetic radiation and particles. These beams have a number of interesting properties such as shortness, brightness and spatial quality, and could lend themselves to applications in many fields, including medicine, radio-biology, chemistry, physics and material science,security (material inspection), and of course in accelerator science.

  11. Biomedical accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  12. Accelerators for America's Future

    NASA Astrophysics Data System (ADS)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  13. Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer

    PubMed Central

    Diaz-Sanchez, Rosa-Maria; Pachón-Ibáñez, Jerónimo; Marín-Conde, Fátima; Rodríguez-Caballero, Ángela; Gutierrez-Perez, Jose-Luis

    2015-01-01

    Background To evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. Material and Methods In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. Results After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Conclusions Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy. Key words: Chlorhexidine, mucositis, head and neck cancer. PMID:25662553

  14. Comparative effects of different enteral feeding methods in head and neck cancer patients receiving radiotherapy or chemoradiotherapy: a network meta-analysis

    PubMed Central

    Zhang, Zhihong; Zhu, Yu; Ling, Yun; Zhang, Lijuan; Wan, Hongwei

    2016-01-01

    Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy were frequently used in the head and neck cancer patients when malnutrition was present. Nevertheless, the evidence was inclusive in terms of the choice and the time of tube placement. The aim of this network meta-analysis was to evaluate the comparative effects of prophylactic percutaneous endoscopic gastrostomy (pPEG), reactive percutaneous endoscopic gastrostomy (rPEG), and NGT in the head and neck cancer patients receiving radiotherapy or chemoradiotherapy. Databases of PubMed, Web of Science, and Elsevier were searched from inception to October 2015. Thirteen studies enrolling 1,631 participants were included in this network meta-analysis. The results indicated that both pPEG and NGT were superior to rPEG in the management of weight loss. pPEG was associated with the least rate of treatment interruption and nutrition-related hospital admission among pPEG, rPEG, and NGT. Meanwhile, there was no difference in tube-related complications. Our study suggested that pPEG might be a better choice in malnutrition management in the head and neck cancer patients undergoing radiotherapy or chemoradiotherapy. However, its effects need to be further investigated in more randomized controlled trials. PMID:27274283

  15. Comparative effects of different enteral feeding methods in head and neck cancer patients receiving radiotherapy or chemoradiotherapy: a network meta-analysis.

    PubMed

    Zhang, Zhihong; Zhu, Yu; Ling, Yun; Zhang, Lijuan; Wan, Hongwei

    2016-01-01

    Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy were frequently used in the head and neck cancer patients when malnutrition was present. Nevertheless, the evidence was inclusive in terms of the choice and the time of tube placement. The aim of this network meta-analysis was to evaluate the comparative effects of prophylactic percutaneous endoscopic gastrostomy (pPEG), reactive percutaneous endoscopic gastrostomy (rPEG), and NGT in the head and neck cancer patients receiving radiotherapy or chemoradiotherapy. Databases of PubMed, Web of Science, and Elsevier were searched from inception to October 2015. Thirteen studies enrolling 1,631 participants were included in this network meta-analysis. The results indicated that both pPEG and NGT were superior to rPEG in the management of weight loss. pPEG was associated with the least rate of treatment interruption and nutrition-related hospital admission among pPEG, rPEG, and NGT. Meanwhile, there was no difference in tube-related complications. Our study suggested that pPEG might be a better choice in malnutrition management in the head and neck cancer patients undergoing radiotherapy or chemoradiotherapy. However, its effects need to be further investigated in more randomized controlled trials. PMID:27274283

  16. Narrow band imaging with magnification can pick up esophageal squamous cell carcinoma more efficiently than lugol chromoendoscopy in patients after chemoradiotherapy.

    PubMed

    Asada-Hirayama, Itsuko; Kodashima, Shinya; Fujishiro, Mitsuhiro; Ono, Satoshi; Niimi, Keiko; Mochizuki, Satoshi; Konno-Shimizu, Maki; Mikami-Matsuda, Rie; Minatsuki, Chihiro; Nakayama, Chiemi; Takahashi, Yu; Yamamichi, Nobutake; Koike, Kazuhiko

    2013-01-01

    Aim. Little is known about the usefulness of narrow band imaging (NBI) for surveillance of patients after chemoradiotherapy for esophageal neoplasia. Its usefulness in detecting esophageal squamous cell carcinoma (SCC) or high-grade intraepithelial neoplasia (HGIN) in these patients was retrospectively compared to Lugol chromoendoscopy. Patients and Methods. We assessed the diagnostic ability of NBI with magnification based on the biopsy specimens obtained from iodine-unstained lesions. Seventy-two iodine-unstained lesions were biopsied and consecutively enrolled for this study. The lesions were divided into NBI positive and NBI negative. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of NBI with magnification and PPV of Lugol chromoendoscopy was calculated using histological assessment as a gold standard. Results. Forty-six endoscopic examinations using NBI with magnification followed by Lugol chromoendoscopy were performed to 28 patients. The prevalence of SCC and HGIN was 21.4%. Sensitivity, specificity, PPV, NPV, and accuracy of NBI were 100.0%, 98.5%, 85.7%, 100%, and 98.6%, respectively. On the contrary, PPV of Lugol chromoendoscopy were 8.3%. Compared to Lugol chromoendoscopy, NBI with magnification showed equal sensitivity and significantly higher PPV (P < 0.0001). Conclusion. NBI with magnification would be able to pick up esophageal neoplasia more efficiently than Lugol chromoendoscopy in patients after chemoradiotherapy.

  17. Diffusive Shock Acceleration and Reconnection Acceleration Processes

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; Le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.; Cummings, A.; Stone, E.; Decker, R.

    2015-12-01

    Shock waves, as shown by simulations and observations, can generate high levels of downstream vortical turbulence, including magnetic islands. We consider a combination of diffusive shock acceleration (DSA) and downstream magnetic-island-reconnection-related processes as an energization mechanism for charged particles. Observations of electron and ion distributions downstream of interplanetary shocks and the heliospheric termination shock (HTS) are frequently inconsistent with the predictions of classical DSA. We utilize a recently developed transport theory for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets. Particle energization associated with the anti-reconnection electric field, a consequence of magnetic island merging, and magnetic island contraction, are considered. For the former only, we find that (i) the spectrum is a hard power law in particle speed, and (ii) the downstream solution is constant. For downstream plasmoid contraction only, (i) the accelerated spectrum is a hard power law in particle speed; (ii) the particle intensity for a given energy peaks downstream of the shock, and the distance to the peak location increases with increasing particle energy, and (iii) the particle intensity amplification for a particular particle energy, f(x,c/{c}0)/f(0,c/{c}0), is not 1, as predicted by DSA, but increases with increasing particle energy. The general solution combines both the reconnection-induced electric field and plasmoid contraction. The observed energetic particle intensity profile observed by Voyager 2 downstream of the HTS appears to support a particle acceleration mechanism that combines both DSA and magnetic-island-reconnection-related processes.

  18. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Lee, Anne W.M. . E-mail: awmlee@ha.org.hk; Tung, Stewart Y.; Chan, Anthony T.C.; Chappell, Rick; Fu, Y.-T.; Lu, Tai-Xiang; Tan, Terence; Chua, Daniel T.T.; O'Sullivan, Brian; Xu, Shirley L.; Pang, Ellie S.Y.; Sze, W.-M.; Leung, T.-W.; Kwan, W.-H.; Chan, Paddy; Liu, X.-F.; Tan, E.-H.; Sham, Jonathan; Siu, Lillian; Lau, W.-H.

    2006-09-01

    Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Methods and Materials: All patients were irradiated with the same RT technique to {>=}66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p {>=} 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.

  19. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1989-01-01

    The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass. The goal of the present program is to demonstrate feasibility of the EPA thruster concept through experimental and theoretical investigations of the EPA acceleration mechanism and discharge chamber performance. Experimental investigations will include operating the test bed ion (TBI) engine as an EPA thruster and parametrically varying the thruster geometry and operating conditions to quantify the electrostatic plasma acceleration effect. The theoretical investigations will include the development of a discharge chamber model which describes the relationships between the engine size, plasma properties, and overall performance. For the EPA thruster to be a viable propulsion concept, overall thruster efficiencies approaching 30% with specific impulses approaching 1000 s must be achieved.

  20. Advanced accelerator theory development

    SciTech Connect

    Sampayan, S.E.; Houck, T.L.; Poole, B.; Tishchenko, N.; Vitello, P.A.; Wang, I.

    1998-02-09

    A new accelerator technology, the dielectric wall accelerator (DWA), is potentially an ultra compact accelerator/pulsed power driver. This new accelerator relies on three new components: the ultra-high gradient insulator, the asymmetric Blumlein and low jitter switches. In this report, we focused our attention on the first two components of the DWA system the insulators and the asymmetric Blumlein. First, we sought to develop the necessary design tools to model and scale the behavior of the high gradient insulator. To perform this task we concentrated on modeling the discharge processes (i.e., initiation and creation of the surface discharge). In addition, because these high gradient structures exhibit favorable microwave properties in certain accelerator configurations, we performed experiments and calculations to determine the relevant electromagnetic properties. Second, we performed circuit modeling to understand energy coupling to dynamic loads by the asymmetric Blumlein. Further, we have experimentally observed a non-linear coupling effect in certain asymmetric Blumlein configurations. That is, as these structures are stacked into a complete module, the output voltage does not sum linearly and a lower than expected output voltage results. Although we solved this effect experimentally, we performed calculations to understand this effect more fully to allow better optimization of this DWA pulse-forming line system.

  1. MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports

    PubMed Central

    Zhao, Yue; Li, Xingde; Kong, Xiangjun

    2015-01-01

    Background Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. Material/Methods A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. Results A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074–1.894), P=0.014), rectal cancer (OR=1.483(1.102–1.996), P=0.009), and TRG 1–2 vs. 3–5 group (OR=1.423(1.046–1.936), P=0.025), while other polymorphism including MTHFR

  2. Thyroid V30 Predicts Radiation-Induced Hypothyroidism in Patients Treated With Sequential Chemo-Radiotherapy for Hodgkin's Lymphoma

    SciTech Connect

    Cella, Laura; Conson, Manuel; Caterino, Michele; De Rosa, Nicola; Liuzzi, Raffaele; Picardi, Marco; Grimaldi, Francesco; Solla, Raffaele; Farella, Antonio; Salvatore, Marco; Pacelli, Roberto

    2012-04-01

    Purpose: Hypothyroidism (HT) is a frequent late side effect of Hodgkin's lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy. Methods and Materials: A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at different times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed. Results: Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p < 0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was {<=} 62.5%, the risk of developing HT was 11.5%, and if V30 was >62.5%, the risk was 70.8% (p < 0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6). Conclusions: The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.

  3. Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer

    PubMed Central

    Lv, Shiliang; Fang, Min; Yang, Jia; Zhan, Wenming; Jia, Yongshi; Xu, Hong’en; Song, Tao

    2016-01-01

    Objective The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer. Patients and methods From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8–2.0 Gy to a total radiation dose of 54.0–60.0 Gy. Preplanned concurrent S-1 (80 mg/m2/d) was given on days 1–14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles. Results The median age of the enrolled patients was 76 years (range: 70–88 years), and the clinical stages were stage I (two patients), stage II (24 patients), stage III (28 patients), and stage IV (14 patients). A total of 51 (75.0%) patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5%) patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS) and progression-free survival (PFS) times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade ≥3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS. Conclusion For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory survival outcomes with tolerable toxicities. More studies are highly warranted to further clarify this issue.

  4. Co-delivery of doxorubicin and (131)I by thermosensitive micellar-hydrogel for enhanced in situ synergetic chemoradiotherapy.

    PubMed

    Huang, Pingsheng; Zhang, Yumin; Wang, Weiwei; Zhou, Junhui; Sun, Yu; Liu, Jinjian; Kong, Deling; Liu, Jianfeng; Dong, Anjie

    2015-12-28

    Combined chemoradiotherapy is potent to defeat malignant tumor. Concurrent delivery of radioisotope with chemotherapeutic drugs, which also act as the radiosensitizer, to tumor tissues by a single vehicle is essential to achieve this objective. To this end, a macroscale injectable and thermosensitive micellar-hydrogel (MHg) depot was constructed by thermo-induced self-aggregation of poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethyleneglycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) triblock copolymer micelles (Ms), which could not only serve as a micellar drug reservoir to locally deliver concentrated nano chemotherapeutic drugs, but also immobilize radioisotopes at the internal irradiation hot focus. Doxorubicin (DOX) and iodine-131 labeled hyaluronic acid ((131)I-HA) were used as the model therapeutic agents. The aqueous mixture of drug-loaded PECT micelles and (131)I-HA exhibited sol-to-gel transition around body temperature. In vitro drug release study indicated that PECT/DOX Ms were sustainedly shed from the native PECT/DOX MHg formulation, which could be internalized by tumor cells with rapid intracellular DOX release. This hydrogel formulation demonstrated considerable in vitro antitumor effect as well as remarkable radiosensitization. In vivo subcutaneous injection of PECT MHg demonstrated that (131)I isotope was immobilized stably at the injection location and no obvious indication of damage to major organs were observed as indicated by the histopathological analysis. Furthermore, the peritumoral injection of chemo-radiation therapeutic agents-encapsulated MHg formulation on tumor-bearing nude mice resulted in the desired combined treatment effect, which significantly improved the tumor growth inhibition efficiency with minimized drug-associated side effects to major organs. Consequently, such a thermosensitive MHg formulation, which enabled the precise control over the dosage and ratio of combination

  5. Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer

    PubMed Central

    Lv, Shiliang; Fang, Min; Yang, Jia; Zhan, Wenming; Jia, Yongshi; Xu, Hong’en; Song, Tao

    2016-01-01

    Objective The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer. Patients and methods From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8–2.0 Gy to a total radiation dose of 54.0–60.0 Gy. Preplanned concurrent S-1 (80 mg/m2/d) was given on days 1–14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles. Results The median age of the enrolled patients was 76 years (range: 70–88 years), and the clinical stages were stage I (two patients), stage II (24 patients), stage III (28 patients), and stage IV (14 patients). A total of 51 (75.0%) patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5%) patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS) and progression-free survival (PFS) times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade ≥3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS. Conclusion For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory survival outcomes with tolerable toxicities. More studies are highly warranted to further clarify this issue. PMID:27660461

  6. Plasma-based accelerator structures

    SciTech Connect

    Schroeder, Carl B.

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  7. Beamlets from stochastic acceleration.

    PubMed

    Perri, Silvia; Carbone, Vincenzo

    2008-09-01

    We investigate the dynamics of a realization of the stochastic Fermi acceleration mechanism. The model consists of test particles moving between two oscillating magnetic clouds and differs from the usual Fermi-Ulam model in two ways. (i) Particles can penetrate inside clouds before being reflected. (ii) Particles can radiate a fraction of their energy during the process. Since the Fermi mechanism is at work, particles are stochastically accelerated, even in the presence of the radiated energy. Furthermore, due to a kind of resonance between particles and oscillating clouds, the probability density function of particles is strongly modified, thus generating beams of accelerated particles rather than a translation of the whole distribution function to higher energy. This simple mechanism could account for the presence of beamlets in some space plasma physics situations.

  8. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  9. Acceleration radioisotope production simulations

    SciTech Connect

    Waters, L.S.; Wilson, W.B.

