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Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda.A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression.A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%).Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

There are no formal guidelines for the management of patients with primary gastrointestinal (GI) cancers who have lung-exclusive or lung-predominant metastases. We performed a retrospective analysis to evaluate host and tumor characteristics of this patient population, model patterns and rates of growth, and describe treatment approaches.Eligible patients had a GI cancer with either synchronous or metachronous lung metastases but no other visceral or peritoneal sites of involvement. In addition to collecting detailed patient-specific and tumor-specific information, all imaging studies (computed tomography±positron emission tomography scans) were reviewed by an independent radiologist. Up to 5 lung metastases were tracked through each patient's clinical course. Growth rate was estimated using a linear mixed model analysis.Forty patients met eligibility criteria (18 pancreatic, 15 colorectal, 6 hepatobiliary, 1 gastroesophageal; synchronous vs. metachronous, 13 and 27, respectively). Median time from original cancer diagnosis to onset of metachronous lung lesions was 16 months. Interval from first appearance of lung metastases to treatment initiation was 6.2 months. Average growth rate of the largest lesion was 0.21 mm/mo (95% confidence interval, 0.12-0.30), with substantial intrapatient and interpatient variability. Sixty percent of patients underwent locoregional interventions in addition to or in lieu of systemic therapy for their lung metastases. Median survival of the entire study cohort from first appearance of lung metastases was 54 months.Lung metastases from primary GI cancers have a variable but overall indolent natural history and are generally associated with prolonged survival outcomes. Further efforts to define patterns of growth of lung metastases, informed by size, number, and clinical/molecular features, are needed to guide appropriate timing and selection of therapy as well as surveillance strategies.

We evaluate cost-effectiveness of primary treatments for localised prostate cancer by uniquely combining prospectively collected real-world outcomes and costs from UCSF Cancer of Prostate Strategic Urologic Research Endeavor (CaPSURE™).Markov models assessed cost-effectiveness of radical prostatectomy (RP), brachytherapy, electron beam radiation therapy (EBRT) and brachytherapy with EBRT by risk from US payers perspective over 8 years. Treatment costs included office visits, hospitalisation, procedures, medication and long-term care. Patients' surveyed HRQoL were mapped into utilities. Incremental cost-effectiveness ratios (ICERs) used cost per quality-adjusted life years (QALYs) and willingness-to-pay of $150,000/QALY.Cost-effectiveness analysis (CEA) showed for low-risk prostate cancer, EBRT dominated the lowest cost brachytherapy, but RPns and brachytherapy plus EBRT were cost-effective compared to brachytherapy with ICERs of $18,926 and $41,662 per QALY. In medium-risk patients, RP, EBRT and brachytherapy plus EBRT all were cost-effective compared with brachytherapy, with ICERs of $30,604, $22,588 and $21,627/QALY. In high-risk, brachytherapy dominated all treatments. Procedure cost and utility are driving ICER, but probabilistic sensitivity analysis showed the model was robust across variables.This first CEA combining prospective real-world evidence for HRQOL outcomes with costs shows cost-effectiveness of treatments vary by risk groups, providing new evidence for treatment decisions.

BackgroundSkeletal-related events (SREs) from bone metastases disease carry significant morbidity in men with metastatic castration resistant prostate cancer (mCRPC). The differential risk of SREs among patients receiving abiraterone acetate (AA) or enzalutamide (ENZ) is unknown.MethodsTo compare the risk of SREs among men with mCRPC receiving AA or ENZ, a retrospective cohort study using the SEER-Medicare Linked Database was conducted. Men with prostate cancer aged ≥65 years at first AA or ENZ prescription (index date) from 2011 to 2015 were identified. Patients were followed until the earliest occurrence of SRE, death, Medicare disenrollment, or December 31, 2016. The primary outcome was a composite endpoint of SRE (pathologic fracture, spinal cord compression, or surgery or radiation to bone) after the index date. Multivariable logistic regressions including key demographic and clinical covariates with death as a competing risk were conducted.ResultsOverall, 5,856 patients were identified (4,207 received AA and 1,649 received ENZ). Median age was 76.5 years (IQR 71.4-82.3), 4,557 (77.8%) were White, 1,112 (19.2%) had recent chemotherapy, and 2,730 (46.6%) had recent zoledronic acid or denosumab. Eight-hundred and thirty-seven (14.3%) patients had ≥1 SRE after index date. In multivariable analyses, there was no difference in SRE risk based on AA and ENZ (HR=0.99 for ENZ, 95%CI 0.84-1.16, P=0.890). Denosumab was associated with lower SRE risk (HR=0.75, 95%CI 0.64-0.88, P=0.001).ConclusionsIn this large cohort of men with mCRPC, there was no difference in risk of SRE between AA and ENZ. Decision-making should be informed by prior therapies, comorbidities, toxicity profiles, and patient preferences. Denosumab has evidence of benefit in preventing SREs in this real-world population.

PURPOSE In describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development. METHODS We retrospectively reviewed all patients with BCR-ABL–positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test. RESULTS One hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days ( P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis ( P = .056) and imatinib initiation ( P = .170) was not significantly different. CONCLUSION Coupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

PURPOSE Hodgkin lymphoma (HL) is highly curable in high-income countries (HICs), yet many patients around the world do not have access to therapy. In 2012, cancer care was established at a rural district hospital in Rwanda through international collaboration, and a treatment protocol using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiotherapy was implemented. METHODS We conducted a retrospective cohort study of all patients with confirmed HL seen at Butaro Hospital from 2012 to 2018 to evaluate quality indicators and clinical outcomes. RESULTS Eighty-five patients were included (median age, 16.8 years; interquartile range, 11.0-30.5 years). Ten (12%) were HIV positive. Most had B symptoms (70%) and advanced stage (56%) on examination and limited imaging. Of 21 specimens evaluated for Epstein-Barr virus, 14 (67%) were positive. Median time from biopsy to treatment was 6.0 weeks. Of 73 patients who started ABVD, 54 (74%) completed 6 cycles; the leading reasons for discontinuation were treatment abandonment and death. Median dose intensity of ABVD was 92%. Of 77 evaluable patients, 33 (43%) are in clinical remission, 27 (36%) are deceased, and 17 (22%) were lost to follow-up; 3-year survival estimate is 63% (95% CI, 50% to 74%). Poorer performance status, advanced stage, B symptoms, anemia, dose intensity < 85%, and treatment discontinuation were associated with worse survival. CONCLUSION Treating HL with standard chemotherapy in a low-resource setting is feasible. Most patients who completed treatment experienced a clinically significant remission with this approach. Late presentation, treatment abandonment, and loss to follow-up contribute to the discrepancy in survival compared with HICs. A strikingly younger age distribution in our cohort compared with HICs suggests biologic differences and warrants further investigation.

PURPOSE Eastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study. MATERIALS AND METHODS From 2013 to 2015, ESCC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for sex and age (± 10 years). Questionnaires were used to assess sociodemographic characteristics and environmental, dietary, and lifestyle risk exposures. Multivariate logistic regression models were used to estimate age-specific odds ratios of ESCC for exposures among participants age 30-44 and ≥ 45 years. RESULTS A total of 471 cases and 471 controls were enrolled. Among cases, 100 (21%) were < 45 years. Multiple exposures were identified as risk factors for early-onset ESCC, several of which were unique to this age group, including infrequent teeth cleaning, secondhand tobacco smoke exposure, and pest infestation of grain and/or nuts. Lower socioeconomic status, family history of ESCC, tobacco smoking, home-brewed alcohol consumption, home storage of grain and/or nuts, and use of firewood for cooking were associated in the older but not the younger age group. Hot beverage intake was associated with increased ESCC risk in both age groups. CONCLUSION Our results suggest that ESCC risk factors in Tanzania vary between age groups. With the data currently available, environmental and behavioral risk factors appear to play an important role in the high incidence of ESCC among young people.

