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PURPOSE The proportion of head and neck cancers (HNCs) with human papillomavirus (HPV) positivity in sub-Saharan Africa (SSA) is poorly characterized. Characterizing this has implications in staging, prognosis, resource allocation, and vaccination policies. This study aims to determine the proportion of HPV-associated HNC in SSA. MATERIALS AND METHODS This systematic review included searches from PubMed, EMBASE, Web of Science, African Index Medicus, Google Scholar, and African Journals Online. All English publications reporting the proportion of HNC specimens from SSA patients who tested positive for HPV and/or p16 were included. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Case Series Studies. RESULTS In this systematic review of 31 studies and 3,850 patients, the overall p16 positivity was 13.6% (41 of 1,037 patients tested) with the highest proportion among oropharyngeal cancers (20.3%, 78 of 384 patients) and the overall HPV polymerase chain reaction positivity was 15.3% (542 of 3,548 samples tested) with the highest proportion among nasopharyngeal cancers (16.5%, 23 of 139 patients). Among the 369 HPV strains detected, the most common genotypes were HPV 16 (226 patients, 59.2%) and HPV 18 (78, 20.4%). CONCLUSION HPV was found to be associated with a significant proportion of HNC in SSA. The genotypes reported suggest that the nine-valent vaccine and gender-neutral vaccination policies should be considered. Given that these studies may not accurately capture prevalence nor causation of HPV in HNC subsites, additional research is needed to provide a more thorough epidemiologic understanding of HPV-associated HNC in SSA, including risk factors and clinical outcomes.

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.

BackgroundThe incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC).MethodsWe studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided.ResultsOf 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93).ConclusionIn this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

Background Moral distress and burnout are highly prevalent among oncology clinicians. Research is needed to better understand how resource constraints and systemic inequalities contribute to moral distress in order to develop effective mitigation strategies. Oncology providers in low‐ and middle‐income countries are well positioned to provide insight into the moral experience of cancer care priority setting and expertise to guide solutions. Methods Semistructured interviews were conducted with a purposive sample of 22 oncology physicians, nurses, program leaders, and clinical advisors at a cancer center in Rwanda. Interviews were recorded, transcribed verbatim, and analyzed using the framework method. Results Participants identified sources of moral distress at three levels of engagement with resource prioritization: witnessing program‐level resource constraints drive cancer disparities, implementing priority setting decisions into care of individual patients, and communicating with patients directly about resource prioritization implications. They recommended individual and organizational‐level interventions to foster resilience, such as communication skills training and mental health support for clinicians, interdisciplinary team building, fair procedures for priority setting, and collective advocacy for resource expansion and equity. Conclusion This study adds to the current literature an in‐depth examination of the impact of resource constraints and inequities on clinicians in a low‐resource setting. Effective interventions are urgently needed to address moral distress, reduce clinician burnout, and promote well‐being among a critical but strained oncology workforce. Collective advocacy is concomitantly needed to address the structural forces that constrain resources unevenly and perpetuate disparities in cancer care and outcomes. Implications for Practice For many oncology clinicians worldwide, resource limitations constrain routine clinical practice and necessitate decisions about prioritizing cancer care. To the authors’ knowledge, this study is the first in‐depth analysis of how resource constraints and priority setting lead to moral distress among oncology clinicians in a low‐resource setting. Effective individual and organizational interventions and collective advocacy for equity in cancer care are urgently needed to address moral distress and reduce clinician burnout among a strained global oncology workforce. Lessons from low‐resource settings can be gleaned as high‐income countries face growing needs to prioritize oncology resources., Oncology providers in low‐ and middle‐income countries face resource priority setting decisions on a routine basis. This article describes the moral experience and recommendations of oncology clinicians, advisors, and program leaders engaged in clinical priority setting at a cancer center in Rwanda.

TPS817 Background: Metastatic disease remains a consistent challenge for patients with gastrointestinal (GI) malignancies. Multiple immune checkpoint inhibitors (ICI) have been FDA approved for several GI indications. Still, patients will progress on these therapies, either immediately or after initial response. Palliative radiation therapy (RT) is an effective treatment that can be delivered to symptomatic metastases. It also has been reported to lead to an abscopal effect, which is an induction of response in a distant tumor. This is thought to result from increased tumor immunogenicity, tumor microenvironment modulation, and immune cell recruitment. Thus, palliative RT could not only relieve symptoms, but also potentially reinvigorate the immune response, prolong ICI efficacy, and delay next-line systemic therapy that carries risks of unknown efficacy and tolerability. Ongoing studies seek to elucidate prognostic and predictive biomarkers of the abscopal effect. However, cohorts of patients with GI malignancies are limited, so there remains a need for research in combining RT and immunotherapy in the context of metastatic GI cancer. ARM-GI aims to study the radiation-augmented immune response in patients with metastatic GI cancers progressing on immunotherapy. Methods: ARM-GI is a phase 2, single arm study. Key eligibility criteria include confirmed metastatic GI malignancy, progressive disease per RECIST v1.1 on any ICI, and at least 2 metastases, one of which can be safely left unirradiated. The target prescription dose is 30 Gy in 5 fractions to symptomatic sites through intensity modulated RT or stereotactic body RT. Patients will continue the same immunotherapy after RT and be evaluated per RECIST v1.1 longitudinally. The primary endpoint is overall response rate (ORR) per RECIST v1.1. Secondary endpoints include ORR per iRECIST, progression free survival, overall survival, local control in radiated lesion(s), effect of distant radiation on unirradiated target lesions, incidence of new metastatic lesions, safety by CTCAE v5.0, and time to new systemic therapy. The study will enroll 28 patients, with recruitment ongoing. Serial peripheral blood samples are collected for exploratory studies that will analyze for association with disease response and quantification of changes in circulating immune cell subsets after RT compared to baseline. Clinical trial information: NCT04221893 .

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

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.

Background We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. Objective This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. Methods Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. Results From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. Conclusions This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. Trial Registration ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716

Background Anal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of the human immunodeficiency virus (HIV). Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of HIV-positive and HIV-negative patients. Methods A retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model. Results During the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5–63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4–87.0) and 74.6% (95% CI, 65.8–84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03–1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm3, there was significantly worse OS (log-ranked p = .015). Conclusion A trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm3. Implications for Practice Human immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective but can result in significant toxicity and a decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk after completion of treatment.