    1996-12-31

    We have identified 96 radionuclides now being used or under consideration for use in medical applications. Previously, we calculated the production of {sup 99}Mo from enriched and depleted uranium targets at the 800-MeV energy used in the LAMPF accelerator at Los Alamos. We now consider the production of isotopes using lower energy beams, which may become available as a result of new high-intensity spallation target accelerators now being planned. The production of four radionuclides ({sup 7}Be, {sup 67}Cu, {sup 99}Mo, and {sup 195m}Pt) in a simplified proton accelerator target design is being examined. The LAHET, MCNP, and CINDER90 codes were used to model the target, transport a beam of protons and secondary produced particles through the system, and compute the nuclide production from spallation and low-energy neutron interactions. Beam energies of 200 and 400 MeV were used, and several targets were considered for each nuclide.

  10. Laser acceleration with open waveguides

    SciTech Connect

    Xie, Ming

    1999-03-01

    A unified framework based on solid-state open waveguides is developed to overcome all three major limitations on acceleration distance and hence on the feasibility of two classes of laser acceleration. The three limitations are due to laser diffraction, acceleration phase slippage, and damage of waveguide structure by high power laser. The two classes of laser acceleration are direct-field acceleration and ponderomotive-driven acceleration. Thus the solutions provided here encompass all mainstream approaches for laser acceleration, either in vacuum, gases or plasmas.

  11. Uniform acceleration in general relativity

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2015-10-01

    We extend de la Fuente and Romero's (Gen Relativ Gravit 47:33, 2015) defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  12. Diffusive Shock Acceleration

    NASA Astrophysics Data System (ADS)

    Baring, Matthew

    2003-04-01

    The process of diffusive acceleration of charged particles in shocked plasmas is widely invoked in astrophysics to account for the ubiquitous presence of signatures of non-thermal relativistic electrons and ions in the universe. This statistical energization mechanism, manifested in turbulent media, was first posited by Enrico Fermi in 1949 to explain the observed cosmic ray population, which exhibits an almost power-law distribution in rigidity. The absence of a momentum scale is a key characteristic of diffusive shock acceleration, and astrophysical systems generally only impose scales at the injection (low energy) and loss (high energy) ends of the particle spectrum. The existence of structure in the cosmic ray spectrum (the "knee") at around 3000 TeV has promoted contentions that there are at least two origins for cosmic rays, a galactic one supplying those up to the knee, and perhaps an extragalactic one that can explain even the ultra-high energy cosmic rays (UHECRs) seen at 1-300 EeV. Accounting for the UHECRs with familiar astrophysical sites of acceleration has historically proven difficult due to the need to assume high magnetic fields in order to reduce the shortest diffusive acceleration timescale, the ion gyroperiod, to meaningful values. Yet active galaxies and gamma-ray bursts remain strong and interesting candidate sources for UHECRs, turning the theoretical focus to relativistic shocks. This review summarizes properties of diffusive shock acceleration that are salient to the issue of UHECR generation. These include spectral indices, anisotropies, acceleration efficencies and timescales, as functions of the shock speed and mean field orientation, and also the degree of field turbulence. Astrophysical sites for UHECR production are also critiqued.

  13. Microelectromechanical acceleration-sensing apparatus

    DOEpatents

    Lee, Robb M.; Shul, Randy J.; Polosky, Marc A.; Hoke, Darren A.; Vernon, George E.

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  14. HIGH GRADIENT INDUCTION ACCELERATOR

    SciTech Connect

    Caporaso, G J; Sampayan, S; Chen, Y; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Krogh, M; Nelson, S; Nunnally, W; Paul, A; Poole, B; Rhodes, M; Sanders, D; Selenes, K; Sullivan, J; Wang, L; Watson, J

    2007-06-21

    A new type of compact induction accelerator is under development at the Lawrence Livermore National Laboratory that promises to increase the average accelerating gradient by at least an order of magnitude over that of existing induction machines. The machine is based on the use of high gradient vacuum insulators, advanced dielectric materials and switches and is stimulated by the desire for compact flash x-ray radiography sources. Research describing an extreme variant of this technology aimed at proton therapy for cancer will be described. Progress in applying this technology to several applications will be reviewed.

  15. Photocathodes in accelerator applications

    SciTech Connect

    Fraser, J.S.; Sheffield, R.L.; Gray, E.R.; Giles, P.M.; Springer, R.W.; Loebs, V.A.

    1987-01-01

    Some electron accelerator applications require bursts of short pulses at high microscopic repetition rates and high peak brightness. A photocathode, illuminated by a mode-locked laser, is well suited to filling this need. The intrinsic brightness of a photoemitter beam is high; experiments are under way at Los Alamos to study the brightness of short bunches with high space charge after acceleration. A laser-illuminated Cs/sub 3/Sb photoemitter is located in the first rf cavity of an injector linac. Diagnostics include a pepper-pot emittance analyzer, a magnetic spectrometer, and a streak camera.

  16. Interfacing to accelerator instrumentation

    SciTech Connect

    Shea, T.J.

    1995-12-31

    As the sensory system for an accelerator, the beam instrumentation provides a tremendous amount of diagnostic information. Access to this information can vary from periodic spot checks by operators to high bandwidth data acquisition during studies. In this paper, example applications will illustrate the requirements on interfaces between the control system and the instrumentation hardware. A survey of the major accelerator facilities will identify the most popular interface standards. The impact of developments such as isochronous protocols and embedded digital signal processing will also be discussed.

  17. Accelerated molecular dynamics methods

    SciTech Connect

    Perez, Danny

    2011-01-04

    The molecular dynamics method, although extremely powerful for materials simulations, is limited to times scales of roughly one microsecond or less. On longer time scales, dynamical evolution typically consists of infrequent events, which are usually activated processes. This course is focused on understanding infrequent-event dynamics, on methods for characterizing infrequent-event mechanisms and rate constants, and on methods for simulating long time scales in infrequent-event systems, emphasizing the recently developed accelerated molecular dynamics methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics). Some familiarity with basic statistical mechanics and molecular dynamics methods will be assumed.

  18. 'Light Sail' Acceleration Reexamined

    SciTech Connect

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for 'optimal' values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple 'light sail' model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  19. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  20. Prospects for Accelerator Technology

    NASA Astrophysics Data System (ADS)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  1. Radioisotope Dating with Accelerators.

    ERIC Educational Resources Information Center

    Muller, Richard A.

    1979-01-01

    Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

  2. The neutrino electron accelerator

    SciTech Connect

    Shukla, P.K.; Stenflo, L.; Bingham, R.; Bethe, H.A.; Dawson, J.M.; Mendonca, J.T.

    1998-01-01

    It is shown that a wake of electron plasma oscillations can be created by the nonlinear ponderomotive force of an intense neutrino flux. The electrons trapped in the plasma wakefield will be accelerated to high energies. Such processes may be important in supernovas and pulsars. {copyright} {ital 1998 American Institute of Physics.}

  3. FPGA Verification Accelerator (FVAX)

    NASA Technical Reports Server (NTRS)

    Oh, Jane; Burke, Gary

    2008-01-01

    Is Verification Acceleration Possible? - Increasing the visibility of the internal nodes of the FPGA results in much faster debug time - Forcing internal signals directly allows a problem condition to be setup very quickly center dot Is this all? - No, this is part of a comprehensive effort to improve the JPL FPGA design and V&V process.

  4. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1974-01-01

    Detailed measurements of the axial velocity profile and electromagnetic structure of a high power, quasi-steady MPD discharge are used to formulate a gasdynamic model of the acceleration process. Conceptually dividing the accelerated plasma into an inner flow and an outer flow, it is found that more than two-thirds of the total power in the plasma is deposited in the inner flow, accelerating it to an exhaust velocity of 12.5 km/sec. The outer flow, which is accelerated to a velocity of only 6.2 km/sec, appears to provide a current conduction path between the inner flow and the anode. Related cathode studies have shown that the critical current for the onset of terminal voltage fluctuations, which was recently shown to be a function of the cathode area, appears to reach an asymptote for cathodes of very large surface area. Detailed floating potential measurements show that the fluctuations are confined to the vicinity of the cathode and hence reflect a cathode emission process rather than a fundamental limit on MPD performance.

  5. Combined generating-accelerating buncher for compact linear accelerators

    NASA Astrophysics Data System (ADS)

    Savin, E. A.; Matsievskiy, S. V.; Sobenin, N. P.; Sokolov, I. D.; Zavadtsev, A. A.

    2016-09-01

    Described in the previous article [1] method of the power extraction from the modulated electron beam has been applied to the compact standing wave electron linear accelerator feeding system, which doesnt require any connection waveguides between the power source and the accelerator itself [2]. Generating and accelerating bunches meet in the hybrid accelerating cell operating at TM020 mode, thus the accelerating module is placed on the axis of the generating module, which consists from the pulsed high voltage electron sources and electrons dumps. This combination makes the accelerator very compact in size which is very valuable for the modern applications such as portable inspection sources. Simulations and geometry cold tests are presented.

  6. Menopause accelerates biological aging.

    PubMed

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  7. Mass spectrometry with accelerators.

    PubMed

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  8. Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I-II Clinical Study

    SciTech Connect

    Strojan, Primoz Karner, Katarina; Smid, Lojze; Soba, Erika; Fajdiga, Igor; Jancar, Boris; Anicin, Aleksandar; Budihna, Marjan; Zakotnik, Branko

    2008-10-01

    Purpose: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Patients and Methods: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m{sup 2} IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m{sup 2}/d IV, applied during the last 10 fractions of irradiation ('chemoboost'). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m{sup 2}/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m{sup 2}/d (Phase I study), which was tested in the subsequent Phase II study. Results: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m{sup 2}/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m{sup 2}/d, the corresponding rates were 40%, 20%, and 22%, respectively. Conclusion: Concomitant chemoradiotherapy with mitomycin C and cisplatin 'chemoboost' at 14 mg/m{sup 2}/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

  9. KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Erben, Philipp; Stroebel, Philipp; Horisberger, Karoline; Popa, Juliana; Bohn, Beatrice; Hanfstein, Benjamin; Kaehler, Georg; Kienle, Peter; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2011-11-15

    Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

  10. Evaluation of Cytogenetic Alterations in Peripheral Blood Lymphocytes of Esophageal Cancer Patients Treated with Radiotherapy or Chemoradiotherapy using Cytokinesis-Blocked Micronucleus Assay.

    PubMed

    Emamgholizadeh Minaei, Soraya; Mozdarani, Hossein; Motazakker, Morteza; Mansouri, Mohsen; R Aghamiri, Seyed Mahmoud

    2016-01-01

    The effects of combined radiotherapy (RT) and chemotherapy in the severity of cytogenetic alterations expressed as micronucleus (MN) in peripheral blood lymphocytes of patients treated for esophageal cancer was evaluated. To do this, blood was obtained from 23 and 15 esophageal cancer patients scheduled for chemo-radiotherapy and RT alone, respectively, before, during, and after treatment. Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 μg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results indicate that there was no significant difference between the frequencies of MN in lymphocytes of individuals before being treated with RT alone or chemo-radiotherapy. In the middle of treatment, (after 12 fractions of RT) the frequency of MN increased significantly compared with their concurrent pre-treatment samples in both groups (four-fold). However, the frequency of MN observed for RT patients was not significantly different with those received chemo- and radiotherapy. At the end of treatment, (after 24 fractions of radiotherapy) an increase in the MN frequency was observed for chemo-radiation group significantly higher than RT group (P=0.022). Mild increase in MN frequency in lymphocytes of patients receiving chemoradiation only after the completion of treatment course might be indicative of resistance induced by chemotherapeutics to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal tissues.

  11. Estimating Optimal Dose of Twice-Weekly Gemcitabine for Concurrent Chemoradiotherapy in Unresectable Pancreatic Carcinoma: Mature Results of GEMRT-01 Phase I Trial

    SciTech Connect

    Girard, Nicolas; Mornex, Francoise; Bossard, Nadine; Ychou, Marc; Chauffert, Bruno; Wautot, Virginie

    2010-08-01

    Purpose: To accurately determine the maximal tolerated dose, feasibility, and antitumor activity of concurrent chemoradiotherapy including twice-weekly gemcitabine in patients with unresectable pancreatic adenocarcinoma. Methods and Materials: Eligible patients with histologically proven adenocarcinoma of the pancreas were included in this Phase I trial. Radiotherapy was delivered to a total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was administered during the 5 weeks of radiotherapy, from an initial dose of 30 mg/m{sup 2}. The gemcitabine doses were escalated in 10-mg/m{sup 2} increments in a three-plus-three design, until dose-limiting toxicities were observed. Results: A total of 35 patients were included in the trial. The feasibility of chemoradiotherapy was high, because all the patients received the planned total radiation dose, and 26 patients (74%) received {>=}70% of the planned chemotherapy dose. The mean total delivered dose of gemcitabine was 417 mg/m{sup 2} (i.e., 77% of the prescribed dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m{sup 2}. Of the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%). Overall, the median survival and the 6-, 12-, and 18-month survival rates were 10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly longer in patients with an initial performance status of 0 or 1 (p = .004). Conclusion: Our mature data have indicated that gemcitabine doses can be increased {<=}70 mg/m{sup 2}, when delivered twice-weekly with concurrent radiotherapy. This combination shows promises to achieve better recurrence-free and overall survival. These results will serve as a basis for further implementation of the multimodal treatment of locally advanced pancreatic carcinoma.

  12. Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

    PubMed Central

    Dreussi, Eva; Pucciarelli, Salvatore; De Paoli, Antonino; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Friso, Maria Luisa; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Zanusso, Chiara; De Mattia, Elena; Toffoli, Giuseppe; Cecchin, Erika

    2016-01-01

    In rectal cancer, a pathologic complete response (pCR) to pre-operative treatment is a favourable prognostic marker, but is reported in a minority of the patients. We aimed at identifying microRNA-related host genetic polymorphisms predictive of pCR. A panel of 114 microRNA-related tagging polymorphisms was selected and analyzed on 265 locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. Patients were stratified in two subgroups according to the radiotherapy dose (50.4Gy for 202 patients, 55.0Gy for 78 patients). Interactions among genetic and clinical-pathological variants were investigated by recursive partitioning analysis. Only polymorphisms with a consistent significant effect in the two subgroups of patients were selected as predictive markers of pCR. The results were validated by bootstrap analysis. SMAD3-rs744910, SMAD3-rs745103, and TRBP-rs6088619 were associated to an increased chance of pCR (p=0.0153, p=0.0471, p=0.0125). DROSHA-rs10719 and SMAD3-rs17228212 had an opposite detrimental effect on pathological tumour response (p=0.0274, p=0.0049). Recursive partitioning analysis highlighted that a longer interval time between the end of radiotherapy and surgery increases the chance of pCR in patients with a specific combination of SMAD3-rs744910 and TRBP-rs6088619 genotypes. This study demonstrated that microRNA-related host genetic polymorphisms can predict pCR to neo-adjuvant chemo-radiotherapy, and could be used to personalize the interval time between the end of radiotherapy and surgery. PMID:26934318

  13. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    PubMed Central

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

  14. Why to start the concomitant boost in accelerated radiotherapy for advanced laryngeal cancer in week 3

    SciTech Connect

    Terhaard, Chris H.J. . E-mail: C.H.J.Terhaard@AZU.nl; Kal, Henk B.; Hordijk, Gerrit-Jan

    2005-05-01

    Purpose: We analyzed toxicity and the local control rates for advanced laryngeal cancer, treated with two accelerated fractionation schedules. The main difference between the schedules was the onset of the concomitant boost, in Week 3 or Week 4. Overall treatment time and total dose were equivalent. Methods and Materials: In a prospective, nonrandomized study of T{sub 3}, T{sub 4}, and advanced T{sub 2} laryngeal cancer, concomitant boost schedules were used in 100 patients. Thirty patients received a schedule of twice daily 1.2 Gy in Weeks 1-3, followed by twice daily 1.7 Gy in Weeks 4 and 5; total dose was 70 Gy (the hyperfractionated accelerated schedule [HAS] regimen). Seventy patients were treated with 5 times 2 Gy in Weeks 1 and 2, followed by daily 1.8 Gy and 1.5 Gy (boost) in Weeks 3-5; total dose 69.5 Gy (the accelerated schedule only [ASO] regimen). Distribution of T stage was 47%, 40%, and 12% for T{sub 2}, T{sub 3}, and T{sub 4}, respectively. In 24% of the patients, lymph nodes were positive. Pretreatment tracheotomy or stridor or both occurred in 8 patients. The distribution of prognostic factors was not significantly different between the two fractionation schedules. Acute and late toxicity was assessed. Results were estimated by the use of actuarial methods. For late toxicity and local control univariate and multivariate analyses were performed. Tumor control probability analysis was used to model cure rate differences. Results: Overall acute mucositis score was equal for both schedules. Acute mucositis started and decreased significantly earlier in the HAS regimen. In all patients acute mucositis healed completely. The treatment was completed within 38 days in all patients. The regional control rate was 100% for clinical N{sub 0}, and 75% for the clinical N{sub +} patients. The 3-year local control rate was 59% and 78% for the HAS and ASO regimens, respectively (p = 0.05); the ultimate local control was 80% and 94%, respectively. In multivariate

  15. Accelerator research studies

    SciTech Connect

    Not Available

    1992-01-01

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the first year of a three-year funding cycle. The program consists of the following three tasks: TASK A, Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams, TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams; TASK C, Study of a Gyroklystron High-power Microwave Source for Linear Colliders. In this report we document the progress that has been made during the past year for each of the three tasks.

