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At least 1,549 records · Page 86
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Phase I Dose Escalation Trial of Vandetanib With Fractionated Radiosurgery in Patients With Recurrent Malignant Gliomas

Purpose: To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. Methods and Materials: Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor {<=}6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. Results: Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. Conclusion: The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Early Outcomes From Three Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

Purpose: To report early outcomes with image-guided proton therapy for prostate cancer. Methods and Materials: We accrued 211 prostate cancer patients on prospective Institutional Review Board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel followed by androgen deprivation for high-risk disease. Minimum follow-up was 2 years. Results: One intermediate-risk patient and 2 high-risk patients had disease progression. Pretreatment genitourinary (GU) symptom management was required in 38% of patients. A cumulative 88 (42%) patients required posttreatment GU symptom management. Four transient Grade 3 GU toxicities occurred, all among patients requiring pretreatment GU symptom management. Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1 Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months, with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy. Univariate and multivariate analyses showed significant correlation between Grade 2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum) receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. Conclusions: Early outcomes with image-guided proton therapy suggest high efficacy and minimal toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Split-Field Helical Tomotherapy With or Without Chemotherapy for Definitive Treatment of Cervical Cancer

Objective: The objective of this study was to investigate the chronic toxicity, response to therapy, and survival outcomes of patients with cervical cancer treated with definitive pelvic irradiation delivered by helical tomotherapy (HT), with or without concurrent chemotherapy. Methods and Materials: There were 15 patients with a new diagnosis of cervical cancer evaluated in this study from April 2006 to February 2007. The clinical stages of their disease were Stage Ib1 in 3 patients, Ib2 in 3, IIa in 2, IIb in 4, IIIb in 2, and IVa in 1 patient. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) simulation was performed in all patients. All patients received pelvic irradiation delivered by HT and high-dose-rate (HDR) brachytherapy. Four patients also received para-aortic irradiation delivered by HT. Thirteen patients received concurrent chemotherapy. Patients were monitored for chronic toxicity using the Common Terminology Criteria for Adverse Events version 3.0 criteria. Results: The median age of the cohort was 51 years (range, 29-87 years), and the median follow-up for all patients alive at time of last follow-up was 35 months. The median overall radiation treatment time was 54 days. One patient developed a chronic Grade 3 GI complication. No other Grade 3 or 4 complications were observed. At last follow-up, 3 patients had developed a recurrence, with 1 patient dying of disease progression. The 3-year progression-free and cause-specific survival estimates for all patients were 80% and 93%, respectively. Conclusion: Intensity-modulated radiation therapy delivered with HT and HDR brachytherapy with or without chemotherapy for definitive treatment of cervical cancer is feasible, with acceptable levels of chronic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704-A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (<PP). Scoring occurred after therapy but before trial analysis and without knowledge of individual patient treatment outcomes. Scoring was done for all tumor locations and for the subset of pancreatic head location. Results: RT was scored for 416 patients: 216 PP and 200 <PP. For all pancreatic sites (head, body/tail) median survival (MS) for PP vs. <PP was 1.74 vs. 1.46 years (log-rank p = 0.0077). In multivariate analysis, PP vs. <PP score correlated more strongly with MS than assigned treatment arm (p = 0.014, p = NS, respectively); for patients with pancreatic head tumors, both PP score and gemcitabine treatment correlated with improved MS (p = 0.016, p = 0.043, respectively). For all tumor locations, PP score was associated with decreased risk of failure (p = 0.016) and, for gemcitabine patients, a trend toward reduced Grade 4/5 nonhematologic toxicity (p = 0.065). Conclusions: This is the first Phase III, multicenter, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Continuous 7-Days-A-Week External Beam Irradiation in Locally Advanced Cervical Cancer: Final Results of the Phase I/II Study

