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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Organochlorine concentrations in adipose tissue and survival in postmenopausal, Danish breast cancer patients

Highlights: • Few studies have explored organochlorine concentrations and breast cancer mortality. • We did so in a survivor-cohort of 399 postmenopausal women, of whom 177 died. • PCBs and several organochlorine pesticides may be inversely associated with breast cancer mortality. • This association was confined to women with adverse prognostic factors. • Dieldrin was associated with a higher mortality, regardless of prognostic factors. Several studies have investigated an association between organochlorine-concentrations and breast cancer incidence, whereas few have investigated an association with breast cancer mortality.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2010

Extrahepatic Bile Duct Cancers: Surgery Alone Versus Surgery Plus Postoperative Radiation Therapy

Purpose: The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bile duct (EHBD) cancers. Methods and Materials: From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors. Results: There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p = 0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival. Conclusions: Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

DNA Repair Gene Expression and Risk of Locoregional Relapse in Breast Cancer Patients

Purpose: Radiation therapy appears to kill cells mainly by inducing DNA double-strand breaks. We investigated whether the DNA repair gene expression status might influence the risk of locoregional recurrence (LRR) in breast cancer patients. Methods and Materials: We used a quantitative reverse transcriptase PCR-based approach to measure messenger RNA levels of 20 selected DNA repair genes in tumor samples from 97 breast cancer patients enrolled in a phase III trial (Centre Rene Huguenin cohort). Normalized mRNA levels were tested for an association with LRR-free survival (LRR-FS) and overall survival (OS). The findings were validated in comparison with those of an independent cohort (Netherlands Cancer Institute (NKI) cohort). Multivariate analysis encompassing known prognostic factors was used to assess the association between DNA repair gene expression and patient outcome. Results: RAD51 was the only gene associated with LRR in both cohorts. With a median follow-up of 126 months in the CRH cohort, the 5-year LRR-FS and OS rates were 100% and 95% in the 61 patients with low RAD51 expression, compared with 70% and 69% in the 36 patients with high RAD51 expression, respectively (p < 0.001). RAD51 overexpression was associated with a higher risk of LRR (hazard ratio [HR], 12.83; 95% confidence interval [CI], 3.6-45.6) and death (HR, 4.10; 95% CI, 1.7-9.7). RAD51 overexpression was also significantly associated with shorter LRR-FS and OS in the NKI cohort. Conclusions: Overexpression of RAD51, a key component of the homologous DNA repair pathway, is associated with poor breast cancer outcome. This finding warrants prospective studies of RAD51 as a prognosticator and therapeutic target.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Stereotactic Radiosurgery for Single Brainstem Metastases: The Cleveland Clinic Experience

Purpose: To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). Materials and Methods: We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. Results: Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range, 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. Conclusion: The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Postradiation Metabolic Tumor Volume Predicts Outcome in Head-and-Neck Cancer

Purpose: To explore the prognostic value of metabolic tumor volume measured on postradiation {sup 18}F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with head-and-neck cancer. Methods and Materials: Forty-seven patients with head-and-neck cancer who received pretreatment and posttreatment PET/computed tomography (CT) imaging along with definitive chemoradiotherapy were included in this study. The PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV{sub 2.0}-MTV{sub 4.0}; where MTV{sub 2.0} refers to the volume above a standardized uptake value threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox regression models were used to test for association between PET endpoints and disease-free survival and overall survival. Results: Multiple postradiation PET endpoints correlated significantly with outcome; however, the most robust predictor of disease progression and death was MTV{sub 2.0}. An increase in MTV{sub 2.0} of 21cm{sup 3} (difference between 75th and 25th percentiles) was associated with an increased risk of disease progression (hazard ratio [HR]= 2.5, p = 0.0001) and death (HR = 2.0, p = 0.003). In patients with nonnasopharyngeal carcinoma histology (n = 34), MTV{sub 2.0} <18 cm{sup 3} and MTV{sub 2.0} {>=}18 cm{sup 3} yielded 2-year disease-free survival rates of 100% and 63%, respectively (p = 0.006) and 2-year overall survival rates of 100% and 81%, respectively (p = 0.009). There was no correlation between MTV{sub 2.0} and disease-free survival or overall survival with nasopharyngeal carcinoma histology (n = 13). On multivariate analysis, only postradiation MTV{sub 2.0} was predictive of disease-free survival (HR = 2.47, p = 0.0001) and overall survival (HR = 1.98, p = 0.003). Conclusions: Postradiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification and will be valuable in the future with risk-adapted therapies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT {>=}80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT {>=}80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Regional Nodal Involvement and Patterns of Spread Along In-Transit Pathways in Children With Rhabdomyosarcoma of the Extremity: A Report From the Children's Oncology Group;Rhabdomyosarcoma; Regional failure; In-transit nodes; Radiotherapy; Extremity

