189 Background: TAS102 (trifluridine/tipiracil hydrochloride) is approved for use alone or with bevacizumab in late line metastatic colorectal cancer (mCRC), with overall survival benefit in phase 3 trials (RECOURSE and SUNLIGHT). Oxaliplatin is frequently reintroduced after progression, resolution of limiting neuropathy, or disease recurrence post adjuvant therapy. In preclinical studies, oxaliplatin combined with TAS102 has shown synergism. We hypothesized TASOX may be an option for patients who have progressed/recurred after FOLFOX. Methods: We assessed safety and efficacy of TAS102 with oxaliplatin, enrolling patients with metastatic CRC progressed on ≥2 lines of therapy including 5FU, oxaliplatin and irinotecan. Patients with recurrence during or within 6 months of adjuvant chemotherapy were allowed. Exclusion: Prior TAS102 exposure, functional impairing peripheral neuropathy, ≥Grade 3 hypersensitivity to oxaliplatin, or uncontrollable grade 1-2 hypersensitivity to oxaliplatin. Treatment continued until disease progression or unacceptable toxicity. Patients received oxaliplatin 85 mg/m2 and TAS-102 35 mg/m2 bid days 1-5 every two weeks, and bevacizumab per MD choice. The primary endpoint was overall response rate (ORR) by RECIST (by independent radiologists). Secondary endpoints included disease control rate (DCR), safety and tolerability. Results: 54 patients enrolled; 53 received treatment on study and 48 had ≥1 disease assessment (median age 59, 58 % male, tumor RAS mutated 69%). Median time on study was 4 months (8 cycles; range 1-37 cycles). ORR was 6% (n=3), with average change in target lesions -45% (range -35 to -67%). 71% (n=34) had SD defined on study, with average change in target lesions -3% (range -29% to +20%). In those treated with bevacizumab (59%; n=28 ), 79% (n=22) had disease control vs. 75% (n=15). The most common reason for study discontinuation was progressive disease (23%, n=11). 68% (n=36) had a treatment-related adverse event (TRAE) ≥Grade 3 at any point during therapy. The most common G3 TRAEs were anemia 19% (n=10) and leukopenia 28% (n=15) at any time. Two (4%) developed grade 3 neuropathy. Conclusions: TASOX is effective as a 3rd line therapy for patients with mCRC. In our study, overall disease control rate was 77% with up to 19 months on study. Anemia and leukopenia are common but manageable. Bevacizumab did not seem to have as great an effect in our trial as observed in SUNLIGHT. Future studies would warrant TASOX in combination to bevacizumab in randomized trials in candidates for oxaliplatin retreatment. Clinical trial information: NCT02848079 .

Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US) and perioperative chemotherapy (PCT). Preoperative therapies have demonstrated survival benefits over US and thus long-term outcomes are expected to vary between the options. However, as these 2 modalities continue to be regularly employed, we sought to perform a decision analysis comparing the costs and quality-of-life associated with the treatment of patients with LAGC to identify the most cost-effective option. We designed a decision tree model to investigate the survival and costs associated with the most commonly utilized management modalities for LAGC in the United States: US and PCT. The tree described costs and treatment strategies over a 6-month time horizon. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life-years (QALYs). One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. PCT was the most cost-effective treatment modality for patients with LAGC over US with a cost of $40,792.16 yielding 3.11 QALYs. US has a cost of $55,575.57 while yielding 3.15 QALYs; the incremental cost-effectiveness ratio (ICER) was $369,585.25. One-way and two-way sensitivity analyses favored PCT in all variations of variables across their standard deviations. Across 100,000 Monte Carlo simulations, 100% of trials favored PCT. In our model simulating patients with LAGC, the most cost-effective treatment strategy was PCT. While US demonstrated improved QALYs over PCT, the associated cost was too great to justify its use.

