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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Task-based modeling and optimization of a cone-beam CT scanner for musculoskeletal imaging

Purpose: This work applies a cascaded systems model for cone-beam CT imaging performance to the design and optimization of a system for musculoskeletal extremity imaging. The model provides a quantitative guide to the selection of system geometry, source and detector components, acquisition techniques, and reconstruction parameters. Methods: The model is based on cascaded systems analysis of the 3D noise-power spectrum (NPS) and noise-equivalent quanta (NEQ) combined with factors of system geometry (magnification, focal spot size, and scatter-to-primary ratio) and anatomical background clutter. The model was extended to task-based analysis of detectability index (d') for tasks ranging in contrast and frequency content, and d' was computed as a function of system magnification, detector pixel size, focal spot size, kVp, dose, electronic noise, voxel size, and reconstruction filter to examine trade-offs and optima among such factors in multivariate analysis. The model was tested quantitatively versus the measured NPS and qualitatively in cadaver images as a function of kVp, dose, pixel size, and reconstruction filter under conditions corresponding to the proposed scanner. Results: The analysis quantified trade-offs among factors of spatial resolution, noise, and dose. System magnification (M) was a critical design parameter with strong effect on spatial resolution, dose, and x-ray scatter, and a fairly robust optimum was identified at M {approx} 1.3 for the imaging tasks considered. The results suggested kVp selection in the range of {approx}65-90 kVp, the lower end (65 kVp) maximizing subject contrast and the upper end maximizing NEQ (90 kVp). The analysis quantified fairly intuitive results--e.g., {approx}0.1-0.2 mm pixel size (and a sharp reconstruction filter) optimal for high-frequency tasks (bone detail) compared to {approx}0.4 mm pixel size (and a smooth reconstruction filter) for low-frequency (soft-tissue) tasks. This result suggests a specific protocol for 1 x 1 (full-resolution) projection data acquisition followed by full-resolution reconstruction with a sharp filter for high-frequency tasks along with 2 x 2 binning reconstruction with a smooth filter for low-frequency tasks. The analysis guided selection of specific source and detector components implemented on the proposed scanner. The analysis also quantified the potential benefits and points of diminishing return in focal spot size, reduced electronic noise, finer detector pixels, and low-dose limits of detectability. Theoretical results agreed quantitatively with the measured NPS and qualitatively with evaluation of cadaver images by a musculoskeletal radiologist. Conclusions: A fairly comprehensive model for 3D imaging performance in cone-beam CT combines factors of quantum noise, system geometry, anatomical background, and imaging task. The analysis provided a valuable, quantitative guide to design, optimization, and technique selection for a musculoskeletal extremities imaging system under development.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2014

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system was used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.

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 OSTI2017

Preprocessing Analysis of the Multi Isotope Process Monitor

The Multi-Isotope Process (MIP) Monitor is a nondestructive monitoring methodology to detect diversion and tampering of nuclear material at a reprocessing facility. The system measures the gamma-emitting isotopes in different stages of the reprocessing cycle through passive gamma spectroscopy. The indicators of isotopic distributions are measured and evaluated in near-real time by comparing measured spectra to expected, normal process spectra through multivariate analysis. The MIP monitor framework is compatible with medium resolution gamma detectors that can be easily deployed in an existing facility. In FY15, the MIP monitor was deployed at the H-Canyon Facility at Savannah River National Laboratory (SRNL) to develop and evaluate analysis algorithms for future in situ deployment. This paper discusses recent results from analysis of the data collected at SRNL. New results examine the preprocessing step of spectral alignment that is associated with the MIP monitor.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2018

Methodological Issues of Gamma-Ray and Neutrino Searches at the Yakutsk Array

The method used to perform searches for extensive air showers (EAS) generated by neutral particles, such as high-energy gamma rays and astrophysical neutrinos, and the results of such searches are presented. A comprehensive analysis of relevant data, including those on EAS electrons, muons, and Cherenkov light and their time responses in scintillation and Cherenkov detectors, is performed for this purpose. An upper limit on the gamma-ray flux at the energies of 3 × 10{sup 18}, 10{sup 19}, and 3 × 10{sup 19} eV is set. A multivariate analysis of EAS properties of neutrino-induced air showers does not reveal neutrino-induced showers.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2011

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

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

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Hypofractionated Versus Standard Radiation Therapy With or Without Temozolomide for Older Glioblastoma Patients

Purpose: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). Methods and Materials: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Results: Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). Conclusions: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Influence of Dose on Risk of Acute Urinary Retention After Iodine-125 Prostate Brachytherapy

Purpose: To assess the influence of dose on the risk of acute urinary retention (AUR) after iodine-125 prostate brachytherapy. Methods and Materials: Between January 2005 and December 2008, 714 consecutive patients with localized prostate cancer were treated with iodine-125 prostate brachytherapy at our department. All patients completed four imaging studies: magnetic resonance imaging before and 4 weeks after treatment and intraoperative three-dimensional transrectal ultrasonography before and after implantation. The development of AUR was prospectively recorded. The evaluated treatment and dosimetric parameters included prostate volume, number of needles and seeds used, intra- and postoperative prostate edema, percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed dose to the prostate, minimal dose received by 90% of the prostate volume, and percentage of the urethra receiving 100%, 150%, and 200% of the prescribed dose. Logistic regression analysis was used to examine which factors were associated with AUR. Results: Of the 714 patients, 57 (8.0%) developed AUR. On univariate analysis, the following treatment and dosimetric factors were significantly associated with AUR: International Prostate Symptom Score (odds ratio [OR], 2.07, per 10-point increase), preimplant prostate volume (OR, 1.06), postimplant prostate volume (OR, 1.04), number of needles used (OR, 1.09), and number of seeds used (OR, 1.03). On multivariate analysis, the only independent predictive factors for AUR were pretreatment prostate volume (OR, 1.05) and International Prostate Symptom Score (OR, 1.76, per 10-point increase). Patients with a pretreatment prostate volume >35 cm{sup 3} had a 10.4% risk of developing AUR compared with 5.4% for those with a prostate volume of {<=}35 cm{sup 3}. No association was found between any of the dosimetric parameters and the development of AUR. Conclusion: The radiation dose, within the range studied, did not influence the risk of AUR after iodine-125 prostate brachytherapy. Prostate volume and International Prostate Symptom Score were the most important predictors of AUR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the optic radiation is a critical radiosensitive structure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacral insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age ({>=}60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age ({>=}60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an increased risk for the development of LMD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