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PURPOSE It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT). METHODS The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy. RESULTS Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P CONCLUSION STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

PURPOSE In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar’s test for rates > 0%. RESULTS Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% ( P < .0001), high-grade diarrhea 38.5% ( P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

349527 Background: Symptoms are common during cancer care but often go undetected. Digital systems that elicit patient-reported outcomes (PRO) surveys may detect symptoms early and prompt clinicians to intervene, thereby alleviating suffering and averting complications. Methods: In a cluster-randomized trial, U.S.-based community oncology practices were randomized 1:1 to digital symptom monitoring with PRO surveys, or to usual care control. Patients receiving systemic treatment for metastatic cancer were eligible. At PRO practices, participants were invited to complete a weekly survey via web or automated telephone system for up to one year, including questions about nine common symptoms, performance status, and falls. Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing longitudinal symptom data were available to oncologists at visits. Pre-specified secondary outcomes included impact on physical function, symptom control, and health-related quality of life (HRQL). The primary outcome of survival is not yet mature. Results: At 52 practices, 1,191 patients were eligible and enrolled (593 PRO; 598 control). Clinically meaningful benefits were experienced in physical function by 13.8% more patients with PRO versus control (P=0.009); symptom control by 16.1% (P=0.003); and HRQL by 13.4% (P=0.006). Mean changes from baseline were superior with PRO versus control for physical function (mean difference 2.47, 95% CI 0.41-4.53; P=0.02), symptom control (2.56, 0.95-4.17; P=0.002), and HRQL (2.43, 0.90-3.96; P=0.002). Patients completed 20,565/22,486 (91.5%) of expected weekly PRO surveys. Conclusions: Digital symptom monitoring during cancer treatment confers clinical benefits. Clinical trial information: NCT03249090.

60 Background: Mapping algorithms informing economic evaluations are often derived using baseline data from clinical trials. It is unclear if these algorithms can predict health utilities accurately in post-intervention data. Thus, this study examines the longitudinal predictive ability of mapping algorithms derived from baseline trial data and explores the factors associated with prediction errors. Methods: This methodological study utilized data from an international, multicenter, randomized controlled trial of patients with low-risk prostate cancer (PC), conducted by NRG Oncology (NCT00331773). In addition to patient demographic and clinical data, this study utilized PRO data collected at baseline and 6, 12 and 24 months post-intervention. The Expanded Prostate Cancer Index Composite (EPIC) questionnaire measures health-related quality-of-life (HRQoL) and has four domains (urinary, sexual, hormonal, and bowel) and two subdomains per domain (function and bother); EuroQOL-5D-3L (EQ5D) captures health utilities. Ordinary Least Squares (OLS) regression models were used to map EPIC scores to EQ5D utilities in the baseline data through 5-fold cross-validation. Predictive performance was tested in the post-intervention data; predicted and reported utilities were compared using t-tests, and the absolute prediction error was modeled using fixed effects, as a function of baseline demographic and clinical covariates, as well as observed and predicted EQ5D utilities. Results: A total of 267 (199) patients had complete EQ5D and EPIC domain (or subdomain) data at baseline and all subsequent assessments. In the EPIC domain sample, mean ± standard deviation observed EQ5D utility was 0.90±0.13 at baseline, 0.92±0.11 at 6 months, 0.90±0.13 at 12 months and 0.89±0.14 at 24 months. Mean absolute differences (MDs) between reported and predicted were lower for models using EPIC subdomain data compared to EPIC domain data, and generally decreased as the time of assessment increased. The mapping functions over-predicted utilities for patients in perfect health while the prediction errors were increasingly negative for lower reported EQ5D scores. According to the fixed effects model for EPIC domain data, lower observed and predicted baseline EQ5D scores, and time of assessment were significant predictors of the absolute prediction error; for EPIC subdomain data, lower observed and predicted baseline EQ5D scores, hormonal bother and function, and bowel function significantly predicted the absolute prediction error. Conclusions: This study is the first to demonstrate the longitudinal validity of EPIC questionnaire, and builds upon existing research on longitudinal validity of mapping functions. The low MDs in prediction errors in post-intervention data indicate that the mapping functions are sensitive to treatment effect, thereby increasing confidence in their use in economic evaluations in PC.