Purpose: To evaluate the incidence and prognostic factors for regional failure, with attention to the in-transit pathways of spread, in children with nonmetastatic rhabdomyosarcoma of the extremity. Methods and Materials: The Intergroup rhabdomyosarcoma studies III, IV-Pilot, and IV enrolled 226 children with rhabdomyosarcoma of the extremity. Failure at the in-transit (epitrochlear/brachial and popliteal) and proximal (axillary/infraclavicular and inguinal/femoral) lymph nodes was evaluated. The median follow-up for the surviving patients was 10.4 years. Results: Of the 226 children, 55 (24%) had clinical or pathologic evidence of either in-transit and/or proximal lymph node involvement at diagnosis. The actuarial 5-year risk of regional failure was 12%. The prognostic factors for poor regional control were female gender and lymph node involvement at diagnosis. In the 116 patients with a distal extremity primary tumor, 5% had in-transit lymph node involvement at diagnosis. The estimated 5-year incidences of in-transit and proximal nodal failure was 12% and 8%, respectively. The in-transit failure rate was 0% for patients who underwent radiotherapy and/or underwent lymph node sampling of the in-transit nodal site but was 15% for those who did not (p = .07). However, the 5-year event-free survival rate did not differ between these two groups (64% vs. 55%, respectively, p = .47). Conclusion: The high incidence of regional involvement necessitates aggressive identification and treatment of regional lymph nodes in patients with rhabdomyosarcoma of the extremity. In patients with distal extremity tumors, in-transit failures were as common as failures in more proximal regional sites. Patients who underwent complete lymph node staging with appropriate radiotherapy to the in-transit nodal site, if indicated, were at a slightly lower risk of in-transit failure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

A Matched Control Analysis of Adjuvant and Salvage High-Dose Postoperative Intensity-Modulated Radiotherapy for Prostate Cancer

Purpose: It is unclear whether immediate adjuvant radiotherapy for high-risk disease at prostatectomy (capsule perforation, seminal vesicle invasion, and/or positive surgical margins) is equivalent to delayed salvage radiotherapy at biochemical recurrence. We performed a matched case analysis comparing high-dose adjuvant intensity modulated radiotherapy (A-IMRT) with salvage IMRT (S-IMRT). Methods and Materials: One hundred forty-four patients with high-risk disease at prostatectomy were referred for A-IMRT, and 134 patients with high-risk disease were referred at biochemical recurrence (rising prostate-specific antigen [PSA], following prostatectomy, above 0.2 ng/ml) for S-IMRT. Patients were matched in a 1:1 ratio according to preoperative PSA level, Gleason score, and pT stage. Median doses of 74 Gy and 76 Gy were prescribed for A-IMRT and S-IMRT, respectively. We report biochemical relapse free survival (bRFS) rates using the Kaplan-Meier method. Univariate and multivariate analyses were used to examine tumour- and treatment-related factors. Results: A total of 178 patients were matched (89:89). From the end of radiotherapy, the median follow-up was 36 months for both groups. The 3-year bRFS rate for the A-IMRT group was 90% compared to 65% for the S-IMRT group (p < 0.05). On multivariate analysis, S-IMRT, Gleason grades of {>=}4+3, perineural invasion, preoperative PSA level of {>=}10 ng/ml, and omission of androgen deprivation (AD) were independent predictors for a reduced bRFS (p < 0.05). From the date of surgery, the median follow-up was 43 and 60 months for A-IMRT and S-IMRT, respectively. The 3-year bRFS rate for A-IMRT was 91% compared to 79% for S-IMRT (p < 0.05). On multivariate analysis, Gleason grades of {>=}4+3, perineural invasion, and omission of AD were independent predictors for a reduced bRFS (p < 0.05). S-IMRT was no longer an independent prognostic factor (p = 0.08). Conclusions: High-dose A-IMRT significantly improves 3-year bRFS compared to S-IMRT. Gleason grades of {>=}4+3, perineural invasion, and omission of AD were independent prognostic factors for a decreased bRFS, both from the dates of surgery and from radiotherapy.