BACKGROUND/AIM Oxaliplatin-induced neurotoxicity (OIN) can be severe and dose-limiting with clinically significant symptoms that persist for years. Few published reports have described postoperative exacerbation of OIN and more longitudinal data are needed to better characterize the phenomenon. PATIENTS AND METHODS We identified 13 patients diagnosed with colon (n=7), rectal (n=4) or pancreatic (n=2) cancer who experienced postoperative OIN exacerbation at our medical center. Charts were reviewed for demographic and clinical data regarding OIN. RESULTS OIN exacerbation was documented 0.5-7.0 months after the first surgery following oxaliplatin exposure, with a median duration of 10.6 months (range=1.4-86.1 months). OIN exacerbation persisted in 3/13 patients at last follow-up, and improved to pre-operative levels in 6/13 patients (with complete resolution in 4/13) within a median of 3.6 months from initial exacerbation. CONCLUSION Given the widespread use of oxaliplatin in neoadjuvant and first-line treatment for gastrointestinal cancers, further study is warranted to prospectively and systematically define risks for postoperative OIN exacerbation.

This Viewpoint evaluates factors introduced by the overturn of Roe v Wade that will further complicate the complex, multidisciplinary decision-making involved in treating patients with pregnancy-associated cancer.

Background In response to the increasing burden of cancer in Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children launched National Cancer Treatment Guidelines (TNCTG) in February 2020. The guidelines aimed to improve and standardize oncology care in the country. At Ocean Road Cancer Institute (ORCI), we developed a theory‐informed implementation strategy to promote guideline‐concordant care. As part of the situation analysis for implementation strategy development, we conducted focus group discussions to evaluate clinical systems and contextual factors that influence guideline‐based practice prior to the launch of the TNCTG. Materials and Methods In June 2019, three focus group discussions were conducted with a total of 21 oncology clinicians at ORCI, stratified by profession. A discussion guide was used to stimulate dialogue about facilitators and barriers to delivery of guideline‐concordant care. Discussions were audio recorded, transcribed, translated, and analyzed using thematic framework analysis. Results Participants identified factors both within the inner context of ORCI clinical systems and outside of ORCI. Themes within the clinical systems included capacity and infrastructure, information technology, communication, efficiency, and quality of services provided. Contextual factors external to ORCI included interinstitutional coordination, oncology capacity in peripheral hospitals, public awareness and beliefs, and financial barriers. Participants provided pragmatic suggestions for strengthening cancer care delivery in Tanzania. Conclusion Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect uptake of the TNCTG. Our findings were used to inform a broader guideline implementation strategy, in an effort to improve uptake of the TNCTGs at ORCI. Implications for Practice This study provides an assessment of cancer care delivery systems in a low resource setting from the unique perspectives of local multidisciplinary oncology clinicians. Situational analysis of contextual factors that are likely to influence guideline implementation outcomes is the first step of developing an implementation strategy for cancer treatment guidelines. Many of the barriers identified in this study represent actionable targets that will inform the next phases of our implementation strategy for guideline‐concordant cancer care in Tanzania and comparable settings., Guidelines to improve and standardize oncology care in Tanzania were developed in 2020. This study utilized focus group discussions to assess the barriers and facilitators to guideline implementation at Ocean Road Cancer Institute.

BACKGROUND: Loneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group. METHODS: A convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the loneliness group. RESULTS: Of the 606 patients, 53.0% were categorized in the lonely group. The lonely group reported higher levels of social isolation, as well as higher symptom severity scores for all of the symptoms evaluated. In the multivariate model, being unmarried, having higher levels of social isolation, as well as higher levels of anxiety and depressive symptoms were associated with membership in the lonely group. CONCLUSIONS: Study findings suggest that a significant number of oncology patients are experiencing loneliness, most likely as a result of mandate social distancing and isolation procedures. The symptom burden of these patients is extremely high and warrants clinical evaluation and interventions.

Background/aim The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed. Case report We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Two cases bear a POLE P286R mutation, which has been associated with lack of immunotherapy response in MSS CRC. Two cases bear alterations in Ataxia-Telangiectasia Mutated (ATM) which may contribute to observed responses, including interaction with a co-administered intratumoral stimulator of interferon genes (STING) pathway agonist in one patient. Conclusion Novel DNA damage repair alterations, including mutations in ATM, can provide insight into additional mechanisms by which genomic alterations can sensitize MSS CRC to diverse immunotherapies.

Following definitive chemoradiation for anal squamous cell carcinoma (ASCC), patients face a variety of chronic issues including: bowel dysfunction, accelerated bone loss, sexual dysfunction, and psychosocial distress. The increasing incidence of this disease, high cure rates, and significant long-term sequelae warrant increased focus on optimal survivorship care following definitive chemoradiation. In order to establish our survivorship care model for ASCC patients, a multi-disciplinary team of experts performed a comprehensive literature review and summarized best practices for the multi-disciplinary management of this unique patient population. We reviewed principle domains of our survivorship approach: (1) management of chronic toxicities; (2) sexual health; (3) HIV management in affected patients; (4) psychosocial wellbeing; and (5) surveillance for disease recurrence and survivorship care delivery. We provide recommendations for the optimization of survivorship care for ASCC patients can through a multi-disciplinary approach that supports physical and psychological wellness.