7018 Background: Standard reporting of symptomatic adverse events (AEs) in oncology relies on clinicians to rate patient (pt) experience using CTCAE; each symptom is represented by a single graded item. To capture direct pt experience, NCI developed PRO-CTCAE to supplement CTCAE. In PRO-CTCAE, the pt answers up to 3 questions per AE about a symptom’s frequency, severity and interference with daily activities. To align PRO-CTCAE with CTCAE, we developed an algorithm for mapping sets of questions for an AE to a single composite numerical grade. Methods: We used a 5-step process. (1) All 187 possible PRO-CTCAE score permutations were presented to clinical investigators to subjectively map permutations to single numerical grades (range 0-3). (2) Permutations with < 75% agreement were presented to investigator committees at a National Clinical Trials Network meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating AEs between study arms was measured in 2 phase III clinical trials (Alliance for Clinical Trials in Oncology A091105 and Exelixis COMET-2). Results: (1) 12/187 score permutations had < 75% initial agreement. (2) Majority consensus was reached for all permutations. (3) 5 mappings were adjusted to assure directional consistency. (4) Composite grades for 46/59 (78%) AEs were higher in pts with ECOG performance status 2-4 vs 0-1 (median effect size 0.23 [range -0.49-0.73]; 32/59 effect size ≥0.2; 25/59 p< 0.05), similar to when conducting analysis on individual unmapped items. The test-retest reliability for 24 selected composite grades ranged from 0.57-0.96 (median intraclass correlation coefficient [ICC] 0.77) with 18/24 (75%) grades having ICC ≥0.7. Median (range) standardized response means in pts reporting worsening, no change, and improvement were 0.20 (0.03-0.34), -0.06 (-0.20-0.03) and -0.12 (-0.32-0.06). (5) Pattern, directionality and statistical significance of between-arm differences in both trials were preserved with composite grades as compared to individual unmapped items. Conclusions: A composite grading algorithm for PRO-CTCAE was rigorously developed and validated. PRO-CTCAE composite grades may be useful in analyses to provide a single metric for each pt-reported AE for trial and real-world reporting. Support: UG1CA189823; U01CA233046; HHSN261200800043C; Bayer (A091105); https://acknowledgments.alliancefound.org .

e24097 Background: Women with gynecological cancer (GynCa) reported an increased risk for acute and long-term sexual dysfunction across cancer treatments, especially radiation therapy (RT). However, limited data exist on the course of sexual dysfunction across RT and its risk factors are unknown. This study sought to characterize women’s sexual dysfunction trajectories and identified risk factors of persistent sexual dysfunction. Methods: Using a longitudinal study design, patient-reported sexual dysfunction, demographic and clinical data were collected. Women receiving RT for GynCa older than 18 years or age, race, and BMI matched healthy controls were enrolled. Female Sexual Function Index (FSFI) was used to assess women’s sexual dysfunction. Patients completed all the questionnaires pre-RT, at the end of RT, 6- and 12-month post-RT. Group-based trajectory modeling was used to identify trajectories of sexual dysfunction and risk factors of persistent sexual dysfunction. Results: Eighty-two patients were analyzed, including 36 GynCa patients receiving RT and 46 healthy post-menopausal women, comprising of 33 Blacks, 44 Whites, and 5 others. Three trajectory groups of sexual dysfunction (total FSFI score) were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). All three trajectory groups were significantly different from each other (p