Purpose There are over 1.3 million colorectal cancer (CRC) survivors in the USA, many of whom report lower health-related quality of life (HRQoL) years after treatment. This study aimed to explore the effect of digital health tools on HRQoL in CRC survivors. Methods We conducted a two-arm, randomized controlled trial of 42 subjects who had completed treatment for CRC. Participants in the intervention arm received a Fitbit Flex™ and daily text messages for 12 weeks. HRQoL was assessed as a secondary endpoint in both arms at enrollment and 12 weeks using the Medical Outcomes Study Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy–Colorectal (FACT-C). Survey score changes from enrollment to 12 weeks were compared between the two arms using independent t tests, and scores at enrollment and 12 weeks were compared using paired t tests. Results An increase in the FACT-C functional well-being subscale was observed in individuals in the intervention arm pre- to post-intervention (median difference, 2; interquartile range (IQR), 1, 4; P = .02). Although the between-group comparison was not statistically significant, no change in the functional well-being subscale was observed in the control arm (median difference, 0; IQR, 1, 1; P = .71). No other measures of HRQoL appeared to differ within arm across time points or between arms. Conclusion A 12-week digital physical activity intervention may improve functional well-being among CRC survivors. Larger randomized studies are needed to determine if digital health tools improve functional well-being among CRC survivors and if this improvement can be sustained over time. Trial registration NCT02966054; registration date, November 17, 2016

Background: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC). Methods: We conducted an incident case–control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran–Mantel–Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone. Results: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41–4.68], former smoking (OR 2.45; 95% CI, 1.46–4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01–2.77), daily spicy chilies (OR 1.62; 1.04–2.52), and daily salted foods (OR 2.02; 95% CI, 1.06–3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16–0.80), fruit (OR 0.47; 95% CI, 0.27–0.82), and smoked fish (OR 0.31; 95% CI, 0.15–0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16–11.73), Northern-Lake (OR 2.40; 95% CI, 1.46–3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56–6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone. Conclusions: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania. Impact: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa. See related commentary by McCormack et al., p. 248

PurposeWe aimed to described 25-hydroxyvitamin D [25(OH)D] levels in newly diagnosed colorectal cancer (CRC) patients and to re-evaluate levels after chemotherapy.MethodsPermanent residents of the San Francisco Bay Area with a new CRC diagnosis of any stage were recruited prior to any non-surgical therapy. Serum 25(OH)D levels were measured at time of diagnosis and 6-month follow-up. Supplement use was not restricted. The primary endpoint was the frequency of vitamin D deficiency in patients with newly diagnosed CRC of all stages. The Kruskal-Wallis and Spearman correlation tests were used to evaluate associations of patient characteristics with 25(OH)D levels.ResultsMedian 25(OH)D level at baseline was 27.0ng/mL (range 7.2, 59.0); 65% of patients had insufficient levels (25(OH)D

Androgen deprivation therapy (ADT) is associated with numerous toxicities that are potentially modifiable. We sought to evaluate the impact of participation in a multidisciplinary clinic, STAND (Supportive Therapy in Androgen Deprivation) Clinic, designed to provide individualized lifestyle modification and management of ADT-related side effects.This phase II study recruited men with prostate cancer who had started ADT6 months prior to enrollment, and in whom ADT was planned for at least 12 months following enrollment. Patients were randomized in a 1:1 ratio to either the STAND Clinic or usual care. Patients randomized to the STAND Clinic were provided monthly multidisciplinary assessment and counseling on exercise, nutrition, and symptom management for 12 months on a rotating schedule. Primary outcome was change from baseline to 12 months in percent body fat. Feasibility outcomes were also assessed by measuring percentage of completed visits. Secondary outcomes included change from baseline to 12 months in 3 domains: (1) metabolic impact and bone health, (2) quality of life (QOL), and (3) physical activity.A total of 25 men were randomized to STAND clinic, and 23 were randomized to usual care. The study did not meet its accrual target of 32 men in each arm and was closed early due to lack of financial support. Overall, 91% (295 of 325) of STAND clinic visits were completed. Eighteen out of the 25 patients in STAND clinic arm (72%) completed all 12 months of STAND clinic visits, and 80% (20 of 25) completed the first 6 months. For all primary and secondary outcomes, there were no statistically significant differences between treatment arms.Individualized and comprehensive management of ADT toxicities in a multidisciplinary clinic was well attended by patients. However, we did not find any differences in the outcomes assessed between the intervention arm and control.

Purpose: Cervical cancer is a leading cause of cancer-related mortality in Africa. As treatment capacity expands, it is critical to evaluate outcomes and identify targets for quality improvement. We describe a cohort of cervical cancer patients at Butaro Cancer Center (BCCOE) in rural Rwanda, many co-managed by gynecologic specialists at the national referral hospital and a subset referred for definitive chemoradiotherapy plus brachytherapy (CRT) in Nairobi based on available funds and estimated curability. Methosd: We conducted a retrospective cohort study of all patients with cervical cancer seen at BCCOE between 6/2016 and 6/2018. Data were extracted from clinical charts and analyzed using descriptive statistics and Kaplan Meier method. Results: 377 patients were included; median age 54 years, 21% HIV positive. Most patients (85%) had squamous cell carcinoma. A majority (67%) had stage III or IV disease at presentation. Several early stage patients underwent radical hysterectomy (n=34). 114 (30%) received CRT, representing 45% of eligible candidates. Of these, 30 (26%) received upfront CRT after a median 126 days from diagnosis, and 83 (73%) received “temporizing” carboplatin/paclitaxel while awaiting CRT, with a median 56 days from diagnosis to chemotherapy. Patients sent for upfront CRT were younger (p Conclusion: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to CRT are anticipated. Expanded and timely access to radiation is urgently needed. Citation Format: Victoria Umutoni, Cyprien Shyirambere, Ethan Katznelson, Cam Nguyen, Jean Bosco Bigirimana, Aline Umwizerwa, Alan Paciorek, Lisa Bazzett-Matabele, Diomede Ntasumbumuyange, Scott Triedman, Lawrence Shulman, Tharcisse Mpunga, Rebecca DeBoer. Clinical Outcomes and Quality Metrics of Cervical Cancer Treatment in Rwanda [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 46.

Background Neuroendocrine neoplasms (NENs) comprise a rare and heterogenous group of cancers, for which the role of radiation therapy continues to evolve. The purpose of this study is to analyze oncologic outcomes after the use of high-dose radiation in management of NENs at a tertiary hospital. Materials and methods We performed a retrospective review of patients who received high-dose radiation with intent to cure or provide durable local control (defined as biologically effective dose (BED) ≥40, α/β = 10) for a localized or metastatic NEN from 2006 to 2019. Evaluation of disease status after radiation was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria when possible. Patients were grouped by differentiation (well-differentiated (WD) or poorly-differentiated (PD)) and stage (localized/locally advanced disease (L) or metastatic (M)) in analysis of probabilities of progression after radiation. Results 45 patients completed a radiation course with BED ≥40 for a NEN (median BED 72). With a median follow-up of 24 months after radiation, the 2-year actuarial rates of local relapse-free survival, new metastasis-free survival, progression-free survival, and overall survival after radiation were 98%, 45%, 41%, and 69%, respectively. 25 patients (56%) developed new metastases after completion of radiation, including 33% (n = 3) of patients with WD-L disease, 44% (n = 8) of WD-M, 77% (n = 10) of PD-L, and 80% (n = 4) of PD-M, with progressively shorter median times to progression (26, 9, 8, and 3 months, respectively; p = 0.093). Of the 25 patients evaluable by RECIST, 68% (n = 17) achieved either a complete or partial best response in the irradiated lesion. Conclusions These data suggest that focal, high-dose radiation has a role in the management of selected patients with NENs. Local failure is rare in patients with both well-differentiated and poorly-differentiated disease, although the predominant pattern of failure remains development of new metastases.

Background East Africa is one of the fastest growing regions in the world and faces a rising burden of cancer; however, few people are equipped to effectively conduct research in this area. Materials and Methods A 31-item questionnaire was distributed to current trainees and recent graduates of the Master in Medicine in Clinical Oncology Program at Muhimbili University of Health and Allied Sciences in Tanzania. Areas that were assessed included (a) demographic information, (b) prior research training, (c) prior and current research activities, (d) attitudes toward the importance of research, and (e) supports and barriers to inclusion of research in an oncology career path. Results A total of 30 individuals responded to the survey, of whom 53% (n = 16) were male and 70% (n = 21) identified as current trainees. Among the majority of respondents, attitudes toward research were strongly favorable. Although only 37% (n = 11) reported receiving any formal training in research methodology, 87% (n = 26) reported intentions to incorporate research into their careers. The absence of protected time for research and lack of access to research funding opportunities were identified by a majority of respondents as critical barriers. Conclusion A majority of current or recent oncology trainees in Tanzania desire to incorporate research into their careers, but most also lack adequate training in research methodology and longitudinal mentorship. Our future collaboration will focus on creation of appropriate research training curriculums and fostering an environment that catalyzes interprofessional development and transforms and extends context-specific cancer research in East Africa. Implications for Practice Current and recent oncology trainees in East Africa expressed a high enthusiasm for research, driven by a sense of urgency related to the burden from cancer that the region faces. This highlights the need for cancer research training and mentorship in this setting. This work hypothesizes that African principal investigators can operate effectively if proper attention is given to selection and provision of high-quality foundational didactic training to learn the theory and implementation of research as well as to the development of an environment conducive to mentoring.

