Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

Introduction: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes.

Methods: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC.

A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier.

Purpose: Intrahepatic cholangiocarcinoma (IHC) is a heterogeneous tumor. The hidden-genome classifier, a supervised machine learning-based algorithm, was used to quantify tumor heterogeneity and improve classification.

Experimental Design: A retrospective review of 1,370 patients with IHC, extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC), hepatocellular carcinoma (HCC), or biphenotypic tumors was conducted.

The Prognostic Nutritional Index in patients with microsatellite instability-high metastatic gastric or gastroesophageal cancers receiving immune checkpoint inhibitors.

Background: Microsatellite instability high (MSI-H) and/or mismatch repair deficient (dMMR) status is the strongest predictive factor for immune checkpoint inhibitors (ICIs) benefit in patients with metastatic gastroesophageal cancer (mGC). Primary resistance to ICIs is a relevant issue, but prognostic and predictive factors are lacking.

Materials And Methods: In this multinational, retrospective cohort of patients with MSI-H/dMMR mGC treated with ICIs without chemotherapy we collected baseline laboratory values to establish the prognostic nutritional index (PNI).

Precision medicine for pancreatic cancer: characterizing the clinicogenomic landscape and outcomes of KRAS G12C-mutated disease.

Background: Mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogene alteration in pancreatic ductal adenocarcinoma, and KRAS glycine to cystine substitution at codon 12 (G12C) mutations (KRAS G12Cmut) are observed in 1%-2%. Several inhibitors of KRAS G12C have recently demonstrated promise in solid tumors, including pancreatic cancer. Little is known regarding clinical, genomics, and outcome data of this population.

Clinical utility of plasma cell-free DNA in pancreatic neuroendocrine neoplasms.

In advanced pancreatic neuroendocrine neoplasms (PanNEN), there are little data detailing the frequency of genetic alterations identified in cell free DNA (cfDNA), plasma-tissue concordance of detected alterations, and clinical utility of cfDNA. Patients with metastatic PanNENs underwent cfDNA collection in routine practice. Next-generation sequencing (NGS) of cfDNA and matched tissue when available was performed.

Impact of infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors.

Background: Gut microbiota composition can influence cancer immunotherapy response. Recent evidence suggests infection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact of on survival in this population.

Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma.

Purpose: Next-generation sequencing (NGS) of tumor-derived, circulating cell-free DNA (cfDNA) may aid in diagnosis, prognostication, and treatment of patients with hepatocellular carcinoma (HCC). The operating characteristics of cfDNA mutational profiling must be determined before routine clinical implementation.

Methods: This was a single-center, retrospective study with the primary objective of defining genomic alterations in circulating cfDNA along with plasma-tissue genotype agreement between NGS of matched tumor samples in patients with advanced HCC.

Clinical Utility of F-2-Fluoro-deoxy-d-glucose PET Imaging in Locally Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma.

Esophageal adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, is uncommon in the United States, but is associated with a rising incidence in young adults, and has a traditionally poor prognosis. Despite the incremental benefits that have been made with multimodality approaches to locally advanced disease, most patients will go on to develop metastatic disease, and long-term outcomes remain suboptimal. Over the last decade, PET-CT has emerged as a key tool in the management of this disease, with several prospective and retrospective studies evaluating its role in this disease.

Durvalumab and PET-Directed Chemoradiation in Locally Advanced Esophageal Adenocarcinoma: A Phase Ib/II Study.

Objective: To determine the safety and efficacy of adding the anti-PD-L1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma.

Background: Neoadjuvant induction FOLFOX followed by positron emission tomography (PET) directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is clear benefit now for the addition of immune checkpoint inhibitors both in early and advanced stage disease.

Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma.

Importance: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis.

Objectives: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival.

Design, Setting, And Participants: In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021.

Emerging RAS-directed therapies for cancer.

RAS oncogenes are the most commonly mutated oncogenes in human cancer, and RAS-mutant cancers represent a major burden of human disease. Though these oncogenes were discovered decades ago, recent years have seen major advances in understanding of their structure and function, including the therapeutic and prognostic significance of diverse isoforms. Targeting of these mutations has proven difficult, despite some successes with inhibition of RAS effector signalling.

Advanced Bile Duct Cancers: A Focused Review on Current and Emerging Systemic Treatments.

Cancers arising in the biliary tract are rare, with varied incidence depending on geographical location. As clinical presentation is typically vague with non-specific symptoms, a large proportion of patients present with unresectable or metastatic disease at diagnosis. When unresectable, the mainstay of treatment is cytotoxic chemotherapy; however, despite this, 5-year overall survival remains incredibly poor.

ATM Germline-Mutated Gastroesophageal Junction Adenocarcinomas: Clinical Descriptors, Molecular Characteristics, and Potential Therapeutic Implications.

Background: Gastroesophageal junction (GEJ) adenocarcinoma is a rare cancer associated with poor prognosis. The genetic factors conferring predisposition to GEJ adenocarcinoma have yet to be identified.

Methods: We analyzed germline testing results from 23 381 cancer patients undergoing tumor-normal sequencing, of which 312 individuals had GEJ adenocarcinoma.

COVID-19-related mortality in cancer patients in an Irish setting.

Background: The COVID-19 pandemic has impacted significantly on healthcare across the globe. It has been reported to have higher incidence and be associated with worse outcomes in patients with cancer.

Aim: To examine the characteristics of patients with cancer who were diagnosed with COVID-19 and to identify factors which may predict a poorer outcome.

Delivery of systemic anti-cancer therapy during the COVID-19 pandemic.

Background: The first confirmed case of COVID-19 in Ireland was on February 29th 2020. From March until late April, the number of cases increased exponentially. The delivery of anti-cancer therapy during the COVID-19 pandemic was extremely challenging.

Chemotherapy in the Covid-19 era: the patient's perception.

Background: The Covid-19 pandemic poses significant challenges for the management of patients with cancer. In our institution, we adapted our delivery of outpatient systemic anti-cancer therapy (SACT) by introducing a number of 'risk-reducing' measures including pre-assessment screening.

Aims: We sought to evaluate the experience and perceptions of patients with cancer undergoing SACT during the Covid-19 pandemic.

Hepatic Resection for Disappearing Liver Metastasis: a Cost-Utility Analysis.

Background: We sought to estimate the cost-effectiveness of hepatic resection (HR) (strategy A) relative to surveillance plus 6 months of additional systemic chemotherapy (sCT) (strategy B) for patients with colorectal disappearing liver metastases (DLM).

Methods: A Markov model was developed using data from a systematic literature review. Three base cases were evaluated: (1) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT, had normalized carcinoembryonic antigen (CEA), and was diagnosed with DLM through a computed tomography (CT) scan; (2) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT, had normalized CEA, and was diagnosed with DLM through a magnetic resonance imaging (MRI) scan; and (3) a 60-year-old patient with three lesions in the right hemi-liver who underwent 6 months of sCT plus hepatic artery infusion (HAI), had normalized CEA, and was diagnosed with DLM through a MRI scan.