55 Background: To compare the predictive ability of health utility mapping algorithms derived using cross-sectional and longitudinal data specific to the Expanded Prostate Cancer Index Composite (EPIC). Methods: This mapping study utilized data from an international, multicenter, randomized controlled trial of patients with low-risk prostate cancer conducted by NRG Oncology (NCT00331773). Health-related quality-of-life (HRQoL) data were collected using EPIC, and health utilities were obtained using EuroQOL-5D (EQ5D) at baseline and 6, 12 and 24 months post-intervention. Data were split into an estimation sample (70%) and a validation sample (30%). Ordinary Least Squares (OLS) regression models were estimated using baseline cross-sectional data as well as pooled data from all assessment periods. Random effects (RE) specifications that explicitly model the longitudinal nature of the data were also estimated. Candidate models were selected based on root mean square error (RMSE). Results: A total of 196 (147) patients in the estimation sample had complete EQ5D and EPIC domain (subdomain) data at all time points. OLS models using combined data outperformed the counter-part RE models as well as OLS models using baseline data in the five-fold cross-validation. Addition of covariates to the models resulted in improved predictive ability. In the external validation, when only EPIC domain/ subdomain data are available, the OLS model using combined data predicted EQ5D utilities better than the counterpart RE model and OLS model using baseline data (RMSE=0.121108 & 0.111345). OLS model using baseline data outperformed other model types for algorithms with EPIC domains and demographics (RMSE=0.121757), while RE models outperformed the other two model types for algorithms with EPIC subdomains and demographic data, (0.112782) and for algorithms with EPIC domains/ subdomains, demographics, and clinical covariates (RMSE=0.123589 & 0.163093). Conclusions: While algorithms using pooled data outperformed other model types in internal validation, RE models showed better predictive ability in external validation for algorithms with covariates. Clinical trial information: NCT00331773.

Purpose Although patient-reported outcomes (PROs) have become a key component of clinical oncology trials, many challenges exist regarding their optimal application. The goal of this article is to methodically review these barriers and suggest strategies to overcome them. This review will primarily focus on radiation oncology examples, will address issues regarding the “why, how, and what” of PROs, and will provide strategies for difficult problems such as methods for reducing missing data. This review will also address cancer survivorship because it closely relates to PROs. Methods Key articles focusing on PROs, quality of life, and survivorship issues in oncology trials are highlighted, with an emphasis on radiation oncology clinical trials. Publications and Web sites of various governmental and regulatory agencies are also reviewed. Results The study of PROs in clinical oncology trials has become well established. There are guidelines provided by organizations such as the US Food and Drug Administration that clearly indicate the importance of and methodology for studying PROs. Clinical trials in oncology have repeatedly demonstrated the value of studying PROs and suggested ways to overcome some of the key challenges. The Radiation Therapy Oncology Group (RTOG) has led some of these efforts, and their contributions are highlighted. The current state of cancer survivorship guidelines is also discussed. Conclusion The study of PROs presents significant benefits in understanding and treating toxicities and enhancing quality of life; however, challenges remain. Strategies are presented to overcome these hurdles, which will ultimately improve cancer survivorship.

2009 Background: NRG CC001, a phase III trial of WBRT plus memantine (WBRT+M) with or without HA, sought to evaluate the neuro-protective effects of lowering the hippocampal radiation dose. Methods: Patients (pts) with BM were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory Brain Tumor module and analyzed using mixed effects models and t-tests. Results: From 7/2016 to 3/2018, 518 pts were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted hazard ratio (HR) = 0.74, p = 0.02) due to lower risk of deterioration in executive function at 4 mos (p = 0.01) and encoding (p = 0.049) and consolidation (p = 0.02) at 6 mos. Age≤61 predicted lower NCF failure risk (HR = 0.60, p = 0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p = 0.036), difficulty speaking (p = 0.049) and problems remembering things (p = 0.013) at 6 mos favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p = 0.011) and symptom interference (p = 0.008) at 6 mos. Treatment arms did not differ in toxicity, overall survival, or intracranial progression. Conclusions: HA during WBRT+M for BM better preserves NCF and patient-reported symptoms, while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute. Clinical trial information: NCT02360215.

