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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 991 records · Page 55
All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Glioblastoma in Children: A Single-Institution Experience

Purpose: Current treatment recommendations for pediatric glioblastoma include surgery, chemotherapy, and radiation therapy. However, even with this multispecialty approach, overall survival remains poor. To assess outcome and evaluate treatment-related prognostic factors, we retrospectively reviewed the experience at our institution. Methods and Materials: Twenty-four glioblastoma patients under the age of 21 were treated with radiation therapy with curative intent at Washington University, St. Louis, from 1970 to 2008. Patients underwent gross total resection, subtotal resection or biopsy alone. Fourteen (58%) of the patients received chemotherapy. All patients received radiation therapy. Radiation consisted of whole-brain radiation therapy in 7 (29%) patients with a median dose of 50.4 Gy. Seventeen (71%) patients received three-dimensional conformal radiation therapy with a median dose of 54 Gy. Results: Median follow-up was 12.5 months from diagnosis. One and 2-year overall survival rates were 57% and 32%, respectively. Median overall survival was 13.5 months. There were no differences in overall survival based on patients' age, race, gender, tumor location, radiation volume, radiation dose, or the use of chemotherapy. There was a significant improvement in overall survival for patients in whom gross total resection was achieved (p = 0.023). Three patients were alive 5 years after gross total resection, and 2 patients were alive at 10 and 24 years after diagnosis. Conclusions: Survival for children with glioblastoma remains poor. Data from this and other studies demonstrate the importance of achieving a gross total resection. Continued investigation into new treatment options is needed in an attempt to improve outcome for these patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Triple-Negative or HER2-Positive Status Predicts Higher Rates of Locoregional Recurrence in Node-Positive Breast Cancer Patients After Mastectomy

Purpose: To evaluate the prognostic value of determining estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression in node-positive breast cancer patients treated with mastectomy. Methods and Materials: The records of 835 node-positive breast cancer patients who had undergone mastectomy between January 2000 and December 2004 were analyzed retrospectively. Of these, 764 patients (91.5%) received chemotherapy; 68 of 398 patients (20.9%) with T1-2N1 disease and 352 of 437 patients (80.5%) with T3-4 or N2-3 disease received postoperative radiotherapy. Patients were classified into four subgroups according to hormone receptor (Rec+ or Rec-) and HER2 expression profiles: Rec-/HER2- (triple negative; n = 141), Rec-/HER2+ (n = 99), Rec+/HER2+ (n = 157), and Rec+/HER2- (n = 438). The endpoints were the duration of locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. Results: Patients with triple-negative, Rec-/HER2+, and Rec+/HER2+ expression profiles had a significantly lower 5-year locoregional recurrence-free survival than those with Rec+/HER2- profiles (86.5% vs. 93.6%, p = 0.002). Compared with those with Rec+/HER2+ and Rec+/HER2- profiles, patients with Rec-/HER2- and Rec-/HER2+ profiles had significantly lower 5-year distant metastasis-free survival (69.1% vs. 78.5%, p = 0.000), lower disease-free survival (66.6% vs. 75.6%, p = 0.000), and lower overall survival (71.4% vs. 84.2%, p = 0.000). Triple-negative or Rec-/HER2+ breast cancers had an increased likelihood of relapse and death within the first 3 years after treatment. Conclusions: Triple-negative and HER2-positive profiles are useful markers of prognosis for locoregional recurrence and survival in node-positive breast cancer patients treated with mastectomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Dose Escalation for Metastatic Spinal Cord Compression in Patients With Relatively Radioresistant Tumors

Purpose: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the 'standard' regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. Methods and Materials: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. Results: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). Conclusions: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative chemotherapy conditioning regimens should be considered.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Integrating Epidermal Growth Factor Receptor Assay With Clinical Parameters Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous Cell Carcinoma

Purpose: Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial. Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density). Results: This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a fivefold difference in the risk of LRR. Conclusions: Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I{sup 125} Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I{sup 125} brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I{sup 125} monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I{sup 125} monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Ten-Year Outcomes: The Clinical Utility of Single Photon Emission Computed Tomography/Computed Tomography Capromab Pendetide (Prostascint) in a Cohort Diagnosed With Localized Prostate Cancer

