Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade.

Background: Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy.

Methods: From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins.

PET-CT-based host metabolic (PETMet) features are associated with pathologic response in gastroesophageal adenocarcinoma.

Background: F-FDG PET-CT-based host metabolic (PETMet) profiling of non-tumor tissue is a novel approach to incorporate the patient-specific response to cancer into clinical algorithms.

Materials And Methods: A prospectively maintained institutional database of gastroesophageal cancer patients was queried for pretreatment PET-CTs, demographics, and clinicopathologic variables. F-FDG PET avidity was measured in 9 non-tumor tissue types (liver, spleen, 4 muscles, 3 fat locations).

Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma.

Differences in Ancestry and Presence of Gastric Precursor Lesions in Individuals With Young- and Average-Onset Gastric Cancer.

Background: There has been a paradoxical rise in young-onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self-reported race is also poorly characterized and may be unreliable as a proxy for genetic differences.

Treatment outcomes of non-curative endoscopic submucosal dissection for superficial gastric neoplasia: A retrospective study at a tertiary care center in the United States.

Objectives: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer; additional treatment may be recommended for patients in whom resection is not curative per the American Society for Gastrointestinal Endoscopy guidelines. The aim of this study was to assess treatment outcomes of ESD for gastric neoplasia, with a focus on cases of non-curative resection.

Methods: This was a retrospective study of all individuals undergoing ESD for the treatment of gastric adenocarcinoma or dysplasia in a high-volume tertiary care center in the United States.

Disappearing Signet Ring Cell Adenocarcinoma in Gastric Cancer Patients.

Background: The incidence of diffuse-type gastric cancer is increasing steadily in the United States, Europe, and Asia. This subtype is known for aggressive clinical characteristics and transmural invasion. However, T1a diffuse-type cancers have been observed to have a better 5-year, disease-specific mortality than stage-matched intestinal tumors, supporting a clinical difference in these early-stage cancers.

Feasibility and Efficacy of Sentinel Lymph Node Mapping in Gastric Cancer.

Background: Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC.

PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.

Purpose: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples.

Methods: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263).

F-BMS-986229 PET to Assess Programmed-Death Ligand 1 Status in Gastroesophageal Cancer.

Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient's disease course, and repeated biopsies are invasive and not always feasible.

Patient metabolic profile defined by liver and muscle F-FDG PET avidity is independently associated with overall survival in gastric cancer.

Background: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care.

Methods: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient.

Unveiling lipid-rich ("clear cell") pancreatic neuroendocrine tumor: A small series of two cases with literature review.

This study presents two cases of lipid-rich pancreatic neuroendocrine tumors (PanNETs), a rare variant posing significant diagnostic challenges in fine needle aspiration (FNA) cytology and small biopsies. The first case involves an elderly male with a pancreatic tumor, displaying distinct cytoplasmic vacuoles, while the second case is a middle-aged male present with a pancreatic tail mass exhibiting foamy cytoplasm and eccentric nuclei, infiltrating in the stroma. Both cases did not exhibit typical morphologic features of PanNET but demonstrated cytomorphologic features and infiltrative growth patterns that mimicked adenocarcinoma.

Morphologic Heterogeneity of Carcinoma with Signet Ring Cell Features at Different Primary Sites.

Introduction: Signet ring cells (SRCs) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features, which can aid in identifying the site of origin.

Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer.

Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer .

Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

Background: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection.

Materials And Methods: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019.

Unique Genomic Alterations and Microbial Profiles Identified in Patients With Gastric Cancer of African, European, and Asian Ancestry: A Novel Path for Precision Oncology.

Objective: Here, we characterize differences in the genetic and microbial profiles of GC in patients of African (AFR), European, and Asian ancestry.

Background: Gastric cancer (GC) is a heterogeneous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes..

A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients With Esophageal Adenocarcinoma.

Objective: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC).

Background: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC.

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines . Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin).

Factors associated with detection of hereditary diffuse gastric cancer on endoscopy in individuals with germline CDH1 mutations.

Background And Aims: Individuals with germline pathogenic CDH1 variants have a high risk of hereditary diffuse gastric cancer. The sensitivity of EGD in detecting signet ring cell carcinoma (SRCC) in this population is low. We aimed to identify endoscopic findings and biopsy practices associated with detection of SRCC.