LBA5009 Background: Pivotal trials of AAP for patients with mCRPC enrolled few B pts, a population with a higher mortality from prostate cancer. Retrospective data suggests B pts may have higher PSA response rates than W pts treated with AAP for mCRPC. Therefore, we prospectively investigated AAP in B vs. W pts with mCRPC. Methods: Abi Race (NCT01940276) is a prospective, multicenter, parallel group study of AP in 100 men (50 B, 50 W) with mCRPC, self-identified by race. All pts received AA 1000 mg/D and P 10 mg/D (AAP) until disease progression or unacceptable adverse events (AE). The primary objective was radiographic progression-free survival (rPFS); key secondary endpoints include PSA kinetics and safety. Exploratory analyses include SNP, metabolomics and hormonal differences by race. Results: Baseline characteristics among pts were similar. The median rPFS for B and W pts was 16.8 months (mo) in each. However, PSA PFS varied by race; median PSA PFS for B and W pts were 16.6 and 11.5 mo [Table]. B pts also had numerically higher rates of ≥30%, ≥50% and ≥90% PSA decline [Table]. AEs were similar in frequency and severity by race including hypertension (42 vs 40%); however, fatigue was higher in W pts (40 vs 26%), and hypokalemia was higher in B pts (36 vs 18%). SNP profiling revealed differences in key genes involved in androgen metabolism and transport. Conclusions: This is the first prospective multicenter study by race of secondary hormonal therapy in mCRPC. B pts may have greater and more durable PSA response to AAP than W pts. SNP patterns vary by race and will be evaluated for prognostic significance. Further prospective studies in B pts are possible and needed to understand the impact of racial determinants on outcome of new hormonal regimens. Clinical trial information: NCT01940276. [Table: see text]

2065Background: Whole brain radiotherapy (WBRT) is a common treatment for BM and is associated with decline in NCF. The APOE e4 allele is associated with increased risk of Alzheimer’s disease, and ...

Purpose To determine the added value of quality of life (QOL) as a prognostic factor for overall survival (OS) in patients with locally advanced non–small-cell lung cancer (NSCLC) treated on Radiation Therapy Oncology Group RTOG-9801. Patients and Methods Two hundred forty-three patients with stage II/IIIAB NSCLC received induction paclitaxel and carboplatin (PC) and then concurrent weekly PC and hyperfractionated radiation (to 69.6 Gy). Patients were randomly assigned to amifostine (AM) or no AM during chemoradiotherapy. The following pretreatment factors were analyzed as prognostic factors for OS: Karnofsky performance status, stage, sex, age, race, marital status, histology, tumor location, hemoglobin, tobacco use, treatment arm (AM v no AM) and QOL scores (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [QLQ-C30] and Lung Cancer 13 [LC-13]). A multivariate (MVA) Cox proportional hazards model was performed using a backwards selection process. Results Of the 239 analyzable patients, 91% had a baseline global QOL score. Median follow-up time was 59 months for patients still alive and 17 months for all patients. Median baseline QLQ-C30 global QOL score was 66.7 on both treatment arms. Whether the global QOL score was treated as a dichotomized variable (based on the median score) or a continuous variable, all other variables fell out of the MVA for OS. Patients with a global QOL score less than 66.7 had an approximately 70% higher rate of death than patients with scores ≥ 66.7 (P = .004). A 10-point higher baseline global QOL score corresponded to a decrease in the hazard of death by approximately 10% (P = .004). The other independent QOL predictors for OS were the QLQ-C30 physical functioning (P = .011) and LC-13 dyspnea scores (P = .012). Conclusion In this analysis, baseline global QOL score replaced known prognostic factors as the sole predictor of long-term OS for patients with locally advanced NSCLC.

Purpose This study evaluated whether males without partners were disadvantaged for survival in Radiation Therapy Oncology Group (RTOG) head and neck cancer clinical trials. Methods Patients treated on three RTOG trials were studied. The Cox proportional hazards model was used to determine if sex and the interaction between sex and marital/partner status were independent prognostic variables for overall survival controlling for Karnofsky performance status, tumor stage, nodal stage, primary site, and protocol treatment. Results A total of 1,901 patients (1,509 men) were entered onto the three RTOG trials, with 1,822 (1,438 men) analyzable patients. Prognostic variables independent of disease-related variables for survival in multivariate analyses restricted to men were age, marital/partner status, and income. Conclusion The apparent disadvantage of unpartnered men is striking, even after controlling for disease and other demographic variables. Possible explanations could easily be tested in observational studies, leading to evaluation of simple interventions to improve their outcome.

Ethnic diversity in recruitment is a vital prerequisite to eliminating health disparities in cancer treatment, control and prevention programs. Much anecdotal reporting, but little scientific rigor, has been applied to the study of methods to improve the recruitment of minorities into cancer control or treatment trials. Even the most innovative research is stymied by the lack of representative samples of the populations that the research is designed to serve. The goals of this article are to describe a theory-driven framework for improving minority recruitment to clinical and cancer control trials, to explain organizational prerequisites to improving minority recruitment, and to provide empirical evidence of success in initial efforts to recruit to cancer control studies. These programs are offered as models for improving minority recruitment to cancer-control and -treatment trials, and minority access to cancer treatment in general.