Purpose: To evaluate the clinical utility of capromab pendetide imaging with single photon emission computed tomography coregistration with computed tomography (SPECT/CT) in primary prostate cancer (CaP) for pretreatment prognostic staging and localization of biologic target volumes (BTV) for individualized image-guided radiotherapy dose escalation (IGRT-DE). Methods and Materials: Patients consecutively presenting for primary radiotherapy (February 1997 to December 2002), having a clinical diagnosis of localized CaP, were evaluated for tumor stage using conventional staging and SPECT/CT (N = 239). Distant metastatic uptake (mets) were identified by SPECT/CT in 22 (9.2%). None of the suspected mets could be clinically confirmed. Thus, all subjects were followed without alteration in disease management. The SPECT/CT pelvic images defined BTV for IGRT-DE (+150% brachytherapy dose) without (n = 150) or with (n = 89) external radiation of 45 Gy. The National Comprehensive Cancer Network criteria defined risk groups (RG). The median survivor follow-up was 7 years. Biochemical disease-free survival (bDFS) was reported by clinical nadir +2 ng/mL (CN+2) criteria. Statistical analyses included Kaplan-Meier, multivariate analysis, and Concordance-index models. Results: At 10-year analyses, overall survival was 84.8% and bDFS was 84.6%. With stratification by RG, CN+2 bDFS was 93.5% for the low-RG (n = 116), 78.7% for the intermediate-RG (n = 94), and 68.8% for the high-RG (n = 29), p = 0.0002. With stratification by pretreatment SPECT/CT findings, bDFS was 65.5% in patients with suspected mets (n = 22) vs. 86.6% in patients with only localized uptake (n = 217), p = 0.0014. CaP disease-specific survival (DSS) was 97.7% for the cohort. With stratification by SPECT/CT findings, DSS was 86.4% (with suspected mets) vs. 99.0% (localized only), p = 0.0001. Using multivariate analysis, the DSS hazard ratio for SPECT/CT findings (mets vs. localized) was 3.58 (p = 0.0026). Concordance-index tests, based on all data, by CN+2 bDFS criteria were 0.710 for RG alone and 0.773 for SPECT/CT + RG. Conclusions: Through long-term outcomes we demonstrate statistically significant bDFS and DSS predictive value for pretreatment capromab pendetide SPECT/CT imaging in primary CaP. Dual clinical utility is demonstrated, using SPECT/CT to define BTV for individualized IGRT-DE.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Quality of Life After Whole Pelvic Versus Prostate-Only External Beam Radiotherapy for Prostate Cancer: A Matched-Pair Comparison

Purpose: Comparison of health-related quality of life after whole pelvic (WPRT) and prostate-only (PORT) external beam radiotherapy for prostate cancer. Methods and Materials: A group of 120 patients (60 in each group) was surveyed prospectively before radiation therapy (RT) (time A), at the last day of RT (time B), at a median time of 2 months (time C) and >1 year after RT (time D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy. Pairs were matched according to the following criteria: age {+-} 5years, planning target volume {+-} 10 cc (considering planning target volume without pelvic nodes for WPRT patients), urinary/bowel/sexual function score before RT {+-} 10, and use of antiandrogens. Results: With the exception of prognostic risk factors, both groups were well balanced with respect to baseline characteristics. No significant differences were found with regard to urinary and sexual score changes. Mean bladder function scores reached baseline levels in both patient subgroups after RT. However, bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times (p < 0.01, respectively). Significant differences were found for most items in the bowel domain in the acute phase. At time D, patients after WPRT reported rectal urgency (>once a day in 15% vs. 3%; p = 0.03), bloody stools ({>=}half the time in 7% vs. 0%; p = 0.04) and frequent bowel movements (>two on a typical day in 32% vs. 7%; p < 0.01) more often than did patients after PORT. Conclusion: In comparison to PORT, WPRT (larger bladder and rectum volumes in medium dose levels, but similar volumes in high dose levels) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Epothilone B Confers Radiation Dose Enhancement in DAB2IP Gene Knock-Down Radioresistant Prostate Cancer Cells