PURPOSE:Pancreatic cancer (PC) has an overall 5-year survival rate of 10%. The use of neoadjuvant chemoradiation is debated in resectable disease. The purpose of this study is to evaluate the cost-effectiveness of neoadjuvant chemoradiation followed by pancreaticoduodenectomy (NACRT) versus upfront pancreaticoduodenectomy and adjuvant chemotherapy (USR) in resectable PC.METHODS:A decision tree model was used to estimate the cost-effectiveness of NACRT versus USR. Values from the published literature populate the tree: costs from Medicare (FY2021) reimbursements, and morbidity and survival data for quality-adjusted life-years (QALYs). Patients with resectable pancreatic adenocarcinoma who qualified for resection were included. The ICER was the primary outcome. The model was validated using one-way and two-way deterministic, as well as probabilistic sensitivity analyses.RESULTS:The base case was modeled using a 65-year-old male. NACRT yielded 1.61 QALYs at $45,483.52 USD. USR yielded 1.47 QALYs at a discount of $6,840.96 USD. The ICER was $48,130 USD, which favors NACRT. One-way sensitivity analyses upheld these results except when <= 21.0% of NACRT patients proceeded to surgery and when <= 85.4% of NACRT patients were resectable at surgery. Two-way sensitivity analyses also favored NACRT except in cases when the proportion of resected disease after NACRT decreased. NACRT was favored in 94.3% of 100,000 random-sampling simulations.CONCLUSION:It is more cost-effective to administer NACRT before surgery for patients with resectable PC. On the basis of sensitivity analyses, USR with adjuvant therapy is only favored if rates of resection and eligibility for resection after NACRT decrease. NACRT should be considered in all patients unless there is an absolute contraindication.

Cancer incidence is rising across sub-Saharan Africa (SSA), and is often characterized by late-stage presentation, early age of onset and poor survival. While a number of oncology drugs are now improving the length and quality of life for cancer patients in high-income countries, significant disparities in access to a range of oncology therapeutics exist for SSA. A number of challenges to drug access such as drug costs, lack of infrastructure and trained personnel must be urgently addressed to advance oncology therapies for SSA. We present a review of selected oncology drug therapies that are likely to benefit cancer patients with a focus on common malignancies in SSA. We collate available data from seminal clinical trials in high-income countries to highlight the potential for these therapeutics to improve cancer outcomes. In addition, we discuss the need to ensure access to drugs within the WHO Model List of Essential Medicines and highlight therapeutics that require consideration. Available and active oncology clinical trials in the region is tabulated, demonstrating the significant gaps in access to oncology drug trials across much of the region. We issue an urgent call to action to address drug access due to the predicted rise in cancer burden in the region in coming years.

Introduction. Pleomorphic rhabdomyosarcoma (RMS) is an aggressive and rare malignant neoplasm with a poor prognosis. As its name suggests, this tumor exhibits extensive pleomorphism with features of skeletal muscle differentiation. Due to its rarity, its diagnosis is often a clinical and pathological challenge. Since only small case series and a few scattered case reports exist in the literature, the impact of different demographic features, tumor site, and/or treatment modality on patient outcomes has yet to be extensively studied. Methods. We report a case of a pleomorphic RMS presenting atypically as an abdominal wall mass. We have also analyzed the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database to determine the factors affecting the outcome of this neoplasm. Moreover, we present a review and summary of pleomorphic RMS cases arising from the abdominal wall reported in the English language literature. Results. We found two hundred and forty-two cases of pleomorphic RMS in the SEER database. The majority of the patients were diagnosed after the age of 40, with the age of diagnosis showing a unimodal distribution. The majority of the patients were Caucasian (82%) and male (59%). Age of diagnosis, tumor stage, and surgical management significantly affected the patients' outcome, while patients' ethnicity, sex, or tumor site did not affect the outcome. We only found five previously reported cases of pleomorphic RMS arising from the abdominal wall. Conclusions. Pleomorphic RMS arising from the abdominal wall is extremely rare. Our data sheds light on the factors affecting the outcome of pleomorphic RMS. We have also discussed the challenges involving the histopathological diagnosis of this rare neoplasm and how to best approach this task.

