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At least 1,261 records · Page 70
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DOE OSTI2011

Association Between Maximal Skin Dose and Breast Brachytherapy Outcome: A Proposal for More Rigorous Dosimetric Constraints

Purpose: Multiple investigations have used the skin distance as a surrogate for the skin dose and have shown that distances <6 mm have been associated with late toxicity after MammoSite brachytherapy. No publications have yet described the relationship between the actual maximal skin dose and the outcome. The present study analyzed the maximal skin dose delivered and the occurrence of late toxicity in a large cohort of patients with prolonged follow-up. Methods: A total of 96 patients treated with breast brachytherapy between 2000 and 2007 for whom complete planning and follow-up data were available were included in the present analysis. The median follow-up was 48 months (range, 24-111). Of the 96 patients, 40 were treated with multicatheter interstitial brachytherapy and 56 with MammoSite. A multivariate statistical analysis was performed to determine the relationship between several dosimetric parameters and patient outcome. Results: The treatment was well tolerated, with 98% of patients experiencing good to excellent cosmesis. Significant late toxicity was uncommon. The maximal dose delivered to the skin was significantly associated with the incidence of any degree of telangiectasia (p = .009) and moderate to severe fibrosis (p = .010). The incidence of late toxicity was significantly increased when the dose to the skin was >4.05 Gy/fraction. Conclusion: The initial skin dose recommendations have been based on safe use and the avoidance of significant toxicity. The results from the present study have suggested that patients might further benefit if more rigorous constraints were applied and if the skin dose were limited to 120% of the prescription dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

The Effect of Adjuvant Postmastectomy Radiotherapy Bolus Technique on Local Recurrence

Purpose: Postmastectomy radiotherapy bolus is heterogenous, with little evidence to guide clinical practise. This study explores the effect of chest wall bolus technique on chest wall recurrence. Methods and Materials: This was a retrospective cohort study of 254 patients treated with adjuvant postmastectomy radiotherapy between 1993 and 2003. Patient and treatment characteristics including bolus details were extracted. Outcomes considered were treatment toxicities, treatment delivery, and local recurrence. Results: In all, 143 patients received radiotherapy with whole chest wall bolus, 88 patients with parascar bolus, and 23 with no bolus. Twenty patients did not complete radiotherapy because of acute skin toxicity: 17 in the whole chest wall bolus group, 2 in the parascar bolus group, and 1 in the group not treated with bolus. On multivariate analysis, whole chest wall bolus and chemotherapy were found to be significant predictors for early cessation of radiotherapy resulting from acute skin toxicity. There were 19 chest wall failures: 13 in the whole chest wall bolus group, 4 in the parascar bolus group, and 2 in the no-bolus group. On multivariate analysis, lymphovascular invasion and failure to complete radiotherapy because of acute skin toxicity were associated with chest wall recurrence. Conclusions: From our results, parascar bolus and no bolus performed no worse than did whole chest wall bolus with regard to chest wall recurrence. However, bolus may have an impact on early cessation of radiotherapy caused by skin toxicity, which then may influence chest wall recurrence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Accelerated Partial Breast Irradiation Is Safe and Effective Using Intensity-Modulated Radiation Therapy in Selected Early-Stage Breast Cancer

Purpose: To report the feasibility, toxicity, cosmesis, and efficacy of using intensity-modulated radiation therapy (IMRT) with respiratory gating to deliver accelerated partial breast irradiation (APBI) in selected Stage I/II breast cancer after breast-conserving surgery. Methods and Materials: Eligible patients with node-negative Stage I/II breast cancer were prospectively enrolled in an institutional review board approved protocol to receive APBI using IMRT after breast-conserving surgery. The target volume was treated at 3.8 Gy/fraction twice daily for 5 days, to a total dose of 38 Gy. Results: Thirty-six patients were enrolled for a median follow-up time of 44.8 months. The median tumor size was 0.98 cm (range, 0.08-3 cm). The median clinical target volume (CTV) treated was 71.4 cc (range, 19-231 cc), with the mean dose to the CTV being 38.96 Gy. Acute toxicities included Grade 1 erythema in 44% of patients and Grade 2 in 6%, Grade 1 hyperpigmentation in 31% of patients and Grade 2 in 3%, and Grade 1 breast/chest wall tenderness in 14% of patients. No Grade 3/4 acute toxicities were observed. Grade 1 and 2 late toxicities as edema, fibrosis, and residual hyperpigmentation occurred in 14% and 11% of patients, respectively; Grade 3 telangiectasis was observed in 3% of patients. The overall cosmetic outcome was considered 'excellent' or 'good' by 94% of patients and 97% when rated by the physician, respectively. The local control rate was 97%; 1 patient died of a non-cancer-related cause. Conclusions: APBI can be safely and effectively administered using IMRT. In retrospective analysis, IMRT enabled the achievement of normal tissue dose constraints as outlined by Radiation Therapy Oncology Group 04-13/NSABP B-13 while providing excellent conformality for the CTV. Local control and cosmesis have remained excellent at current follow-up, with acceptable rates of acute/late toxicities. Our data suggest that cosmesis is dependent on target volume size. Further prospective multi-institutional trials should be performed to evaluate IMRT to deliver APBI.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiation Therapy in the Treatment of Intermediate-Risk Prostate Cancer - Long Term Results

Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Methods and Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Radiation Therapy Oncology Group 0247: A Randomized Phase II Study of Neoadjuvant Capecitabine and Irinotecan or Capecitabine and Oxaliplatin With Concurrent Radiotherapy for Patients With Locally Advanced Rectal Cancer

Purpose: To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study. Methods and Materials: Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m{sup 2}/d Mondays through Friday) and irinotecan (50 mg/m{sup 2} weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m{sup 2}/d Monday through Friday) and oxaliplatin (50 mg/m{sup 2} weekly in five doses) (Arm 2). Surgery was performed 4-8 weeks after chemoRT, and adjuvant chemotherapy 4-6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm. Results: A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint-the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively. Conclusions: Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformal RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54%, 31%, and 20% respectively. Conclusions: Continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin has an acceptable toxicity profile and offers a potentially curative option in a subset of patients with few other options.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Single-Institutional Experience of 15 Years of Treating T3 Laryngeal Cancer With Primary Radiotherapy, With or Without Chemotherapy

Purpose: To retrospectively analyze the outcomes, toxicity, quality of life, and voice quality of patients with T3 laryngeal cancer treated with radiotherapy and to identify subgroups of patients in whom the addition of chemotherapy to radiotherapy is necessary. Methods and Materials: Between March 1996 and November 2009, 170 consecutive patients with T3 tumor were treated with (chemo)radiotherapy. Endpoints of the study were local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), late toxicity, quality of life, and voice handicap index. Results: After a median follow-up time of 32 months (range, 7-172), the 3-year actuarial rates of LC, LRC, DFS, and OS were 73%, 70%, 64%, and 61%, respectively, and the 5-year figures were 68%, 65%, 60%, and 49%, respectively. At last follow-up, 84 patients (49.5%) were still alive, 65 of them (77.3%) without local progression. Laryngectomy was performed in 16 patients, leaving 49 patients with anatomic organ preservation, corresponding to an actuarial laryngectomy-free survival of 58.3% at 3 years. The figures for patients treated with chemoradiotherapy and radiotherapy alone were 76.8% and 53.5%, respectively (p = 0.001). Chemoradiotherapy was the only significant predictor for LC on multivariate analysis. The overall 5-year cumulative incidence of late Grade {>=}2 toxicity was 28.2%. Chemoradiotherapy, compared with radiotherapy alone, resulted in slight increase in late toxicity and slight deterioration of quality of life and voice-handicap-index scores. However, the differences were statistically not significant. Conclusion: The addition of chemotherapy to radiotherapy in T3 laryngeal cancer significantly improved LC and laryngectomy-free survival without statistically significant increases in late toxicity or deterioration of quality of life or voice handicap index.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

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

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy/decortication, followed by pleural IMRT to prospectively evaluate the toxicity and survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Multi-Institutional Study of Feasibility, Implementation, and Early Clinical Results With Noninvasive Breast Brachytherapy for Tumor Bed Boost