  16. Accelerators for Cancer Therapy

    DOE R&D Accomplishments Database

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  17. SUPERDIFFUSIVE SHOCK ACCELERATION

    SciTech Connect

    Perri, S.; Zimbardo, G.

    2012-05-10

    The theory of diffusive shock acceleration is extended to the case of superdiffusive transport, i.e., when the mean square deviation grows proportionally to t{sup {alpha}}, with {alpha} > 1. Superdiffusion can be described by a statistical process called Levy random walk, in which the propagator is not a Gaussian but it exhibits power-law tails. By using the propagator appropriate for Levy random walk, it is found that the indices of energy spectra of particles are harder than those obtained where a normal diffusion is envisaged, with the spectral index decreasing with the increase of {alpha}. A new scaling for the acceleration time is also found, allowing substantially shorter times than in the case of normal diffusion. Within this framework we can explain a number of observations of flat spectra in various astrophysical and heliospheric contexts, for instance, for the Crab Nebula and the termination shock of the solar wind.

  18. Hardware Accelerated Simulated Radiography

    SciTech Connect

    Laney, D; Callahan, S; Max, N; Silva, C; Langer, S; Frank, R

    2005-04-12

    We present the application of hardware accelerated volume rendering algorithms to the simulation of radiographs as an aid to scientists designing experiments, validating simulation codes, and understanding experimental data. The techniques presented take advantage of 32 bit floating point texture capabilities to obtain validated solutions to the radiative transport equation for X-rays. An unsorted hexahedron projection algorithm is presented for curvilinear hexahedra that produces simulated radiographs in the absorption-only regime. A sorted tetrahedral projection algorithm is presented that simulates radiographs of emissive materials. We apply the tetrahedral projection algorithm to the simulation of experimental diagnostics for inertial confinement fusion experiments on a laser at the University of Rochester. We show that the hardware accelerated solution is faster than the current technique used by scientists.

  19. Accelerated expansion through interaction

    SciTech Connect

    Zimdahl, Winfried

    2009-05-01

    Interactions between dark matter and dark energy with a given equation of state are known to modify the cosmic dynamics. On the other hand, the strength of these interactions is subject to strong observational constraints. Here we discuss a model in which the transition from decelerated to accelerated expansion of the Universe arises as a pure interaction phenomenon. Various cosmological scenarios that describe a present stage of accelerated expansion, like the {lambda}CDM model or a (generalized) Chaplygin gas, follow as special cases for different interaction rates. This unifying view on the homogeneous and isotropic background level is accompanied by a non-adiabatic perturbation dynamics which can be seen as a consequence of a fluctuating interaction rate.

  20. Hypervelocity plate acceleration

    SciTech Connect

    Marsh, S.P.; Tan, T.H.

    1991-01-01

    Shock tubes have been used to accelerate 1.5-mm-thick stainless steel plates to high velocity while retaining their integrity. The fast shock tubes are 5.1-cm-diameter, 15.2-cm-long cylinders of PBX-9501 explosive containing a 1.1-cm-diameter cylindrical core of low-density polystyrene foam. The plates have been placed directly in contact with one face of the explosive system. Plane-wave detonation was initiated on the opposite face. A Mach disk was formed in the imploding styrofoam core, which provided the impulse required to accelerate the metal plate to high velocity. Parametric studies were made on this system to find the effect of varying plate metal, plate thickness, foam properties, and addition of a barrel. A maximum plate velocity of 9.0 km/s has been observed. 6 refs., 17 figs.

  1. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1971-01-01

    Experimental data were combined with one-dimensional conservation relations to yield information on the energy deposition ratio in a parallel-plate accelerator, where the downstream flow was confined to a constant area channel. Approximately 70% of the total input power was detected in the exhaust flow, of which only about 20% appeared as directed kinetic energy, thus implying that a downstream expansion to convert chamber enthalpy into kinetic energy must be an important aspect of conventional high power MPD arcs. Spectroscopic experiments on a quasi-steady MPD argon accelerator verified the presence of A(III) and the absence of A(I), and indicated an azimuthal structure in the jet related to the mass injection locations. Measurements of pressure in the arc chamber and impact pressure in the exhaust jet using a piezocrystal backed by a Plexiglas rod were in good agreement with the electromagnetic thrust model.

  2. Commissioning the GTA accelerator

    SciTech Connect

    Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P. Stevens, R.R. Jr.; Vaughn, G.; Wadlinger, E.A.; Yuan, V.; Connolly, R.; Weiss, R.; Saadatmand, K.

    1992-09-01

    The Ground Test Accelerator (GTA) is supported by the Strategic Defense command as part of their Neutral Particle Beam (NPB) program. Neutral particles have the advantage that in space they are unaffected by the earth`s magnetic field and travel in straight lines unless they enter the earth`s atmosphere and become charged by stripping. Heavy particles are difficult to stop and can probe the interior of space vehicles; hence, NPB can function as a discriminator between warheads and decoys. We are using GTA to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H{sup -} beam and then neutralizing it. Our immediate goal is to produce a 24-MeV, 50mA device with a 2% duty factor.

  3. Adaptive control for accelerators

    DOEpatents

    Eaton, Lawrie E.; Jachim, Stephen P.; Natter, Eckard F.

    1991-01-01

    An adaptive feedforward control loop is provided to stabilize accelerator beam loading of the radio frequency field in an accelerator cavity during successive pulses of the beam into the cavity. A digital signal processor enables an adaptive algorithm to generate a feedforward error correcting signal functionally determined by the feedback error obtained by a beam pulse loading the cavity after the previous correcting signal was applied to the cavity. Each cavity feedforward correcting signal is successively stored in the digital processor and modified by the feedback error resulting from its application to generate the next feedforward error correcting signal. A feedforward error correcting signal is generated by the digital processor in advance of the beam pulse to enable a composite correcting signal and the beam pulse to arrive concurrently at the cavity.

  4. Modulational effects in accelerators

    SciTech Connect

    Satogata, T.

    1997-12-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed.

  5. Linear induction accelerator

    DOEpatents

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

    1988-06-21

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

  6. Accelerated plate tectonics.

    PubMed

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  7. ION ACCELERATION SYSTEM

    DOEpatents

    Luce, J.S.; Martin, J.A.

    1960-02-23

    Well focused, intense ion beams are obtained by providing a multi- apertured source grid in front of an ion source chamber and an accelerating multi- apertured grid closely spaced from and in alignment with the source grid. The longest dimensions of the elongated apertures in the grids are normal to the direction of the magnetic field used with the device. Large ion currents may be withdrawn from the source, since they do not pass through any small focal region between the grids.

  8. Computer assisted accelerator tuning

    SciTech Connect

    Boyd, J.K.

    1993-04-14

    The challenge of tuning an induction accelerator in real time has been addressed with the new TUNE GUIDE code. The code initializes a beam at a particular position using a tracer particle representation of the phase space. The particles are transported, using a matrix formulation, element by element along the beamline assuming that the field of a solenoid, or steering element is constant over its length. The other allowed elements are gaps and drift sections. A great deal of effort has been spent programming TUNE GUIDE to operate under the IBMPC Windows 3.1 system. This system features an intuitive, menu driven interface, which provides an ability to rapidly change beamline component parameter values. Consequently various accelerator setups can be explored and new values determined in real time while the accelerator is operating. In addition the code has the capability of varying a capability value over a range and then plotting the resulting beam properties, such as radius or centroid position, at a down stream position. Element parameter editing is also included along with an on-line hyper text oriented help package.

  9. TRACKING ACCELERATOR SETTINGS.

    SciTech Connect

    D OTTAVIO,T.; FU, W.; OTTAVIO, D.P.

    2007-10-15

    Recording setting changes within an accelerator facility provides information that can be used to answer questions about when, why, and how changes were made to some accelerator system. This can be very useful during normal operations, but can also aid with security concerns and in detecting unusual software behavior. The Set History System (SHS) is a new client-server system developed at the Collider-Accelerator Department of Brookhaven National Laboratory to provide these capabilities. The SHS has been operational for over two years and currently stores about IOOK settings per day into a commercial database management system. The SHS system consists of a server written in Java, client tools written in both Java and C++, and a web interface for querying the database of setting changes. The design of the SHS focuses on performance, portability, and a minimal impact on database resources. In this paper, we present an overview of the system design along with benchmark results showing the performance and reliability of the SHS over the last year.

  10. Accelerator mass spectrometry.

    PubMed

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples.

  11. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1995-01-01

    The application of electric propulsion to communications satellites, however, has been limited to the use of hydrazine thrusters with electric heaters for thrust and specific impulse augmentation. These electrothermal thrusters operate at specific impulse levels of approximately 300 s with heater powers of about 500 W. Low power arcjets (1-3 kW) are currently being investigated as a way to increase specific impulse levels to approximately 500 s. Ion propulsion systems can easily produce specific impulses of 3000 s or greater, but have yet to be applied to communications satellites. The reasons most often given for not using ion propulsion systems are their high level of overall complexity, low thrust with long burn times, and the difficulty of integrating the propulsion system into existing commercial spacecraft busses. The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass.

  12. ACCELERATION INTEGRATING MEANS

    DOEpatents

    Wilkes, D.F.

    1961-08-29

    An acceleration responsive device is described. A housing has at one end normally open electrical contacts and contains a piston system with a first part of non-magnetic material having metering orifices in the side walls for forming an air bearing between it and the walls of the housing; this first piston part is normally held against the other end of the housing from the noted contacts by a second piston or reset part. The reset part is of partly magnetic material, is separable from the flrst piston part, and is positioned within the housing intermediate the contacts and the first piston part. A magnet carried by the housing imposes a retaining force upon the reset part, along with a helical compression spring that is between the reset part and the end with the contacts. When a predetermined acceleration level is attained, the reset part overcomes the bias or retaining force provided by the magnet and the spring'' snaps'' into a depression in the housing adjacent the contacts. The first piston part is then free to move toward the contacts with its movement responsive tc acceleration forces and the metering orifices. (AEC)

  13. Acceleration during magnetic reconnection

    SciTech Connect

    Beresnyak, Andrey; Li, Hui

    2015-07-16

    The presentation begins with colorful depictions of solar x-ray flares and references to pulsar phenomena. Plasma reconnection is complex, could be x-point dominated or turbulent, field lines could break due to either resistivity or non-ideal effects, such as electron pressure anisotropy. Electron acceleration is sometimes observed, and sometimes not. One way to study this complex problem is to have many examples of the process (reconnection) and compare them; the other way is to simplify and come to something robust. Ideal MHD (E=0) turbulence driven by magnetic energy is assumed, and the first-order acceleration is sought. It is found that dissipation in big (length >100 ion skin depths) current sheets is universal and independent on microscopic resistivity and the mean imposed field; particles are regularly accelerated while experiencing curvature drift in flows driven by magnetic tension. One example of such flow is spontaneous reconnection. This explains hot electrons with a power-law tail in solar flares, as well as ultrashort time variability in some astrophysical sources.

  14. Berkeley Proton Linear Accelerator

    DOE R&D Accomplishments Database

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  15. Overview of accelerators in medicine

    SciTech Connect

    Lennox, A.J. |

    1993-06-01

    Accelerators used for medicine include synchrotrons, cyclotrons, betatrons, microtrons, and electron, proton, and light ion linacs. Some accelerators which were formerly found only at physics laboratories are now being considered for use in hospital-based treatment and diagnostic facilities. This paper presents typical operating parameters for medical accelerators and gives specific examples of clinical applications for each type of accelerator, with emphasis on recent developments in the field.

  16. Particle acceleration on Galactic scales

    NASA Astrophysics Data System (ADS)

    Axford, W. I.

    The history of and current ideas concerning the origin of cosmic rays in the Galaxy and in extragalactic sources are surveyed. The observed properties of Galactic cosmic rays and shock acceleration are discussed. It is argued that shock acceleration in various guises is an essential and conceptually the most economical acceleration mechanism.

  17. APT accelerator. Topical report

    SciTech Connect

    Lawrence, G.; Rusthoi, D.

    1995-03-01

    The Accelerator Production of Tritium (APT) project, sponsored by Department of Energy Defense Programs (DOE/DP), involves the preconceptual design of an accelerator system to produce tritium for the nation`s stockpile of nuclear weapons. Tritium is an isotope of hydrogen used in nuclear weapons, and must be replenished because of radioactive decay (its half-life is approximately 12 years). Because the annual production requirements for tritium has greatly decreased since the end of the Cold War, an alternative approach to reactors for tritium production, based on a linear accelerator, is now being seriously considered. The annual tritium requirement at the time this study was undertaken (1992-1993) was 3/8 that of the 1988 goal, usually stated as 3/8-Goal. Continued reduction in the number of weapons in the stockpile has led to a revised (lower) production requirement today (March, 1995). The production requirement needed to maintain the reduced stockpile, as stated in the recent Nuclear Posture Review (summer 1994) is approximately 3/16-Goal, half the previous level. The Nuclear Posture Review also requires that the production plant be designed to accomodate a production increase (surge) to 3/8-Goal capability within five years, to allow recovery from a possible extended outage of the tritium plant. A multi-laboratory team, collaborating with several industrial partners, has developed a preconceptual APT design for the 3/8-Goal, operating at 75% capacity. The team has presented APT as a promising alternative to the reactor concepts proposed for Complex-21. Given the requirements of a reduced weapons stockpile, APT offers both significant safety, environmental, and production-fexibility advantages in comparison with reactor systems, and the prospect of successful development in time to meet the US defense requirements of the 21st Century.

  18. VLHC accelerator physics

    SciTech Connect

    Michael Blaskiewicz et al.