Purpose: Oncologic emergencies contribute to a large proportion of morbidity and mortality for oncology patients, who present unique medical challenges due to disease and treatment complexities. Emergencies training of medical staff is important, particularly if there is high turnover. We describe the development and implementation of a program to enhance timely recognition and treatment of oncologic emergencies. Due to the COVID19 pandemic, sessions were conducted virtually. Methods: Healthcare workers who normally care for oncology patients at Princess Marina Hospital (PMH) were invited to participate in a series of weekly virtual case-based lectures. Didactic content was developed between Botswana and Rutgers faculty and fellows to reflect specific management and resources available at PMH. Participation was through live chat case reviews and pre- and post- session questions. Feedback was elicited through Likert-scale surveys. Results: An average of 19 participants (range 13-29) attended the training sessions. Average make-up per session were as follows: 16% physicians, 26% Medical Officers, 4% Internal Medicine Residents, 32% nurses, 21% other. Healthcare workers from Botswana were invited to participate in content preparation and presentation to their peers; 3 of 8 presentations were by Botswana personnel. Average pre-session test score was 70% (range 40-89%); post-session score was 82% (range 55-97%). In post sessions surveys, average confidence in diagnosis and recognition across emergencies was 84% (range 71-100%); average confidence in management was 81% (range 57-100%). Conclusions: We describe the successful piloting of a case-based virtual training program in oncologic emergencies, which to our knowledge is the first of its kind. The program was adapted to the Botswana health care setting. Overall, confidence in diagnosis, recognition and management of oncologic emergencies appeared to increase after sessions. Plans are in place to expand the series to more sites within the country, most of which do not have dedicated oncology trained staff. Citation Format: Sharon Li, Sadaf Qureshi, Reena Antony, Kara Wilson, Robert Moumakwa, Refeletswe Lebelonyane, Tendani Gaolathe, Mansi Shah, Pallvi Popli, Ashwin Chandar, Sukhdeep Kaur, Richard Marlink, Tina Mayer, Peter Vuylsteke, Tlotlo Ralefala. Development and Implementation of a Case-based Virtual Training Program for Oncologic Emergencies in Botswana [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 84.

e15515 Background: Colorectal cancers (CRC) with pathogenic mutations in POLE (mPOLE) represent a unique subgroup with distinct clinical and molecular features and may exhibit a robust response to immune checkpoint blockade. Due to low prevalence, clinical features of this subgroup remain incompletely characterized. Methods: We utilized data from the Oncology Research Information Exchange Network (ORIEN) , using the Total Cancer Care (TCC) protocol in 18 centers across the US, to identify mPOLE CRC cases through October 2020. Prevalence, genomic and clinical features of mPOLE CRC within ORIEN were compared with other public databases, including AACR GENIE (version 8.0) , TCGA pan-cancer atlas, and a cohort from DFCI via cbioportal . Given the small sample size of mPOLE patients in each cohort, we pooled available data to compare characteristics of mPOLE CRC with CRC cases without pathogenic mutations in POLE (wtPOLE). Results: Detailed results are illustrated in the table. Out of 1564 CRC patients in ORIEN, 140 patients (9%) had POLE mutations, but only 11 patients (<1%) had pathogenic POLE mutations, compared to <2% in TCGA, <1% in DFCI, and <0.5% in the AACR GENIE cohorts. mPOLE CRC was associated with significantly higher tumor mutational burden and lower copy number alterations in all cohorts with data. In ORIEN, median age at diagnosis was significantly lower in mPOLE patients and at least 5 years younger than mPOLE patients from other cohorts. No other variable was statistically significant within ORIEN. When available clinical data from all cohorts were pooled, mPOLE was significantly associated with male sex, younger age at diagnosis, and early stage (I/II) disease. Conclusions: The ORIEN data set showed <1% patients with pathogenic POLE mutations. When pooled with the available public data sets, we see emergence of a unique clinical phenotype. Additional outcome data from ORIEN TCC database will be reported. We acknowledge the participation and assistance of the ORIEN investigators, with thanks. wtPOLE vs mPOLE in pooled and individual large cohort studies.[Table: see text]