128 Background: Neurocognitive functional decline is a common sequalae of cranial irradiation (CI) that significantly impacts quality of life. Preclinical studies and randomized clinical trials show that following traumatic brain injury and cerebrovascular accidents, premenopausal women demonstrate decreased mortality and improved neurocognitive function, with these benefits presumed to be derived from progesterone. We hypothesized that progesterone may serve similar role in neuroprotection following cranial irradiation. Methods: Adult non-tumor bearing wild type C57BL/6 male mice were treated with two separate fractionated radiation therapy regimen (9 Gy and 15 Gy) to the brain. Cohorts of these mice were administered progesterone (16mg/kg daily) as a pretreatment for 3 days and concurrent with the radiotherapy for a total of 14 days with tapering during the last two days. The animals were then tested using different behavioral measures for cognitive function including morris water maze (MWM) for assessing spatial and related forms of learning and memory, elevated plus maze (EPM), , and spontaneous locomotor activity (SLA) tests. Mice were tested for cognitive function on day 10 and after 30 days of treatment for short and long-term effects of (CI) on memory function. Results: All irradiated mice showed statistically significant decline in MWM, EPM, and SLA measures. There were no significant differences in the 9 Gy versus 15 Gy cohorts. Progesterone administration produced a statistically significant group effect (F (4, 25) = 8.553; P(4, 25) = 8.613; P(4, 25)= 7.993; P

27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience & resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel & Urinary domains EPIC instrument(EPIC B&U). Secondary objectives included acute & late GI & GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a & PSA < 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) > 5 points & in EPIC urinary domain score > 2 points were felt to be clinically significant. The frequency for > 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for > 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( > 80%). The 1 year FREQE-B for 5 fr was 23.5% (p < 0.001) & 12 fr was 23.1% (p < 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p < 0.001) & 12 fr was 34.7% (p < 0.001). Conclusions: This study confirms that based on changes in EPIC B&U (baseline to 1-year), acute & late toxicity, both the 5 & 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy & toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

9525 Background: Determine if prophylactic tadalafil maintains spontaneous (off-drug) erectile function (EF) compared to placebo in patients (pts) treated with radiotherapy (RT) for prostate cancer. Methods: Double-blind 1:1 randomization to tadalafil 5mg daily for 6 mos vs placebo starting with RT. Primary outcomes measured by International Index of Erectile Function (IIEF). Eligibility included pre-RT IIEF Question [Q] 1 response “sometimes/most times/always” able to get an erection. Ps treated with hormones were excluded. Primary outcome was response to IIEF Q1 at 30 wks (6 wks off drug). Pts were stratified by RT modality (external vs. brachytherapy) and age (≤65 vs. >65 years). 182 pts were needed in an intent-to-treat analysis to show a difference from 20% responders with placebo to 40% with tadalafil based on a 2-sided Fishers exact test with α=0.05 and 80% power. Results: We report on 155/222 analyzable/eligible pts. Median age was 63 years, white (73%), and external RT (63%). Mean total dose for external RT was 77.23 Gy and 136.74 Gy for brachytherapy with penile bulb D50 of 24.46 Gy and 31.24 Gy respectively. Most pts completed treatment per protocol (84% tadalafil, 70% placebo). Spontaneous EF at 30 wks from drug start was not different (p=0.99) between arms based on IIEF Q1 response, total IIEF score (52.5 drug vs 52.8 placebo), or score change from baseline (-8.0 drug vs -8.8 placebo). No difference in these outcomes was noted at 1 year. Non-responders at 30 wks were likely to be older (age≥65; p=0.432), but there were no significant predictors at 1 year. About 80% of pts maintained spontaneous EF in both arms. Conclusions: Low-dose daily tadalafil did not preserve EF within the first year of RT for prostate cancer. If tadalafil positively influences delayed RT-induced vasogenic injury, additional time may be needed to observe a benefit to tadalafil as a preventive agent. Alternatively, tadalafil dose modification or altered dosing schedules may be needed to demonstrate a protective effect of this agent when used with RT. Clinical trial information: NCT00951184.