    2001-11-01

    A six-month design study for a future high energy hadron collider was initiated by the Fermilab director in October 2000. The request was to study a staged approach where a large circumference tunnel is built that initially would house a low field ({approx}2 T) collider with center-of-mass energy greater than 30 TeV and a peak (initial) luminosity of 10{sup 34} cm{sup -2}s{sup -1}. The tunnel was to be scoped, however, to support a future upgrade to a center-of-mass energy greater than 150 TeV with a peak luminosity of 2 x 10{sup 34} cm{sup -2} sec{sup -1} using high field ({approx} 10 T) superconducting magnet technology. In a collaboration with Brookhaven National Laboratory and Lawrence Berkeley National Laboratory, a report of the Design Study was produced by Fermilab in June 2001. 1 The Design Study focused on a Stage 1, 20 x 20 TeV collider using a 2-in-1 transmission line magnet and leads to a Stage 2, 87.5 x 87.5 TeV collider using 10 T Nb{sub 3}Sn magnet technology. The article that follows is a compilation of accelerator physics designs and computational results which contributed to the Design Study. Many of the parameters found in this report evolved during the study, and thus slight differences between this text and the Design Study report can be found. The present text, however, presents the major accelerator physics issues of the Very Large Hadron Collider as examined by the Design Study collaboration and provides a basis for discussion and further studies of VLHC accelerator parameters and design philosophies.

  19. Muon Acceleration - RLA and FFAG

    SciTech Connect

    Bogacz, Alex

    2011-10-01

    Various acceleration schemes for muons are presented. The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and 'beam shaping' can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a non-scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. The RLAs offer very efficient usage of high gradient superconducting RF and ability to adjust path-length after each linac pass through individual return arcs with uniformly periodic FODO optics suitable for chromatic compensation of emittance dilution with sextupoles. However, they require spreaders/recombiners switchyards at both linac ends and significant total length of the arcs. The non-scaling Fixed Field Alternating Gradient (FFAG) ring combines compactness with very large chromatic acceptance (twice the injection energy) and it allows for large number of passes through the RF (at least eight, possibly as high as 15).

  20. Accelerating Commercial Remote Sensing

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Through the Visiting Investigator Program (VIP) at Stennis Space Center, Community Coffee was able to use satellites to forecast coffee crops in Guatemala. Using satellite imagery, the company can produce detailed maps that separate coffee cropland from wild vegetation and show information on the health of specific crops. The data can control coffee prices and eventually may be used to optimize application of fertilizers, pesticides and irrigation. This would result in maximal crop yields, minimal pollution and lower production costs. VIP is a mechanism involving NASA funding designed to accelerate the growth of commercial remote sensing by promoting general awareness and basic training in the technology.

  1. Accelerated Innovation Pilot

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey

    2012-01-01

    Opportunities: I. Engage NASA team (examples) a) Research and technology calls . provide suggestions to AES, HRP, OCT. b) Use NASA@Work to solicit other ideas; (possibly before R+D calls). II. Stimulate collaboration (examples) a) NHHPC. b) Wharton Mack Center for Technological Innovation (Feb 2013). c) International ] DLR ] :envihab (July 2013). d) Accelerated research models . NSF, Myelin Repair Foundation. III. Engage public Prizes (open platform: InnoCentive, yet2.com, NTL; Rice Business Plan, etc.) IV. Use same methods to engage STEM.

  2. Ion wave breaking acceleration

    NASA Astrophysics Data System (ADS)

    Liu, B.; Meyer-ter-Vehn, J.; Bamberg, K.-U.; Ma, W. J.; Liu, J.; He, X. T.; Yan, X. Q.; Ruhl, H.

    2016-07-01

    Laser driven ion wave breaking acceleration (IWBA) in plasma wakefields is investigated by means of a one-dimensional (1D) model and 1D/3D particle-in-cell (PIC) simulations. IWBA operates in relativistic transparent plasma for laser intensities in the range of 1020- 1023 W /cm2 . The threshold for IWBA is identified in the plane of plasma density and laser amplitude. In the region just beyond the threshold, self-injection takes place only for a fraction of ions and in a limited time period. This leads to well collimated ion pulses with peaked energy spectra, in particular for 3D geometry.

  3. Accelerating the loop expansion

    SciTech Connect

    Ingermanson, R.

    1986-07-29

    This thesis introduces a new non-perturbative technique into quantum field theory. To illustrate the method, I analyze the much-studied phi/sup 4/ theory in two dimensions. As a prelude, I first show that the Hartree approximation is easy to obtain from the calculation of the one-loop effective potential by a simple modification of the propagator that does not affect the perturbative renormalization procedure. A further modification then susggests itself, which has the same nice property, and which automatically yields a convex effective potential. I then show that both of these modifications extend naturally to higher orders in the derivative expansion of the effective action and to higher orders in the loop-expansion. The net effect is to re-sum the perturbation series for the effective action as a systematic ''accelerated'' non-perturbative expansion. Each term in the accelerated expansion corresponds to an infinite number of terms in the original series. Each term can be computed explicitly, albeit numerically. Many numerical graphs of the various approximations to the first two terms in the derivative expansion are given. I discuss the reliability of the results and the problem of spontaneous symmetry-breaking, as well as some potential applications to more interesting field theories. 40 refs.

  4. Laser acceleration in vacuum

    SciTech Connect

    Hsu, J.L.; Katsouleas, T.; Mori, W.B.; Schroeder, C.B.; Wurtele, J.S.

    1997-02-01

    This paper explores the use of the large electric fields of high-brightness lasers (e.g., up to order TV/cm) to accelerate particles. Unfortunately, as is well known, it is difficult to couple the vacuum field of the laser to particles so as to achieve a net energy gain. In principle, the energy gain near the focus of the laser can be quite high, i.e., on the order of the work done in crossing the focus {Delta}{gamma}={radical}({pi})eEw{approximately}30MeV{radical}(P/1TW), where P is the laser power. In order to retain this energy, the particles must be in the highly nonlinear regime (Vosc/c{gt}1) or must be separated from the laser within a distance on the order of a Rayleigh length from the focus. In this work, we explore the acceleration and output energy distribution of an electron beam injected at various angles and injection energies into a focused laser beam. Insight into the physical mechanism of energy gain is obtained by separating the contributions from the longitudinal and transverse laser field components. {copyright} {ital 1997 American Institute of Physics.}

  5. Introduction to Korean Accelerator Science and Activities in Industrial Accelerators

    NASA Astrophysics Data System (ADS)

    Namkung, Won

    2012-03-01

    After 20 years of the first large-scale accelerator in Korea, the Pohang Light Source (PLS) of 2.0 GeV at POSTECH, its upgrade (PLS-II) is now under commissioning with energy of 3.0 GeV. The users' service for synchrotron radiation is scheduled in April 2012. There are five big accelerator projects in various stages of construction, namely a high-intensity proton linac of 100 MeV, the PAL-XFEL of 10-GeV, a carbon therapy cyclotron of 400 MeV/u, and rare isotope accelerators for isotope separator on-line (ISOL) and In-flight Fragmentation (IFF). There are also strong demands for industrial uses of accelerators, especially in sterilization applications. In this paper, we report the current status of accelerator projects and its science in Korea, along with a brief review of accelerator R&D going back to the early 1960s at universities.

  6. Acceleration in Linear and Circular Motion

    ERIC Educational Resources Information Center

    Kellington, S. H.; Docherty, W.

    1975-01-01

    Describes the construction of a simple accelerometer and explains its use in demonstrating acceleration, deceleration, constant speed, measurement of acceleration, acceleration and the inclined plane and angular and radial acceleration. (GS)

  7. Randomized, Multicenter, Phase IIB Study of Preoperative Chemoradiotherapy in T3 Mid-Distal Rectal Cancer: Raltitrexed + Oxaliplatin + Radiotherapy Versus Cisplatin + 5-Fluorouracil + Radiotherapy

    SciTech Connect

    Valentini, Vincenzo Coco, Claudio; Minsky, Bruce D.; Gambacorta, Maria Antonietta; Cosimelli, Maurizio; Bellavita, Rita; Morganti, Alessio G.; La Torre, Giuseppe; Trodella, Lucio; Genovesi, Domenico; Portaluri, Maurizio; Maurizi-Enrici, Riccardo; Barbera, Fernando; Maranzano, Ernesto; Lupattelli, Marco

    2008-02-01

    Purpose: To prospectively compare the rates of pathologic response, acute toxicity, and sphincter preservation with two different schedules of preoperative chemoradiotherapy in patients with cT3 mid-distal rectal cancer. Methods and Materials: Patients with cT3 and/or N+ resectable rectal carcinoma were randomized to receive one of the two following chemoradiotherapy regimens: cisplatin, 5-fluorouracil, and radiotherapy (PLAFUR) or raltitrexed, oxaliplatin, and radiotherapy (TOMOX-RT). For PLAFUR, cisplatin (60 mg/m{sup 2}) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and 29-32, plus concurrent radiotherapy (50.4 Gy in 1.8-Gy fractions daily). For TOMOX-RT, raltitrexed (3 mg/m{sup 2}) and oxaliplatin (130 mg/m{sup 2}) was given on Days 1, 19, and 38 with the same radiotherapy regimen as used for PLAFUR. Surgery was performed 6-8 weeks after completion of chemoradiotherapy. All pathologic specimens were reviewed by a designated expert pathologist. The primary endpoint of this study was pathologic tumor downstaging (defined as tumor regression grade 1-2). Secondary endpoints included the incidence of ypT0, clinical tumor downstaging, sphincter-saving surgery, and acute treatment-related toxicity. Results: Between 2002 and 2005, 164 patients were accrued in 10 Italian centers, 83 patients in the PLAFUR arm and 81 in the TOMOX-RT arm. Overall, tumor regression grade 1-2 was observed in 76 patients (46.4%) and ypT0 in 49 (29.9%). The tumor regression grade 1-2 rate was 41.0% vs. 51.9% (p = 0.162) and the ypT0 rate was 24.1% vs. 35.8% (p = 0.102) for the PLAFUR vs. TOMOX-RT arm, respectively. The overall rate of tumor regression grade 1 and ypN+ was 4.6%. The occurrence of ypT downstaging was significantly greater in the TOMOX-RT arm (p = 0.035). Grade 3-4 acute toxicity occurred in 19 patients (11.6%): 7.1% in the PLAFUR arm vs. 16.4% in the TOMOX-RT arm. Sphincter-saving surgery was performed in 143 patients

  8. Pulsed Plasma Accelerator Modeling

    NASA Technical Reports Server (NTRS)

    Goodman, M.; Kazeminezhad, F.; Owens, T.

    2009-01-01

    This report presents the main results of the modeling task of the PPA project. The objective of this task is to make major progress towards developing a new computational tool with new capabilities for simulating cylindrically symmetric 2.5 dimensional (2.5 D) PPA's. This tool may be used for designing, optimizing, and understanding the operation of PPA s and other pulsed power devices. The foundation for this task is the 2-D, cylindrically symmetric, magnetohydrodynamic (MHD) code PCAPPS (Princeton Code for Advanced Plasma Propulsion Simulation). PCAPPS was originally developed by Sankaran (2001, 2005) to model Lithium Lorentz Force Accelerators (LLFA's), which are electrode based devices, and are typically operated in continuous magnetic field to the model, and implementing a first principles, self-consistent algorithm to couple the plasma and power circuit that drives the plasma dynamics.

  9. The Accelerating Universe

    SciTech Connect

    Blandford, Roger

    2013-05-15

    From keV electrons in terrestrial aurorae to Ultra High Energy Cosmic Rays from unidentified "Zevatrons", the cosmos shows a plutocratic proclivity to concentrate energy in a tiny minority of suprathermal particles. The mechanisms involved can be traced back to the ideas of Faraday, Fermi and Alfvén though we are learning that the details are idiosyncratic to the many environments that we have observed and that much can be learned from comparing and contrasting particle acceleration in laboratory and diverse astronomical locations. It will be argued that new mechanisms are required to account for recent observations of galactic nuclei, pulsar wind nebulae and interplanetary, interstellar and intergalactic media and some candidates will be discussed.

  10. HIGH ENERGY PARTICLE ACCELERATOR

    DOEpatents

    Courant, E.D.; Livingston, M.S.; Snyder, H.S.

    1959-04-14

    An improved apparatus is presented for focusing charged particles in an accelerator. In essence, the invention includes means for establishing a magnetic field in discrete sectors along the path of moving charged particles, the magnetic field varying in each sector in accordance with the relation. B = B/ sub 0/ STAln (r-r/sub 0/)/r/sub 0/!, where B/sub 0/ is the value of the magnetic field at the equilibrium orbit of radius r/sub 0/ of the path of the particles, B equals the magnetic field at the radius r of the chamber and n equals the magnetic field gradient index, the polarity of n being abruptly reversed a plurality of times as the particles travel along their arcuate path. With this arrangement, the particles are alternately converged towards the axis of their equillbrium orbit and diverged therefrom in successive sectors with a resultant focusing effect.

  11. Lectures in accelerator theory

    SciTech Connect

    Month, M

    1980-01-01

    Lecture I deals with the behavior of particles in the nonlinear field arising from the electromagnetic interaction of colliding beams. The case treated, that of counter-rotating proton beams crossing each other at a non-zero angle, has the simple feature that the force between the beam is one dimensional. In lecture II, an analysis of the development of traveling waves on particle beams is presented. The situation studied is that of a uniform beam current in a circular accelerator and the excitation for the coherent motion is induced by the resistivity of the vacuum chamber wall. Finally, in lecture III, a description of the current accumulation process used at the proton storage rings at CERN (The ISR) is given. Particle pulses of rather low average current are injected and stored along the length and width of the vacuum chamber. The efficiency is very high and large currents (over 40 amperes) have been achieved.

  12. Network acceleration techniques

    NASA Technical Reports Server (NTRS)

    Crowley, Patricia (Inventor); Awrach, James Michael (Inventor); Maccabe, Arthur Barney (Inventor)

    2012-01-01

    Splintered offloading techniques with receive batch processing are described for network acceleration. Such techniques offload specific functionality to a NIC while maintaining the bulk of the protocol processing in the host operating system ("OS"). The resulting protocol implementation allows the application to bypass the protocol processing of the received data. Such can be accomplished this by moving data from the NIC directly to the application through direct memory access ("DMA") and batch processing the receive headers in the host OS when the host OS is interrupted to perform other work. Batch processing receive headers allows the data path to be separated from the control path. Unlike operating system bypass, however, the operating system still fully manages the network resource and has relevant feedback about traffic and flows. Embodiments of the present disclosure can therefore address the challenges of networks with extreme bandwidth delay products (BWDP).

  13. Accelerator mass spectrometry

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.; Finkel, R.; Nelson, D.E.

    1995-06-01

    Accelerator mass spectroscopy (AMS) can be used for efficient detection of long-lived isotopes at part-per-quadrillion sensitivities with good precision. In this article we present an overview of AMS and its recent use in archaeology, geochemistry and biomolecular tracing. All AMS systems use cesium sputter ion sources to produce negative ions from a small button of a solid sample containing the element of interest, such as graphite, metal halide, or metal oxide, often mixed with a metal powder as binder and thermal conductor. Experience shows that both natural and biomedical samples are compatible in a single AMS system, but few other AMS sites make routine {sup 14}C measurements for both dating and tracing. AMS is, in one sense, just `a very sensitive decay counter`, but if AMS sensitivity is creatively coupled to analytical chemistry of certain isotopes, whole new areas of geosciences, archaeology, and life sciences can be explored. 29 refs., 2 figs., 1 tab.