Purpose: To evaluate the feasibility and efficacy of definitive continuous 7-days-a-week pelvic irradiation without breaks between external beam radiotherapy and brachytherapy in locally advanced cervical cancer. Methods and Materials: Between November 1998 and December 1999, 30 patients with International Federation of Obstetrics and Gynecology Stage IIB or IIIB cervical cancer were included in a prospective Phase I/II study of continuous 7-days-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (Group A) were given a daily tumor dose of 1.6 Gy, and the remaining 17 patients (Group B) were given 1.8 Gy. One or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. Results: Two patients did not complete the irradiation because of apparent early progression of disease during the irradiation. Eleven of the 28 evaluable patients (39%; 45% and 35% in Groups A and B, respectively) completed their treatment within the prescribed overall treatment time. Acute toxicity (including severe European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 and 4 effects in 40%) was experienced by 83% of patients and resulted in unplanned treatment interruptions in 40% of all patients (31% and 47% of patients in Groups A and B, respectively). Severe intestinal side effects occurred in 31% and 41% of Patients in Groups A and B, respectively (p = 0.71). The 5-year overall survival probability was 33%. Cancer recurrence occurred in 63% of patients: 20% inside and 57% outside the pelvis. Cumulative incidence of late severe bowel and urinary bladder toxicity at 24 months was 15%. Conclusion: Continuous irradiation in locally advanced cervical cancer is associated with a high incidence of severe acute toxicity, resulting in unplanned treatment interruptions. Late severe effects and survival after continuous radiotherapy do not substantially differ from those obtained with conventionally fractionated radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

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

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

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prospective Study of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Concurrent With Individualized Radiotherapy for Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

Purpose: To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity, and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS). Results: Median gross tumor volume, mean lung dose, and lung V20 were 56 cm{sup 3}, 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively. Conclusion: Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally advanced or metastatic NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Weekly Gemcitabine and Cisplatin in Combination With Radiotherapy in Patients With Locally Advanced Head-and-Neck Cancer: Phase I Study

Purpose: To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation. Methods and Materials: Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m{sup 2} and that of gemcitabine was 10 mg/m{sup 2} in 3 patients, with a subsequent dose escalation of 10 mg/m{sup 2} of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m{sup 2} for each new cohort was used (Level 1, 10 mg/m{sup 2} of gemcitabine and 20 mg/m{sup 2} of cisplatin; Level 2, 10 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin; and Level 3, 20 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy. Results: From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free. Conclusion: Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin with an acceptable tolerability profile.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Cervical Lymph Node Metastases From Unknown Primary Cancer: A Single-Institution Experience With Intensity-Modulated Radiotherapy

Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Hyperfractionated Concomitant Boost Proton Beam Therapy for Esophageal Carcinoma

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

Objectives: Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis. Patients and Methods: Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed. Results: The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities. Conclusions: The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Dose-Volume Parameters Predict for the Development of Chest Wall Pain After Stereotactic Body Radiation for Lung Cancer

Purpose: Chest wall (CW) pain has recently been recognized as an important adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). We developed a dose-volume model to predict the development of this toxicity. Methods and Materials: A total of 126 patients with primary, clinically node-negative NSCLC received three to five fractions of SBRT to doses of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were examined for all 126 patients. Results: With a median follow-up of 16 months, the 2-year estimated actuarial incidence of Grade {>=} 2 CW pain was 39%. The median time to onset of Grade {>=} 2 CW pain (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive advantage for biologically corrected dose over physical dose. Neither fraction number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated with the development of Grade {>=} 2 CW pain. Cox Proportional Hazards analysis identified significant correlation with a broad range of dose-volume combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest predictors (p < 0.001). CW2cm consistently enabled better prediction of CW toxicity. When a physical dose of 30 Gy was received by more than 70 cm{sup 3} of CW2cm, there was a significant correlation with Grade {>=} 2 CW pain (p = 0.004). Conclusions: CW toxicity after SBRT is common and long-term follow-up is needed to identify affected patients. A volume of CW {>=} 70 cm{sup 3} receiving 30 Gy is significantly correlated with Grade {>=} 2 CW pain. We are currently applying this constraint at our institution for patients receiving thoracic SBRT. An actuarial atlas of our data is provided as an electronic supplement to facilitate data-sharing and meta-analysis relating to CW pain.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma-A Prospective Randomized Study

Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Methods and Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