9527 Background: Depression screening is recommended in routine cancer care. Brief tools are needed to identify depressed patients in radiation oncology treatment settings. Methods: Patients starting radiotherapy for first diagnosis of any tumor were eligible. Screening measures administered prior to or within the first 2 weeks of radiation therapy included: Hopkins Symptom Checklist (HSCL-25), Patient Health Questionnaire (PHQ-9; PHQ-2), and the National Comprehensive Cancer Network-Distress Thermometer (NCCN-DT). Patients exceeding validated cutoff scores on the HSCL-25, PHQ-9 or PHQ-2, and a systematic sample of patients who screened negative, completed telephone-based administration of the Structured Clinical Interview for DSM-IV (SCID) Mood Disorder modules. Results: 463 patients from 35 community-based and 2 academic radiation oncology sites were accrued. The majority were women (n=298, 66%). Participants had breast (45%), GI (11%), lung (10%), gynecologic (6%), or other (27%) cancers. All 454 eligible patients completed the screening questionnaires and 100% of questionnaire items were completed. 75 (16%) screened positive for depressive symptoms. A total of 70 SCID interviews were administered to 37 patients who screened positive and 33 who screened negative. Among those who screened positive, 14 (20%) met SCID criteria for major depression. One participant who screened negative met depression criteria (1.4%). Results indicate the prevalence of depression is 3%. The PHQ-2 demonstrated good psychometric properties for identifying current major depressive episode, using a cut-off score > 3 (ROC area under the curve=0.839). The PHQ-9 > 9 was comparable (AUC=0.837). The NCCN-DT > 4 did not adequately detect depression (AUC=0.64). Conclusions: The prevalence of depression was low (3%) among this community-based sample of adults receiving radiotherapy. The PHQ-2 demonstrated excellent psychometric properties to detect depression, which were equivalent to the PHQ-9 and superior to the NCCN-DT. Our findings support using the PHQ-2 to identify patients in need of further assessment and treatment for depression, a low prevalence but clinically significant comorbidity.

4607 Background: The external validity of randomized trials (generalizability) has been called into question following the finding that patients treated on clinical trials vary substantially from p...

6061 Background: We assessed the association of deterioration (D) in patient-reported quality of life (QOL) with survival following curative-intent treatment for limited-disease small cell lung can...

9156 Background: Aromatase inhibitor-associated arthralgia (AIAA) has recently been recognized as a significant symptom burden among breast cancer survivors (BCS). Several radiological studies have...

6596 Background: Many breast cancer patients use complementary and alternative medicine (CAM), which warrant rigorous evaluation of the safety and efficacy of these therapies. As with conventional cancer treatment studies, researchers face challenges in accruing patients to CAM trials. This study aims to identify the factors associated with willingness to participate (WTP) in a trial evaluating use of acupuncture for arthralgia among breast cancer patients. Methods: We conducted a cross-sectional survey study among outpatient postmenopausal breast cancer patients who were receiving aromatase inhibitors. Self-reported WTP in an acupuncture trial was used as the main outcome variable. Expectation towards acupuncture efficacy was measured using a previously validated Acupuncture Expectancy Scale. Multivariate logistic regression was used to identify factors associated with WTP. Results: 300 patients participated (92% response rate), with a mean age of 61 ± 10 years, 252 (84%) White, and 38 (13%) Black. Of the participants, 148 (49.8%) reported WTP in an acupuncture trial should they be offered an opportunity for such research. In a multivariate model, higher likelihood of WTP was associated with having a college education, adjusted odds ratio (95% confidence interval), 3.78 (1.83–7.81); having previous radiation therapy 2.02 (1.13–3.62); and current experience of arthralgia 2.36 (1.11–4.98). Positive expectancy of acupuncture outcome was also associated with greater likelihood of WTP 1.20 (1.12–1.28). Age and race were not predictors of WTP in the multivariate model. Conclusions: Almost half of the outpatient breast cancer patients expressed WTP in an acupuncture clinical trial for arthralgia. Higher education, previous radiation therapy, current experience of arthralgia, and positive expectancy related to acupuncture may affect breast cancer patients’ willingness to participate in an acupuncture trial for arthralgia. No significant financial relationships to disclose.