Background: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors. Methods: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521). Results: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days. Conclusions: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed. Impact: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors. See all articles in this CEBP Focus section, “Modernizing Population Science.”

Background As survival with metastatic colorectal cancer (CRC) and imaging modalities improve, detection of ovarian metastases may be increasing. The ovary may serve as a sanctuary site for malignant cells; however, there is a paucity of data regarding the role for oophorectomy. Methods This is a single-institution retrospective study of patients with CRC with ovarian metastases from 2009 to 2017. We evaluated patient, disease, and treatment related factors associated with overall survival (OS) from initial diagnosis of metastatic CRC. Results Of 108 patients assessed, the median age was 50, 19% had localized disease at initial presentation, 64% had ovarian metastases at initial CRC diagnosis, and 77% underwent oophorectomy. Median OS was 29.6 months across all patients, and it was 36.7 months in patients who underwent oophorectomy versus 25.0 months in patients who did not (hazard ratio [HR] 0.54). In multivariate analysis, the effect of oophorectomy on OS suggested protection but was not statistically significant (HR 0.57). Resection of primary tumor was performed in 71% of patients, which was independently associated with improved OS (HR 0.21). Twelve patients (11%) remained alive at 5 years after diagnosis of metastatic disease. Conclusion Although it has been previously reported that patients with CRC with ovarian metastases have poor prognosis, the median OS for this cohort was comparable to existing OS data for patients with metastatic CRC. In patients treated with chemotherapy, we did not find the ovarian metastasis to frequently serve as a sanctuary site of disease. However, we found that in carefully selected patients, oophorectomy may confer a survival benefit. Implications for Practice In colorectal cancer (CRC) ovarian metastasis is not necessarily associated with worse prognosis than metastasis to other sites. In carefully selected patients with ovarian metastases from CRC, oophorectomy may confer a survival benefit. Specifically, development of ovarian metastasis early in the disease course, resection of the primary tumor, and limited extraovarian metastatic disease are clinical features that are potentially associated with benefit from oophorectomy. A subset of patients with ovarian metastasis from CRC have potential to become long-term survivors (>5 years).

e17038 Background: Skeletal-related events are common in men with prostate cancer, and are associated with significant morbidity and mortality. AA and ENZ are novel androgen signaling inhibitors used in the treatment of metastatic prostate castration-resistant prostate cancer (mCRPC). As directly comparative efficacy data do not exist between AA and ENZ, the differing toxicity profiles inform treatment selection. It is unknown whether SRE rates differ in a real-world population between AA, which is given with corticosteroids, and ENZ, which is associated with imbalance and falls. Methods: The national SEER-Medicare linked database was used to identify men with prostate cancer who received AA or ENZ between 2011-2015; approval during this period was solely for mCRPC. Inclusion criteria included Medicare Part A+B coverage 1 year before and after first receipt of AA/ENZ, without any HMO enrollment. Baseline demographic and comorbidity data were gathered. Diagnosis and procedure claims codes were used to identify SREs, defined as pathologic fracture, surgery to bone, radiation to bone, or spinal cord compression. The time to SRE was defined as time from first receipt of AA/ENZ to the first SRE of any type. A multivariable competing risk regression analysis including death as a competing risk was performed. Results: 5,856 men with prostate cancer who first received AA (N = 4,207) or ENZ (N = 1,649) were identified. The median age at initiation of AA/ENZ was 70 years (range 65-101); 78% were White, 12% Black, 4% Hispanic, 3% Asian, and 4% Other. The median follow-up was 14 months. The overall SRE rate was 13.1% after AA/ENZ start: 574 (13.6%) AA and 194 (11.8%) ENZ, with a cumulative incidence of 11.9% at 2 years. Median overall survival was 16 months (14.4 months for AA and 18.3 months for ENZ). Age, stage at diagnosis, race/ethnicity, baseline comorbidities, and prior history of SRE were balanced between AA vs ENZ, aside from baseline osteoarthritis or rheumatoid arthritis (48.0% AA vs 53.2% ENZ, P < 0.001) and baseline Alzheimer’s dementia (9.2% AA vs 11.1% ENZ, P = 0.03). After controlling for these potential risk factors, receipt of AA versus ENZ was not associated with time to SRE (relative risk ratio [RR] = 0.90, 95% CI 0.77-1.06, P = 0.22). Osteoporosis (RR 1.22, 95% CI 1.01-1.49, P = 0.04), osteoarthritis or rheumatoid arthritis (RR 1.23, 95% CI 1.06-1.43, P < 0.01), and prior history of SRE (RR 1.31, 95% CI 1.07-1.59, P < 0.01) were statistically significant risk factors for SRE. Conclusions: In this real-world population of men with prostate cancer, there was no difference in time to SRE between AA and ENZ. Clinical decision-making on whether to prescribe AA or ENZ should be informed by other potential toxicities as well as cross-resistance with sequencing of these therapies. Analysis of impact of bone protective agent use is underway.

442 Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course than metastatic disease occurring at other anatomic sites. We performed a retrospective analysis at a high-volume tertiary care center to evaluate host and tumor characteristics of this pt population, describe treatment approaches, and model patterns and rates of growth. Methods: Eligible pts were identified through Cancer Center registry data, provider recall, and electronic record review. Criteria included LM occurring either synchronously (SLM) or metachronously (MLM) w/primary cancer diagnosis; nodal, but not visceral or peritoneal, mets allowed. Data re: demographics, tumor characteristics, and rx modalities were collected. We reviewed all eligible CT +/- PET scan reports to gather data on #, location, and size of pulm mets, with all images subsequently reviewed by an independent radiologist. Up to 5 pulm mets were tracked through each pt’s clinical course. Growth rate was estimated using a linear mixed model analysis considering patients as the random. Results: Forty pts were identified between 9/2009 - 12/2019 (23 F/17 M; 28 white/7 Asian/5 other/multi; median age 62 y.o.; n = 15 w/tobacco hx). Tumor types: pancreatic (n = 18), colorectal (n = 12), hepatobiliary (n = 7), other (n = 3). SLM vs MLM:13/27; intact vs resected primary = 16/24. Median time from orig cancer dx to onset of MLM = 16 mos (range, 1 to 60 mos). No. of pulm mets at 1st appearance: 1 (n = 7); 2-5 (n = 17); 6-10 (n = 16). Median size of largest pulm met at 1st appearance = 6 mm (range, 0-39 mm); avg growth rate of largest pulm met = 0.18 mm/month (95% CI, 0.08-0.27). Avg growth rate of up to 5 largest lesions (sum) = 0.35 mm/month (95% CI, 0.07-0.64). Median f/u time prior to rx initiation for MLM = 172 days (range, 25-1547 days); 18 pts developed additional mets during their observation period. Rx modalities for LM: surg (n = 6), radiation (n = 18), systemic rx (n = 32). Addn details specific to cancer type, progression patterns, and pt outcomes will be presented at the meeting. Conclusions: The natural hx of LM varies across the spectrum of GI malignancies. Further larger-scale efforts to define patterns of growth of LM for different GI cancers, informed by size, #, and clinical/molecular features, are needed to guide appropriate timing and selection of rx as well as surveillance strategies.