Abstract Introduction: Anxiety and depression are well-documented comorbid conditions that many patients with head and neck cancer experience. Furthermore, radiation therapy for many head and neck cancers is associated with significant morbidity. Dysgeusia, in particular, is almost universally experienced with total taste loss occurring in up to 73% of individuals radiated for head and neck cancers. Prior studies have demonstrated a significant correlation between decreased quality of life and dysgeusia. In this retrospective study, we wish to further characterize the association between taste disturbance and patient-reported anxiety and mood. With better understanding of this relationship, we may be able to effectively intervene in improving the quality of life for head and neck patients. Methods: Forty-nine patients at The University of Vermont Medical Center who completed radiation therapy for head and neck cancer completed the University of Washington Quality of Life (QOL) Questionnaire at scheduled follow-up visits. Surveys were reviewed retrospectively for QOL measures, specifically patient-reported anxiety, mood, and taste. Results: Taste scores were the lowest at follow-up weeks 0-3 and more than tripled by the last follow-up, at 48 weeks (p>0.0001). The trend in taste improvement was most rapid during the first few weeks after radiation, but leveled off after 12 weeks. Mood and anxiety similarly improved across weeks after radiation when compared against taste. Conclusion: Our data suggest a correlation between taste disturbance, mood, and anxiety in patients after head and neck radiation. This suggests that targeting treatments to improve patients’ sense of taste post-radiation may improve their psychiatric well-being. Citation Format: Thomas Arnell, Quinn Self, Sharon Li, Carl Nelson. Dysgeusia may play a role in negatively affecting mood and anxiety in post-radiation head and neck patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A20.

Meta-regression and Wald-type tests with Bonferroni correction were used to evaluate primary and secondary outcomes with respect to treatment modality.Results: Fifty-eight studies met inclusion criteria; of these, 24 used CE, 13 used MMS, 19 used EBRT, and 7 used BT (5 studies not mutually exclusive in modality), with a combined 21,371 patients.Median age was 74 years and median follow-up was 35 months across all RT studies.Median age was 68 years and median follow-up was 47 months across all surgery studies.Summary eff ect size for "good" cosmesis was 81.0% (95% CI: 70.6-89.6%),74.6% (95% CI: 63.0-84.6%),and 97.6% (95% CI: 91.3-100%) for CE, EBRT, and BT, respectively.Good cosmesis was 96% in the only MMS study that reported cosmesis outcome.BT had improved good cosmesis over EBRT (p=0.0025), but there was no signifi cant diff erence between CE and BT based on p-value with Bonferroni correction.Summary eff ect size for "fair" cosmesis was 17.4% (95% CI: 8.6-28.4%),18.2% (95% CI: 7.8-31.7%),and 0.9% (95% CI: 0-5.6%) for CE, EBRT, and BT, respectively.BT had improved fair cosmesis over EBRT (p=0.0139) and CE (p=0.0159).Poor cosmesis summary eff ect sizes were similar for all modalities.1-year LR summary eff ect sizes were similar: 0.8% (95% CI: 0.3-1.6%),0.2% (95% CI: 0-0.6%), 2.0% (95% CI: 1.3-2.7%),and 0% (95% CI: 0-0.5%) for CE, MMS, EBRT, and BT, respectively.5-year LR summary eff ect sizes were also similar: 2.1% (95% CI: 1.0-3.5%),1.8% (95% CI: 1.1-2.7%),and 2.5% (95% CI: 0.8-5.1%)for CE, MMS, and BT, respectively.However, EBRT demonstrated inferior 5-year LR summary eff ect size to both surgical modalities at 6.7% (95% CI: 5.0-8.5%)(p<0.0001).Conclusions: For early, cutaneous BCCs and SCCs, BT and MMS have improved cosmesis over EBRT and CE.It is unclear if this is due to treatment superiority or selection and reporting bias.Local control is similar among all modalities at 1-year.