  14. Accelerating Spectrum Sharing Technologies

    SciTech Connect

    Juan D. Deaton; Lynda L. Brighton; Rangam Subramanian; Hussein Moradi; Jose Loera

    2013-09-01

    Spectrum sharing potentially holds the promise of solving the emerging spectrum crisis. However, technology innovators face the conundrum of developing spectrum sharing technologies without the ability to experiment and test with real incumbent systems. Interference with operational incumbents can prevent critical services, and the cost of deploying and operating an incumbent system can be prohibitive. Thus, the lack of incumbent systems and frequency authorization for technology incubation and demonstration has stymied spectrum sharing research. To this end, industry, academia, and regulators all require a test facility for validating hypotheses and demonstrating functionality without affecting operational incumbent systems. This article proposes a four-phase program supported by our spectrum accountability architecture. We propose that our comprehensive experimentation and testing approach for technology incubation and demonstration will accelerate the development of spectrum sharing technologies.

  15. Pulsed electromagnetic acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1973-01-01

    Direct measurements of the power deposited in the anode of a multimegawatt MPD accelerator using thermocouples attached to a thin shell anode reveal a dramatic decrease in the fractional anode power from 50% at 200 KW input power to less than 10% at 20 MW power. The corresponding local power flux peak at a value of 10,000 W/sq cm at the lip of the anode exhaust orifice, a distribution traced to a corresponding peak in the local current density at the anode. A comparison of voltage-current characteristics and spectral photographs of the MPD discharge using quartz, boron nitride and plexiglas insulators with various mass injection configurations led to the identification of different voltage modes and regions of ablation free operation. The technique of piezoelectric impact pressure measurement in the MPD exhaust flow was refined to account for the effects due to probe yaw angle.

  16. Paraelectric gas flow accelerator

    NASA Technical Reports Server (NTRS)

    Sherman, Daniel M. (Inventor); Wilkinson, Stephen P. (Inventor); Roth, J. Reece (Inventor)

    2001-01-01

    A substrate is configured with first and second sets of electrodes, where the second set of electrodes is positioned asymmetrically between the first set of electrodes. When a RF voltage is applied to the electrodes sufficient to generate a discharge plasma (e.g., a one-atmosphere uniform glow discharge plasma) in the gas adjacent to the substrate, the asymmetry in the electrode configuration results in force being applied to the active species in the plasma and in turn to the neutral background gas. Depending on the relative orientation of the electrodes to the gas, the present invention can be used to accelerate or decelerate the gas. The present invention has many potential applications, including increasing or decreasing aerodynamic drag or turbulence, and controlling the flow of active and/or neutral species for such uses as flow separation, altering heat flow, plasma cleaning, sterilization, deposition, etching, or alteration in wettability, printability, and/or adhesion.

  17. Dynamics of pyroelectric accelerators

    SciTech Connect

    Ghaderi, R.; Davani, F. Abbasi

    2015-01-26

    Pyroelectric crystals are used to produce high energy electron beams. We have derived a method to model electric potential generation on LiTaO{sub 3} crystal during heating cycle. In this method, effect of heat transfer on the potential generation is investigated by some experiments. In addition, electron emission from the crystal surface is modeled by measurements and analysis. These spectral data are used to present a dynamic equation of electric potential with respect to thickness of the crystal and variation of its temperature. The dynamic equation's results for different thicknesses are compared with measured data. As a result, to attain more energetic electrons, best thickness of the crystals could be extracted from the equation. This allows for better understanding of pyroelectric crystals and help to study about current and energy of accelerated electrons.

  18. Hadron accelerators for radiotherapy

    NASA Astrophysics Data System (ADS)

    Owen, Hywel; MacKay, Ranald; Peach, Ken; Smith, Susan

    2014-04-01

    Over the last twenty years the treatment of cancer with protons and light nuclei such as carbon ions has moved from being the preserve of research laboratories into widespread clinical use. A number of choices now exist for the creation and delivery of these particles, key amongst these being the adoption of pencil beam scanning using a rotating gantry; attention is now being given to what technologies will enable cheaper and more effective treatment in the future. In this article the physics and engineering used in these hadron therapy facilities is presented, and the research areas likely to lead to substantive improvements. The wider use of superconducting magnets is an emerging trend, whilst further ahead novel high-gradient acceleration techniques may enable much smaller treatment systems. Imaging techniques to improve the accuracy of treatment plans must also be developed hand-in-hand with future sources of particles, a notable example of which is proton computed tomography.

  19. Laser acceleration and its future

    PubMed Central

    Tajima, Toshiki

    2010-01-01

    Laser acceleration is based on the concept to marshal collective fields that may be induced by laser. In order to exceed the material breakdown field by a large factor, we employ the broken-down matter of plasma. While the generated wakefields resemble with the fields in conventional accelerators in their structure (at least qualitatively), it is their extreme accelerating fields that distinguish the laser wakefield from others, amounting to tiny emittance and compact accelerator. The current research largely falls on how to master the control of acceleration process in spatial and temporal scales several orders of magnitude smaller than the conventional method. The efforts over the last several years have come to a fruition of generating good beam properties with GeV energies on a table top, leading to many applications, such as ultrafast radiolysis, intraoperative radiation therapy, injection to X-ray free electron laser, and a candidate for future high energy accelerators. PMID:20228616

  20. Particle acceleration in pulsar magnetospheres

    NASA Technical Reports Server (NTRS)

    Baker, K. B.

    1978-01-01

    The structure of pulsar magnetospheres and the acceleration mechanism for charged particles in the magnetosphere was studied using a pulsar model which required large acceleration of the particles near the surface of the star. A theorem was developed which showed that particle acceleration cannot be expected when the angle between the magnetic field lines and the rotation axis is constant (e.g. radial field lines). If this angle is not constant, however, acceleration must occur. The more realistic model of an axisymmetric neutron star with a strong dipole magnetic field aligned with the rotation axis was investigated. In this case, acceleration occurred at large distances from the surface of the star. The magnitude of the current can be determined using the model presented. In the case of nonaxisymmetric systems, the acceleration is expected to occur nearer to the surface of the star.

  1. Accelerator simulation of astrophysical processes

    NASA Technical Reports Server (NTRS)

    Tombrello, T. A.

    1983-01-01

    Phenomena that involve accelerated ions in stellar processes that can be simulated with laboratory accelerators are described. Stellar evolutionary phases, such as the CNO cycle, have been partially explored with accelerators, up to the consumption of He by alpha particle radiative capture reactions. Further experimentation is indicated on reactions featuring N-13(p,gamma)O-14, O-15(alpha, gamma)Ne-19, and O-14(alpha,p)F-17. Accelerated beams interacting with thin foils produce reaction products that permit a determination of possible elemental abundances in stellar objects. Additionally, isotopic ratios observed in chondrites can be duplicated with accelerator beam interactions and thus constraints can be set on the conditions producing the meteorites. Data from isotopic fractionation from sputtering, i.e., blasting surface atoms from a material using a low energy ion beam, leads to possible models for processes occurring in supernova explosions. Finally, molecules can be synthesized with accelerators and compared with spectroscopic observations of stellar winds.

  2. Muon Collider Progress: Accelerators

    SciTech Connect

    Zisman, Michael S.

    2011-09-10

    A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance (“cooling”). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.

  3. Planned FDG PET-CT Scan in Follow-Up Detects Disease Progression in Patients With Locally Advanced NSCLC Receiving Curative Chemoradiotherapy Earlier Than Standard CT

    PubMed Central

    Pan, Yi; Brink, Carsten; Schytte, Tine; Petersen, Henrik; Wu, Yi-long; Hansen, Olfred

    2015-01-01

    Abstract The role of positron emission tomography-computed tomography (PET-CT) in surveillance of patients with nonsmall cell lung cancer (NSCLC) treated with curatively intended chemoradiotherapy remains controversial. However, conventional chest X-ray and computed tomography (CT) are of limited value in discriminating postradiotherapy changes from tumor relapse. The aim of this study was to evaluate the clinical value of PET-CT scan in the follow-up for patients with locally advanced (LA) NSCLC receiving concomitant chemoradiotherapy (CCRT). Between 2009 and 2013, eligible patients with stages IIB–IIIB NSCLC were enrolled in the clinical trial NARLAL and treated in Odense University Hospital (OUH). All patients had a PET-CT scan scheduled 9 months (PET-CT9) after the start of the radiation treatment in addition to standard follow-up (group A). Patients who presented with same clinical stage of NSCLC and received similar treatment, but outside protocol in OUH during this period were selected as control group (group B). Patients in group B were followed in a conventional way without PET-CT9. All patients were treated with induction chemotherapy followed by CCRT. Group A included 37 and group B 55 patients. The median follow-up was 16 months. Sixty-six (72%) patients were diagnosed with progression after treatment. At the time of tumor progression, patients in group A had better performance status (PS) than those in group B (P = 0.02). Because of death (2 patients), poor PS (3) or retreatment of relapse (9), only 23 patients had PET-CT9 in group A. Eleven (48%) patients were firstly diagnosed with progression by PET-CT9 without any clinical symptoms of progression. The median progression-free survival (PFS) was 8.8 months in group A and 12.5 months in group B (P = 0.04). Hazard function PFS showed that patients in group A had higher risk of relapse than in group B. Additional FDG PET-CT scan at 9 months in surveillance increases probability of early

  4. Pharmacogenetic Study in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy: Polymorphisms in Thymidylate Synthase, Epidermal Growth Factor Receptor, GSTP1, and DNA Repair Genes

    SciTech Connect

    Paez, David; Salazar, Juliana; Pare, Laia; Pertriz, Lourdes; Targarona, Eduardo; Rio, Elisabeth del; Barnadas, Agusti; Marcuello, Eugenio; Baiget, Montserrat

    2011-12-01

    Purpose: Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy. Methods and Materials: Blood samples were obtained from 128 patients with Stage II-III rectal cancer. DNA was extracted from the peripheral blood nucleated cells, and the genotypes were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were thymidylate synthase, (VNTR/5 Prime UTR, 2R G>C single nucleotide polymorphism [SNP], 3R G>C SNP), epidermal growth factor receptor (Arg497Lys), GSTP1 (Ile105val), excision repair cross-complementing 1 (Asn118Asn, 8092C>A, 19716G>C), X-ray repair cross-complementing group 1 (XRCC1) (Arg194Trp, Arg280His, Arg399Gln), and xeroderma pigmentosum group D (Lys751Gln). The pathologic response, pathologic regression, progression-free survival, and overall survival were evaluated according to each genotype. Results: The Asterisk-Operator 3/ Asterisk-Operator 3 thymidylate synthase genotype was associated with a greater response rate (pathologic complete remission and microfoci residual tumor, 59% in Asterisk-Operator 3/ Asterisk-Operator 3 vs. 35% in Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk-Operator 3; p = .013). For the thymidylate synthase genotype, the median progression-free survival was 103 months for the Asterisk-Operator 3/ Asterisk-Operator 3 patients and 84 months for the Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk

  5. Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

    SciTech Connect

    Nakamura, Akira; Shibuya, Keiko; Matsuo, Yukinori; Nakamura, Mitsuhiro; Shiinoki, Takehiro; Mizowaki, Takashi; Hiraoka, Masahiro

    2012-10-01

    Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel

  6. A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

    SciTech Connect

    Soltys, Scott G.; Choi, Clara Y.H.; Fee, Willard E.; Pinto, Harlan A.; Le, Quynh-Thu

    2012-07-01

    Purpose: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. Methods and Materials: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. Results: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR{yields}pCR, and cPR{yields}pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR{yields}pCR, and cPR{yields}pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). Conclusion: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

  7. Particle acceleration in solar flares

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Forman, M. A.

    1987-01-01

    The most direct signatures of particle acceleration in flares are energetic particles detected in interplanetary space and in the Earth atmosphere, and gamma rays, neutrons, hard X-rays, and radio emissions produced by the energetic particles in the solar atmosphere. The stochastic and shock acceleration theories in flares are reviewed and the implications of observations on particle energy spectra, particle confinement and escape, multiple acceleration phases, particle anistropies, and solar atmospheric abundances are discussed.

  8. Cast dielectric composite linear accelerator

    DOEpatents

    Sanders, David M.; Sampayan, Stephen; Slenes, Kirk; Stoller, H. M.

    2009-11-10

    A linear accelerator having cast dielectric composite layers integrally formed with conductor electrodes in a solventless fabrication process, with the cast dielectric composite preferably having a nanoparticle filler in an organic polymer such as a thermosetting resin. By incorporating this cast dielectric composite the dielectric constant of critical insulating layers of the transmission lines of the accelerator are increased while simultaneously maintaining high dielectric strengths for the accelerator.

  9. High field gradient particle accelerator

    DOEpatents

    Nation, J.A.; Greenwald, S.

    1989-05-30

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications is disclosed. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle. 10 figs.

  10. High field gradient particle accelerator

    DOEpatents

    Nation, John A.; Greenwald, Shlomo

    1989-01-01

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle.

  11. Accelerators for research and applications

    SciTech Connect

    Alonso, J.R.

    1990-06-01

    The newest particle accelerators are almost always built for extending the frontiers of research, at the cutting edge of science and technology. Once these machines are operating and these technologies mature, new applications are always found, many of which touch our lives in profound ways. The evolution of accelerator technologies will be discussed, with descriptions of accelerator types and characteristics. The wide range of applications of accelerators will be discussed, in fields such as nuclear science, medicine, astrophysics and space-sciences, power generation, airport security, materials processing and microcircuit fabrication. 13 figs.

  12. Compact accelerator for medical therapy

    DOEpatents

    Caporaso, George J.; Chen, Yu-Jiuan; Hawkins, Steven A.; Sampayan, Stephen E.; Paul, Arthur C.

    2010-05-04

    A compact accelerator system having an integrated particle generator-linear accelerator with a compact, small-scale construction capable of producing an energetic (.about.70-250 MeV) proton beam or other nuclei and transporting the beam direction to a medical therapy patient without the need for bending magnets or other hardware often required for remote beam transport. The integrated particle generator-accelerator is actuable as a unitary body on a support structure to enable scanning of a particle beam by direction actuation of the particle generator-accelerator.

  13. Superdiffusive shock acceleration and short acceleration times at interplanetary shocks

    NASA Astrophysics Data System (ADS)

    Perri, Silvia; Zimbardo, Gaetano

    2016-04-01

    The analysis of time profiles of particles accelerated at interplanetary shock waves has shown evidence for superdiffusive transport in the upstream region. Superdiffusive transport is characterized by a mean square displacement that grows faster than linearly in time and by non Gaussian statistics for the distribution of the particle jump lengths. In the superdiffusive framework it has been shown that particle time profiles upstream of a planar shock decay as power laws, at variance with exponential particle time profiles predicted in the case of diffusive transport. A large number of interplanetary shocks, including coronal mass ejection driven shocks, exhibit energetic particle time profiles that decay as power laws far upstream. In order to take this evidence into account, we have extended the standard theory of diffusive shock acceleration to the case of particle superdiffusive transport (superdiffusive shock acceleration). This has allowed us to derive both hard energy spectral indices and short acceleration times. This new theory has been tested for a number of interplanetary shock waves, observed by the Ulysses and the ACE spacecraft, and for the termination shock. The superdiffusive shock acceleration leads to a strong reduction of the acceleration times (even of about one order of magnitude) with respect to the diffusive shock acceleration. Thus, this new framework provides a substantial advancement in the understanding of the processes of particle acceleration and particle transport, which are among the main objectives of the new Solar Probe and Solar Orbiter space missions.