Background: Dietary factors after CRC are associated with risk of recurrence and death. Our objective was to develop a digital health intervention to help individuals with CRC adopt healthy dietary habits. Methods: We conducted an unblinded 12-week (wk) pilot randomized trial to determine the feasibility and acceptability of a web-based dietary intervention with text messaging among individuals with CRC at the University of California, San Francisco. Eligible patients (pts) had colon or rectal adenocarcinoma, were not receiving chemotherapy, were disease-free or had stable disease, were able to speak and read English, and had a mobile phone. We excluded pts meeting ≥4 of the 6 target dietary behaviors. Pts were randomized 1:1 to intervention or control. All pts received print materials on diet after CRC. Pts in the intervention group received 12 wks of access to a website and daily text messaging that recommended ≥5 servings (serv)/day (d) of vegetables, ≥3 serv/d of whole grains, ≥2 serv/wk of fish, ≤2 alcoholic drinks/d for men and ≤1 alcoholic drinks/d for women, and no processed meat or sugar-sweetened beverages. Pts were encouraged to use the website to track intake of target dietary factors. Primary outcomes included feasibility (enrollment, time spent on website, text message response rate) and acceptability (self-administered online questionnaire). Secondarily, we estimated the effect of the intervention on diet using 4-d diet records, body size, blood pressure, and fasting C-reactive protein, hemoglobin A1c, glucose, cholesterol, and triglycerides using linear regression. Results: We screened 94 pts for eligibility; 75 were eligible and we randomized 50 to intervention (25) or control (25) between April 2017-May 2018. Over the course of the 12-wk study, the intervention arm accessed the website on a median of 2 d [interquartile range (IQR): 1-9 d] and spent a median of 28 min on the site (IQR: 4-51 min). Pts responded to a median of 15/21 text messages that asked for a reply (IQR: 8-20). 22/25 intervention pts completed the feedback survey; 82% were satisfied or very satisfied with the text messages. When asked to rate the quality of the website on a scale from 0-100, the median rating was 72 (IQR: 55-83). Diet records were available at baseline and 12 wks for 23 control and 22 intervention pts. Comparing baseline and 12 wks, intervention pts increased intake of whole grains (0.7 serv/d to 1.6 serv/d) and fatty fish (0 serv/d to 0.4 serv/d); controls did not change intake of whole grains (0.7 and 0.6 serv/d) or fatty fish (0.1 and 0 serv/d). We did not observe changes in either arm for other dietary factors, body size, blood pressure, or circulating markers. Conclusion: Individuals with CRC participating in a digital health dietary intervention engaged with text messaging more than a study website. The intervention led to changes in certain dietary behaviors. Additional work is needed to find strategies to increase engagement and modify other dietary factors. Trial Registration: NCT02965521 Funding: 5K07CA197077. Citation Format: Erin L. Van Blarigan, Stacey A. Kenfield, June M. Chan, Alan Paciorek, Li Zhang, Hilary Chan, Marissa Savoie, Andrea Grace Bocobo, Louis X. Wong, Angela Laffan, Katherine Van Loon, Chloe Atreya, Anthony Riberi, Olivier Riberi, Christine Miaskowski, Yoshimi Fukuoka, Jeffrey A. Meyerhardt, Alan P. Venook. Feasibility and acceptability of the Survivor Choices for Eating and Drinking (SUCCEED) digital health dietary intervention after colorectal cancer (CRC): A randomized pilot trial [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A18.

PURPOSE Esophageal cancer (EC) is one of the most common cancers in East Africa; however, risk factors that underly the high incidence in this region are not well understood. We aimed to investigate the association between exposure to specific alcohol subtypes and EC in Tanzania. METHODS We performed a secondary analysis of data from a hospital-based, case-control study conducted at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Cases of EC were identified between 2014 and 2016. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for gender and age (± 10 years). Interviews were conducted using a survey with culturally relevant and context-specific questions on alcohol and smoking exposure. Conditional logistic regression analyses were applied to evaluate specific associations of potential exposures and EC. RESULTS A total of 473 EC cases and 473 controls were enrolled. Alcohol consumption was reported in 61% and 64% of cases and controls, respectively. Neither ‘current use of alcohol (any type)’, nor ‘ever use’ were associated with EC; however, local brew consumption was associated with increased EC risk (odds ratio [OR], 2.01; 95% CI, 1.53 to 2.66; P < .01). Increased risk was observed with consumption of gongo (OR, 2.91), komoni (OR, 2.41), wanzuki (OR, 2.40), kindi (OR, 3.13), and kangara (OR, 2.86). Smoking increased EC risk; however, it did not significantly modify the association between EC and alcohol subtypes. CONCLUSION This is the first case-control study to report a detailed analysis of alcohol exposures as a potential risk factor for EC in Tanzania. Although combined measures of alcohol use were not found to be associated with EC, several types of locally brewed alcohols emerged as risk factors. Additional research is needed to investigate these findings and examine the carcinogenic role of ingredients and/or contaminants, as well as any interactions with other putative risk factors in this region.

Background. Neuroendocrine neoplasms (NEN) are a heterogeneous group of rare tumors. There is a paucity of epidemiologic data regarding risk factors. We aimed to characterize the burden of NEN in California with its diverse racial/ethnic populations. Methods Using California Cancer Registry, we identified all newly diagnosed NEN from gastroenteropancreatic (GEP) sites 1992-2015. Annual age-adjusted incidence rates (AIR) per 100,000 person-years were compared, and average annual percent change (APC) in rates were compared according to sex, race-ethnicity (non-Hispanic (NH) white, NH black, Asian/Pacific Islander, American Indian, Hispanic), primary tumor site (stomach, small intestine, colon or rectum, appendix, pancreas), stage, and type of county of residence (urban, suburban, rural) using incidence rate ratios (IRR). Overall survival from diagnosis to death by any cause was estimated by Kaplan-Meier method and compared using log-rank tests. Results There were 23,983 GEP NEN incident cases and 9,910 deaths 1992-2015. All AIRs increased over the 24 years, with the greatest increase in Hispanics with pancreatic NEN (APC 8.9). Rates for the period 2011-2015 varied according to primary tumor site: colorectal (AIR 1.41); small intestinal (AIR 0.97); pancreatic (AIR 0.92); stomach (AIR 0.44); and appendiceal (AIR 0.36). Comparing rates by populations the greatest disparities were for NH blacks vs. Asians with small intestinal NEN (IRR 7.01 95% confidence interval (CI) [5.37-9.21]) or appendiceal NEN (IRR 3.74 95% CI [2.34-6.08]), for NH whites vs. Asians with small intestinal NEN (IRR 4.34 95% CI [3.44-5.53]) or appendiceal NEN (IRR 5.10 95% CI [3.54-7.59]), for NH blacks vs. NH whites with colorectal NEN (IRR 2.59 95% CI [2.27-2.94]), and for NH whites vs. Hispanics with appendiceal NEN (IRR 2.54 95% CI [2.08-3.12]). Statistically significantly longer survival estimates were observed in women (median 13.1 years) vs. men (11.6 years), and in Asians/Pacific Islanders (20.7 years) and Hispanics (16.7 years) vs. NH blacks (12.3 years) and NH whites (9.6 years). No significant survival differences were detected across county types. Survival estimates were significantly different across primary tumor sites: colorectal (median 19.9 years); appendiceal (16.0 years); small intestinal (10.1 years); stomach (9.7 years); and pancreatic (4.4 years). Conclusions Incidence rates of GEP NEN in California steadily increase from 1992 through 2015 for all populations. Recent AIRs for particular race-ethnicities and primary tumor sites are more than double others, exposing large disparities. Survival estimates differ significantly by primary tumor site, sex, race-ethnicity, and stage, but not by county. These findings show some higher incidence rates and longer survival than in previously published estimates nationwide and add information about GEP NEN in Hispanic and Asian/Pacific Islander populations in California. Additional research is needed to clarify reasons for the disparities. Citation Format: Alan Paciorek, Brandon Shih, Meg McKinley, Iona Cheng, Li Zhang, Claire Mulvey, Ann Griffin, Eric Nakakura, Quan-Yang Duh, Insoo Suh, Katherine Van Loon, Emily Bergsland. Incidence and survival patterns of gastroenteropancreatic neuroendocrine neoplasms in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D111.

Background: Malignant pheochromocytomas (PHEO), paragangliomas (PGL), and adrenocortical carcinomas (ACC) are rare endocrine malignancies with limited data regarding risk factors. To further elucidate their epidemiology, we sought to characterize the burden of malignant PHEO, PGL, and ACC in California. Methods: Using the population-based California Cancer Registry, we identified all new diagnoses of malignant PHEO, PGL, and ACC in California from 1992-2016 (ICD-O-3 codes 8700/3, 8680/3, and 8393/3). We calculated age-adjusted incidence rates (AIR) standardized to the 2000 United States census. We compared AIRs by sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian/Pacific Islander), and county of residence (categorized as urban versus suburban/rural) using SEER*Stat and generated IR ratios (IRR). Results: Between 1992-2016, there were 261 incident cases of malignant PHEO, 271 of malignant PGL, and 866 of ACC in California. Overall AIR per 100,000 person-years were 0.03 for PHEO, 0.03 for PGL, and 0.10 for ACC. Incidence differed by both sex and race/ethnicity. Men had a higher incidence of PGL than women (IRR 1.49, 95% confidence interval [CI] 1.13-1.98; p Citation Format: Claire K. Mulvey, Alan Paciorek, Brandon Shih, Meg McKinley, Dawn Pearson, Iona Cheng, Li Zhang, Ann Griffin, Quan-Yang Duh, Sanziana Roman, Julie Ann Sosa, Insoo Suh, Chienying Liu, Katherine Van Loon, Emily Bergsland. Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A108.

BackgroundCTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.MethodsWe used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman’s rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.ResultsWhile melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=−0.81, pTrial registration numbersNCT00064129;NCT01363206.

616 Background: In this study, we analyze outcomes after the use of high-dose radiation therapy (RT) in management of neuroendocrine neoplasms (NENs) at a high-volume center. Methods: We performed a retrospective review of patients who received high-dose RT (defined as biologically effective dose (BED) >40, α/β = 10) for their NEN. Patients with small cell lung cancer and Merkel cell carcinoma were excluded, given their unique treatment paradigms. Results: 61 patients completed a radiation course with BED >40 for their NEN (median BED 70, range 44-180). Most tumors were gastroenteropancreatic in origin (n = 20); additional primary sites included lung (n = 11), head and neck (n = 10), cervix (n = 6), other (n = 9) and unknown (n = 5). 56% (n = 34) had well-differentiated (WD) neuroendocrine tumors, and 44% (n = 27) had poorly-differentiated (PD) neuroendocrine carcinomas. Disease stage at the time of RT was localized/locally advanced (LLA, n = 27), or metastatic/recurrent (MR, n = 34). The intent of RT was definitive (n = 18), post-operative (n = 10), for oligoprogression (n = 18), or purely palliative (n = 15). 48 patients had follow-up imaging at a median follow-up of 20 months after radiation. Outcomes were grouped by differentiation and stage, with median time to progression (mTTP) in months (Table). 8% of patients had local progression, while 44% developed new metastases, including 38% of WD-LLA, 47% of PD-LLA, 37% of WD-MR, and 67% of PD-MR disease with progressively shorter median time to progression (26, 10, 8, and 3 months, respectively). Conclusions: These data suggest that focal, high-dose radiation has a role in the management of NENs. Local failure is rare in patients with both WD-LLA and PD-LLA disease. The predominant pattern of failure is development of new metastases, which appear to occur sooner and more frequently in patients with PD and MR disease. [Table: see text]

242 Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that typically account for < 5% of tumors arising in any organ site. Both the low incidence and heterogeneity contribute to the paucity of epidemiologic data regarding risk factors. However, evidence suggests that incidence rates in the U.S. are rising. We aimed to further characterize the burden of NENs in California. Methods: Using data from the California Cancer Registry (CCR), we identified all newly diagnosed NENs arising from pulmonary (including SCLC) and gastrointestinal (GI) sites from 1992-2015. We estimated age-adjusted incidence rates (AIR) standardized to the 2000 U.S. census population. We calculated annual percent change (APC) in AIRs using Joinpoint regression and compared AIRs by sex, race-ethnicity, primary tumor site, and county of residence categorized as urban, suburban or rural using SEER∗Stat. Results: From 1992-2015, 97,398 NENs were reported, with 40,099 GI (not lung or bronchus). Overall AIR was 12.5 per 100,000 person-years. Most NENs were of pulmonary (AIR 7.6) or colorectal (AIR 1.3) origin. Females had lower AIR with IR ratio (IRR) vs. males (0.80 95% CI 0.79-0.81). However, females had higher rates of gastric (IRR 1.22 95% CI 1.12-1.32) and appendiceal (IRR 1.19 95% CI 1.07-1.33) primaries vs. males. Compared to non-Hispanic (NH) whites, NH blacks had an IRR of 1.06 (95% CI 1.03-1.09), Asian/Pacific Islanders had an IRR of 0.46 (95% CI 0.45-0.48), and Hispanics had an IRR of 0.57 (95% CI 0.56-0.58). For all NEN subtypes, we estimated lower rates for residents of urban counties (IRR 0.83 95% CI 0.80-0.86) and suburban counties (IRR 0.94 95% CI 0.90-0.97) vs. rural counties. However for GI NENs, we estimated higher rates for residents of suburban counties (IRR 1.11 95% CI 1.03-1.18) and urban counties (IRR 1.10 95% CI 1.03-1.18) vs. rural counties. We found that rates of pulmonary NENs decreased since 1992 (APC -2.6), but rates increased in colorectal (APC 3.9) and all other GI primaries (all APCs ≥ 2.8). Conclusions: Based on these results we conclude that incidence rates for GI NENs reported to CCR steadily increased from 1992-2015. Residence in a suburban or urban county was associated with increased incidence of GI NENs. Additional analyses are ongoing.

BACKGROUND In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. METHODS From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. RESULTS In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P

BACKGROUND Prostate cancer treatment after failure of primary therapy by either radical prostatectomy or radiation therapy can vary greatly. This study sought to determine trends and predictors of salvage treatment after failure of primary treatment in a community cohort over the past 10 years. METHODS From the community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, 6275 patients were identified who initiated a form of primary treatment for prostate cancer; 839 of these were identified as failing treatment by biochemical recurrence or initiation of secondary treatment between 2000 and 2010. Salvage therapy was categorized as either systemic, local, or none. Patient characteristics were tested for association with salvage therapy using analysis of variance, Pearson chi-square tests, and multinomial logistic regression analysis. RESULTS Of the 839 patients identified as failing therapy, 390 (47%), 146 (17%), and 303 (36%) received systemic, local, or no salvage therapy, respectively. Type of primary treatment received was associated with type of salvage therapy (P

BACKGROUND: The aim of this study was to determine the optimal treatment for a patient with newly diagnosed prostate cancer weighing the individual's risk of disease progression against his risk of non-cancer death.METHODS: We developed a predictive model incorporating clinicopathological tumor variables, patient age, comorbidity status, and primary treatment modality. We identified 6091 patients with clinically-localized prostate cancer managed with radical prostatectomy (n4117) or radiation therapy (n1974) from the Cancer of the Prostate Strategic Urologic Research Endeavor database. Fine and Gray competing-risks proportional hazards regression models were used to calculate the risks of prostate cancer-specific mortality (PCSM) and non-prostate cancer death and to generate a nomogram.RESULTS: The median follow-up after treatment was 53 months (interquartile range 30, 80 months). In total, 983 men died during follow-up, including 167 who died of prostate cancer and 816 who died of non-prostate cancer causes. On multivariate analysis, higher Cancer of the Prostate Risk Assessment score and primary treatment with radiation were associated with an increased risk of PCSM, whereas older age, African-American race, and treatment with radiation predicted non-prostate cancer death. The number of comorbidities and receipt of androgen deprivation therapy correlated with an increased risk of non-prostate cancer death, but not PCSM. The resulting nomogram allows quantification and comparison of the 10-year risk of PCSM and non-prostate cancer death.CONCLUSIONS: Integrating clinicopathological variables with comorbid conditions in a competing-risks model affords quantification and comparison of relative probabilities of PCSM and non-prostate cancer death following treatment. Our model thereby facilitates an individualized approach for counseling patients regarding prostate cancer management. © 2012 Macmillan Publishers Limited All rights reserved.

Vigorous activity after diagnosis was recently reported to be inversely associated with prostate cancer–specific mortality. However, men with metastatic disease may decrease their activity due to their disease; thus, a causal interpretation is uncertain. We therefore prospectively examined vigorous activity and brisk walking after diagnosis in relation to risk of prostate cancer progression, an outcome less susceptible to reverse causation, among 1,455 men diagnosed with clinically localized prostate cancer. Cox proportional hazards regression was used to examine vigorous activity, nonvigorous activity, walking duration, and walking pace after diagnosis and risk of prostate cancer progression. We observed 117 events (45 biochemical recurrences, 66 secondary treatments, 3 bone metastases, 3 prostate cancer deaths) during 2,750 person-years. Walking accounted for nearly half of all activity. Men who walked briskly for 3 h/wk or more had a 57% lower rate of progression than men who walked at an easy pace for less than 3 h/wk (HR = 0.43; 95% CI: 0.21–0.91; P = 0.03). Walking pace was associated with decreased risk of progression independent of duration (HR brisk vs. easy pace = 0.52; 95% CI: 0.29–0.91; Ptrend = 0.01). Few men engaged in vigorous activity, but there was a suggestive inverse association (HR ≥3 h/wk vs. none = 0.63; 95% CI: 0.32–1.23; Ptrend = 0.17). Walking duration and total nonvigorous activity were not associated with risk of progression independent of pace or vigorous activity, respectively. Brisk walking after diagnosis may inhibit or delay prostate cancer progression among men diagnosed with clinically localized prostate cancer. Cancer Res; 71(11); 3889–95. ©2011 AACR.