3565 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. Methods: Single-center, phase 2 trial with safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts (NCT03396926). Key eligibility: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: Capecitabine 1000 mg/m2 PO BID D1-14 Q21 days (confirmed RP2D) plus pembrolizumab 200 mg IV D1 Q21 days and bevacizumab 7.5 mg/kg IV D1 Q21 days. Endpoints: Primary: Objective response rate (ORR) by RECIST 1.1. Key secondary: Safety, duration of response (DOR), progression-free survival (PFS), overall survival (OS). Results: From 04/2018-10/2021, 44 patients (pts) were enrolled. Overall: Median age 53 years (range 28-79); female 50%; Caucasian 61%. Liver metastases at enrollment 80%. Prior therapies: median prior lines of therapy 2 (range 1-5); PD on fluoropyrimidine-containing regimens 91%; prior exposure to bevacizumab 86%. Complete toxicity data are available for 36 off-treatment pts. Grade ≥ 3 treatment-related (tr)AEs occurred in 10 (28%) pts, including grade 3 immune-related AEs in 4 (11%) pts. All-cause serious (s)AEs occurred in 13 (36%) pts and trSAEs in 5 (14%) pts. (tr)AEs leading to dose interruptions, reductions, or delays occurred in 21 (58%) pts, most commonly palmar-plantar erythrodysesthesia syndrome in 17 (47%) pts. Disposition: of 44 pts enrolled, 35 were removed for PD and 1 was removed for treatment noncompliance; 8 treatment ongoing. ORR in 40 evaluable pts was 5% (95% CI: 0.6,16.9). Best response by RECIST 1.1: partial response (PR) in 2 (5%); SD in 26 (65%); PD in 12 (30%). 2 responders: DOR 12 and 15 months, both with liver metastases. Median follow up was 7 months (range 1-45), with median PFS 4.3 months (95% CI: 3.9, 6.1), PFS at 6 months 31.1% (95% CI: 19.2%, 50.4%), and median OS 9.6 months (95% CI: 6.2, 13). Median time on treatment was 5 months (range 1-26). Single cell RNA sequencing on a subset of paired pre- and on-treatment biopsies demonstrated changes in the frequency of dendritic cells. Conclusions: The combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. The ORR of 5% did not meet the prespecified target of ≥ 15%, however nearly a third of pts had PFS > 6 months. Immune profiling of tumor biopsies and peripheral blood is ongoing. Clinical trial information: NCT03396926.

PURPOSE Serious illness communication (SIC) in cancer care describes conversations between clinicians, patients, and families about prognosis and treatment decisions. Cultural context influences SIC. Researchers have studied SIC across diverse settings in Africa. We aimed to describe and synthesize the heterogeneous body of research on SIC practices, preferences, and needs in Africa to identify research and training priorities. METHODS Our search strategy identified studies that focused on SIC within cancer or palliative care in Africa. Following PRISMA guidelines, a systematic literature search was performed using PubMed, Embase, Web of Science, CINAHL, African Index Medicus, and PsycINFO, yielding 1811 unique titles. After sequential review of abstracts, full text, and cited references, 42 articles met inclusion criteria. Quantitative and qualitative data describing study characteristics, aims, methods, and findings were abstracted and analyzed using descriptive statistics and thematic analysis. Critical appraisal was performed using the Mixed Methods Appraisal Tool. RESULTS The 42 included articles were published from 1997-2021, half since 2017, representing 16 countries and all African Union regions: West (33%), East (29%), South (21%), North (12%), and Central (5%). Most study designs were qualitative (45%) or quantitative surveys (50%). Study participants included patients (35%), family caregivers (18%), doctors (18%), nurses (12%), and/or other (11%). Study aims focused on disclosure of diagnosis (27%) or prognosis (20%), breaking bad news (15%), general patient-clinician communication (12%), truth-telling (8%), shared decision-making (7%), information needs/preferences (5%), and/or advance care planning (5%). Despite diverse contexts, common themes emerged. Study authors frequently recommended communication skills training. Critical appraisal demonstrated high quality of studies overall. CONCLUSION Research on SIC in Africa has increased in recent years. Most studies have focused on information delivery by clinicians; fewer on eliciting information from patients (eg, shared decision-making, advanced care planning). Significant opportunities exist for further study and for communication skills training.

Purpose Age-standardized incidence rates for esophageal cancer (EC) in East Africa have been reported as disproportionately high compared with the worldwide incidence of nine per 100,000 population. This study aimed to characterize EC cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Methods Demographic, clinical, and treatment variables were abstracted from charts of patients who received care for a diagnosis of EC at one or both institutions between 2011 and 2013. Categorical data were summarized as frequency counts and percentages. Continuous data were presented as medians and ranges. To compare men and women, Pearson’s χ2 and two-sample t tests were applied. Results Seven hundred thirty-eight unique cases of EC were identified, of whom 68% were men and the median age was 60 years (range, 19 to 95 years). Notably, 93 cases (13%) were ≤ 40 years old at diagnosis. Squamous cell carcinoma was the dominant histology, comprising 90% of cases with documented histopathology. However, 34% of cases with a diagnosis of EC were not pathologically confirmed. The stage was documented as locoregional in 4% of cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer Institute, 76% were treated with radiation, 44% were treated with chemotherapy, 3% underwent a cancer-related surgical procedure, and 10% of cases received no cancer-directed therapy. The median overall survival for all patients was 6.9 months (95% CI, 5.0 to 12.8), regardless of stage at presentation. Conclusion Between 2011 and 2013, cases of EC represented a large clinical burden at both institutions.

PURPOSE Clinical breast examination (CBE) is one of the most common methods used for early detection of breast cancer in low- and middle-income countries. CBE alone is limited by lack of specificity and may result in unnecessary diagnostic procedures. We evaluated the feasibility of integrating CBE, fine-needle aspiration biopsy (FNAB), and rapid on-site evaluation (ROSE) in triaging palpable breast masses for specialized cancer care. MATERIALS AND METHODS An intensive breast cancer screening event was conducted at a national trade fair by a multidisciplinary team of care providers targeting a healthy population in Dar es Salaam, Tanzania. All adults age ≥ 18 years were invited to participate. CBE was performed by oncologists and/or pathologists. FNAB was performed by a pathologist on palpable masses that were then categorized as benign, indeterminate, or suspicious for malignancy or definitively malignant based on ROSE. RESULTS A total of 208 individuals (207 females, one male; median age, 36 years; range, 18-68 years) were screened. Most (90.8%, 189 of 208) had normal findings, whereas 7.2% (15 of 208), 1% (2 of 208), and 1% (2 of 208) had a palpable mass, breast pain, and nipple discharge, respectively. Two participants had lesions too small for palpation-guided biopsy and clinically consistent with fibroadenomas; the participants were counseled, and observation was recommended. FNAB was performed on 13 breast masses, with 9 of 13 (69%) categorized as benign and 4 of 13 (31%) suspicious for malignancy. Final cytopathologic review of referred patients confirmed one case to be breast adenocarcinoma, one was suggestive of fibroadenoma, and two showed inflammations. CONCLUSION Integration of CBE with ROSE and FNAB was feasible in a breast cancer screening program in Tanzania. In settings with constrained resources for cancer care, this may be an effective method for triaging patients with breast masses.

