Multi-omics machine learning to study host-microbiome interactions in early-onset colorectal cancer.

The incidence of early-onset colorectal cancer (eoCRC) is rising, and its pathogenesis is not completely understood. We hypothesized that machine learning utilizing paired tissue microbiome and plasma metabolome features could uncover distinct host-microbiome associations between eoCRC and average-onset CRC (aoCRC). Individuals with stages I-IV CRC (n = 64) were categorized as eoCRC (age ≤ 50, n = 20) or aoCRC (age ≥ 60, n = 44).

Differences in tumor-associated T-cell receptor repertoires between early-onset and average-onset colorectal cancer.

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020.

COMPANION-002 A clinical trial of investigational drug CTX-009 plus paclitaxel vs paclitaxel in second line advanced BTC.

Treatment options for patients with biliary tract cancer are limited, and the prognosis is poor. CTX-009, a novel bispecific antibody targeting both DLL4 and VEGF-A, has demonstrated antitumor activity in patients with advanced cancers as both a monotherapy and in combination with chemotherapy. In a phase II study of patients with advanced biliary tract cancer who had received one or two prior therapies, CTX-009 with paclitaxel demonstrated a 37.

Tumor Mutational Burden From Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance.

Objective: Describe the utility of circulating tumor DNA in the postoperative surveillance of hepatocellular carcinoma (HCC).

Background: Current biomarkers for HCC like alpha-fetoprotein (AFP) are lacking. Circulating tumor DNA (ctDNA) has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown.

Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: A novel pretransplant protocol.

We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag.

Colorectal Cancer Screening in Free Clinics: A Systematic Review.

Objective: There are significant inequities in colorectal cancer (CRC) screening and outcomes. Via literature review, we assessed CRC screening rates for the vulnerable populations served by free clinics.

Methods: A systematic review was conducted for publications on CRC screening in free clinics.

Emerging and Clinically Accepted Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients.

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept.

Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored.

Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included.

Plasma metabolomic differences in early-onset compared to average-onset colorectal cancer.

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I-IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or  ≥ 60 years (aoCRC or older non-CRC controls).

Preoperative Strategies for Locally Advanced Colon Cancer.

Neoadjuvant chemotherapy is safe for patients with locally advanced colon cancer (LACC). The FOxTROT trial demonstrated a reduction in residual and recurrent cancer at 2 years with neoadjuvant chemotherapy for patients with cT3-4 LACC. Preoperative chemotherapy should be avoided, if possible, for patients with dMMR LACC, as over 50% of dMMR cancers have no pathologic response.

Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer.

Background: The unexplained rise of young-onset CRC (yoCRC, age <50 years) is of concern. Evidence suggests that microbial dysbiosis may be a contributing factor, but the tumor microbial profile of yoCRC in comparison to average-onset CRC (aoCRC, age >60) has not been fully investigated.

Methods: 16S rRNA amplicon sequencing was performed in tumor and paired adjacent non-malignant fresh frozen tissue specimens prospectively collected from 136 yoCRC and 140 aoCRC patients.

Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs.

Disparities in National Cancer Institute and Nonprofit Organization Funding Disproportionately Affect Cancers With Higher Incidence Among Black Patients and Higher Mortality Rates.

Purpose: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy but may not be equitable across cancers.

Methods: This study evaluated funding from the NCI and NPOs supporting lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers, leukemia, lymphoma, and melanoma from 2015 to 2018. The primary objectives were to assess for funding disparities across different cancers compared with their incidence and mortality and across racial groups.

A Narrative Medicine Pilot Curriculum for Internal Medicine Residents.

Narrative medicine (NM) is the practice of reflecting on patient stories, which can improve physician empathy and has been linked to higher levels of well-being. We implemented a NM curriculum for a large internal medicine residency program and report the curriculum's positive effects.

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

Background And Aims: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC.

Immunotherapy Plus Locoregional Therapy Leading to Curative-Intent Hepatectomy in HCC: Proof of Concept Producing Durable Survival Benefits Detectable with Liquid Biopsy.

Background: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

Background: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC.

Circulating Tumor DNA in Colorectal Cancer Liver Metastasis: Analysis of Patients Receiving Liver Resection and Transplant.

Purpose: Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool.

Methods: Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit.

Immunotherapy for Advanced Hepatocellular Carcinoma-a Large Tertiary Center Experience.

Introduction: Combination of immune-checkpoint inhibitor (ICI) and vascular endothelial growth factor (VEGF) antagonist has become the first line systemic treatment for advanced hepatocellular carcinoma (HCC). However, two-thirds of patients do not respond to ICI-based treatments and biomarkers for response remain elusive.

Methods: Patients with advanced HCC who received Atezolizumab/Bevacizumab combination or Nivolumab during 2016-2022 were identified in our Liver Cancer Database.

Liquid Biopsy by ctDNA in Liver Transplantation for Colorectal Cancer Liver Metastasis.

Introduction: Colorectal cancer is a leading cause of cancer-related death worldwide. Metastatic liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach.

Biomarkers for Response to Anti-PD-1/Anti-PD-L1 Immune Checkpoint Inhibitors: A Large Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) that block PD-1/PD-L1 have consistently demonstrated durable clinical activity across multiple histologies but have low overall response rates for many cancers-indicating that too few patients benefit from ICIs. Many studies have explored potential predictive biomarkers (eg, PD-1/PD-L1 expression, tumor mutational burden [TMB]), no consensus biomarker has been identified.

Methods: This meta-analysis combined predictive accuracy metrics for various biomarkers, across multiple cancer types, to determine which biomarkers are most accurate for predicting ICI response.