20510 Background: Quality of life (QOL) is an important component of cancer research and allows fuller appraisal of the costs and benefits of treatments to patients. Evaluating similarities and differences in the patterns of missing QOL assessments can provide insight into predictors of missingness and optimal data collection schedules. Methods: Eighteen RTOG studies in symptom management (CCOP), brain, head and neck, gastrointestinal and lung disease sites with 5,846 eligible patients and five QOL instruments: Spitzer (981 pts), FACT (2665 pts), UW-QOL (882 pts), ADLS (122 pts), EORTC-QLQ (242 pts)] and MMSE (1957pts) were analyzed. The missing data patterns are categorized as follows: a patient complies at all time points (Complete), a patient does not comply at a time point and any subsequent time points but complies at all the previous time points (Monotone dropout), a patient does not comply at any time point (All missing), and all other patterns (Mixed). Results: There is no significant difference w...

6007 Background: RTOG 9003 compared altered fractionated radiotherapy (AIFX) to standard radiotherapy (SFX). Overall and disease-free survival was improved in the AIFX schedules but with increased toxicity. The specific aim of this study was to compare the cost-effectiveness of AIFX to SFX. Methods: Costs data included Medicare Part A and Part B costs from all providers—inpatient, outpatient, skilled nursing facility, home health, hospice, and physicians and other Part B providers were obtained from the Centers for Medicare & Medicaid Services (CMS) for patients treated on RTOG 9003 from 1992–1996. Claims were restricted to those with a diagnosis of head and neck cancer. We calculated 56-month expected discounted costs for each arm of the trial in 1996 dollars, with Kaplan-Meier sampling average estimates of survival probabilities for each month and mean monthly costs. Costs were discounted back to the time of entry onto the trial, using an annual discount rate of 3% and indexed to 1996 dollars using the Consumer Price Index. The analysis was performed from a payer’s perspective. Incremental cost-effective ratios were calculated comparing AIFX schedules to SFX. Results: Of the 1,130 patients entered, 1,073 patients were analyzable for outcomes and Medicare cost data and clinical outcomes were available for 130 patients. The expected mean 56-month cost and incremental cost-effectiveness ratios (ICER) compared to SFX are presented in the table . Sensitivity analysis and 95% confidence ellipses will be presented. Conclusions: Although more toxic altered fractionated radiotherapy schedules were found to be cost-effective using a willingness to pay of $50,000/life year in patients >65 years old. These results need to be confirmed in a cohort of younger patients. [Table: see text] No significant financial relationships to disclose.

6073 Background: It is unclear whether there are gender-based differences in pain response and survival after palliative external beam radiotherapy (XRT) for painful bone metastases from breast or ...

4557 Background: African-American (AA) males and Caucasian males with a family history of prostate cancer (PCA) have been shown to be at increased risk of developing prostate cancer. We report the results of the first 520 males enrolled in a high-risk prostate cancer screening program. Methods: AA men and Caucasian men with at least one first-degree or ≥ 2 second degree relatives diagnosed with PCA between the ages of 35 and 69 were eligible for enrollment into the Prostate Cancer Risk Assessment Program. Caucasian men testing positive for the BRAC1 gene were also eligible. Biopsy criteria included abnormal DRE, PSA >4 ng/ml and PSA ≥ 2 &

6043 Background: The specific aim of this study was to evaluate the influence of socio-demographic factors on local-regional (LR) control and survival of patients treated on RTOG head and neck cancer clinical trials. Methods:Patients treated on RTOG 9003, RTOG 9111 and RTOG 9703 were utilized. The model was stratified by protocol and a step-up procedure using a 0.05 significance level was initially used to build the model. The Cox proportional hazards model was used to determine if any tumor or socio-demographic variables (age, gender, race, Karnofsky Performance Status (KPS), T-stage, N-stage, marital status, number of persons in household, education level, household income prior to cancer diagnosis, and tobacco use) are independent prognostic variables for LR control and/or survival. Results:A total of 1901 patients were entered onto the 3 RTOG trials of which 1822 were analyzable. Fifty-nine percent of the analyzable patients were from 9003, 28% from 9111 and 13% from 9703. In multivariate analyses T a...