PURPOSE The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa. METHODS In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability. RESULTS Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor. CONCLUSION The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

PURPOSE At the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer. METHODS Representatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session. RESULTS From across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized. CONCLUSION The concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient’s journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.

Colorectal cancer is preventable and treatable by screening and early detection. Fecal immunochemical tests (FIT) for average risk individuals is an effective strategy for screening. Incidence and mortality in Mexico is increasing and large-scale screening programs do not yet exist. The aim of this study was to evaluate the feasibility of FIT-based colorectal cancer screening program in Mexico City. For more than 15 months, average risk individuals in Mexico City were invited to participate at Mexico's Instituto Nacional de Cancerologia (INCan, Mexico City, Mexico). Participants received an FIT kit for stool collection, results ≥20 ng/mL were referred for high quality colonoscopy. Participants' results were classified according to the most advanced clinical finding as: adenocarcinoma, high-risk adenomas, low-risk adenomas, serrated lesions, hyperplastic polyps, and no polyps. Sequential analyses were performed to assess the positive predictive value (PPV) of FIT. A total of 810 participants were eligible, 737 (91.0%) returned the FIT and 112 (15.2%) had an abnormal result. Of these participants, 87 (77.7%) completed colonoscopy. Clinical findings of participants included: seven (8.1%) adenocarcinomas, 18 (20.7%) high-risk adenomas, 23 (26.4%) low-risk adenomas, one (1.2%) serrated lesions, 14 (16.1%) hyperplasic polyps, and 24 (27.6%) no polyps. The PPV of FIT using the ≥20 ng/mL was 8.1% for cancer and 20.7% for high-risk adenomas. In conclusion, colorectal cancer screening with FIT is feasible at INCan in Mexico City, where resources are available. Further studies are needed to determine feasibility of colorectal cancer screening in other settings, as well as optimal hemoglobin detection cut-off points to maximize the population benefits of colorectal cancer screening with FIT in Mexico.

444 Background: Immune checkpoint inhibitors (ICI) have limited activity as monotherapy in unselected patients with ABC; the objective response rate (ORR) of PEM was 5.8% in the multicenter phase 2 KEYNOTE-158 trial. GM-CSF modulates immune cells including monocytes and the innate immune response and has demonstrated safety and prolonged survival (OS) in combination with ipilimumab in melanoma. This phase 2 trial was designed to evaluate the efficacy and safety of PEM in combination with GM-CSF in ABC. Methods: Single-center, phase 2 trial with Simon’s 2-stage design and expansion cohort (EC) (NCT02703714). Key eligibility: ABC with progression/intolerance on ≥ 1 standard therapy, no prior ICI, bilirubin ≤1.5xULN. Treatment: PEM 200 mg IV Q21 days plus 2 cycles of GM-CSF 250 µg SC D1-14 Q21 days in cycles 2 and 3 (Stage 1 and EC) or in cycles 1 and 2 (Stage 2). Primary endpoint was objective response rate (ORR) by RECIST 1.1, H0 5% vs. H1 20%. Key secondary endpoints were safety, progression-free survival (PFS), OS, PD-L1 expression. Exploratory endpoints included relationship between efficacy outcomes and anatomic subsite, risk factors, and tumor genotype. Results: Overall, 42 patients enrolled between 5/2016-12/2019: n = 9 in Stage 1, n = 18 in Stage 2, and n = 15 in EC. Overall: median age 61; female 67%; intrahepatic (ICC) 67%, extrahepatic (ECC) 26%, gallbladder (GBC) 7%; stage IV 90%; hepatitis B/C virus positive (HBV/HCV+) 24%; microsatellite instability (MSI-H)/stable (MSS)/unknown n = 1/35/6. Immune-related (ir)AE occurred in 69%, grade 3/4 treatment-related (tr)AE in 10%, all-cause serious (S)AE in 36%, and trSAE in 7%. ORR was 12% (95% CI: 4, 26), with median PFS of 63 days (95% CI: 55, 125), PFS at 6 months in 27% (95% CI: 14, 43), and median OS 3of 93 days (95% CI: 243, 573). There was no significant difference in ORR, PFS, or OS by anatomic subsite or tumor PD-L1 expression; HBV/HCV+ showed trends toward higher ORR (30% vs 6%, p = 0.08) and longer median PFS (276 vs 63 days, p = 0.06) and OS (1033 vs 323 days, p = 0.052). Conclusions: The combination of PEM plus GM-CSF was safe and well-tolerated with higher ORR than expected for PEM monotherapy in a predominantly MSS ABC population but did not meet target ORR threshold for efficacy. ORR and median PFS and OS were highest in patients with underlying HBV or HCV infection. Immune profiling of on-treatment biopsies and peripheral blood are ongoing to ascertain influence of both PEM and GM-CSF on circulating and tumor immune microenvironment. Clinical trial information: NCT02703714.