  14. SHORT ACCELERATION TIMES FROM SUPERDIFFUSIVE SHOCK ACCELERATION IN THE HELIOSPHERE

    SciTech Connect

    Perri, S.; Zimbardo, G.

    2015-12-10

    The analysis of time profiles of particles accelerated at interplanetary shocks allows particle transport properties to be inferred. The frequently observed power-law decay upstream, indeed, implies a superdiffusive particle transport when the level of magnetic field variance does not change as the time interval from the shock front increases. In this context, a superdiffusive shock acceleration (SSA) theory has been developed, allowing us to make predictions of the acceleration times. In this work we estimate for a number of interplanetary shocks, including the solar wind termination shock, the acceleration times for energetic protons in the framework of SSA and we compare the results with the acceleration times predicted by standard diffusive shock acceleration. The acceleration times due to SSA are found to be much shorter than in the classical model, and also shorter than the interplanetary shock lifetimes. This decrease of the acceleration times is due to the scale-free nature of the particle displacements in the framework of superdiffusion. Indeed, very long displacements are possible, increasing the probability for particles far from the front of the shock to return, and short displacements have a high probability of occurrence, increasing the chances for particles close to the front to cross the shock many times.

  15. The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

    PubMed

    Tang, Jing-Hua; An, Xin; Lin, Xi; Gao, Yuan-Hong; Liu, Guo-Chen; Kong, Ling-Heng; Pan, Zhi-Zhong; Ding, Pei-Rong

    2015-10-20

    Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders.

  16. A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review.

    PubMed

    Okabe, Hirohisa; Chikamoto, Akira; Maruno, Masataka; Hashimoto, Daisuke; Imai, Katsunori; Taki, Katsunobu; Arima, Kota; Ishiko, Takatoshi; Uchiyama, Hideaki; Ikegami, Toru; Harimoto, Norifumi; Itoh, Shinji; Yoshizumi, Tomoharu; Beppu, Toru; Baba, Hideo; Maehara, Yoshihiko

    2016-12-01

    The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma. PMID:27376654

  17. Diffusion-weighted magnetic resonance imaging for prediction of tumor response to neoadjuvant chemoradiotherapy using irinotecan plus S-1 for rectal cancer

    PubMed Central

    DOI, HIROSHI; BEPPU, NAOHITO; KATO, TAKASHI; NODA, MASASHI; YANAGI, HIDENORI; TOMITA, NAOHIRO; KAMIKONYA, NORIHIKO; HIROTA, SHOZO

    2015-01-01

    The purpose of this study was to investigate the clinical value of diffusion-weighted (DW) magnetic resonance imaging (MRI) as a predictor of tumor response in patients receiving neoadjuvant chemoradiotherapy (NA-CRT) for rectal cancer (RC) through measurement of the apparent diffusion coefficient (ADC) value in each tumor. Neoadjuvant radiotherapy with a total dose of 45 Gy in 25 fractions was performed in all 16 patients with RC, combined with irinotecan and S-1. MRI was performed before and after NA-CRT. Multiple factors were assessed to predict the pathological response to NA-CRT. The pathological response rate was determined in 9 patients (56.3%). Statistical analyses indicated that the ADC value prior to NA-CRT was significantly lower in patients with a better response to NA-CRT (P=0.023). A cut-off value of 0.750×10−3 mm2/sec obtained by a receiver operating characteristic curve analysis indicated a sensitivity of 77.8% and specificity of 85.7% for pathological responders to NA-CRT. In addition, the patients with lower ADC values exhibited a greater pathological response to NA-CRT (P=0.041). In conclusion, the ADC value of MRI of RC patients treated with NA-CRT followed by surgery may provide valuable information to predict the response to NA-CRT. PMID:26623064

  18. Neoadjuvant Chemoradiotherapy vesus Chemotherapy alone Followed by Surgery for Resectable Stage III Non-Small-Cell Lung Cancer: a Meta-Analysis

    PubMed Central

    Guo, Shan xian; Jian, Yan; Chen, Ying lan; Cai, Yun; Zhang, Qing yuan; Tou, Fang fang

    2016-01-01

    Neoadjuvant Chemotherapy has been used for the stage III of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, the survival benefits of radiation therapy added in induction regimens remains controversial. We therefore conducted a meta-analysis of the published clinical trials to quantitatively evaluate the benefit of preoperative chemoradiotherapy. After searching the database of Pubmed, CNKI, EMBASE, ESMO, The Cochrane Library databases, The American Society of Clinical Oncology and Clinical Trials.gov. Trials were selected for meta-analysis if they provided an independent assessment of neoadjuvant chemoradiation and neoadjuvant chemotherapy, odds ratio(OR) for tumor downstaging, mediastinal lymph nodes pathological complete response and local control, hazard ratios (HRs) for 5-year survival and progression-free survival were pooled by the stata software version 12.0. Twelve studies involving 2,724 patients were identified, tumor downstaging (p = 0.01), mediastinal lymph nodes pathological complete responses (p = 0.028) and local control (P = 0.002) were achieved, when compared with neoadjuvant chemotherapy. The meta-analysis demonstrated neither 5-year survival nor progression-free-survival benefit in survival from adding radiation. In conclusion, the addition of radiotherapy into chemotherapy was not superior to neoadjuvant chemotherapy. The higher quality of trials need be investigated combining with the histopathological type and genotyping of lung cancer by clinicians. PMID:27677242

  19. Long-term oncologic outcomes of neoadjuvant concurrent chemoradiotherapy with capecitabine and radical surgery in locally advanced rectal cancer: 10-year experiences at a single institution

    PubMed Central

    Lee, Kyung Ha; Kim, Jin Soo

    2016-01-01

    Purpose Oral capecitabine has demonstrated to be safe and efficient as neoadjuvant concurrent chemoradiotherapy (NCRT) for locally advanced rectal cancers. The aim of this study was to evaluate the long-term oncologic outcomes of NCRT with capecitabine and radical surgery. Methods From January 2000 to June 2010, 238 patients were treated at our center for locally advanced rectal cancers using conventional NCRT with capecitabine and radical surgery. Univariate and multivariate analyses were used to evaluate the factors associated with oncologic outcomes with log rank and Cox regression tests. Results The incidence of grade >3 capecitabine-related toxicity was found to be 4.6%. A pathologic complete response was observed in 14.7% of patients. The 5-year overall and 5-year disease-free survival rate, local and systemic recurrence rate were 82.8%, 75.1%, 4.8%, and 20.3%. Abdominoperineal resection and node-positive disease were independent prognostic factors of 5-year overall survival, 5-year disease-free survival, and systemic recurrence. Conclusion NCRT with capecitabine and radical surgery showed favorable long-term oncologic outcomes with benefits of acceptable toxicity and convenience. We suggest that capecitabine can be one of the favorable therapeutic options for NCRT in rectal cancer. PMID:27757395

  20. Evaluation of Various Nuclear Cytological Changes in Normal Buccal Mucosa and Peritumoural Area in Patients with Oral Squamous Cell Carcinoma Receiving Concomitant Chemoradiotherapy

    PubMed Central

    Minhas, Sadia; Kashif, Muhammad; Nagi, A. H.

    2016-01-01

    Objectives. To evaluate the role of serial cytological assay in calculating the nuclear response of contralateral normal buccal mucosa and peritumoural area of squamous cell carcinoma of oral cavity in patients receiving fractionated radiotherapy (RT) and chemotherapy. Materials and Methods. This prospective, nonrandomized study was comprised of 76 histologically confirmed cases of oral squamous cell carcinoma on cyclical chemoradiation treatment. Chemoradiosensitivity was evaluated using serial scrape smears taken before and after immediate exposure to CCRT, at 17th day of CCRT (mid of treatment), and at the end of treatment. The nuclear changes, such as multinucleation, micronucleation, karyorrhexis, karyolysis, nuclear budding, prominent nucleoli, and binucleation occurring in both irradiated cancer cells and contralateral normal buccal mucosa, had a statistically significant dose related increase with concomitant chemoradiotherapy (p < 0.05). Conclusion. We recommend regular use of serial cytological assay during CCRT as it may prove to be a valuable tool for assessment of chemoradiosensitivity and persistence of tumour/dysplastic cells after radiotherapy. PMID:27148467

  1. [Squamous cell carcinoma of the anal canal showing complete response after concurrent chemoradiotherapy and S-1 plus mitomycin C - a case report].

    PubMed

    Nakashima, Susumu; Kiuchi, Jun; Konishi, Tomoki; Umehara, Seiji; Fukuda, Kenichiro; Fujiyama, Junshin; Masuyama, Mamoru

    2014-11-01

    The patient was a 65-year-old man who underwent colonoscopy for melena. Following a biopsy, the patient was diagnosed with anal canal squamous cell carcinoma. A computed tomography (CT) scan revealed metastasis to the regional lymph nodes. The proposed treatment regimen comprised radiotherapy combined with S-1 and mitomycin C (MMC). Dur- ing radiotherapy (59.6 Gy in 32 fractions), 10mg/m² MMC was administered, as an intravenous bolus injection, on days 1 and 29. S-1 was administered orally, at a dose of 80 mg/m², on days 1-14 and 29-42. No serious adverse events were observed during chemoradiotherapy; the observed adverse events were leukemia (Grade 2), diarrhea (Grade 1), anorexia (Grade 1), and radiation dermatitis (Grade 1). After 8 weeks of treatment, no tumors, only scar tissue could be detected by using colonoscopy, and a CT scan revealed a remarkable reduction in regional lymph node metastases. The patient achieved a complete response.

  2. Nephrotoxicity as a Dose-Limiting Factor in a High-Dose Cisplatin-Based Chemoradiotherapy Regimen for Head and Neck Carcinomas

    PubMed Central

    Hoek, Jantien; Bloemendal, Karen M.; van der Velden, Lilly-Ann A.; van Diessen, Judi N.A.; van Werkhoven, Erik; Klop, Willem M.C.; Tesselaar, Margot E.T.

    2016-01-01

    Purpose: Loco-regional control and organ preservation are significantly improved with concomitant cisplatin/radiotherapy and are compromised with less than 5% grade 3 nephrotoxicity (creatinine clearance 15–29 mL/min). However, although clinically important, in none of the randomized trials is grade 2 nephrotoxicity (defined as creatinine clearance 59–30 mL/min) mentioned. In this study, we assessed nephrotoxicity in daily practice among patients treated with high-dose cisplatin (100 mg/m2 on days 1, 22, and 43), concurrently with chemoradiotherapy (CCRT) and the impact on treatment modifications. Methods: 208 patients with advanced-stage malignancies of the head and neck region were evaluated. All patients were treated with high-dose cisplatin CCRT. The main outcome parameters were nephrotoxicity (defined as creatinine clearance grade 2 or more) and cumulative doses of cisplatin and radiation. Results: 133 patients (64%) completed all pre-planned courses of cisplatin. Nephrotoxicity was the main reason to discontinue the chemotherapy. Grade 3 nephrotoxicity was seen in 16 patients (8%) while grade 2 nephrotoxicity was seen in 53 patients (25%). Thirty six patients (17%) could not complete the pre-planned chemotherapy due to nephrotoxicity. Conclusions: In head and neck cancer patients, nephrotoxicity grade 2 is under-reported but is the major factor for discontinuing cisplatin during CCRT. PMID:26891330

  3. Dynamic Contrast-Enhanced MRI Parameters as Biomarkers in Assessing Head and Neck Lesions After Chemoradiotherapy Using a Wide-Bore 3 Tesla Scanner.

    PubMed

    Lerant, Gergely; Sarkozy, Peter; Takacsi-Nagy, Zoltan; Polony, Gabor; Tamas, Laszlo; Toth, Erika; Boer, Andras; Javor, Laszlo; Godeny, Maria

    2015-09-01

    Pilot studies have shown promising results in characterizing head and neck tumors (HNT) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), differentiating between malignant and benign lesions and evaluating changes in response to chemoradiotherapy (CRT). Our aim was to find DCE-MRI parameters, biomarkers in evaluating the post-CRT status. Two hundred and five patients with head and neck lesions were examined with DCE-MRI sequences. The time intensity curves (TIC) were extracted and processed to acquire time-to-peak (TTP), relative maximum enhancement (RME), relative wash-out (RWO), and two new parameters attack and decay. These parameters were analyzed using univariate tests in SPSS (Statistical Package for the Social Sciences, version 17, SPSS Inc. Chicago, USA) to identify parameters that could be used to infer tumor malignancy and post-CRT changes. Multiple parameters of curve characteristics were significantly different between malignant tumors after CRT (MACRT) and changes caused by CRT. The best-performing biomarkers were the attack and the decay. We also found multiple significant (p < 0.05) parameters for both the benign and malignant status as well as pre- and post-CRT status. Our large cohort of data supports the increasing role of DCE-MRI in HNT differentiation, particularly for the assessment of post-CRT status along with accurate morphological imaging. PMID:25920367

  4. New directions in linear accelerators

    SciTech Connect

    Jameson, R.A.

    1984-01-01

    Current work on linear particle accelerators is placed in historical and physics contexts, and applications driving the state of the art are discussed. Future needs and the ways they may force development are outlined in terms of exciting R and D challenges presented to today's accelerator designers. 23 references, 7 figures.

  5. Thomas Edison Accelerated Elementary School.

    ERIC Educational Resources Information Center

    Levin, Henry M.; Chasin, Gene

    This paper describes early outcomes of a Sacramento, California, elementary school that participated in the Accelerated Schools Project. The school, which serves many minority and poor students, began training for the project in 1992. Accelerated Schools were designed to advance the learning rate of students through a gifted and talented approach,…

  6. General purpose programmable accelerator board

    DOEpatents

    Robertson, Perry J.; Witzke, Edward L.

    2001-01-01

    A general purpose accelerator board and acceleration method comprising use of: one or more programmable logic devices; a plurality of memory blocks; bus interface for communicating data between the memory blocks and devices external to the board; and dynamic programming capabilities for providing logic to the programmable logic device to be executed on data in the memory blocks.

  7. Natural Acceleration: Supporting Creative Trajectories

    ERIC Educational Resources Information Center

    Cohen, LeoNora M.

    2011-01-01

    "Natural acceleration" happens through an internal fire that burns to learn and may transcend school boundaries. Based on their passionate interests and connections with a domain, children who hunger for domain understandings outside school curricula require different types of acceleration, motivated by these interests. The lifeworks, domains, and…

  8. The Brookhaven Accelerator Test Facility

    SciTech Connect

    Batchelor, K.; Ben-Zvi, I.; Fernow, R.C.; Fischer, J.; Fisher, A.S.; Gallardo, J.; Jialin, Xie; Kirk, H.G.; Parsa, Z.; Palmer, R.B.; Rao, T.; Rogers, J.; Sheehan, J.; Tsang, T.Y.F.; Ulc, S.; Van Steenbergen, A.; Woodle, M.; Zhang, R.S. ); McDonald, K.T.; Russell, D.P. ); Jiang, Z.Y. (State Univ. of New York, Stony Brook, NY (Un

    1990-01-01

    The Accelerator Test Facility (ATF), presently under construction at Brookhaven National laboratory, is described. It consists of a 50-MeV electron beam synchronizable to a high-peak power CO{sub 2} laser. The interaction of electrons with the laser field will be probed, with some emphasis on exploring laser-based acceleration techniques. 5 refs., 2 figs.

  9. Remote handling and accelerators

    NASA Astrophysics Data System (ADS)

    Wilson, M. T.

