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DOE OSTI2025

Time-Varying Output Delay Compensation-A Model-Free Approach and its Application on Cooperative On-Ramp Merging

This paper presents a model-free approach to compensate for time-varying output delay in networked control systems. The proposed architecture combines a model-free observer and the Smith predictor. The model-free observer estimates the current state while handling modeling errors and uncertainties of the system. The Smith predictor moves the effect of time delay outside the control closed-loop using the estimated delayed output and the actual output of the plant. The proposed method is applied to a cooperative on-ramp merging problem. First, an ultra-local model predictive control is implemented to provide a computationally efficient online speed planner agnostic to the vehicle dynamics. After that, a model-free observer is designed to estimate the current state. Finally, the proposed architecture is tested against a time-varying output delay with an upper bound of 200 milliseconds. The results demonstrate the effectiveness of the proposed method with improved tracking of intervehicle distance.

Waleed khan, Muhammad [The University of Texas at ↗
DOE OSTI2011

Risk Factors for Cataract After Palladium-103 Ophthalmic Plaque Radiation Therapy

Purpose: To examine how tumor characteristics and dose affect cataract development after plaque radiation therapy. Methods and Materials: Three hundred and eighty-four patients were diagnosed with uveal melanoma and treated with palladium-103 ({sup 103}Pd) plaque radiation therapy. Of these, 282 (74%) inclusion met exclusion criteria for follow-up time, tumor location, and phakic status. Then patient-, ophthalmic-, and radiation-specific factors (patient age, diabetes, hypertension, tumor location, tumor dimensions, and lens dose) were examined (by a Cox proportional regression model) as predictors for the development of radiation-related cataract. Results: Radiation cataract developed in 76 (24%) of patients at a mean follow-up of 39.8 months (range, 1-192). Patients with anteriorly located tumors were noted to have a higher incidence of cataract at 43.0% (43 of 100 patients) vs. 18.1% (33 cataracts per 182 patients) for posteriorly located tumors (p <0.0001). However, multivariate Cox proportional modeling showed that increasing patient age at time of treatment (p for trend = 0.0003) and higher lens dose (p for trend = 0.001) were the best predictors (biomarkers) for radiation cataract. Conclusions: Although anterior tumor location, greater tumor height, and increased patient age (at treatment) were associated with significantly greater risk for radiation cataract, dose to lens was the most significant factor.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Temporal Lobe Reactions After Radiotherapy With Carbon Ions: Incidence and Estimation of the Relative Biological Effectiveness by the Local Effect Model

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations and magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3--6.6 years). Age and maximum dose applied to at least 1 cm{sup 3} of the temporal lobe (D{sub max,V-1cm}3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm{sup 3} with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D{sub max,V-1cm}3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 {+-} 3.3 Gy equivalents (GyE) and 87.3 {+-} 2.8 GyE, respectively. Conclusions: D{sub max,V-1cm}3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

10-Year Experience With I-125 Prostate Brachytherapy at the Princess Margaret Hospital: Results for 1,100 Patients

Purpose: To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution. Methods and Materials: A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure. Results: Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years. Conclusion: Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.

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 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

Comparative Study of Different {beta}-Radiation Doses for Preventing Pterygium Recurrence

Purpose: To compare the pterygium recurrence rates after treatment with two different {beta}-radiation doses. Methods and Materials: A total of 84 patients with a mean age of 63.0 {+-} 10.3 years (men, 48 eyes, and women, 47 eyes) and initially treated with {beta}-radiation after pterygium excision were recruited. The mean follow-up period was 49.9 {+-} 51.3 months. The patients were assigned to two dose groups: a high-dose (40 Gy) or a low-dose (20 Gy) group. The statistical significance of differences in patient age, pterygium size, and interval between surgery and radiotherapy were analyzed in the 20-Gy group using the Cox proportional hazard model at p < .05. Results: The high- and low-dose groups included 28 and 67 eyes, respectively. Pterygia recurred in 11 eyes, all in the low-dose group. The interval between surgery and radiotherapy was not a significant predictor of recurrence. Smaller pterygia had a lower risk of recurrence than pterygia that had encroached the pupillary area (pterygium located within one-third of the corneal radius from the limbus, corrected hazard ratio [HR], 0.069; 95% confidence interval [CI], 0.006-0.766; p = .030; pterygium extending beyond one-third of the corneal radius, corrected HR, 0.188; 95% CI, 0.018-0.696; p = 0.019; and pterygium reaching the pupillary area, corrected HR, 0.184; 95% CI, 0.036-0.929; p = .040). Older age was marginally significant as a negative predictor of recurrence (HR, 0.943; 95% CI, 0.887-1.003; p = .061). No scleromalacia developed during the follow-up period. Conclusions: {beta}-Radiation at 40 Gy was more efficacious than at 20 Gy in preventing pterygium recurrence without scleromalacia development, particularly for large-size pterygia and those in young patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Ductal Carcinoma In Situ With Microinvasion: Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation

Purpose: To compare the clinical-pathologic features and long-term outcomes for women with ductal carcinoma in situ (DCIS) vs. DCIS with microinvasion (DCISM) treated with breast conservation therapy (BCT), to assess the impact of microinvasion. Patients and Methods: A total of 393 patients with DCIS/DCISM from our database were analyzed to assess differences in clinical-pathologic features and outcomes for the two cohorts. Results: The median follow-up was 8.94 years, and the mean age was 55.8 years for the entire group. The DCISM cohort was comprised of 72 of 393 patients (18.3%). Surgical evaluation of the axilla was performed in 58.3% (n = 42) of DCISM vs. 18.1% (n = 58) of DCIS, with only 1 of 42 DCISM (2.3%) vs. 0 of 58 DCIS with axillary metastasis. Surgical axillary evaluation was not an independent predictor of local-regional relapse (LRR), distant relapse-free survival (DRFS), or overall survival (OS) in Cox proportional hazards analysis (p > 0.05). For the DCIS vs. DCISM groups, respectively, the 10-year breast relapse-free survival was 89.0% vs. 90.7% (p = 0.36), DRFS was 98.5% vs. 97.9% (p = 0.78), and OS was 93.2% vs. 95.7% (p = 0.95). The presence of microinvasion did not correlate with LRR, age, presentation, race, family history, margin status, and use of adjuvant hormonal therapy (all p > 0.05). In univariate analysis, pathology (DCIS vs. DCISM) was not an independent predictor of LRR (hazard ratio [HR], 1.58; 95% confidence interval [CI], 0.58-4.30; p = 0.36), DRFS (HR, 0.72; 95% CI, 0.07-6.95; p = 0.77), or OS (HR, 1.03; 95% CI, 0.28-3.82; p = 0.95). Conclusions: Our data imply that the natural history of DCISM closely resembles that of DCIS, with a low incidence of local-regional and distant failures. On the basis of our large dataset, the incidence of axillary metastasis in DCISM appears to be small and not appear to correlate to outcomes, and thus, microinvasion alone should not be the sole criterion for more aggressive treatment.

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 OSTI2011

Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Radiotherapy Doses of 80 Gy and Higher Are Associated With Lower Mortality in Men With Gleason Score 8 to 10 Prostate Cancer

Purpose: Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to {>=}80 Gy. Methods and Materials: There were 226 men treated consecutively with RT {+-} ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) {>=}80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM). Results: Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose {>=}80 Gy (p = 0.011) and androgen deprivation therapy duration {>=}24 months (p = 0.033). In a similar model of DM, only RT dose {>=}80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose {>=}80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables. Conclusion: The results indicate that RT dose escalation to {>=}80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Hypoxic Prostate/Muscle PO{sub 2} Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results

Purpose: To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Methods and Materials: Custom-made Eppendorf PO{sub 2} microelectrodes were used to obtain PO{sub 2} measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO{sub 2}, mean PO{sub 2}, and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO{sub 2} ratio on BF. Results: With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO{sub 2} ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO{sub 2} ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. {>=}0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). Conclusions: Hypoxia in prostate cancer (low mean P/M PO{sub 2} ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC patients treated with definitive radiotherapy are distinct from those observed in patients who undergo surgical resection. The ultimate efficacy of radiation in locally advanced NSCLC is dependent on the intrinsic biology of the tumor.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Predicting Chest Wall Pain From Lung Stereotactic Body Radiotherapy for Different Fractionation Schemes

Purpose: Recent studies with two fractionation schemes predicted that the volume of chest wall receiving >30 Gy (V30) correlated with chest wall pain after stereotactic body radiation therapy (SBRT) to the lung. This study developed a predictive model of chest wall pain incorporating radiobiologic effects, using clinical data from four distinct SBRT fractionation schemes. Methods and Materials: 102 SBRT patients were treated with four different fractionations: 60 Gy in three fractions, 50 Gy in five fractions, 48 Gy in four fractions, and 50 Gy in 10 fractions. To account for radiobiologic effects, a modified equivalent uniform dose (mEUD) model calculated the dose to the chest wall with volume weighting. For comparison, V30 and maximum point dose were also reported. Using univariable logistic regression, the association of radiation dose and clinical variables with chest wall pain was assessed by uncertainty coefficient (U) and C statistic (C) of receiver operator curve. The significant associations from the univariable model were verified with a multivariable model. Results: 106 lesions in 102 patients with a mean age of 72 were included, with a mean of 25.5 (range, 12-55) months of follow-up. Twenty patients reported chest wall pain at a mean time of 8.1 (95% confidence interval, 6.3-9.8) months after treatment. The mEUD models, V30, and maximum point dose were significant predictors of chest wall pain (p < 0.0005). mEUD improved prediction of chest wall pain compared with V30 (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.11). The mEUD with moderate weighting (a = 5) better predicted chest wall pain than did mEUD without weighting (a = 1) (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.14). Body mass index (BMI) was significantly associated with chest wall pain (p = 0.008). On multivariable analysis, mEUD and BMI remained significant predictors of chest wall pain (p = 0.0003 and 0.03, respectively). Conclusion: mEUD with moderate weighting better predicted chest wall pain than did V30, indicating that a small chest wall volume receiving a high radiation dose is responsible for chest wall pain. Independently of dose to the chest wall, BMI also correlated with chest wall pain.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleason score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel techniques, such as intensity-modulated radiotherapy, for the treatment of pancreatic cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes. The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