5072Background: Sip-T, an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), induces antibody responses to prostati...

11008Background: As interest in global oncology increases, the need to support early career investigators is a priority, as advocated by the ASCO Global Oncology Leadership Task Force. The Global C...

180 Background: The number of individuals living after a diagnosis of gastrointestinal (GI) cancer is increasing. Emerging data suggest modifiable lifestyle factors impact survival after colorectal cancer (CRC), however very little is known about survivorship in other GI cancers. Given the common thread of multimodality therapy among many GI cancer survivors, there is a paucity of data on sexual function, fertility, anxiety/depression, changes in comorbidities, and quality of life after cancer treatment. Additionally, existing cohort studies of GI survivors are primarily European, and further data are needed from survivor populations in the US . Methods: Patients of the University of California, San Francisco GI Oncology Survivorship Clinic who are designated disease-free are recruited by mail or in clinic. We send secure online questionnaires to participants every six months for five years and annually thereafter. At varying intervals, questionnaires solicit sociodemographics, diet, physical activity, fertility, medical and smoking history, fear of cancer recurrence, sexual health, quality of life, psychological well-being, and sleep quality. Pathoclinical disease characteristics, treatment, and recurrence status are abstracted from the medical record at baseline and updated annually. Results: Between February and August 2017, 111 patients were enrolled; 68% of participants completed ≥1 and 57% completed all baseline questionnaires. Most patients had a history of colon cancer (52%, n = 58) or rectal cancer (31%, n = 34). Other diseases include: anal cancer (12%, n = 13), gastrointestinal stromal tumor (3%, n = 3), and other GI cancers (3%, n = 3). Fifty-eight percent of patients were female, 76% identified as white and median age at diagnosis was 55 (range 20-81). Median time from initial GI cancer diagnosis to study entry was 27 months. Following the initial recruitment wave of established patients, the average rate of enrollment is ~3 patients/week. Conclusions: Results from this ongoing cohort study will improve our understanding of modifiable risk factors for GI cancer recurrence and key survivorship issues related to psychological well-being, sexual function, fertility management, and quality of life.

168 Background: There are over 1.3 million colorectal cancer (CRC) survivors in the United States, and many of whom suffer from lower health-related quality-of-life (HRQoL) years after diagnosis and treatment. Physical activity may improve survival outcomes and HRQoL for CRC survivors. Feasible interventions to support physical activity after CRC diagnosis are needed. Methods: We conducted a two-arm randomized controlled trial of 41 men and women who had completed treatment for CRC. Participants in the intervention arm were given a Fitbit Flex™ and received daily text messages for 12 weeks. HRQoL was assessed in both arms at baseline and 12 weeks using the RAND Short Form Survey (SF-36) and the Functional Assessment of Cancer Treatment – Colorectal (FACT-C). Survey score changes from baseline to 12 weeks were compared between the two arms using independent t-tests, and scores at baseline and 12 weeks were compared using paired t-tests. SAS was used for analysis, and statistical significance was declared at p < 0.05. Results: We observed a statistically significant increase in the FACT-C functional well-being sub-scale in individuals in the intervention arm pre- and post- intervention (mean ∆ 1.81 ± 2.76; p: 0.02). There was no change in functional well-being in the control arm (mean ∆ -0.35 ± 4.12; p: 0.71). The between-arm comparison of change from baseline to 12 weeks was not statistically significantly ( p: 0.08). There was a statistically significant increase in the FACT-C emotional well-being sub-scale in the control arm (mean ∆ 1.20 ± 2.48; p: 0.04) and in the SF-36 role physical sub-scale in the control arm (mean ∆ 22.5 ± 38.8; p: 0.02). No other measures of HRQoL were statistically significantly different within groups, across time points, or between groups. Conclusions: A 12-week physical activity intervention using a Fitbit Flex and daily text messages may improve functional well-being among CRC survivors. Larger randomized studies are needed to definitively determine if a digital physical activity intervention improves functional well-being among CRC survivors, and if the improvement can be sustained over time. Clinical trial information: NCT02966054.

Abstract 89 Purpose Previous studies have characterized geographic clusters of esophageal cancer (EC) in East Africa. Many of the epidemiologic features of EC in this context are shared globally with other clusters, including high rates, male predominance, and squamous cell histology. A unique feature in East Africa is the high proportion of young patients, with a recent case series reporting up to 24% of patients age < 45 years. The aim of the current study was to assess factors that are associated with early-onset EC in Tanzania (TZ). Methods We performed a secondary analysis of a previous case-control study. Patients with newly diagnosed EC were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in 2014 to 2016. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for gender and age ± 10 years. Risk factors were assessed through interviews. Logistic regression was used to estimate age-specific odds ratios (ORs) of EC for exposures across age groups (30 to 44 years, 45 to 59 years, and ≥ 60 years) and for interactions with age. Results A total of 473 cases and 473 controls were enrolled. Median ages were 59 years (range, 30 to 91 years) for cases and 55 years (range, 31 to 88 years) for controls. Among cases, 102 patients (22%) were age 30 to 44 years, 144 patients (30%) were age 45 to 59 years, and 227 patients (48%) were age ≥ 60 years. High household income was protective for those age 30 to 44 years (OR, 0.08; 95% CI, 0.01 to 0.69) and 45 to 59 years (OR, 0.13; 95% CI, 0.04 to 0.45), but not for those age ≥ 60 years (effect modification P = .047). Family history of EC was associated with a higher risk of EC among those age 45 to 59 years (OR, 3.8; 95% CI, 1.02 to 14.47) and age ≥ 60 years (OR, 6.63; 95% CI, 1.50 to 29.37), with no effect among those age 30 to 44 years (effect modification P = .019). Second-hand smoke and infrequent teeth cleaning were also associated with early-onset EC, but did not differ significantly across age groups. Additional factors associated with EC risk across all ages were firewood use (cooking), kerosene use (lighting), work on a maize farm, and in-home grain and nut storage. Protective factors were the regular use of medication, surrogates of high socioeconomic status (TV, radio, refrigerator, indoor toilet, and electricity), and charcoal or gas cooking. Conclusion Multiple exposures were identified as risk factors for early-onset EC in TZ. In age-stratified analyses, household income, second-hand smoke, and poor dental hygiene emerged as possible risk factors, whereas family history of EC had strong associations among the older but not the young age group. Our results suggest that environmental factors may underlie the high incidence of young patients with EC in TZ. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004‐2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. Am J Clin Nutr 2010;91:712‐21.

309 Background: Sip-T is an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T’s induction of B-cell responses to PAP and other antigens correlates with improved survival (Sheikh 2013, GuhaThakurta 2015). Cancer vaccine-induced changes to BCR repertoire are unknown. To assess changes in BCR repertoire upon booster treatment, we compared patients retreated with sip-T (P10-1) to treatment-naïve patients (STRIDE). Methods: STRIDE pts (N = 52) received sip-T with concurrent or sequential enzalutamide for mCRPC (Petrylak 2015). P10-1 pts (N = 8) previously treated with sip-T for androgen-dependent PC were retreated with a booster course for mCRPC, after a median of 8.9 years (Beer 2017). Blood samples were collected at baseline (wk 0) and during (wk 2, 4)/post-sip-T (wk 6, 26, 52). Deep sequencing was performed using the ImmunoSEQ assay (Adaptive Biotechnologies). BCR diversity was assessed by clonality, and BCR dynamics by fold-change analysis (Zhang 2017). Results: BCR repertoire had significantly higher clonality in P10-1 vs STRIDE (wk 0: p = 0.003, wk 2: p < 0.001, wk 4: p < 0.001), suggestive of a more focused BCR repertoire. P10-1 also showed increased clonality from wk 0 to 4 (p = 0.063), whereas STRIDE showed a significant increase in clonality from wk 0 to 6 (p = 0.039), suggesting that BCR repertoire focused earlier in P10-1. Starting at wk 2, more clones remained in the repertoire in P10-1, indicating that sip-T stimulated immunologic memory early, after 1st retreatment (p < 0.05). There was less change over time (clonal shuffling) within the 100 most abundant baseline clones in P10-1 (p = 0.080), suggesting more relevant clones preexisted at baseline and enriched over time. After the first two sip-T infusions, more clones contracted in P10-1 (p = 0.027, p = 0.014), whereas more new clones were generated in STRIDE (p = 0.083, p = 0.003). Conclusions: Sip-T induces long-lasting changes in the BCR repertoire. Sip-T retreatment leads to quicker focusing of BCR repertoire than initial treatment. These results are consistent with sip-T inducing durable immunologic memory.

