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Objectives/HypothesisHuman papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV‐positive and HPV‐negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratificationStudy DesignRetrospective case series.MethodsA retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California–San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan‐Meier and unadjusted and adjusted Cox regression models.ResultsOne hundred thirty‐four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV‐positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20‐1.07; P = .06) but not HPV‐negative (HR: 0.73, 95% CI: 0.43‐1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV‐positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12‐0.96; P = .04). Survival did not vary significantly by race among HPV‐positive patients. Among HPV‐negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08‐0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11‐7.36; P = .94) analysis.ConclusionsWomen with HPV‐positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV‐negative OPSCC. There are no differences in prognosis by race among HPV‐positive or HPV‐negative patients.Level of Evidence4 Laryngoscope, E288–E296, 2018

Background— Women have higher rates of all-cause mortality after percutaneous coronary intervention. Whether this is because of greater age and comorbidity burden or a sex-specific factor remains unclear. Methods and Results— We retrospectively assessed cause-specific long-term mortality after index percutaneous coronary intervention over 3 time periods (1991–1997, 1998–2005, and 2006–2012). Cause of death was determined using telephone interviews, medical records, and death certificates. We performed competing risks analyses of cause-specific mortality. A total of 6847 women and 16 280 men survived index percutaneous coronary intervention hospitalization 1991 to 2012. Women were older (mean±SD: 69.4±12 versus 64.8±11.7 years; P <0.001) with more comorbidities (mean±SD: Charlson index 2.1±2.1 versus 1.9±2.1; P <0.001). Across the 3 time periods, both sexes exhibited a decline in cardiac deaths at 5 years (26% relative decrease in women, 17% in men, trend P <0.001 for each). Although women had higher all-cause mortality compared with men in all eras, the excess mortality was because of noncardiac deaths. In the contemporary era, only a minority of deaths were cardiac (33.8% in women, 38.0% in men). After adjustment, there was no evidence for a sex-specific excess of risk for cardiac or noncardiac mortality. The commonest causes of death were chronic diseases and heart failure in women (5-year cumulative mortality, 5.4% and 3.9%) but cancer and myocardial infarction/sudden death in men (5.4% and 4.3%). Conclusions— The higher mortality after percutaneous coronary intervention in women is because of death from noncardiac causes. This is accounted for by baseline age and comorbidities rather than an additional sex-specific factor. These findings have implications for sex-specific clinical care and trial design.

TPS389 Background: Recent data have shown that up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or another homologous recombination DNA repair gene. Such mutations can be used as a molecular marker to select patients for targeted treatment with poly(ADP-ribose) polymerase inhibitors (PARPis), which are lethal to cells with HRD. Treatment with PARPis has shown preliminary evidence of antitumor activity in patients with mCRPC and a mutation in a homologous recombination DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent inhibitor of PARP1, PARP2, and PARP3, in patients with mCRPC associated with HRD. Methods: TRITON3 (NCT02975934) is a randomized, phase 3 study evaluating rucaparib 600 mg BID vs physician’s choice of abiraterone, enzalutamide, or docetaxel in patients with mCRPC and a deleterious germline or somatic BRCA1, BRCA2, or ATM mutation (identified by prior local testing or central testing during screening). Patients must have progressed on androgen receptor signaling–directed therapy in the mCRPC setting; prior PARPi treatment or chemotherapy for mCRPC are exclusion criteria. Patients will be randomly assigned in a 2:1 ratio to either rucaparib or physician’s choice, with the possibility for cross over from the comparator treatment to rucaparib upon radiographic progression confirmed by independent radiology review. The primary endpoint is radiographic progression-free survival (modified RECIST v1.1/PCWG3 criteria) assessed by independent radiology review. Secondary endpoints include objective response rate, duration of response, patient-reported outcomes, overall survival, and safety. Pretreatment blood samples collected from all patients will enable development of a noninvasive plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈400) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02975934.