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

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

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 of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

The Role of Pretreatment FDG-PET in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

Purpose: Pretreatment with 2- [{sup 18}F] fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG-PET) was evaluated as a predictor of local failure-free survival (LFFS), disease-free survival (DFS), and overall survival (OS) in patients with nonkeratinizing nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) alone or concurrently with chemotherapy (CCRT). Patients and Methods: Seventy-five M0 NPC patients who received FDG-PET before treatment were analyzed. The primary tumor FDG uptake was measured as the maximum standardized uptake value (SUVmax). The LFFS, DFS, and OS were calculated by the Kaplan-Meier method, and the differences were evaluated on log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. Results: Eighteen patients received IMRT alone and 57 received CCRT. The mean SUVmax was significantly higher in 12 patients with locoregional or distant failure than in those without failure (p <0.001). On multivariate analysis, the SUVmax was the only significant variable for 5-year LFFS (p = 0.017) and DFS (p = 0.000) but not for OS (p = 0.065). Conclusion: SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with nasopharyngeal carcinoma treated with IMRT alone or with CCRT. A high {sup 18}F-FDG uptake (SUVmax >5) indicates poor outcome in patients with NPC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Clinical Outcomes of 174 Nasopharyngeal Carcinoma Patients With Radiation-Induced Temporal Lobe Necrosis

Purpose: To retrospectively study the clinical outcomes of nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis (TLN) treated with steroids, surgery, or observation only. Methods and Patients: We performed a retrospective analysis of 174 consecutive patients diagnosed with TLN between 1990 and 2008. Before 1998, symptomatic patients were treated with oral steroids, while asymptomatic patients were treated conservatively. After 1998, most symptomatic and asymptomatic patients with a large volume of necrosis were treated by intravenously pulsed-steroid therapy with a standardized protocol. We examined factors affecting grade 4 complication-free survival and overall survival. Outcomes of the three treatment groups, those receiving conservative treatment, those receiving oral steroid, and those receiving intravenous pulse steroid, were compared. Results: The mean follow-up time was 115 months. Rates of grade 4 complication-free survival at 2 years and at 5 years after diagnosis of TLN were 72.2% and 54.1%, respectively. The 2-year and 5-year overall survival rates were 57.5% and 35.4%, respectively. Multivariate analysis revealed that being symptomatic at diagnosis (relative risk [RR], 4.5; p = 0.0001), re-irradiation of the nasopharynx (NP) (RR, 1.56; p = 0.008), salvage brachytherapy to the NP (RR, 1.75; p = 0.012), and a short latency period before the diagnosis of TLN (RR, 0.96, p < 0.0001) were independent prognosticators of poor grade 4 complication-free survival. Patients with all four factors had a 100% risk of developing grade 4 complications within 5 years; whereas if no factor was present, the risk was 12.5%. Intravenous pulse steroid therapy was associated with a higher clinical response rate compared with conventional steroid therapy (p < 0.0001); however, it did not affect complication-free survival in multivariate analysis. Conclusions: TLN patients with good prognosticators could be observed without active treatment. Although treatment with intravenously pulsed steroid was associated with better clinical response than conventional steroid delivery, it did not affect the complication-free survival rate of TLN patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Retrospective Comparison of Chemoradiotherapy Followed by Adjuvant Chemotherapy, With or Without Prior Gliadel Implantation (Carmustine) After Initial Surgery in Patients With Newly Diagnosed High-Grade Gliomas