107 Background: Sip-T is an FDA-approved autologous cellular immunotherapy for asymptomatic or minimally symptomatic mCRPC. Neoadjuvant sip-T induced activated T-cell infiltration to the prostate tissue (Fong 2014) and broadened the T cell receptor (TCR) repertoire vs control (Sheikh 2016). To test if sip-T induces memory T-cell responses, we compared treatment-induced changes in TCR repertoire of treatment-naïve pts (STRIDE) with those retreated with sip-T (P10-1). Methods: In STRIDE (N=52), pts received sip-T with concurrent or sequential enzalutamide (Petrylak 2015). In P10-1 (N=8), pts previously treated with sip-T in an androgen-dependent setting were retreated with a booster course after a median of 8.6 years (Beer 2013). PBMCs were collected at baseline and during/post–sip-T. Deep sequencing was performed using the ImmunoSEQ assay (Adaptive Biotechnologies). TCR diversity was assessed by Shannon diversity index and clonality. TCR dynamics was evaluated by Morisita’s distance (Zhang 2017). Results: Baseline TCR diversity was similar between the two trials (p=0.590, Shannon diversity index; p=0.700, clonality). Significant decreases in clonality were observed from baseline to wk 4 (p

779 Background: As overall survival (OS) with metastatic colorectal cancer (mCRC) and imaging modalities improve, detection of ovmets may be increasing. The ovary is often a sanctuary site for mCRC; however, there is a paucity of data to guide decision-making regarding the role for oophorectomy. Methods: This is a single-institution retrospective review of patients (pts) who received care for mCRC (incl. appendiceal primaries) with ovmets from 2009-2017. Pts were identified through a hospital-based cancer registry, provider recall, and pathology and radiology databases. Clinicopathologic and treatment data were abstracted. Cox proportional hazards models were used to evaluate for associations with OS. Results: Of 108 pts, median age was 50 (range 19-106), 62 (57%) were Caucasian, and 69 (64%) had ovmets at initial CRC diagnosis. Primary tumor location was left-sided in 54 (50%), right-sided in 27 (25%), appendiceal in 18 (17%), and unknown in 9 (8%). Median OS from diagnosis of mCRC was 29.6 months (mo) with median follow-up of 21.9 mo (range 0.77-172.47). Younger age, absence of signet-ring or mucinous features, well/moderately differentiated grade, and resection of primary tumor were associated with improved OS (p < 0.05). Of 83 (76%) pts who underwent oophorectomy median OS was 36.7 mo vs. 25 mo in those who underwent non-operative management (HR 0.54, 95% CI 0.31-0.94, p = 0.03). Among 94 pts with extra-ovarian disease, 70 (74%) underwent oophorectomy; however, no significant difference in median OS was detected vs. those who did not (30.9 vs 25.0 mo, p = 0.07). In a multivariate model, oophorectomy was not associated with OS (HR 0.63, 95% CI 0.29-1.36, p = 0.24). Conclusions: While ovmets have been previously reported as associated with a poor prognosis, the median OS for this cohort was comparable to existing OS data for mCRC pts. Although oophorectomy for ovmets from mCRC was associated with improved OS in univariate analysis, this effect was not significant in the presence of extra-ovarian metastases. Ovmets from mCRC remain a difficult challenge in clinical care. Oophorectomy may improve OS in select cases; however, further evaluation of predictors of benefit is needed.

226 Background: Neuroendocrine tumors (NETs) are known to be associated with hereditary syndromes stemming from MEN1, VHL, SDH or TSC mutations. Recent data suggest that additional germline mutations may be relevant, implying a role of germline testing with multigene panels. We examined genetic counseling (GC) referral and testing patterns, test results, and their changes over time in NET patients (pts). Methods: Retrospective chart review was conducted in 236 NET pts referred to UCSF Cancer Genetics and Prevention Program 2004-2017. Univariate logistic models were used to assess relationship between binary outcome and covariate. STATA was used for analysis and statistical significance was based on p < 0.05. Results: 139 referred pts (59%) followed up with GC. Pts with >1 family members diagnosed with cancer were more likely to attend GC [OR=2.75, p=0.010]. Among 107 pts tested, small bowel NETs were less associated with testing than pancreatic NETs [OR=0.15, p=0.001]. Single-gene tests were routine until 2015, when panels up to 130 genes became standard. Overall, 31 pts (29% of 107 tested) had a pathogenic/likely pathogenic (P/LP) result. There was no significant difference between single and multi-gene tests in identifying P/LP mutations (likely due to changes in threshold for testing over time), but greater diversity in P/LP mutations was noted with larger panels. Functional tumors showed lower rate of P/LP mutations than non-functional [OR=0.17, p=0.037]. Conclusions: Only 59% of referred pts followed up with GC, suggesting significant barriers to testing exist. Of those tested, 29% harbored a P/LP mutation. Germline mutations not traditionally associated with NETs were identified, highlighting the potential importance of larger panels to detect rare mutations. [Table: see text]

615 Background: Over 1.3 million people in the US are living with CRC. Physical activity is associated with lower risk of CRC mortality. Interventions are needed to increase physical activity after CRC diagnosis. Methods: We conducted a pilot RCT to determine the feasibility (adherence, attrition) and acceptability of a 12-wk intervention using a Fitbit Flex™ and daily text messages to increase physical activity after CRC. Eligible patients had to have colon or rectal cancer of any stage, be disease free or have stable disease, able to speak and read English, and access to Internet and a mobile phone. Individuals with contraindications to moderate-to-vigorous physical activity (MVPA) or exercising ≥30 min ≥5 d/wk were excluded. We explored the impact of the intervention (n = 20) vs. usual care (n = 21) on MVPA via ActiGraph GT3X+ accelerometers pre-/post-intervention. Results: The intervention was feasible and acceptable. On average, participants were 54 y, BMI 28 kg/m2 and enrolled 1.5 y after diagnosis; 59% were women, 73% were White, and 61% were stage III. The intervention arm wore their Fitbits a median of 74 d (89% of study days, IQR: 23-83 d) and responded to 74% (34) of the 46 text messages that asked for a reply (IQR: 28-82%). Older participants were more likely to wear the Fitbit ( r: 0.72; p < 0.001). Married participants were more likely to wear the Fitbit and respond to texts compared to unmarried (96% vs. 32% wear time, p: 0.02 and 85% vs. 46% response rate, p: 0.006). Most patients (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. On average, the intervention arm increased MVPA by 14 min/d, while the control arm increased by only 1 min/d, but there was no statistically significant difference in change in MVPA between groups (mean difference comparing change in MVPA in the intervention vs. control: 13 min/d; 95% CI: -14, 40; p: 0.33). Conclusions: A 12-wk physical activity intervention with a Fitbit and text messages is feasible and acceptable among CRC patients after treatment. Larger studies are needed to determine whether the intervention increases physical activity. Clinical trial information: NCT02966054.

Purpose Men diagnosed with prostate cancer have multiple options available for treatment. Previous reports have indicated a trend of differing modalities of treatment chosen by African American and white men. We investigated the role of ethnicity in primary treatment choice and how this affected overall and cancer-specific mortality. Methods By utilizing data abstracted from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), patients were compared by ethnicity, primary treatment, number of comorbidities, risk level according to modified D'Amico criteria, age, highest educational level attained, type of insurance, treatment facility, and perception of general health. Multinomial logistic regression analysis was performed to determine the effect of the tested variables on primary treatment and mortality. Results African American men were more likely to receive nonsurgical therapy than white men with equivalent disease characteristics. Whites were 48% less likely than African Americans to receive androgen deprivation therapy (ADT) compared with surgery (P = .02) and were 25% less likely than African Americans to receive radiation therapy compared with surgery (P = .08). Whites with low-risk disease were 71% less likely to receive ADT than African American men with similar disease (P = .01). Adjusted overall and prostate cancer–specific mortality were not significantly different between whites and African Americans (hazard ratios, 0.73 and 0.37, respectively). Risk level, type of treatment, and type of insurance had the strongest effects on risk of mortality. Conclusion There is a statistically significant difference in primary treatment for prostate cancer between African American and white men with similar risk profiles. Additional research on the influence of patient/physician education and perception and the role that socioeconomic factors play in mortality from prostate cancer may be areas of focus for public health initiatives.

