Decitabine reverses innate immune gene suppression in rare melanomas.

Rare melanoma subtypes, including acral, mucosal, and uveal melanomas, exhibit limited responses to immune checkpoint inhibitors (ICIs), yet the molecular mechanisms of immune resistance remain poorly defined. Here, we performed transcriptomic profiling of patient-derived xenografts (PDXs) and publicly available tumor datasets to systematically compare intratumoral gene expression across cutaneous and rare melanoma subtypes. We identified a convergent downregulation of innate immune pathogen sensing (IIPS) and type I interferon signaling pathways in rare melanomas compared to cutaneous, with lower expression also observed in anti-PD-1 non-responder tumors.

Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma: long-term survival update.

Background: Primary analysis of the phase I/II clinical trial combining pembrolizumab with all-trans retinoic acid (ATRA) for patients with metastatic melanoma showed a median progression-free survival (PFS) of 20.3 months and median overall survival (OS) not reached.

Objective: Report 5-year OS and PFS rates.

Ongoing Implications of the COVID-19 Pandemic Environment on Esophageal Cancer Characteristics and Treatment in the United States.

Background: The first year of the COVID-19 pandemic significantly impacted the characteristics and care of esophageal cancer patients. We aimed to assess for continued implications of the altered healthcare landscape on esophageal cancer presentation and treatment in the second year of the pandemic.

Methods: This was a retrospective review of the United States National Cancer Database (2019-2021).

Impact of socioeconomic determinants of health on delays to care in gastric cancer: A national cancer database analysis.

Introduction: The impact of demographic and socioeconomic backgrounds on delays to cancer care and subsequent mortality for those with resectable gastric adenocarcinoma is not well studied. We sought to investigate the relationship between sociodemographic determinants of health, delays to consensus guideline therapy, and survival outcomes for gastric cancer.

Methods: Patients with gastric cancer from the National Cancer Database (2004-2020) were partitioned into early-stage (AJCC Stage 0-I) and locoregionally advanced (Stage II-resectable stage IV) disease receiving upfront surgery and neoadjuvant therapy (NAT) followed by surgical resection, respectively.

Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) in young adults (age of diagnosis < 50 years old) has been rapidly increasing. Although ~20% of early-onset (EO) CRC cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Non-genetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased incidence of sporadic EOCRC.

Real world experience with omission of therapeutic lymph node dissection in clinical stage III malignant melanoma treated with checkpoint or kinase inhibition systemic therapy.

Background: Management of clinical stage III melanoma, which historically was treated with surgical therapeutic lymph node dissection (TLND), has changed significantly due to the introduction of effective systemic therapies including immune checkpoint and BRAF/MEK inhibitors. We asked how surgical interventions changed progression free survival and overall survival in this population.

Methods: The Flatiron Health electronic health records database for Advanced Melanoma was queried for patients with clinical stage III melanoma treated between 2018 and 2022 with systemic therapy.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Patient, facility, and surgical factors associated with significant delays to esophagectomy and subsequent poor outcomes: An analysis of 16,486 cases.

Objective: Delays to definitive surgery in esophageal cancer may be associated with disease progression and worsened survival. The objective of this study was to perform a national assessment for predictors of delay to esophagectomy and to assess for their impact on oncologic and survival outcomes.

Methods: The National Cancer Database, 2010 to 2020, was queried for patients with locally advanced esophageal adenocarcinoma (stage I-III).

More May Not Be Better: Comparison of Oncologic Outcomes Following Induction Chemotherapy Plus Chemoradiation and Chemoradiation Alone for Esophageal Adenocarcinoma.

Introduction: The oncologic benefit of induction chemotherapy (IC) before chemoradiation (CRT) compared to CRT alone for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is not well defined. We hypothesized that IC with CRT would improve survival and pathologic complete response rate compared to CRT alone.

Methods: A retrospective review of patients with biopsy proven esophageal or GEJ adenocarcinoma treated with preoperative CRT and IC + CRT and surgical resection from 2007 to 2023 at a single institution was performed.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Introduction: Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking.

Methods: A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted.

Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study.

Background: This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC).

Methods: A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data.

Pathological Features Associated with Lymph Node Disease in Patients with Appendiceal Neuroendocrine Tumors.

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis.

Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma.

Background: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis.

Methods: Retrospective chart review was performed.

The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.

Unlabelled: Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICI). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs.

Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center.

MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule inhibitors that bind and inhibit anti-apoptotic members of the BCL2 family proteins such as BCL2 or MCL1, have been very successful in treating hematologic malignancies.

The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

Background: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied.

Methods: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022).

Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.

Introduction: Epstein-Barr virus-associated gastric cancer (EBVaGC) may be a meaningful biomarker for potential benefit from immunotherapy. Further investigation is needed to characterize the immune landscape of EBVaGC. We assessed our institutional frequency of surgically treated EBVaGC and analyzed the immunologic biomarker profile and tumor-infiltrating lymphocyte (TIL) phenotypes of a series of EBVaGC compared to non-EBVaGC cases.

A Bioinformatics Tool for Identifying Intratumoral Microbes from the ORIEN Dataset.

Unlabelled: Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses.

Differences in Co-Expression of T Cell Co-Inhibitory and Co-Stimulatory Molecules with PD-1 Across Different Human Cancers.

Purpose: The promise of immune checkpoint inhibitor (ICI) therapy underlines the importance of comprehensively investigating the rationale for combinations with diverse immune modulators across different cancer types. Given the progress made with PD1 blockade to date, we examined mRNA co-expression levels of PD-1 with 13 immune checkpoints, including co-inhibitory receptors (LAG3, CTLA4, PD-L1, TIGIT, TIM3, VISTA, BTLA) and co-stimulatory molecules (CD28, OX40, GITR, CD137, CD27, HVEM), using RNA-Seq by Expectation-Maximization (RSEM).

Methods: We analyzed real-world clinical and transcriptomic data from the Total Cancer Care Protocol (NCT03977402) and Avatar project of patients with cancer treated within the Oncology Research Information Exchange Network (ORIEN) network.