    The high-current levels of contemporary and proposed accelerator facilities induce radiation levels into components, requiring consideration be given to maintenance techniques that reduce personnel exposure. Typical components involved include beamstops, targets, collimators, windows, and instrumentation that intercepts the direct beam. Also included are beam extraction, injection, splitting, and kicking regions, as well as purposeful spill areas where beam tails are trimmed and neutral particles are deposited. Scattered beam and secondary particles activate components all along a beamline such as vacuum pipes, magnets, and shielding. Maintenance techniques vary from hands-on to TV-viewed operation using state-of-the-art servomanipulators. Bottom- or side-entry casks are used with thimble-type target and diagnostic assemblies. Long-handled tools are operated from behind shadow shields. Swinging shield doors, unstacking block, and horizontally rolling shield roofs are all used to provide access. Common to all techniques is the need to make operations simple and to provide a means of seeing and reaching the area.

  10. Hot Spot Cosmic Accelerators

    NASA Astrophysics Data System (ADS)

    2002-11-01

    length of more than 3 million light-years, or no less than one-and-a-half times the distance from the Milky Way to the Andromeda galaxy, this structure is indeed gigantic. The region where the jets collide with the intergalactic medium are known as " hot spots ". Superposing the intensity contours of the radio emission from the southern "hot spot" on a near-infrared J-band (wavelength 1.25 µm) VLT ISAAC image ("b") shows three distinct emitting areas; they are even better visible on the I-band (0.9 µm) FORS1 image ("c"). This emission is obviously associated with the shock front visible on the radio image. This is one of the first times it has been possible to obtain an optical/near-IR image of synchrotron emission from such an intergalactic shock and, thanks to the sensitivity and image sharpness of the VLT, the most detailed view of its kind so far . The central area (with the strongest emission) is where the plasma jet from the galaxy centre hits the intergalactic medium. The light from the two other "knots", some 10 - 15,000 light-years away from the central "hot spot", is also interpreted as synchrotron emission. However, in view of the large distance, the astronomers are convinced that it must be caused by electrons accelerated in secondary processes at those sites . The new images thus confirm that electrons are being continuously accelerated in these "knots" - hence called "cosmic accelerators" - far from the galaxy and the main jets, and in nearly empty space. The exact physical circumstances of this effect are not well known and will be the subject of further investigations. The present VLT-images of the "hot spots" near 3C 445 may not have the same public appeal as some of those beautiful images that have been produced by the same instruments during the past years. But they are not less valuable - their unusual importance is of a different kind, as they now herald the advent of fundamentally new insights into the mysteries of this class of remote and active

  11. EXOTIC MAGNETS FOR ACCELERATORS.

    SciTech Connect

    WANDERER, P.

    2005-09-18

    Over the last few years, several novel magnet designs have been introduced to meet the requirements of new, high performance accelerators and beam lines. For example, the FAIR project at GSI requires superconducting magnets ramped at high rates ({approx} 4 T/s) in order to achieve the design intensity. Magnets for the RIA and FAIR projects and for the next generation of LHC interaction regions will need to withstand high doses of radiation. Helical magnets are required to maintain and control the polarization of high energy protons at RHIC. In other cases, novel magnets have been designed in response to limited budgets and space. For example, it is planned to use combined function superconducting magnets for the 50 GeV proton transport line at J-PARC to satisfy both budget and performance requirements. Novel coil winding methods have been developed for short, large aperture magnets such as those used in the insertion region upgrade at BEPC. This paper will highlight the novel features of these exotic magnets.

  12. Pulsars and Acceleration Sites

    NASA Technical Reports Server (NTRS)

    Harding, Alice

    2008-01-01

    Rotation-powered pulsars are excellent laboratories for the studying particle acceleration as well as fundamental physics of strong gravity, strong magnetic fields and relativity. But even forty years after their discovery, we still do not understand their pulsed emission at any wavelength. I will review both the basic physics of pulsars as well as the latest developments in understanding their high-energy emission. Special and general relativistic effects play important roles in pulsar emission, from inertial frame-dragging near the stellar surface to aberration, time-of-flight and retardation of the magnetic field near the light cylinder. Understanding how these effects determine what we observe at different wavelengths is critical to unraveling the emission physics. Fortunately the Gamma-Ray Large Area Space Telescope (GLAST), with launch in May 2008 will detect many new gamma-ray pulsars and test the predictions of these models with unprecedented sensitivity and energy resolution for gamma-rays in the range of 30 MeV to 300 GeV.

  13. Actinides, accelerators and erosion

    NASA Astrophysics Data System (ADS)

    Tims, S. G.; Fifield, L. K.

    2012-10-01

    Fallout isotopes can be used as artificial tracers of soil erosion and sediment accumulation. The most commonly used isotope to date has been 137Cs. Concentrations of 137Cs are, however, significantly lower in the Southern Hemisphere, and furthermore have now declined to 35% of original values due to radioactive decay. As a consequence the future utility of 137Cs is limited in Australia, with many erosion applications becoming untenable within the next 20 years, and there is a need to replace it with another tracer. Plutonium could fill this role, and has the advantages that there were six times as many atoms of Pu as of 137Cs in fallout, and any loss to decay has been negligible due to the long half-lives of the plutonium isotopes. Uranium-236 is another long-lived fallout isotope with significant potential for exploitation as a tracer of soil and sediment movement. Uranium is expected to be more mobile in soils than plutonium (or caesium), and hence the 236U/Pu ratio will vary with soil depth, and so could provide an independent measure of the amount of soil loss. In this paper we discuss accelerator based ultra-sensitive measurements of plutonium and 236U isotopes and their advantages over 137Cs as tracers of soil erosion and sediment movement.

  14. Is Global Warming Accelerating?

    NASA Astrophysics Data System (ADS)

    Shukla, J.; Delsole, T. M.; Tippett, M. K.

    2009-12-01

    A global pattern that fluctuates naturally on decadal time scales is identified in climate simulations and observations. This newly discovered component, called the Global Multidecadal Oscillation (GMO), is related to the Atlantic Meridional Oscillation and shown to account for a substantial fraction of decadal fluctuations in the observed global average sea surface temperature. IPCC-class climate models generally underestimate the variance of the GMO, and hence underestimate the decadal fluctuations due to this component of natural variability. Decomposing observed sea surface temperature into a component due to anthropogenic and natural radiative forcing plus the GMO, reveals that most multidecadal fluctuations in the observed global average sea surface temperature can be accounted for by these two components alone. The fact that the GMO varies naturally on multidecadal time scales implies that it can be predicted with some skill on decadal time scales, which provides a scientific rationale for decadal predictions. Furthermore, the GMO is shown to account for about half of the warming in the last 25 years and hence a substantial fraction of the recent acceleration in the rate of increase in global average sea surface temperature. Nevertheless, in terms of the global average “well-observed” sea surface temperature, the GMO can account for only about 0.1° C in transient, decadal-scale fluctuations, not the century-long 1° C warming that has been observed during the twentieth century.

  15. RFQ accelerator tuning system

    DOEpatents

    Bolie, Victor W.

    1990-01-01

    A cooling system is provided for maintaining a preselected operating temperature in a device, which may be an RFQ accelerator, having a variable heat removal requirement, by circulating a cooling fluid through a cooling system remote from the device. Internal sensors in the device enable an estimated error signal to be generated from parameters which are indicative of the heat removal requirement from the device. Sensors are provided at predetermined locations in the cooling system for outputting operational temperature signals. Analog and digital computers define a control signal functionally related to the temperature signals and the estimated error signal, where the control signal is defined effective to return the device to the preselected operating temperature in a stable manner. The cooling system includes a first heat sink responsive to a first portion of the control signal to remove heat from a major portion of the circulating fluid. A second heat sink is responsive to a second portion of the control signal to remove heat from a minor portion of the circulating fluid. The cooled major and minor portions of the circulating fluid are mixed in response to a mixing portion of the control signal, which is effective to proportion the major and minor portions of the circulating fluid to establish a mixed fluid temperature which is effective to define the preselected operating temperature for the remote device. In an RFQ environment the stable temperature control enables the resonant frequency of the device to be maintained at substantially a predetermined value during transient operations.

  16. RFQ accelerator tuning system

    DOEpatents

    Bolie, V.W.

    1990-07-03

    A cooling system is provided for maintaining a preselected operating temperature in a device, which may be an RFQ accelerator, having a variable heat removal requirement, by circulating a cooling fluid through a cooling system remote from the device. Internal sensors in the device enable an estimated error signal to be generated from parameters which are indicative of the heat removal requirement from the device. Sensors are provided at predetermined locations in the cooling system for outputting operational temperature signals. Analog and digital computers define a control signal functionally related to the temperature signals and the estimated error signal, where the control signal is defined effective to return the device to the preselected operating temperature in a stable manner. The cooling system includes a first heat sink responsive to a first portion of the control signal to remove heat from a major portion of the circulating fluid. A second heat sink is responsive to a second portion of the control signal to remove heat from a minor portion of the circulating fluid. The cooled major and minor portions of the circulating fluid are mixed in response to a mixing portion of the control signal, which is effective to proportion the major and minor portions of the circulating fluid to establish a mixed fluid temperature which is effective to define the preselected operating temperature for the remote device. In an RFQ environment the stable temperature control enables the resonant frequency of the device to be maintained at substantially a predetermined value during transient operations. 3 figs.

  17. Compact plasma accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E. (Inventor)

    2004-01-01

    A compact plasma accelerator having components including a cathode electron source, an anodic ionizing gas source, and a magnetic field that is cusped. The components are held by an electrically insulating body having a central axis, a top axial end, and a bottom axial end. The cusped magnetic field is formed by a cylindrical magnet having an axis of rotation that is the same as the axis of rotation of the insulating body, and magnetized with opposite poles at its two axial ends; and an annular magnet coaxially surrounding the cylindrical magnet, magnetized with opposite poles at its two axial ends such that a top axial end has a magnetic polarity that is opposite to the magnetic polarity of a top axial end of the cylindrical magnet. The ionizing gas source is a tubular plenum that has been curved into a substantially annular shape, positioned above the top axial end of the annular magnet such that the plenum is centered in a ring-shaped cusp of the magnetic field generated by the magnets. The plenum has one or more capillary-like orifices spaced around its top such that an ionizing gas supplied through the plenum is sprayed through the one or more orifices. The plenum is electrically conductive and is positively charged relative to the cathode electron source such that the plenum functions as the anode; and the cathode is positioned above and radially outward relative to the plenum.

  18. Accelerating momentum for change!

    PubMed

    Wenzel, S; Panetta, J

    1995-05-01

    As we develop strategies to compete globally, we are challenged with integrating our resources to execute these strategies effectively. Many companies are in the midst of dramatic shifts in corporate cultures, giving more responsibility to employees while raising expectations for their performance. The extent of these changes is far reaching and brings significant challenges to both employees and corporations. This article is a continuation of the evolution (over five years) of a corrective action/continuous improvement process implemented at Exide Electronics. It discusses organizational structures, including steering committees, corrective action teams, task teams, and work cells. Specific expectations, goals, and results of the teams are presented, along with ground rules for functioning within the organization. After structuring the organization and coordinating the resources effectively, the next challenge is accelerating momentum for change. The presentation also discusses the evolutionary process required to make a culture focused on change, including ongoing communication and feedback, constant evaluation and direction of the process, and measuring and paying for performance.

  19. Maximal acceleration and radiative processes

    NASA Astrophysics Data System (ADS)

    Papini, Giorgio

    2015-08-01

    We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass m has the upper limit 𝒜m = 2mc3/ℏ. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to 𝒜m and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws due to the maximal acceleration (MA) with that for particles in gravitational fields, we find that the model of Caianiello allows, in principle, the use of charged particles as tools to distinguish inertial from gravitational fields locally.

  20. The ISAC post-accelerator

    NASA Astrophysics Data System (ADS)

    Laxdal, R. E.; Marchetto, M.

    2014-01-01

    The acceleration chain of the ISAC facility boosts the energy of both radioactive and stable light and heavy ions for beam delivery to both a medium energy area in ISAC-I and a high energy area in ISAC-II. The post-accelerator comprises a 35.4 MHz RFQ to accelerate beams of A/q ≤ 30 from 2 keV/u to 150 keV/u and a post stripper, 106.1 MHz variable energy drift tube linac (DTL) to accelerate ions of A/q ≤ 6 to a final energy between 0.15 MeV/u to 1.5 MeV/u. A 40 MV superconducting linac further accelerates beam from 1.5 MeV/u to energies above the Coulomb barrier. All linacs operate cw to preserve beam intensity.

  1. Electron cyclotron harmonic wave acceleration

    NASA Technical Reports Server (NTRS)

    Karimabadi, H.; Menyuk, C. R.; Sprangle, P.; Vlahos, L.

    1987-01-01

    A nonlinear analysis of particle acceleration in a finite bandwidth, obliquely propagating electromagnetic cyclotron wave is presented. It has been suggested by Sprangle and Vlahos in 1983 that the narrow bandwidth cyclotron radiation emitted by the unstable electron distribution inside a flaring solar loop can accelerate electrons outside the loop by the interaction of a monochromatic wave propagating along the ambient magnetic field with the ambient electrons. It is shown here that electrons gyrating and streaming along a uniform, static magnetic field can be accelerated by interacting with the fundamental or second harmonic of a monochromatic, obliquely propagating cyclotron wave. It is also shown that the acceleration is virtually unchanged when a wave with finite bandwidth is considered. This acceleration mechanism can explain the observed high-energy electrons in type III bursts.

  2. Electron acceleration in a two-stage laser wakefield accelerator

    NASA Astrophysics Data System (ADS)

    Li, Ruxin; Liu, Jiansheng; Xia, Changquan; Wang, Wentao; Lu, Haiyang; Wang, Cheng; Deng, Aihua; Li, Wentao; Zhang, Hui; Liang, Xiaoyan; Leng, Yuxin; Lu, Xiaoming; Wang, Cheng; Wang, Jianzhou; Shen, Baifei; Nakajima, Kazuhisa; Xu, Zhizhan

    2012-07-01

    Near-GeV electron beam generation from a two-stage laser wakefield accelerator (LWFA) is reported. Electron injection and acceleration are separated into two distinct LWFA stages and controlled independently from each other by employing two gas cells filled with a He/O2 mixture and pure He gas, respectively. Electrons with a Maxwellian spectrum, generated from the injection stage assisted by ionization-induced injection, are seeded into the acceleration stage with a 3-mm long gas cell and accelerated to produce a 0.8-GeV quasimonoenergetic electron beam for a 45 TW 40 fs laser pulse, corresponding to an acceleration gradient of 187 GV/m. In the injection stage, the produced electron beam properties can be optimized by adjusting the input laser intensity and the plasma density so that quasimonoenergetic electron beams are obtained owing to the self-focusing effects of the laser beam. The ionization-induced injection scheme has been extensively employed for a capillary discharge plasma waveguide to demonstrate channel-guided LWFA beyond 1 GeV. Using a 4-cm capillary made of oxygen containing acrylic resin results in optically guiding 130 TW 55 fs laser pulse that accelerates electrons up to 1.8 GeV in contrast with no electron acceleration in a polyethylene capillary free of oxygen.

  3. Beam acceleration through proton radio frequency quadrupole accelerator in BARC

    NASA Astrophysics Data System (ADS)

    Bhagwat, P. V.; Krishnagopal, S.; Mathew, J. V.; Singh, S. K.; Jain, P.; Rao, S. V. L. S.; Pande, M.; Kumar, R.; Roychowdhury, P.; Kelwani, H.; Rama Rao, B. V.; Gupta, S. K.; Agarwal, A.; Kukreti, B. M.; Singh, P.