BACKGROUND: Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate-resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT. METHODS: Of the 13,740 men with biopsy–proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi-square tests in a Cox proportional hazards regression model. RESULTS: The mean age of the men in the cohort was 70 years (range, 39-94 years). One hundred ninety-one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1-139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P 33% (HR, 3.36; P = .003), age ≤65 years at diagnosis (HR, 2.11; P = .001, and prostate–specific antigen velocity on ADT (HR, 1.04; P < .001) were found to be significantly associated with the development of metastatic disease after ADT. CONCLUSIONS: Younger men with high–risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate-resistant disease. Cancer 2009. © 2009 American Cancer Society.

Background: Observational studies suggest potential chemopreventive benefits of statins on prostate cancer outcomes, but data on the impact of postdiagnostic use are sparse. Methods: We examined the association of postdiagnostic statin use and risk of lethal prostate cancer (metastases or prostate cancer death, N = 242) among 3,949 men diagnosed with localized prostate cancer from the Health Professionals Follow-Up Study between 1992 and 2008 and followed through 2010 (33,302 person years). We used Cox proportional hazards regression models to estimate relative risks and 95% confidence intervals (CI), adjusting for age, time period, time from diagnosis to questionnaire, body mass index, vigorous physical activity, smoking, aspirin use, clinical stage, PSA at diagnosis, Gleason score, primary treatment, and comorbidities. Results: We found no statistically significant association between postdiagnostic current use of statins or duration of statin usage and the outcome of lethal prostate cancer [N = 242 cases; multivariate HR = 0.97 (95% CI, 0.72–1.31) for current use yes/no; HR = 0.85 (95% CI, 0.59–1.22) for 1 to 5 years of use, 0.96 (95% CI, 0.66–1.38) for 6+ years of use vs. never use]. Conclusions: We observed little evidence that statin usage after diagnosis of localized prostate cancer reduces risk of progression to metastatic disease or prostate cancer–specific death. Impact: These results do not support statins as a chemopreventive agent for prostate cancer progression. Cancer Epidemiol Biomarkers Prev; 24(10); 1638–40. ©2015 AACR.

© 2015 Elsevier Ltd. All rights reserved. Background The optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown. Methods We identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (≤ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting. Results Of 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ≥7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%). Conclusion Our analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently utilized as an adjuvant in cancer immunotherapies, and has known effects as a growth factor. However the extent to which GM-CSF modulates the adaptive immune response, including possible effects on the antigenic repertoire, remains unclear. We used next-generation sequencing of T cell receptor (TCR) beta chain sequences amplified from total RNA from peripheral blood mononuclear cells using consensus primers to assess changes in the circulating antigenic repertoire of prostate cancer patients treated with GM-CSF in multiple clinical trials. Administration of systemic GM-CSF monotherapy to patients with localized prostate cancer prior to planned radical prostatectomy (NCT00305669) results in a significant decline in clonality from the pre-treatment timepoint to the 2-week timepoint on treatment, indicative of increased early repertoire diversity (p=0.039 by Wilcoxon signed rank test). In a separate clinical trial (NCT00064129), the combination of systemic GM-CSF (250 μg/m2/day on days 1-14 of each cycle) with ipilimumab in metastatic castrate-resistant prostate cancer (mCRPC) patients also resulted in a significant decline in clonality from pre-treatment samples to the 2-week timepoint on treatment (p=0.002). In contrast, mCRPC patients who received ipilimumab alone in a separate study (NCT00323882) did not experience a similar decline in clonality after 3 weeks on treatment (p=0.625). In addition, comparison of the dynamics of specific clonotypes between the paired timepoints in the two mCRPC studies demonstrates that while there is no significant difference in the ratios of post-treatment to pre-treatment clonality between studies, patients treated with the combination of iplilimumab and GM-CSF show more repertoire change, with lower Morisita’s distance for all clones found at either timepoint (p=0.023), smaller intraclass correlation coefficient (p=0.028), and a smaller proportion of clonotypes that remain unchanged (defined by +/- 2-fold change for clones found at both timepoints) (p=0.002). These results indicate increased repertoire turnover when GM-CSF is combined with checkpoint inhibition. Hence data from both localized and metastatic prostate cancer, and from monotherapy and combination therapy regimens, supports a role for GM-CSF in inducing early diversification of the TCR repertoire. Citation Format: David Y. Oh, Li Zhang, Jason Cham, Alan Paciorek, Mark Klinger, Malek Faham, Susan F. Slovin, Lawrence Fong. Systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increases T cell receptor diversity in localized and metastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1694. doi:10.1158/1538-7445.AM2017-1694

e15689 Background: Carcinoid crisis is a life-threatening event caused by release of vasoactive substances from neuroendocrine tumors (NETs). Octreotide is often used in the periprocedural setting as prophylaxis against carcinoid crisis; however, there is no standardized protocol for its use. We aimed to describe the periprocedural management of patients with metastatic NETs who underwent liver-directed procedures at UCSF. Methods: We identified 54 patients with NETs with hepatic metastases who underwent either liver resection/ablation (n = 30) or liver-directed embolization (n = 24) between 2012 and 2016. Anesthesia records and clinical data were abstracted. Carcinoid crisis was defined by physician documentation. Hemodynamic instability was defined as ≥10 minutes of systolic blood pressure < 80 mmHg or > 180 mmHg or heart rate > 120. Pearson chi-squared tests were used to test associations with three outcomes: crisis, instability, or none. Results: Three (6%) patients were documented to have developed carcinoid crisis. Another 14 (26%) patients developed hemodynamic instability. Of 16 patients who received preprocedural octreotide, 1 (6%) had a carcinoid crisis and 5 (31%) developed hemodynamic instability. History of carcinoid syndrome, degree of hepatic involvement, and use of pre or intraprocedural octreotide were not associated with carcinoid crisis or at least hemodynamic instability. Patients undergoing embolization were less likely to develop hemodynamic instability versus those undergoing liver resection (17% vs 43%, Pearson chi-squared p = 0.04). Conclusions: Occurrence of documented carcinoid crisis was low in this high-risk population. However, a significant proportion of patients developed hemodynamic instability, suggesting that carcinoid crisis is a spectrum diagnosis and may be clinically under-recognized. Use of octreotide was not associated with risk of carcinoid crisis or hemodynamic instability; however, this analysis was limited by our modest sample size at a single institution. There remains a need to establish an objective definition of carcinoid crisis and to inform standardization of periprocedural use of octreotide for at-risk patients.

793 Background: A growing body of literature suggests that 25-hydroxyvitamin D [25(OH)D] levels are inversely related to the risk of developing CRC and that deficiency is associated with CRC-specific mortality. Due to the unique racial-ethnic diversity and UV exposure patterns of the San Francisco Bay Area, we aimed to evaluate vitamin D levels among our CRC patients at time of diagnosis and during treatment. Methods: Permanent residents of the SF Bay Area with a new diagnosis of CRC of any stage were recruited between 2011 and 2015 prior to initiation of therapy. Self-reported data on sun exposure, diet, and exercise patterns were collected. Clinical data including disease stage and primary tumor location were abstracted from charts. Serum 25(OH)D levels at time of diagnosis and at 6-month follow-up were batched and measured using the Liaison XL assay (Heartland Assays). Supplement use was not restricted. Kruskal-Wallis and Pearson correlation tests were used for categorical or continuous variables, respectively, to evaluate the associations of patient characteristics with 25(OH)D levels. Results: Among 94 patients with a new diagnosis of CRC, median 25(OH)D level at baseline was 27.0 ng/mL (range 7.2-59.0); 26% had deficient levels (

5003 Background: The optimal timing to start androgen deprivation therapy (ADT) in patients with rising PSA as the only sign of relapse is unknown. ASCO guidelines state “the critical issue is to d...