Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.

Preventing Chronic Disease (PCD) is a peer-reviewed electronic journal established by the National Center for Chronic Disease Prevention and Health Promotion. PCD provides an open exchange of information and knowledge among researchers, practitioners, policy makers, and others who strive to improve the health of the public through chronic disease prevention.

Eponyms have historically been used to honor individual contributions or discoveries in the field of medicine. More recently, some eponyms have been criticized for imprecision or for being misnomers. Eponyms attributed to discoveries made by Nazi German scientists have also fallen out of favor. However, despite these criticisms, eponyms remain popular for their ease of use. Eponyms generate interest in medical history and may help humanize the study of medicine. Here, we describe several eponyms in medical oncology with a focus on basic disease pathophysiology, epidemiology, and brief background on the individuals for whom the eponym was named.

Checkpoint inhibitors have shown improvement in recurrence-free survival in the post-operative setting for node-positive melanoma and were first approved in late 2015. However, single-agent checkpoint therapies have yet to show benefit to overall survival (OS) for lower-risk stage III cancers. We evaluated the OS benefit of post-operative immunotherapy in the National Cancer Database (NCDB). Patient cases were selected from the NCDB 2020 Participant Use File. Patients diagnosed with stage III cutaneous melanoma between 2016 and 2019 who underwent definitive resection for their melanoma were included. OS between those who received post-operative immunotherapy within 84 days of surgery and those who did not was analyzed by the Kaplan-Meier method. Demographic and clinical characteristics between the two groups were compared via Cox proportional hazard models. 14 978 patients with stage III melanoma were included. Of those, 34.9% (n = 5234) received post-operative immunotherapy and 65.1% (n = 9744) did not. Using the American Joint Committee on Cancer version 8 (AJCCv8) staging, 36-month survival was significantly higher in patients who received post-operative immunotherapy compared to no post-operative systemic therapy in those diagnosed with stage IIIB (88.0% versus 84.7%, P = 0.011), IIIC (75.6% versus 68.1%, P < 0.001), or IIID (59.2% versus 48.4%, P = 0.002). No significant improvement in 36-month survival was seen in patients who received post-operative immunotherapy in patients with stage IIIA disease (93.0% versus 92.2%, P = 0.218). Post-operative immunotherapy had an OS benefit in patients with AJCCv8 stage IIIB, IIIC, and IIID disease, but had no significant survival benefit for patients with stage IIIA melanomas.

Purpose: We analyzed adherence to the National Comprehensive Cancer Network treatment guidelines for anal squamous cell carcinoma in California and the associated impacts on survival. Methods: This was a retrospective study of patients in the California Cancer Registry aged 18 to 79 years with recent diagnoses of anal squamous cell carcinoma. Predefined criteria were used to determine adherence. Adjusted odds ratios and 95% confidence intervals were estimated for those receiving adherent care. Disease-specific survival (DSS) and overall survival (OS) were examined with a Cox proportional hazards model. Results: 4740 patients were analyzed. Female sex was positively associated with adherent care. Medicaid status and low socioeconomic status were negatively associated with adherent care. Non-adherent care was associated with worse OS (Adjusted HR 1.87, 95% CI = 1.66, 2.12, p < 0.0001). DSS was worse in patients receiving non-adherent care (Adjusted HR 1.96, 95% CI = 1.56, 2.46, p < 0.0001). Female sex was associated with improved DSS and OS. Black race, Medicare/Medicaid, and low socioeconomic status were associated with worse OS. Conclusions: Male patients, those with Medicaid insurance, or those with low socioeconomic status are less likely to receive adherent care. Adherent care was associated with improved DSS and OS in anal carcinoma patients.

Introduction: MCC is a rare and highly aggressive cutaneous neuroendocrine carcinoma with increasing incidence over the last few decades. Cytotoxic chemotherapy and checkpoint inhibitors have provided modest treatment options, however, there are no approved or standard of care targeted treatment options. Here we surveyed the presence of targetable alterations in the AACR Project Genie Database Methods: Individual patient data were accessed from the cBioPortal. Variables of interest include demographic data, alterations annotated by OncoKB therapeutic evidence level, and TCGA PanCancer pathway alterations. Results: A total of 295 patients with MCC were cataloged in the database. Patients included were 34.6% (n=102) female with a median age of 71. Patients identified race as 91.2% (n=269) white, 2.4% (n=7) African American, and 0.4% (n=2) Asian. The median number of alterations was 3.00 (SD 21.4, Range 0-178). Oncogenic alterations represented 17.4% (n=660 of 3799) of mutations. Sampled tissue originated from primary tumor in 54% (n=161) verses metastases in 42.4% (n=125). NGS identified 18.5% (n=55) with an FDA approved drug for use in a biomarker approved indication or approved drug in another indication (Level 1-3). An additional 13.9% (n=41) had a Level 4 (L4) mutation. The most common Level 3B gene mutations include PIK3CA (4.1%, n=12), and BRCA1/2 (4.1%, n=12), HRAS (1.7%, n=5), TSC1/2 (1.7%, n=5). The most common L4 mutations include PTEN (4.4%, n=13), ARID1A (3.7%, n=11), and CDKN2A (2.4%, n=7). Only three fusions were identified; L3B fusions ATM-CDK12 and TSC2 along with Level 4 PTEN. Copy number alterations were identified in a small subset of patients. L3B CNAs include ATM, CHEK1 (n=1), BARD1 (n=1), BRCA2 (n=1), RAD51B (n=1), RAD51D (n=1). Level 4 CNAs identified CDKN2A (n=4) and PTEN (n=1). In 60.7% cases, PanCancer pathways were altered and 28.5% had alterations in multiple pathways. The most commonly altered pathways were RTK-RAS (37.6%, n=111), TP53 (33.9%, n=100), Cell Cycle (33.9, n=100), PI3K (32.2%, n=95) and NOTCH (30.8%, n=91). Additionally, oncogenic DNA damage repair gene alterations (BRCA1/2, CHEK1/2, ATM, PALB2, BRIP1, RAD51) were present in 7.5% (n=22) of cases. Conclusions: Here we identified a subset of patients with targetable mutations in MCC. The majority of patients had oncogenic alterations in cancer pathways which may support the investigation of kinase inhibitors as single agent or in combination with immunotherapy or cytotoxic chemotherapy in Merkel Cell Carcinoma. Citation Format: Danielle Brazel, Priyanka Kumar, Hung Doan, Justin T. Moyers. Survey of genomic alterations in Merkel cell carcinoma (MCC) in the AACR Project Genie real-world database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1185.