Purpose: Retrospective study of patients treated for high-grade glioma, with or without biodegradable carmustine wafers and according to the Stupp protocol. Methods and Materials: Between May 2007 and June 2008, 65 patients underwent surgery for high-grade glioma, 28 had implantation of Gliadel and 37 patients did not. Patients received radiotherapy with concomitant temozolomide followed by 5 consecutive days of temozolomide every month for 6 months. Results: Overall median follow-up was 17.1 months; the median relapse-free survival (RFS) was 14 months with a RFS of 54% at 12 months, and 38% at 24 months. For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89). According to pathology, Gliadel did not influence RFS of patients with Grade III or glioblastoma. However, for all patients, in multivariate analysis, non-methylated methylguanine methyltransferase (MGMT) was the only unfavorable prognostic factor of RFS (p = 0.017; HR 2.8; CI [1.2-7]). Median overall survival (OS) was 20.8 months; the OS rate at 12 months was 78.5%, and at 24 months 35.4%. For patients treated with and without Gliadel, median and 1-year OS were 20.6 months and 78.6% vs. 20.8 months and 78.4%, respectively. According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma. For all patients, in multivariate analysis, unfavorable prognosticators for OS were non-methylated MGMT (p = 0.001; HR: 6.5; CI [2-20]) and irradiation dose <60 Gy (p = 0.02; HR: 6.3; CI [2-20]). With carmustine wafers, before irradiation, median gross tumor volume plus edema was 84 mL (27-229), whereas it was 68 mL (10-362) without carmustine (p = nonsignificant). Four cases of Grade 3 thrombopenia occurred, all in the carmustine wafer group. Conclusion: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Dose-Response for Stereotactic Body Radiotherapy in Early-Stage Non-Small-Cell Lung Cancer

Purpose: To compare the efficacy of three lung stereotactic body radiotherapy (SBRT) regimens in a large institutional cohort. Methods: Between 2004 and 2009, 130 patients underwent definitive lung cancer SBRT to a single lesion at the Mallinckrodt Institute of Radiology. We delivered 18 Gy Multiplication-Sign 3 fractions for peripheral tumors (n = 111) and either 9 Gy Multiplication-Sign 5 fractions (n = 8) or 10 Gy Multiplication-Sign 5 fractions (n = 11) for tumors that were central or near critical structures. Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model. Results: Median follow-up was 11, 16, and 13 months for the 9 Gy Multiplication-Sign 5, 10 Gy Multiplication-Sign 5, and 18 Gy Multiplication-Sign 3 groups, respectively. Local control statistics for Years 1 and 2 were, respectively, 75% and 50% for 9 Gy Multiplication-Sign 5, 100% and 100% for 10 Gy Multiplication-Sign 5, and 99% and 91% for 18 Gy Multiplication-Sign 3. Median overall survival was 14 months, not reached, and 34 months for the 9 Gy Multiplication-Sign 5, 10 Gy Multiplication-Sign 5, and 18 Gy Multiplication-Sign 3 treatments, respectively. No difference in local control or overall survival was found between the 10 Gy Multiplication-Sign 5 and 18 Gy Multiplication-Sign 3 groups on log-rank test, but both groups had improved local control and overall survival compared with 9 Gy Multiplication-Sign 5. Treatment with 9 Gy Multiplication-Sign 5 was the only independent prognostic factor for reduced local control on multivariate analysis, and increasing age, increasing tumor volume, and poor performance status predicted independently for reduced overall survival. Conclusion: Treatment regimens of 10 Gy Multiplication-Sign 5 and 18 Gy Multiplication-Sign 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy Multiplication-Sign 5.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure and Death From Prostate Cancer After Dose-Escalated Radiation Therapy and Hormonal Ablation

Purpose: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. Methods and Materials: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). Results: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. Conclusion: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

62 RADIOLOGY AND NUCLEAR MEDICINE↗