    2016-05-01

    A 3 MeV proton Radio Frequency Quadrupole (RFQ) accelerator has been designed at the Bhabha Atomic Research Centre, Mumbai, India, for the Low Energy High Intensity Proton Accelerator (LEHIPA) programme. The 352 MHz RFQ is built in 4 segments and in the first phase two segments of the LEHIPA RFQ were commissioned, accelerating a 50 keV, 1 mA pulsed proton beam from the ion source, to an energy of 1.24 MeV. The successful operation of the RFQ gave confidence in the physics understanding and technology development that have been achieved, and indicate that the road forward can now be traversed rather more quickly.

  4. EDITORIAL: Laser and plasma accelerators Laser and plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bingham, Robert

    2009-02-01

    This special issue on laser and plasma accelerators illustrates the rapid advancement and diverse applications of laser and plasma accelerators. Plasma is an attractive medium for particle acceleration because of the high electric field it can sustain, with studies of acceleration processes remaining one of the most important areas of research in both laboratory and astrophysical plasmas. The rapid advance in laser and accelerator technology has led to the development of terawatt and petawatt laser systems with ultra-high intensities and short sub-picosecond pulses, which are used to generate wakefields in plasma. Recent successes include the demonstration by several groups in 2004 of quasi-monoenergetic electron beams by wakefields in the bubble regime with the GeV energy barrier being reached in 2006, and the energy doubling of the SLAC high-energy electron beam from 42 to 85 GeV. The electron beams generated by the laser plasma driven wakefields have good spatial quality with energies ranging from MeV to GeV. A unique feature is that they are ultra-short bunches with simulations showing that they can be as short as a few femtoseconds with low-energy spread, making these beams ideal for a variety of applications ranging from novel high-brightness radiation sources for medicine, material science and ultrafast time-resolved radiobiology or chemistry. Laser driven ion acceleration experiments have also made significant advances over the last few years with applications in laser fusion, nuclear physics and medicine. Attention is focused on the possibility of producing quasi-mono-energetic ions with energies ranging from hundreds of MeV to GeV per nucleon. New acceleration mechanisms are being studied, including ion acceleration from ultra-thin foils and direct laser acceleration. The application of wakefields or beat waves in other areas of science such as astrophysics and particle physics is beginning to take off, such as the study of cosmic accelerators considered

  5. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, Daniel L.; Reginato, Louis L.

    1988-01-01

    An electron beam accelerator comprising an electron beam generator-injector to produce a focused beam of .gtoreq.0.1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electrons by about 0.1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially .gtoreq.0.1-1 MeV maximum energy over a time duration of .ltoreq.1 .mu.sec.

  6. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, Daniel L.; Reginato, Louis L.

    1987-01-01

    An electron beam accelerator comprising an electron beam generator-injector to produce a focused beam of .gtoreq.0.1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electrons by about 0.1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially 0.1-1 MeV maximum energy over a time duration of .ltoreq.1 .mu.sec.

  7. Electron beam accelerator with magnetic pulse compression and accelerator switching

    DOEpatents

    Birx, D.L.; Reginato, L.L.

    1984-03-22

    An electron beam accelerator is described comprising an electron beam generator-injector to produce a focused beam of greater than or equal to .1 MeV energy electrons; a plurality of substantially identical, aligned accelerator modules to sequentially receive and increase the kinetic energies of the beam electron by about .1-1 MeV per module. Each accelerator module includes a pulse-forming network that delivers a voltage pulse to the module of substantially .1-1 MeV maximum energy over a time duration of less than or equal to 1 ..mu..sec.

  8. Operation of the accelerator

    SciTech Connect

    Pardo, R.C.; Batzka, B.; Billquist, P.J.

    1995-08-01

    Fiscal Year 1994 was the first year of seven-day operation since ATLAS became a national user facility in 1985. ATLAS made the most of the opportunity this year by providing 5200 hours of beam on-target to the research program. A record number of 60 experiments were completed and the {open_quotes}facility reliability{close_quotes} remained near the 90% level. Seven-day operation was made possible with the addition to the staff of two operator positions providing single-operator coverage during the weekend period. The normally scheduled coverage was augmented by an on-call list of system experts who respond to emergencies with phone-in advice and return to the Laboratory when necessary. This staffing approach continues but we rearranged our staffing patterns so that we now have one cryogenics engineer working a shift pattern which includes 8-hour daily coverage during the weekend. ATLAS provided a beam mix to users consisting of 26 different isotopic species, 23% of which were for A>100 in FY 1994. Approximately 60% of the beam time was provided by the Positive Ion Injector, slightly less than the usage rate of FY 1993. Experiments using uranium or lead beams accounted for 16.4% of the total beam time. The ECR ion source and high-voltage platform functioned well throughout the year. A new technique for solid material production in the source was developed which uses a sputtering process wherein the sample of material placed near the plasma chamber wall is biased negatively. Plasma ions are accelerated into the sample and material is sputtered from the surface into the plasma. This technique is now used routinely for many elements. Runs of calcium, germanium, nickel, lead, tellurium, and uranium were carried out with this technique.

  9. Accelerating DSMC data extraction.

    SciTech Connect

    Gallis, Michail A.; Piekos, Edward Stanley

    2006-10-01

    In many direct simulation Monte Carlo (DSMC) simulations, the majority of computation time is consumed after the flowfield reaches a steady state. This situation occurs when the desired output quantities are small compared to the background fluctuations. For example, gas flows in many microelectromechanical systems (MEMS) have mean speeds more than two orders of magnitude smaller than the thermal speeds of the molecules themselves. The current solution to this problem is to collect sufficient samples to achieve the desired resolution. This can be an arduous process because the error is inversely proportional to the square root of the number of samples so we must, for example, quadruple the samples to cut the error in half. This work is intended to improve this situation by employing more advanced techniques, from fields other than solely statistics, for determining the output quantities. Our strategy centers on exploiting information neglected by current techniques, which collect moments in each cell without regard to one another, values in neighboring cells, nor their evolution in time. Unlike many previous acceleration techniques that modify the method itself, the techniques examined in this work strictly post-process so they may be applied to any DSMC code without affecting its fidelity or generality. Many potential methods are drawn from successful applications in a diverse range of areas, from ultrasound imaging to financial market analysis. The most promising methods exploit relationships between variables in space, which always exist in DSMC due to the absence of shocks. Disparate techniques were shown to produce similar error reductions, suggesting that the results shown in this report may be typical of what is possible using these methods. Sample count reduction factors of approximately three to five were found to be typical, although factors exceeding ten were shown on some variables under some techniques.

  10. Accelerated coffee pulp composting.

    PubMed

    Sánchez, G; Olguín, E J; Mercado, G

    1999-02-01

    The effect of two abundant, easily available and very low-cost agro-industrial organic residues, i.e., filter cake from the sugar industry and poultry litter, on the composting stabilization time of coffee pulp and on the quality of the produced compost, was evaluated. Piles of one cubic meter were built and monitored within the facilities of a coffee processing plant in the Coatepec region of the State of Veracruz, Mexico. Manual aeration was carried out once a week. A longer thermophilic period (28 days) and a much lower C/N ratio (in the range of 6.9-9.1) were observed in the piles containing the amendments, as compared to the control pile containing only coffee pulp (14 days and a C/N ratio of 14.4, respectively). The maximum assimilation rate of the reducing sugars was 1.6 g kg-1 d-1 (from 7.5 to 5.3%) during the first two weeks when accelerators were present in the proportion of 20% filter cake plus 20% poultry litter, while they accumulated at a rate of 1.2 g kg-1 d-1 (from 7.4 to 9.13%) during the same period in the control pile. The best combination of amendments was 30% filter cake with 20% poultry litter, resulting in a final nitrogen content as high as 4.81%. The second best combination was 20% filter cake with 10% poultry litter, resulting in a compost which also contained a high level of total nitrogen (4.54%). It was concluded that the use of these two residues enhanced the composting process of coffee pulp, promoting a shorter stabilization period and yielding a higher quality of compost.

  11. A Fundamental Theorem on Particle Acceleration

    SciTech Connect

    Xie, Ming

    2003-05-01

    A fundamental theorem on particle acceleration is derived from the reciprocity principle of electromagnetism and a rigorous proof of the theorem is presented. The theorem establishes a relation between acceleration and radiation, which is particularly useful for insightful understanding of and practical calculation about the first order acceleration in which energy gain of the accelerated particle is linearly proportional to the accelerating field.

  12. Acceleration: Still an Option for the Gifted.

    ERIC Educational Resources Information Center

    Heinbokel, Annette

    2002-01-01

    In response to an article (Hany, 2001) discouraging the practice of acceleration through grade skipping for gifted students, this article defends acceleration as one option for gifted students, describes use of acceleration in Germany including early school entrance, individual grade skipping, acceleration in one subject, and acceleration in…

  13. Is the Universe's Acceleration Eternal?

    NASA Astrophysics Data System (ADS)

    Bean, Rachel; Magueijo, Joao; Barrow, John

    2002-12-01

    We present a new interpretation of recent observations suggesting that the expansion of the Universe has recently started to accelerate. First we introduce a cosmological model with a minimally coupled quintessence field driven by a potential motivated by M-theory. We find that late-time acceleration does not have to lead to the usual predictions of perpetual acceleration. The model allows another broad class of scenarios in which today's acceleration is a transient phenomenon which is succeeded by a return to matter domination and decelerating expansion. Quintessence scenarios provide a simple explanation for the observed acceleration of the Universe. Yet, explaining why acceleration did not start a long time ago remains a challenge. The idea that the transition from radiation to matter domination played a dynamical role in triggering acceleration has been put forward in various guises. We, secondly, propose a simple dilaton-derived quintessence model in which temporary vacuum domination is naturally triggered by the radiation to matter transition. In this model Einstein's gravity is preserved but quintessence couples non-minimally to the cold dark matter, but not to "visible" matter. Such couplings have been attributed to the dilaton in the low-energy limit of string theory beyond tree level.

  14. Teleportation with Multiple Accelerated Partners

    NASA Astrophysics Data System (ADS)

    Sagheer, A.; Hamdoun, H.; Metwally, N.

    2015-09-01

    As the current revolution in communication is underway, quantum teleportation can increase the level of security in quantum communication applications. In this paper, we present a quantum teleportation procedure that capable to teleport either accelerated or non-accelerated information through different quantum channels. These quantum channels are based on accelerated multi-qubit states, where each qubit of each of these channels represents a partner. Namely, these states are the W state, Greenberger-Horne-Zeilinger (GHZ) state, and the GHZ-like state. Here, we show that the fidelity of teleporting accelerated information is higher than the fidelity of teleporting non-accelerated information, both through a quantum channel that is based on accelerated state. Also, the comparison among the performance of these three channels shows that the degree of fidelity depends on type of the used channel, type of the measurement, and value of the acceleration. The result of comparison concludes that teleporting information through channel that is based on the GHZ state is more robust than teleporting information through channels that are based on the other two states. For future work, the proposed procedure can be generalized later to achieve communication through a wider quantum network.

  15. Acceleration of polarized protons in the IHEP accelerator complex

    SciTech Connect

    Anferov, V.A.; Ado, Yu.M.; Shoumkin, D.

    1995-04-01

    The paper considers possibility to accelerate polarized beam in the IHEP accelerator complex (including first stage of the UNK). The scheme of preserving beam polarization is described for all acceleration stages up to 400 GeV beam energy. Polarization and intensity of the polarized proton beam are estimated. The suggested scheme includes using two Siberian snakes in opposite straight sections of the UNK-1, where each snake consists of five dipole magnets. In the U-70 it is suggested to use one helical Siberian snake, which is turned on adiabatically at 10 GeV, and four pulsed quadrupoles. To incorporate the snake into the accelerator lattice it is proposed to make modification of one superperiod. This would make a 13 m long straight section. Spin depolarization in the Booster is avoided by decreasing the extraction energy to 0.9 GeV. Then no additional hardware is required in the Booster.

  16. Phase motion of accelerated electrons in vacuum laser acceleration

    SciTech Connect

    Hua, J. F.; Lin, Y. Z.; Tang, Ch. X.; Ho, Y. K.; Kong, Q.

    2007-01-15

    The phase stability in the capture and acceleration scenario (CAS) is studied and compared with that of conventional linear electron accelerators (CLEAs). For the CAS case, it has been found that a slow phase slippage occurs due to the difference between the electron velocity and the phase velocity of the longitudinal accelerating electric field. Thus, CAS electrons cannot remain in a fixed small phase region of the accelerating field to obtain a quasimonoenergy gain in contrast to the stability of phase oscillation in CLEAs. Also, the energy spread of the output electron beam for the CAS case cannot be kept as small as the CLEA because there is no good phase bunching phenomenon generated by phase oscillation.

  17. Experimental test accelerator (ETA) II

    SciTech Connect

    Fessenden, T.J.; Atchison, W.L.; Birx, D.L.

    1981-03-06

    The Experimental Test Accelerator (ETA) is designed to produce a 10 kAmp electron beam at an energy of 4.5 MeV in 40 nsec pulses at an average rate of 2 pps. The accelerator also operates in bursts of 5 pulses spaced by as little as one millisec at an average rate of 5 pps. The machine is currently operating near 80% of its design values and has accumulated over 2.5 million pulses - mostly at a rate of one pps. The plasma cathode electron source, the remainder of the accelerator, and the operating characteristics of the machine are discussed.

  18. Imaging using accelerated heavy ions

    SciTech Connect

    Chu, W.T.

    1982-05-01

    Several methods for imaging using accelerated heavy ion beams are being investigated at Lawrence Berkeley Laboratory. Using the HILAC (Heavy-Ion Linear Accelerator) as an injector, the Bevalac can accelerate fully stripped atomic nuclei from carbon (Z = 6) to krypton (Z = 34), and partly stripped ions up to uranium (Z = 92). Radiographic studies to date have been conducted with helium (from 184-inch cyclotron), carbon, oxygen, and neon beams. Useful ranges in tissue of 40 cm or more are available. To investigate the potential of heavy-ion projection radiography and computed tomography (CT), several methods and instrumentation have been studied.

  19. Electromagnetic modeling in accelerator designs

    SciTech Connect

    Cooper, R.K.; Chan, K.C.D.

    1990-01-01

    Through the years, electromagnetic modeling using computers has proved to be a cost-effective tool for accelerator designs. Traditionally, electromagnetic modeling of accelerators has been limited to resonator and magnet designs in two dimensions. In recent years with the availability of powerful computers, electromagnetic modeling of accelerators has advanced significantly. Through the above conferences, it is apparent that breakthroughs have been made during the last decade in two important areas: three-dimensional modeling and time-domain simulation. Success in both these areas have been made possible by the increasing size and speed of computers. In this paper, the advances in these two areas will be described.

  20. Cascaded target normal sheath acceleration

    SciTech Connect

    Wang, W. P.; Shen, B. F.; Zhang, X. M.; Wang, X. F.; Xu, J. C.; Zhao, X. Y.; Yu, Y. H.; Yi, L. Q.; Shi, Y.; Zhang, L. G.; Xu, T. J.; Xu, Z. Z.

    2013-11-15

    A cascaded target normal sheath acceleration (TNSA) scheme is proposed to simultaneously increase energy and improve energy spread of a laser-produced mono-energetic proton beam. An optimum condition that uses the maximum sheath field to accelerate the center of the proton beam is theoretically found and verified by two-dimensional particle-in-cell simulations. An initial 10 MeV proton beam is accelerated to 21 MeV with energy spread decreased from 5% to 2% under the optimum condition during the process of the cascaded TNSA. The scheme opens a way to scale proton energy lineally with laser energy.