42 Background: Diet may be associated with survival and health-related quality of life (HRQOL) among CRC survivors. Behavioral interventions using web and mobile technology are feasible and acceptable approaches to modify dietary behavior. Little is known about the effect of web-based dietary interventions on HRQOL among CRC survivors. Methods: The Survivor Choices for Eating and Drinking study (SUCCEED) was a pilot randomized wait-list controlled trial designed to determine the feasibility and acceptability of a 12-week (wk) web-based dietary intervention with daily text messages. In this secondary analysis, we estimated the effect of the intervention on HRQOL. Between 2017-2018, 50 CRC survivors were randomized (1:1) to intervention or control. Participants in the intervention arm received the intervention in wk 1-12 and were followed from wks 12-24. Participants assigned to the control arm for 1-12 wks had the option to receive the intervention in wks 13-24. In both arms, HRQOL and sleep quality were assessed using the EORTC QLQ–C30 and CR29 and the Pittsburgh Sleep Quality Index at 0, 12, and 24 wks. Within- and between-group mean changes in HRQOL from enrollment to 12 and 24 wks were evaluated using independent t-test and paired t-test. Results: Follow-up was 88% complete at 12 and 24 wks in the intervention arm and 92% and 80% complete at 12 and 24 wks in controls. Participants mean age was 56 ± 9 y; 34% were men, 70% identified as non-Latinx White, 12% identified as Latinx, and 70% had stage III cancer. Between 0 and 12 wks, an increase in emotional functioning was observed in the intervention arm [mean change: 9.1; 95% confidence interval (CI): 2.2,16.0], while a decrease in emotional functioning was observed in controls (mean change: -5.1; 95%CI: -14.5,4.1; between-group mean difference: 14.3; 95%CI: 3.0,25.6). Between 0 and 24 wks, an increase in social functioning (mean change in intervention: 12.1; 95%CI: 2.1,22.1; between-group mean difference: 13.8; 95%CI: 2.1,25.5) and a decrease in fatigue (mean change in intervention: -9.1; 95%CI: -17.1,-1.1; between-group mean difference: -4.1; 95% CI: -15.8,7.6) was observed in the intervention arm. No other measures of HRQOL or sleep quality differed within or between arms. Conclusions: A web-based dietary intervention with daily text messages may improve emotional and social functioning among CRC survivors. Further study to evaluate the effect of web-based interventions on HRQOL among CRC survivors in larger studies may be merited. Clinical trial information: NCT02965521.

Importance The coronavirus disease 2019 (COVID-19) pandemic has forced oncology clinicians and administrators in the United States to set priorities for cancer care owing to resource constraints. As oncology practices adapt to a contracted health care system, expertise gained from partnerships in low-resource settings can be used for guidance. This article provides a primer on priority setting in oncology and ethical guidance based on lessons learned from experience with cancer care priority setting in low-resource settings. Observations Lessons learned from real-world experiences are myriad. First, in the setting of limited resources, a utilitarian approach to maximizing survival benefit should guide decision-making. Second, conflicting principles will often arise among stakeholders and decision makers. Third, fair decision-making procedures should be established to ensure moral legitimacy and accountability. Fourth, proactive safeguards must be implemented to protect vulnerable individuals, or disparities in cancer treatment and outcomes will only widen further. Fifth, communication with patients and families about priority setting decisions should be intentional and standardized. Sixth, moral distress among clinicians must be addressed to avoid burnout during a time when resilience is critical. Conclusions and Relevance Although the need to triage cancer care may be new to those who underwent training and now practice oncology in high-resource settings, it is familiar for those who practice in low- and middle-income countries. Oncologists in the United States facing unprecedented decisions about prioritization can draw on ethical frameworks and lessons learned from real-world cancer care priority setting in resource-constrained environments.

Esophageal cancer (EC) is a leading cause of cancer morbidity and mortality in Africa. Despite the high burden of disease, optimal management strategies for EC in resource-constrained settings have yet to be established. This systematic review evaluates the literature on treatments for EC throughout Africa and compares the efficacy and safety of varying treatment strategies in this context (PROSPERO CRD42017071546). PubMed, Embase and African Index Medicus were searched for studies published on treatment strategies for EC in Africa from 1980 to 2020. Searches were supplemented by examining bibliographies of included studies and relevant conference proceedings. Methodological quality/risk of bias was assessed using the Cochrane Risk-of-Bias tool and the Newcastle-Ottawa Scale. Forty-six studies were included. Case series constituted the majority of studies: 13 were case series reporting on outcomes of esophagectomies, 17 on palliative luminal or surgical interventions, four on radiotherapy and three on concurrent chemoradiation. Nine randomized controlled trials were identified, of which four prospectively compared different treatment modalities (one investigating radiotherapy vs chemoradiation, three evaluating rigid plastic stents vs other treatments). This review summarizes the research on EC treatments in Africa published over the last four decades and outlines critical gaps in knowledge related to management in this context. Areas in need of further research include (a) evaluation of the safety and efficacy of neoadjuvant therapy in patients with locally advanced disease; (b) strategies to improve long-term survival in patients treated with definitive chemoradiation; and (c) the comparative effectiveness of modern palliative interventions, focusing on quality of life and survival as outcome measures.

3565 Background: Over half of patients (pts) with oligometastatic CRC treated with curative intent surgery or radiotherapy experience cancer recurrence with or without adjuvant chemotherapy. ctDNA detection post-definitive treatment could identify high risk pts for additional intervention to eliminate molecular residual disease. Here we report results of a prospective observational study aiming to determine ctDNA detection rates using a sensitive liquid biopsy and to correlate post-procedure ctDNA detection (post-ctDNA (+)) with radiographic mCRC recurrence. Methods: Pts with mCRC intending to undergo a curative intent procedure were prospectively recruited at two US sites. ctDNA was collected pre-procedure, 3 weeks post-procedure, and at multiple structured follow-up timepoints. The presence of ctDNA was evaluated using a plasma-only integrated genomic and epigenomic assay (Guardant Reveal, Guardant Health). A bioinformatic classifier was applied to differentiate tumor derived versus non-tumor derived cell-free DNA. Results: Among 52 enrolled pts, post-ctDNA data is available for 45 pts (87%), with a median of 4 (range 1-10) timepoints per pt. The sample analysis failure rate was 1% (2/217). As of 1/1/2021, the radiographic recurrence rate was 60% with a median follow-up time of 50 (range 4-192) weeks. 23 of 25 pts with post-ctDNA(+) have had recurrence (Positive Predictive Value [PPV], 92%). On average, ctDNA was detected 28 weeks before radiographic recurrence (mean 12 vs. 40 weeks, respectively). The two pts with post-ctDNA(+) but no recurrence have > 3 years follow-up; one pt received adjuvant chemotherapy and cleared ctDNA. With a median event-free follow-up time of 97 (range 4-192) weeks, 4 of 20 pts with no post-ctDNA detection (-) have recurred (Negative Predictive Value, 80%). 3 of 4 pts with recurrence despite post-ctDNA(-) also were pre-ctDNA(-). We observed a sensitivity of 85% and a specificity of 89% for the ctDNA assay. The median time to radiographic recurrence was 36 wks for ctDNA(+) vs. not reached for ctDNA(-) (Hazard Ratio, 7.7; 95% CI, 2.6-22.5; P

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.