e15069 Background: Immune checkpoint inhibitors have become an integral part of treatment for a variety of malignancies. Given the favorable side effect profile compared to chemotherapy, there is increased interest in using immunotherapy in senior adults. Unfortunately, there is limited and conflicting data exploring the effect of age on checkpoint blockade efficacy and toxicity. We hypothesize that due to increased immune-senescence, older patients will experience less treatment limiting immune toxicity. Methods: A total of 170 patients were identified as receiving anti CTLA-4 or -1/PDL-1 antibodies between 2012 and 2017 at TJUH. Data was analyzed by age cohorts: age < 65, age 65-74, and age > 75. Chi-square analysis was used to compare the various reasons for therapy discontinuation between age groups. Results: 47% of patients were less than age 65; 37% were between age 65 and 75 and 16% of patients were older than age 75. Baseline characteristics between the groups were similar. Median CCI and RMH score was similar across the groups. Interestingly, the rate of immune toxicity requiring therapy discontinuation was higher among patients > 75 compared to < 65 though not significantly different (p = .098). Conversely, rates of disease progression while on immunotherapy were significantly higher in patients < 65 compared to those > 75 years (p = value here 0.037). Conclusions: Despite evidence for immuno-senescence in the elderly, rates of immune toxicity did not differ significantly by age. Further studies are needed to explore interplay of aging, the immune system and check point inhibitors. Reasons for Discontinuing Checkpoint Blockade, n (%) Age Group (yrs) < 65 65-75 > 75 Number of Patients 80 (47.1) 63 (37.0) 27 (15.9) Number of disease sites; mean (median) 2.91 (3) 2.82 (3) 3.08 (3) Charleston Comorbidity Index at Immunotherapy Initiation; mean (median) 0.76 (1) 0.80 (1) 1.41 (1) Royal Marsden Score at Immunotherapy Initiation; mean (median) 7.22 (8) 8.85 (9) 8.22 (9) Doses of Immunotherapy; mean (median) 7.6 (4) 7.6 (4) 8.7 (4.5) Disease progression Rate 32 (40.0) 33 (52.4) 6 (22.2) Immunotoxicity Rate 10 (12.5) 13 (20.6) 7 (25.9) Death Rate 9 (11.3) 6 (9.5) 4 (18.5) Never discontinued treatment 21 (26.3) 6 (9.5) 5 (18.5)

e15068Background: Immune Checkpoint Blockade (ICB) has demonstrated efficacy across a variety of tumor types. However, treatment is often complicated by immune related adverse events (irAEs), leadi...

e15095 Background: Immune checkpoint blockade is being used with increasing frequency across a variety of tumor types. Corticosteroids are used in diverse clinical scenarios and can have immune-modulatory effects. The administration of steroids with immune checkpoint blockade in combination with cytotoxic chemotherapy has not diminished treatment efficacy in select patient populations1. However, the effect of steroids on the development of immune-related adverse events (irAEs) across tumor types is unknown. We hypothesized that pretreatment with corticosteroids reduces treatment-limiting irAEs. Methods: A single institution registry of patients (n = 163) receiving immune checkpoint blockade, including anti-CTLA-4 antibody (n = 51) or anti-PD-1 antibody (n = 112), was reviewed. Various primary tumor types were included (33% melanoma, 31% non-small cell lung, 36% other). Patients were determined to have discontinued treatment because of irAEs versus any other cause (disease progression, infection, comorbidity, or death). Results: None of the 17 patients (0%) who were receiving corticosteroids prior to starting immunotherapy experienced treatment-limiting irAEs (average dose 34mg/day prednisone or equivalent, only one patient taking < 10mg/day prednisone). This is compared to 29 of 146 patients (19.9%) who were not taking steroids at the start of treatment (p = 0.045). Interestingly, pretreatment steroids were not associated with an increase in disease progression or death. Conclusions: Incidence of treatment-limiting immune-related adverse events was significantly decreased, regardless of tumor type, in patients receiving corticosteroids prior to initiation of immunotherapy. An associated decrease in treatment efficacy was not seen. Table: Incidence of treatment-limiting adverse events in patients undergoing immunotherapy Treatment-Limiting Adverse Events - n (%) Immune Infection or Comorbidity Disease Progression or Death Ongoing Treatment Total On Steroids When Immunotherapy Initiated? Yes 0 (0) 7 (41.1) 8 (47.1) 2 (11.8) 17 (100) No 29 (19.9) 19 (13.0) 71 (48.6) 27 (18.5) 146 (100) Total 29 (17.8) 26 (16.0) 79 (48.4) 29 (17.8) 163 (100)