Purpose: In metastatic prostate cancer, DOC-2/DAB2 interactive protein (DAB2IP) is often downregulated and has been reported as a possible prognostic marker to predict the risk of aggressive prostate cancer (PCa). Our preliminary results show that DAB2IP-deficient PCa cells are radioresistant. In this study, we investigated the anticancer drug Epothilone B (EpoB) for the modulation of radiosensitivity in DAB2IP-deficient human PCa cells. Methods and Materials: We used a stable DAB2IP-knock down human PCa cell line, PC3 shDAB2IP, treated with EpoB, ionizing radiation (IR), or the combined treatment of EpoB and IR. The modulation of radiosensitivity was determined by surviving fraction, cell cycle distribution, apoptosis, and DNA double-strand break (DSB) repair. For in vivo studies, the PC3shDAB2IP xenograft model was used in athymic nude mice. Results: Treatment with EpoB at IC{sub 50} dose (33.3 nM) increased cellular radiosensitivity in the DAB2IP-deficient cell line with a dose enhancement ratio of 2.36. EpoB delayed the DSB repair kinetics after IR and augmented the induction of apoptosis in irradiated cells after G{sub 2}/M arrest. Combined treatment of EpoB and radiation enhanced tumor growth delay with an enhancement factor of 1.2. Conclusions: We have demonstrated a significant radiation dose enhancement using EpoB in DAB2IP-deficient prostate cancer cells. This radiosensitization can be attributed to delayed DSB repair, prolonged G{sub 2} block, and increased apoptosis in cells entering the cell cycle after G{sub 2}/M arrest.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Preoperative Versus Postoperative Radiotherapy in Soft-Tissue Sarcoma: Multi-Institutional Analysis of 821 Patients

Purpose: To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS). Methods and Materials: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included. Patients were also required to have known stage and grade. Prognostic factors for survival were identified using multivariate techniques. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p < 0.05) using the log-rank test. Results: A total of 821 patients met inclusion criteria. The median follow-up time was 63 months. Age, stage, histology, gender, tumor size, and RT sequence were independent predictors for OS (p < 0.05). Preop RT was associated with significantly improved OS and CSS compared with postop RT (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.56-0.91, p < 0.01, and HR = 0.64, 95% CI 0.46-0.88, p < 0.01, respectively). The 5-year CSS was 79% and 74%, in favor of preop RT (log-rank, p < 0.05). Preop RT was also significantly associated with a reduced risk for local and distant relapse compared with postop RT. Conclusion: Preoperative RT is associated with a reduced cancer-specific mortality compared with postoperative RT in STS. The results of this study may serve as motivation to conduct future prospective studies with larger patient numbers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

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

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

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prolongation of Total Treatment Time Because of Infrequently Missed Days of Treatment Is Not Associated With Inferior Biochemical Outcome After Dose-Escalated Radiation Therapy for Prostate Cancer

Purpose: Prolongation of treatment time with radiation therapy (RT) is associated with inferior disease control for many rapidly proliferating tumors, but it is uncertain whether the same effect is seen in prostate cancer. Methods and Materials: 596 patients underwent with curative-intent RT for adenocarcinoma of the prostate. By National Comprehensive Cancer Network criteria, men were classified as having low-risk (30%), medium-risk (40%), or high-risk (30%) disease. The median RT dose was 72 Gy. Androgen-deprivation therapy (ADT) was used in 45%. The idealized treatment time was defined as the total elapsed time (including weekends) to complete treatment if started on a Monday. Missed days of treatment, defined as the number of days beyond the idealized treatment time, was recorded for all patients. Missed days were added to the end of therapy resulting in a longer treatment time. Analysis was conducted for missed days and other standard prognostic variables against freedom from biochemical failure (FFBF). Results: The median number of missed days was 2 (range, -3 to 22). With a median follow-up of 51 months, men with 5 or more missed days had similar 4-year FFBF rates (79% vs. 83% in men with <5 missed days, p = 0.0809), especially in the subset of men receiving 74 Gy or greater (89% for both groups, p = 0.8008). Analysis of missed days was performed for the subsets of dose, ADT, and risk category. Men without ADT had a lower FFBF rate with more missed days (p = 0.0030), but this association was not seen in men treated to a dose of 74 Gy or greater (p = 0.7425). On multivariate analysis, dose (p = 0.0010), T stage (p = 0.0145), and prostate-specific antigen level (p < 0.0001) were associated with FFBF, but Gleason score (p = 0.1351) and missed days (p = 0.3767) were not. Conclusions: Slight prolongation of treatment time (e.g., {<=}7 days) was not associated with inferior FFBF, especially in men receiving an RT dose of 74 Gy or greater.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Retrospective Study of Palliative Radiotherapy in Newly Diagnosed Head and Neck Carcinoma