Gallium (Ga)-DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake.We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUVmax) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient.Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0-2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5-10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26-34). There was a correlation between Ki-67 PI and SUVmax (r = -0.3, P = 0.018).Our analysis demonstrates an inverse correlation between Ki-67 PI and SUVmax in NETs. Somatostatin receptor-PET provides additional information that can help guide management of NETs.

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).

Background Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques. Methods A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants. Results Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears. Conclusion An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

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.

Purpose: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab. Experimental Design: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors. Results: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration. Conclusions: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D. Clin Cancer Res; 22(6); 1348–55. ©2015 AACR.

Importance Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote. Objective To determine whether a PC educational video and booklet at treatment initiation could improve patients’ understanding of its benefits and risks. Interventions Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review. Design, Setting, and Participants Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019. Main Outcomes and Measures The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding “not at all likely” to “What is your understanding of how likely the chemotherapy is to cure your cancer?” (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy–General emotional well-being subscale). Results Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted “a lot” of information or “as much information as possible” about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%;P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar. Conclusions and Relevance Provision of an educational video and booklet did not alter patients’ expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies. Trial Registration ClinicalTrials.gov Identifier:NCT02282722

PURPOSE In response to the increasing burden of cancer in Tanzania, the Tanzanian Ministry of Health Community Development, Gender, Elderly, and Children plans to launch their first National Cancer Treatment Guidelines. These guidelines will provide an opportunity to improve and standardize care at Ocean Road Cancer Institute (ORCI), the national cancer center, where previous data suggest that patients do not consistently receive standard treatment. A theory-informed implementation strategy will be conducted to facilitate the routine use of guidelines among health care providers at ORCI. As part of the needs assessment for this effort, this study explored the barriers to and facilitators of guideline-concordant care at ORCI. METHODS We conducted three focus groups with participants stratified by profession, which included oncologists, radiotherapists, oncology residents, and nurses. A discussion guide was used to generate discussion about multiple aspects of current clinical processes at ORCI. Audio recordings were transcribed and translated to English, and data were analyzed using the framework method. RESULTS A total of 21 participants helped identify institutional and systemic factors that were internal and external to the clinical systems at ORCI that may affect guideline-concordant care. These can be categorized into the following: strengths and facilitators, barriers, and suggestions for improvement. Internal facilitators include multidisciplinary patient management, government-sponsored free cancer care, community engagement, and providers’ motivation for continuous learning and improvement. Internal barriers include interdepartmental and interinstitutional communication gaps, resource limitations for specialized services, high patient volumes, and patient misconceptions and nonadherence. Participants offered many practical suggestions for improving clinical systems at ORCI. CONCLUSION Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect the uptake of the National Cancer Treatment Guidelines. Findings have been used to recommend quality improvement and environmental restructuring measures at ORCI that will inform the broader guideline implementation strategy.

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.

PURPOSE Tanzania and other low-income countries face a growing burden of cancer and a pressing need to strengthen cancer care delivery systems. The overall case fatality from cancer is disproportionately higher in low-income countries, and adherence to standard treatment guidelines is a critical component of addressing disparities in outcomes. In 2017, Tanzania’s Ministry of Health, Community Development, Gender, Elderly, and Children (MOHCDGEC) commissioned leaders at Ocean Road Cancer Institute to develop Tanzania’s first National Cancer Treatment Guidelines. METHODS In 2017, we convened 90 stakeholders from 15 institutions in Tanzania to form 10 different technical working groups (TWGs). TWGs were organized according to disease-specific categories and were composed of representatives from relevant disciplines, including surgeons, gynecologists, pediatricians, radiologists, pathologists, oncologists, social workers, dieticians, and nurses. Each TWG conducted a review of the current literature and prepared a summary of the epidemiology, diagnostic, and staging procedures; options for management; and essential medicines currently available in Tanzania. In 2018, after multiple revisions and meetings of each TWG, the guidelines underwent an external review with 2 oncologists from Tanzania participating in consultations with approximately 30 disease-specific experts at the University of California, San Francisco. RESULTS Guidelines were developed for a total of 70 diseases. The guidelines are intended to be facilitative, enabling, and providing the basis for the attainment of high standards in the management of cancers in a resource-constrained setting. Guidelines were formatted for dissemination in both hard copy and soft copy using the AgileMD platform. CONCLUSION In February 2020, Tanzania’s MOHCDGEC disseminated its first-ever National Cancer Treatment Guidelines. After dissemination, MOHCDGEC will implement a monitoring and evaluation strategy that ensures and promotes the use of the guidelines. We have developed a theory-informed implementation strategy that focuses on education, workflow modifications, and behavior change that will be piloted at Ocean Road Cancer Institute.

1573 Background: Prior studies have shown an increase in the rate of colorectal cancer (CRC) in young individuals in the United States. However, few studies have evaluated the health disparities that exist in this population, particularly using large, national cohorts. We examined differences in age, race, stage, region, and tumor location in younger and older patients with CRC. Methods: Data were extracted from the United States Cancer Statistics (USCS) for individuals diagnosed between 2001 and 2014. CRC incidence data among individuals < 50 years old were compared to those > 50 years old. Age-specific and age-adjusted incidences and trend analyses reported as annual percent change (APC) were performed using SEER*Stat and Joinpoint regression. Results: Of 1,886,441 individuals, the overall age-adjusted incidence of CRC decreased from 52.59 (per 100,000) in 2001 to 35.22 in 2014, with an APC of -3.24. Although over 35% cases were diagnosed in the Southern United States, the Northeast had the highest age-adjusted incidence at 45.26 per 100,000 patients. Younger patients were diagnosed with distant disease at 25.8% compared to only 18.4% in older patients. Younger patients were also more likely to have sigmoid or rectal cancers compared to older patients (64.3% vs. 45.7%). Of the 170,244 individuals < 50 years, 90,855 (53.4%) were men and 79,389 (46.6%) were women. The age-specific incidence in this younger cohort increased from 5.63 to 6.48 between 2001-2014, with an APC of +1.24 in 2001-2008 compared to +2.55 in 2012-2014. The incidence of CRC in patients aged 0-29, 30-39, and 40-49 years was 0.41 (per 100,000), 6.08, and 21.09, respectively. Black individuals < 50 years had the highest age-specific incidence of CRC (7.16 per 100,000) compared to Asian (6.43), White (6.07), or Hispanic (4.76) individuals. Conclusions: Our data suggests that CRC is increasing in young patients, particularly for those between 40-49 years and Black individuals. In our younger cohort, CRC was more commonly found in the sigmoid colon and rectum compared to older patients. Further research is warranted to direct resources towards improved colonoscopy or sigmoidoscopy screening for younger patients at risk.