Purpose: To evaluate the feasibility, implementation, and early results of noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT). Methods and Materials: NIBB is a commercially available (AccuBoost, Billerica, MA) mammography-based, brachytherapy system in which the treatment applicators are centered on the planning target volume (PTV) to direct {sup 192}Ir emissions along orthogonal axes. A privacy-encrypted online data registry collected information from 8 independent academic and community-based institutions. Data were from 146 consecutive women with early-stage breast cancer after lumpectomy and WBRT receiving boost with NIBB between July 2007 and March 2010. Toxicity and cosmesis were graded according to the Common Toxicity Criteria (v. 3.0) and the Harvard scale. Median follow-up was 6 months (1-39 months). Results: Grade 1-2 skin toxicity was observed in 64%, 48%, and 21% during the acute (1-3 weeks), intermediate (4-26 weeks), and late-intermediate (>26 weeks) periods. There was no Grade 4 toxicity. At 6 months, for the entire cohort, cosmesis was excellent/good in 62%/38%. The subset receiving NIBB before WBRT had cosmetic scores of 32% and 63%, whereas during WBRT, 58% and 37% were rated as excellent and good, respectively. Breast compression was scored as 'uncomfortable' in 12%, 29%, and 59% when NIBB was delivered before, during, or after WBRT. For each patient, the fraction-to-fraction variability in PTV was low. Skin flash was associated with a higher proportion of excellent cosmesis (58% vs. 42%) relative to having the applicator all within breast tissue. Conclusions: These data indicate that NIBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIBB is associated with acceptably mild normal tissue toxicity and favorable early cosmesis. The application of NIBB before WBRT may be associated with better patient tolerance at the expense of less favorable cosmetic outcome.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Effect of Increasing Experience on Dosimetric and Clinical Outcomes in the Management of Malignant Pleural Mesothelioma With Intensity-Modulated Radiation Therapy

Purpose: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Methods and Materials: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Results: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. Conclusions: With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

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

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Hypofractionated Whole-Breast Radiation Therapy: Does Breast Size Matter?

Purpose: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). Materials and Methods: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation >25 cm or planning target volume [PTV] >1500 cm{sub 3}) (n=97) and small-breasted patients (chest wall separation <25 cm and PTV <1500 cm{sub 3}) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). Results: The mean PTV V95 (percentage of volume receiving >= 95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving >= 105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). Conclusions: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable to that reported in the literature. Taken together, these data suggest that hypofractionated radiation therapy using IMRT is a viable and appropriate therapeutic modality in large-breasted patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Conformal Postoperative Radiotherapy in Patients With Positive Resection Margins and/or pT3-4 Prostate Adenocarcinoma

Purpose: To evaluate outcome and toxicity of high-dose conformal radiotherapy (RT) after radical prostatectomy. Methods and Materials: Between August 1998 and December 2007, 182 consecutive patients with positive resection margins and/or pT3-4, node-negative prostate adenocarcinoma underwent postoperative conformal RT. The prescribed median dose to the prostate/seminal vesicle bed was 66.6 Gy (range 50-70). Hormone therapy (a luteinizing hormone-releasing hormone analogue and/or antiandrogen) was administered to 110/182 (60.5%) patients with high-risk features. Biochemical relapse was defined as an increase of more than 0.2 ng/mL over the lowest postoperative prostate-specific antigen (PSA) value measured on 3 occasions, each at least 2 weeks apart. Results: Median follow-up was 55.6 months (range 7.6-141.9 months). The 3- and 5-year probability of biochemical relapse-free survival were 87% and 81%, respectively. In univariate analysis, more advanced T stages, preoperative PSA values {>=}10 ng/mL, and RT doses <70 Gy were significant factors for biochemical relapse. Pre-RT PSA values >0.2 ng/mL were significant for distant metastases. In multivariate analysis, risk factors for biochemical relapse were higher preoperative and pre-RT PSA values, hormone therapy for under 402 days and RT doses of <70 Gy. Higher pre-RT PSA values were the only independent predictor of distant metastases. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 72 (39.6%) and 91 (50%) patients, respectively. There were 2 cases of Grade III GI toxicity but no cases of Grade IV. Late GU and GI toxicities occurred in 28 (15.4%) and 14 (7.7%) patients, respectively: 11 cases of Grade III toxicity: 1 GI (anal stenosis) and 10 GU, all urethral strictures requiring endoscopic urethrotomy. Conclusions: Postoperative high-dose conformal RT in patients with high-risk features was associated with a low risk of biochemical relapse as well as minimal morbidity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Hypofractionated High-Dose Radiation Therapy for Prostate Cancer: Long-Term Results of a Multi-Institutional Phase II Trial

Purpose: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). Methods and Materials: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Results: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade {>=}2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. Conclusions: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