Purpose: To examine the patterns of care, outcomes, and prognostic factors for patients with head-and-neck cancer (HNC) treated with palliative radiotherapy (RT). Methods and Materials: An institutional HNC anthology and electronic patient records were used to identify patients with previously untreated HNC of mucosal or salivary gland origin who underwent palliative RT at our institution between July 2003 and June 2008. Overall survival was determined from the start date of RT to either the date of death or the date of last follow-up for living patients. The data were censored if the subject was either lost to follow-up or had not been seen for follow-up at our institution for {>=}4 months. Results: We identified 148 eligible patients. The median age was 72 years (range, 19-94). Of the 148 patients, 12 had Stage II-III, 39 Stage IVA, 36 Stage IVB, and 54 Stage IVC; for 7 patients, the stage was unknown. Oropharyngeal primary cancer (40) was the most common primary site. The Eastern Cooperative Oncology Group performance status was 0 in 15, 1 in 69, 2 in 40, 3 in 19, and 4 in 5 patients. The Adult Co-morbidity Evaluation-27 scale was 0 in 33, 1 in 47, 2 in 44, and 3 in 21. The median radiation dose was 50 Gy (range, 2-70), the median fraction number was 20 (range, 1-40), and the median total treatment time (including breaks) was 29 days (range, 1-80). At analysis, 108 patients (73%) had died, 20 (13.5%) were alive, and 20 (13.5%) had been censored. The median follow-up was 4.8 months, and the median survival time was 5.2 months. Information on the treatment response was available for 103 patients (70%). On multivariate analysis, the radiation dose was an independent predictor of both overall survival (hazard ratio 0.97, 95% confidence interval 0.96-0.99, p <.01) and treatment response (odds ratio 1.05, 95% confidence interval 1.01-1.08, p <.01). Conclusion: For patients considered unsuitable for curative RT, the radiation dose might be an independent predictive factor for both overall survival and treatment response. Additional research is required to more effectively select those patients who might benefit from more aggressive treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Five-Year Results From a Scandinavian Sarcoma Group Study (SSG XIII) of Adjuvant Chemotherapy Combined With Accelerated Radiotherapy in High-Risk Soft Tissue Sarcoma of Extremities and Trunk Wall

Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall. Methods and Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size {>=}8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients. RT to a total dose of 36 Gy (1.8 Gy twice daily) was inserted between two chemotherapy cycles after marginal margin resection regardless of tumor depth or after wide-margin resection for deep-seated tumors. RT was boosted to 45 Gy in a split-course design in the case of intralesional margin resection. Results: A total of 119 patients were eligible, with a median follow-up of 5 years. The 5-year estimate of the local recurrence, metastasis-free survival, and overall survival rate was 12%, 59%, and 68%, respectively. The group receiving RT to 36 Gy had a local recurrence rate of 10%. In contrast, the local recurrence rate was 29% in the group treated with RT to 45 Gy. The presence of vascular invasion and low chemotherapy dose intensity had a negative effect on metastasis-free and overall survival. Toxicity was moderate after both the chemotherapy and the RT. Conclusions: Accelerated RT interposed between chemotherapy cycles in a selected population of patients with high-risk soft tissue sarcoma resulted in good local and distant disease control, with acceptable treatment-related morbidity. The greater radiation dose administered after intralesional surgery was not sufficient to compensate for the poorer surgical margin. Vascular invasion was the most important prognostic factor for metastasis-free and overall survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Carcinoma: Final Results of Phase III Randomized Trial

Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 {mu}g/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

A Method for the Prediction of Late Organ-at-Risk Toxicity After Radiotherapy of the Prostate Using Equivalent Uniform Dose

Purpose: To evaluate the predictive value of equivalent uniform doses (EUD) for late bladder and rectal toxicity after high-dose three-dimensional conformal radiation therapy (3D-CRT) to the prostate. Materials and Methods: Using the method developed by Kutcher et al., EUDs for whole bladder and rectum were calculated from the dose-volume histograms of 180 patients with localized prostate cancer treated to 70-74 Gy with 3D-CRT. Late complications were recorded using the Radiation Therapy Oncology Group scale, correlated against EUD and known physical predictive indicators. Results: EUD is an independent prognostic factor for Grade 2+ long-term rectal and bladder toxicity after radiation treatment to the prostate. Patients receiving an EUD >63.1 Gy to the rectum have a statistically significant (10% vs. 30%; p = 0.002) higher risk of developing Grade 2+ late complications. Patients receiving an EUD >53.4 Gy to the bladder have a statistically significant (10% vs. 33%; p = 0.001) higher risk of developing Grade 2+ late complications. Conclusions: It has been demonstrated that EUD is a strong independent predictive factor for Grade 2+ late complications after 3D-CRT to the prostate. Threshold values have been demonstrated for both bladder and rectum, above which there is a clinically significant increased risk of complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