Background: Esophageal cancer is a leading cause of cancer-associated deaths worldwide. Notably, there is a disproportionately high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa. One possible explanation for the unique geographic distribution of ESCC may be the human microbiome, which has been shown to influence other gastrointestinal (GI) cancers, including gastric and colorectal cancer (CRC). Methods: To address this question, we conducted RNA sequencing (RNAseq) and whole-genome sequencing (WGS) of samples from 61 Tanzanian ESCC patients. We used the computational microbial identification and classification software PathSeq to conduct a microbial abundance analysis of these samples. Next, we implemented linear discriminant analysis with LEfSe to determine which, if any, microbial taxa are enriched in the ESCC tumors of Tanzanian patients relative to ESCC samples from North America patients available through The Cancer Genome Atlas (TCGA). Results: Analysis of these RNAseq and WGS data reveals an extremely high abundance of Fusobacterium, Prevotella, and Streptococcus in the tumors of a subset of these patients. Based on the WGS data in particular, 14, 45, and 27 of the 61 ESCC samples maintain at least 10% relative abundance of Fusobacterium, Prevotella, and Streptococcus, respectively. The RNAseq data are consistent and reveal that as much as 75% of all bacterially derived reads in these samples are from these genera. Furthermore, LEfSe analysis suggest that these bacteria are significantly enriched in Tanzanian ESCC samples compared to North American ESCC samples. Discussion: These data suggest that the microbiome may be involved in ESCC incidence in Tanzania. Fusobacterium, Prevotella, and Streptococcus are notable for their association with CRC and are correlated with distinct clinical and molecular CRC characteristics. Members of these bacterial genera have been observed to modulate the carcinogenesis of GI cancers in a variety of ways, including through the selective stimulation or inhibition of various classes of immune cells. Furthermore, species within these genera have been observed invasively within cancerous GI tissues. Current studies are under way to visualize these microorganisms in tumor tissue, to characterize their association with molecular subtypes of ESCC, and to understand the relationship between tumor-associated bacteria and bacteria in the oral microbiome of ESCC patients in Tanzania. Citation Format: Jason Nomburg, Susan Bullman, Eric Collisson, Beatrice Mushi, Msiba Seleka, Charlie Vaske, Yulia Newton, Amie Radenbuagh, Larry Akoko, James A. DeCaprio, Matthew Meyerson, Elia J. Mmbaga, Katherine Van Loon. Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B06.

110 Background: Clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) is limited by extrahepatic disease progression. TAS-102 (trifluride and tipiracil) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. We aimed to evaluate the safety of the combination of TAS-102 and 90Y resin TARE in a Phase I dose-escalation trial. Methods: Adult patients with bilobar liver-dominant chemo-refractory mCRC were treated with sequential Y90 resin TARE (body surface area dosimetry) in combination with TAS-102 (20mg/m2, 27mg/m2, and 35mg/m2) in 28-day cycles according to 3+3 dose-escalation design. Beginning with cycle 3, TAS-102 was administered as monotherapy until disease progression or development of intolerable toxicity. Primary objectives were to determine maximum tolerated dose (MTD) of TAS-102, to assess toxicity, and to establish safety of TAS-102 in combination with 90Y TARE. Results: A total of 14 patients (10 women, 4 men) have been treated to date. Among 9 patients enrolled in the dose-escalation phase, no dose limiting toxicities were observed. The MTD of TAS-102 in combination with Y90 was 35mg/m2, which was selected for the dose expansion phase. Severe adverse events (AEs) included: neutropenia (46%); anemia (23%); and thrombocytopenia (8%), which were attributed to TAS-102. All other AEs were mild and transient. At least one follow-up imaging study has been obtained for 13 patients, and 10 patients have completed trial participation. Disease control rate in the liver was 100%. Conclusions: The combination of TAS-102 and 90Y TARE for patients with liver-dominant mCRC is safe and consistently achieved disease control within the liver. Severity and incidence of AEs is within the expected range of TAS-102 and 90Y TARE monotherapy. A dose-expansion phase with planned enrollment of 12 patients is ongoing. Clinical trial information: NCT02602327.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward?

BACKGROUND Phase 3 studies of bevacizumab in patients with advanced pancreatic cancer (APCA) demonstrated no improvement in outcome. To the authors' knowledge, no validated predictive biomarkers for bevacizumab exist, although emerging data suggest that subsets of patients with APCA may benefit from treatment with bevacizumab. The authors evaluated baseline serum albumin (b-alb) as a predictive biomarker in a pooled analysis from 7 prospective clinical trials of gemcitabine-based therapy with or without bevacizumab. METHODS Data were collected from individual databases from 7 prospective clinical trials. Patients were grouped by exposure to bevacizumab and by b-alb level (≥ 3.4 g/L or