TPS388 Background: Up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM or another homologous recombination (HR) DNA repair gene that can serve as a molecular marker to select those who may respond to poly(ADP-ribose) polymerase inhibitors (PARPis). PARPis are lethal to cells with HRD, and PARPi treatment has shown preliminary evidence of an antitumor effect in patients with mCRPC who harbor a mutation in an HR DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent PARP1, PARP2 and PARP3 inhibitor, in patients with mCRPC associated with HRD. Methods: TRITON2 (NCT02952534) is a phase 2 study evaluating rucaparib 600 mg BID in patients with mCRPC. Patients with a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per prior local test or central test during screening) will be enrolled into 1 of 2 cohorts based on the presence or absence of measurable visceral and/or nodal disease. An exploratory cohort will enroll patients with an alteration in any of 12 other prespecified HR genes (eg, RAD51C, RAD51D and PALB2), with or without measurable visceral and/or nodal disease. Patients must have progressed on androgen receptor signaling–directed therapy and 1 prior taxane-based chemotherapy for mCRPC. Patients who received prior treatment with a PARPi, mitoxantrone, cyclophosphamide or platinum-based chemotherapy are excluded. The primary endpoint is objective response rate measured using modified RECIST v1.1/PCWG3 for patients with soft-tissue disease and prostate-specific antigen response for patients with nonmeasurable disease. Secondary endpoints include duration of response, radiographic progression-free survival, overall survival, clinical benefit rate and safety. Pretreatment blood samples collected from all patients will enable development of a plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈160) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02952534.

147 Background: Prostate cancer patients treated with external beam radiation therapy are instructed to present daily with a full bladder to decrease small bowel and bladder toxicity and to increase reproducibility of treatment. However, older patients may have difficulty presenting with full bladders and variation of bladder volume with treatment is unknown. The objective of this study was to assess bladder filling at the time of radiation treatment (RT) using a bladder ultrasound in patients undergoing treatment for prostate cancer. Methods: Patients with prostate cancer were prospectively enrolled prior to CT simulation from January to August 2017. Bladder volume was recorded during CT simulation and daily immediately prior to RT. Patients were instructed to drink 8-12 ounces of water 30-60 minutes prior to RT. Three bladder volume measurements were recorded daily and averaged at the time of each treatment. Average bladder volume during treatment and the number of treatments with low bladder volumes ( < 50cc, < 60cc, and < 100cc) were reported using descriptive statistics. Results: A total of 13 patients completed a median of 42 days of RT during the study period, resulting in 550 daily bladder volumes. Ten patients were treated definitively and 3 with salvage radiation after prostatectomy. The median age of patients in the study was 72 years. Older patients were statistically more likely to present with low bladder volumes, with percentage of treatments with a bladder volume less than 50cc, 60cc, and 100cc being 29%, 42%, and 66% compared to only 4%, 7%, and 18% in patients aged < 70 (P < 0.01). The average bladder volume at the time of CT simulation was 176cc ± 57cc and the average volume during treatment was 140cc± 93cc, which was not statistically different (P = 0.28). The bladder volume did not significantly change over the course of treatment. Conclusions: Older patients (age 70+) with prostate cancer were more likely to present for RT with low bladder volumes in this prospective study. Our findings suggest that older patients should receive extra counseling about bladder filling and/or may require less bladder filling at the time of CT simulation to provide more accurate bowel dosimetry measurements.

AbstractHepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver, and is steadily becoming one of the most lethal cancers worldwide. Liver resection, which is the recommended procedure for early localized HCC, results in frequent recurrence (50–70%), while the standard of care for late-stage HCC, multikinase inhibitors, only improves survival by a few months. The lack of success for these treatment modalities is attributable, at least in part, to marked phenotypic heterogeneity within the tumor. Intratumoral heterogeneity (ITH) has emerged as a defining characteristic of human tumors, with individual cancer cells displaying distinct differences in properties including growth rate, metastatic capacity, and response to treatment. This heterogeneity, which is unlikely to be captured from a biopsy, impacts outcome because a single treatment targeting one cancer-specific pathway would spare tumor cells having distinct characteristics. Development of effective biomarkers remains a major challenge for similar reasons. Understanding, interpreting, and circumventing the impact of ITH is therefore paramount for developing reliable biomarkers and designing effective individualized treatment strategies for HCC.

BackgroundWith radiotherapy having entered the era of image guidance, or image‐guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed.AimsThis task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV‐CT, megavoltage cone‐beam CT (MV‐CBCT) and kilovoltage cone‐beam CT (kV‐CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients.Materials & MethodsWe briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures.ResultsWe provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose.DiscussionAlthough the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care.ConclusionBalancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.