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Whereas systemic IL12 is associated with potentially life-threatening toxicity, intratumoral delivery of IL12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples from 29 patients with cutaneous melanoma with in-transit disease were assessed for immune responses induced with this treatment. Within the blood circulating immune cell population, we found that the frequencies of circulating PD-1+ CD4+ and CD8+ T cells declined with treatment. Circulating immune responses to gp100 were also detected following treatment as measured by IFNγ ELISpot. Patients with a greater antigen-specific circulating immune response also had higher numbers of CD8+ T cells within the tumor. Clinical response was also associated with increased intratumoral CD3+ T cells. Finally, intratumoral T-cell clonality and convergence were increased after treatment, indicating a focusing of the T-cell receptor repertoire. These results indicated that local treatment with tavo can induce a systemic T-cell response and recruit T cells to the tumor microenvironment.

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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 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.

Background Increasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis. Objective To determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer. Design, setting, and participants A 12-wk pilot randomized controlled trial among 76 men with clinical stage T1–T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline. Intervention Website, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements. Outcome measurements and statistical analysis Our primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall "P8 score" (range 0–8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12wk, and behaviors after 1yr. Results and limitations At baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n=32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82d (interquartile range [IQR]: 72–83), replied to a median of 71% of text messages (IQR: 57–89%), and visited the website a median of 3d (IQR: 2–5) over 12wk. Median (IQR) absolute changes in the P8 score from baseline to 12wk were 2 (1, 3) for the intervention and 0 (−1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12wk (ANCOVA p Conclusions Overall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals' needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels. Patient summary Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial.

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

Whereas systemic IL12 is associated with potentially life-threatening toxicity, intratumoral delivery of IL12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples from 29 patients with cutaneous melanoma with in-transit disease were assessed for immune responses induced with this treatment. Within the blood circulating immune cell population, we found that the frequencies of circulating PD-1+ CD4+ and CD8+ T cells declined with treatment. Circulating immune responses to gp100 were also detected following treatment as measured by IFNγ ELISpot. Patients with a greater antigen-specific circulating immune response also had higher numbers of CD8+ T cells within the tumor. Clinical response was also associated with increased intratumoral CD3+ T cells. Finally, intratumoral T-cell clonality and convergence were increased after treatment, indicating a focusing of the T-cell receptor repertoire. These results indicated that local treatment with tavo can induce a systemic T-cell response and recruit T cells to the tumor microenvironment.

BACKGROUND There are over 1.3 million colorectal cancer (CRC) survivors in the United States, many of whom report lower health-related quality-of-life (HRQoL) for 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. OBJECTIVE This pilot study aimed to explore the impact of digital health intervention on physical activity and HRQoL. 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 enrollment and 12 weeks using the Medical Outcomes Study Short Form Survey (SF-36) and the Functional Assessment of Cancer Treatment – 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 We observed an increase in the FACT-C functional well-being sub-scale in individuals in the intervention arm pre- to post- intervention (median difference: 2; interquartile range (IQR): 1,4; P = .02). In contrast, no change in functional well-being sub-scale was found 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. 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 this improvement can be sustained over time. CLINICALTRIAL ClinicalTrials.gov NCT02966054

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: Vitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients. Methods: Thirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/− 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise. Results: Median serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P>0.05). Household members were more likely than CRC patients to be overweight and to exercise more. Conclusions: Vitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted.

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).

OBJECTIVES The objective of this study was to describe the periprocedural management of patients with well-differentiated neuroendocrine tumors with hepatic metastases who underwent liver-directed procedures. METHODS We performed a retrospective review of patients with metastatic neuroendocrine tumors who underwent liver resection, ablation, or embolotherapy at a single center from 2012 to 2016. The primary outcome was occurrence of documented carcinoid crisis (CC) or hemodynamic instability (HDI), defined as 10 minutes or more of systolic blood pressure less than 80 or greater than 180 mm Hg, or pulse greater than 120 beats per minute. RESULTS We identified 75 patients who underwent liver resection/ablation (n = 38) or embolotherapy (n = 37). Twenty-four patients (32%) experienced CC or HDI (CC/HDI); CC occurred in 3 patients. No clinicopathologic or procedural factors, including procedure type, octreotide or long-acting somatostatin analog use, and history of carcinoid syndrome, were associated with CC/HDI. Grades 2 to 4 complications were reported in 42% of patients who experienced CC/HDI versus in 16% of patients who did not experience CC/HDI (P < 0.05). CONCLUSIONS A significant portion of patients developed CC/HDI, and these patients were more likely to develop severe postprocedural complications. Periprocedural octreotide use was not associated with lower CC/HDI occurrence, but continued use is advised given its safety profile until additional studies definitively demonstrate lack of benefit.

Prostate cancer (PCa) is the leading cancer in men in the United States. This study evaluated direct costs of treating urinary problems after PCa treatments and determined predictors of long-term costs for urinary problems. Data from the Cancer of Prostate Strategic Urologic Research Endeavor registry was analyzed for this study. Annual treatment costs for urinary problems for up to 14 years were compared among different primary PCa treatments, which included radical prostatectomy, external beam radiation therapy, brachytherapy, and watchful waiting. A multivariate generalized estimating equation (GEE) model with bootstrapping was estimated to identify the predictors associated with treatment costs for urinary problems. A total of 3,062 eligible patients were identified with a mean age of 65 years at diagnosis. Mean annual treatment cost for urinary problems across all patients with PCa was $118/patient. Those greater than 74 years old had the highest cost ($238/patient). Mean annual cost for urinary problems among only those with urinary problems was $432. Multivariate regression showed patients undergoing radical prostatectomy had significantly lower (−63%, p = .01) costs for urinary problems than those treated with watchful waiting. This study helps to understand the importance of treating urinary problems associated with different PCa treatments and highlights their medical care costs. The pattern of treatment costs for urinary problems across all PCa treatments suggests that clinicians need to offer treatment for urinary problems to all PCa patients over longer time periods, even to those choosing watchful waiting.

BackgroundVitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients.MethodsThirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/- 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise.ResultsMedian serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P>0.05). Household members were more likely than CRC patients to be overweight and to exercise more.ConclusionsVitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted.

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]