The detection of somatic single nucleotide variants is a crucial component to the characterization of the cancer genome. Traditional mutation calling algorithms have focused on comparing the normal and tumor DNA from the same individual. For projects like The Cancer Genome Atlas (TCGA), it became routine to also sequence the tumor RNA. Our computational method, RADIA (RNA and DNA Integrated Analysis), combines the patient-matched normal and tumor DNA with the tumor RNA to detect somatic mutations. The inclusion of the RNA increases the power to detect somatic mutations, especially at low DNA allelic frequencies or when tumor purity is low. By integrating an individual’s DNA and RNA, we are able to detect mutations that would otherwise be missed by traditional algorithms that examine only the DNA. Mutations with high support in the RNA and low support in the DNA are termed RNA Rescue mutations. RNA editing is a post-transcriptional modification of pre-mRNA that has recently been identified as an additional epigenetic mechanism relevant to cancer development and progression. Using patient-matched normal and tumor DNA along with tumor RNA, we are able to identify RNA editing events across the entire transcriptome. There exists a remarkable geographic variability observed in incidence rates for Esophageal Cancer where more than 80% of cases and deaths occur in developing countries. There is an urgent demand to address the unmet clinical needs for these regions. Mutation of the tumor suppressor gene TP53 is the most frequent genetic alteration in both Esophageal Squamous Cell Cancer (ESCC) and Esophageal Adenocarcinoma (EAC). In a previous study of 59 tumors in Malawi a high proportion of tumors without TP53 mutations was reported. Here, we apply RADIA to a cohort of 61 tumors from Tanzania, and identify RNA Rescue Mutations that were previously missed by DNA mutation callers in significantly mutated genes such as TP53, CDK6, NOTCH1, VEGFA, KMT2D. RNA Editing events in the 3’UTR regions of genes are very common, especially when Alu elements are present, and are known to deregulate microRNA mediated gene regulation. MDM2 is a key oncogene in the p53 pathway with elevated gene expression in many tumor types and is known to be transcriptionally repressed by microRNAs. Here we detect transcriptome-wide RNA Editing events, and identify RNA Editing events in the seed regions of microRNA target sites of genes such as MDM2. We will also show how RNA Editing of certain genes are significantly associated with an RNA-Seq clustering solution. These genes show significantly differential expression between RNA-Seq clusters, indicating that these editing events have a functional impact on the genes they affect. We will further investigate these functional effects and downstream implications on the molecular characterization of the RNA-Seq subtypes. Citation Format: Amie J. Radenbaugh, J Zachary Sanborn, Yulia Newton, Charlie Vaske, Katherine Van Loon, Eric Collisson. RNA rescue somatic mutations and RNA editing in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2522.

3572 Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p < 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p < 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking < 50 days to complete treatment (p = 0.03), and < 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 < 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.

552 Background: Over half of patients (pts) with oligometastatic CRC treated with definitive surgery or radiotherapy experience cancer recurrence. Early detection of ctDNA could identify high risk pts for additional intervention to eliminate micrometastatic disease. Here we report interim results of a prospective study aiming to determine ctDNA detection rates using a sensitive multigene assay and to correlate post-procedure ctDNA detection with radiographic mCRC recurrence. Methods: Pts with mCRC intending to undergo a curative intent procedure were prospectively recruited at a single site. ctDNA was collected pre-procedure, 3 weeks (wks) post-procedure, and at multiple follow-up timepoints. ctDNA detection utilizing a multi-gene sequencing panel (Guardant Health) included somatic variant and epigenetic assessments. A novel variant classifier was applied to differentiate tumor derived versus non-tumor derived alterations. A Simon’s two-stage design with planned interim analysis to assess 3wk post-procedure ctDNA detection rate was employed. Results: Of 25 pts enrolled, 21 (84%) had evaluable paired pre- and post-procedure samples. In these 21 pts, the 3 wks post-procedure sample was collected after surgery (N = 20) or radiation (N = 1) to address liver (N = 17), lung (N = 3), or ovarian (N = 1) metastases ± colon resection (N = 6). ctDNA was detected (+) in 15/21 (71%) pre- and 11/21 (52%) post-procedure samples. ctDNA was (+) in 8/12 (67%) pre- and 8/17 (47%) post-procedure samples with carcinoembryonic antigen < 5 ng/ml. Conclusions: In this interim analysis of pts with mCRC undergoing curative intent procedures, the post-procedure ctDNA detection rate was 52%. The similarity between the observed post-procedure ctDNA detection and expected recurrence rate suggests promise for recurrence prediction using this approach. Given post-procedure ctDNA was (+) in > 3 pts, the study will continue to enroll, and pts are being followed for future correlation of ctDNA with radiographic recurrence. [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.

Purpose Low-income countries (LICs) face a growing cancer burden and a pressing need to strengthen cancer care delivery systems. Overall case fatality from cancer is estimated to be 30% higher in LICs than in high-income countries, and adherence to standard treatment guidelines is a critical component of addressing this disparity. Despite several recent international efforts to develop resource-stratified cancer treatment guidelines, little research has been done on their implementation. In 2018, Tanzania’s Ministry of Health will publish a new set of national cancer treatment guidelines for all cancers. The objective of this work is to evaluate the feasibility, adoption, and effectiveness of a theory-informed implementation strategy to facilitate the uptake of guideline-based clinical practice at the national referral center, Ocean Road Cancer Institute (ORCI). Our central hypothesis is that this implementation strategy will be undertaken with fidelity and context-appropriate adaptations and will effectively increase guideline-concordant treatment at ORCI. Methods Qualitative data demonstrate that major barriers to guideline-based practice at ORCI include a lack of familiarity with standard treatment guidelines and a culture that prioritizes experience-based expertise over guidelines. We developed a multifaceted intervention to target these barriers using the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel framework. Our intervention has three phases: distribution of national cancer treatment guidelines in hard and soft copy, with an accompanying publicity campaign; dedicated multidisciplinary trainings for oncology providers and implementation champions; and reinforcement strategies, such as environmental restructuring and point-of-care clinical forms, to promote guideline-based practice. We will use a pre–post design that uses a mixed-methods approach to measure process and outcomes, including clinical data collection, survey administration, and qualitative interviews, focus groups, and field observation. Conclusion In Tanzania and other LICs, shifting to guideline-based practice entails a change in clinical culture and behavior, and guideline publication alone is unlikely to result in meaningful change. A theory-informed implementation strategy is the optimal way to ensure the adoption and sustained use of guideline-based practice. Systematic evaluation will allow us to make necessary modifications, disseminate findings, and advance knowledge in the field of cancer treatment guideline implementation in LICs. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Li Zhang Consulting or Advisory Role: Dendreon, Unity