What Is the Optimal Locoregional Approach for Recurrent Hepatocellular Carcinoma?

Journal Journal of Clinical Oncology

BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy.

Appendiceal Adenocarcinoma (AA) is a rare gastrointestinal cancer with no FDA-approved targeted therapies. Here, we retrospectively compare BRAF-mutant AA and colorectal cancer (CRC). BRAF mutation is rare in AA (3%).

Meta-analysis of randomized controlled trials of external-beam radiation versus transarterial chemoembolization for hepatocellular carcinoma.

Background: External-beam radiation (EBRT) is a noninvasive therapeutic alternative to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). The objective of this study was to conduct a systematic review and meta-analysis of prospective randomized clinical trials to assess the clinical efficacy of EBRT versus TACE for HCC as either a definitive monotherapy or as a bridge to transplantation/surgery.

Methods: A systematic review and meta-analysis were performed to include prospective randomized trials comparing EBRT versus TACE.

Barriers to Offering Organ Preservation for Rectal Cancer in a Predominantly Hispanic Safety Net Hospital.

Background: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has shown promise in achieving pathologic complete response (pCR) and enabling organ preservation through watch-and-wait (WW) strategies. However, implementation of WW protocols in diverse patient populations and safety-net hospitals faces unique challenges. The objective of this study is to evaluate TNT outcomes and identify barriers to WW implementation in a predominantly Hispanic safety-net hospital in South Texas.

Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.

Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS).

Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset.

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations.

Association between Mutations and Expression in Paired Pancreatic Ductal Adenocarcinoma Tumor Specimens: Data from Two Independent Molecularly-Characterized Cohorts.

Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC). alterations and low expression/modified "Moffitt" basal-like phenotype have each been associated with inferior survival uniquely for patients receiving 5-FU-based therapies. may directly regulate the expression of in PDAC, pointing to a common predictive biomarker.

Genomic Biomarkers Associated with Response to Induction Chemotherapy in Patients with Localized Pancreatic Ductal Adenocarcinoma.

Purpose: There is increasing use of neoadjuvant chemotherapy in the management of localized pancreatic ductal adenocarcinoma (PDAC), yet there are few validated biomarkers to guide therapy selection. We aimed to determine whether somatic genomic biomarkers predict response to induction FOLFIRINOX or gemcitabine/nab-paclitaxel.

Experimental Design: This single-institution cohort study included consecutive patients (N = 322) with localized PDAC (2011-2020) who received at least one cycle of FOLFIRINOX (N = 271) or gemcitabine/nab-paclitaxel (N = 51) as initial treatment.

Local Therapy for Oligoprogression or Consolidation in High Mutational Burden Stage 4 Colorectal Cancer Treated With PD-1 or PD-L1 Blockade.

Background: Immune checkpoint blockade (ICI) of programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1) can induce durable responses in patients who have colorectal cancer (CRC) with a high tumor mutational burden (TMB). Two recurring clinical dilemmas show how to manage oligoprogressive disease and stable disease after ICI.

Methods: A cohort study was conducted to analyze patients with metastatic CRC who underwent PD-1 or PD-L1 blockade.

Alterations in Somatic Driver Genes Are Associated with Response to Neoadjuvant FOLFIRINOX in Patients with Localized Pancreatic Ductal Adenocarcinoma.

Background: There is increased use of neoadjuvant fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the management of localized pancreatic ductal adenocarcinoma (PDAC), yet there are few validated biomarkers of treatment response.

Study Design: Consecutive patients (n = 196) with resectable, borderline resectable or locally advanced PDAC (2012-2019) receiving FOLFIRINOX as initial treatment and with targeted sequencing of a pretreatment biopsy were identified in a prospective institutional database. Genomic alterations were determined in the 4 driver mutations (KRAS, TP53, CDKN2A, SMAD4), and associations between genomic alterations and clinical outcomes were assessed.

Validation of the Memorial Sloan Kettering Gastric Cancer Post-Resection Survival Nomogram: Does It Stand the Test of Time?

Background: The Memorial Sloan Kettering Cancer Center (MSK) nomogram combined both gastroesophageal junction (GEJ) and gastric cancer patients and was created in an era from patients who generally did not receive neoadjuvant chemotherapy. We sought to reevaluate the MSK nomogram in the era of multidisciplinary treatment for GEJ and gastric cancer.

Study Design: Using data on patients who underwent R0 resection for GEJ or gastric cancer between 2002 and 2016, the C-index of prediction for disease-specific survival (DSS) was compared between the MSK nomogram and the American Joint Committee on Cancer (AJCC) 8th edition staging system after segregating patients by tumor location (GEJ or gastric cancer) and neoadjuvant treatment.

Genomic Stratification of Resectable Colorectal Liver Metastasis Patients and Implications for Adjuvant Therapy and Survival.

Objective: To determine whether genomic risk groups identified by somatic mutation testing of colorectal liver metastasis (CRLM) can be used for "molecularly-guided" selection for adjuvant systemic chemotherapy and hepatic artery infusion of FUDR (SYS+HAI-FUDR).

Background: Several genomic biomarkers have been associated with clinical phenotype and survival for patients with resectable CRLM. It is unknown whether prognostication afforded by genomic stratification translates into enhanced patient selection for adjuvant hepatic artery infusion therapy.

Hepatocellular Carcinoma-Circulating Tumor Cells Expressing PD-L1 Are Prognostic and Potentially Associated With Response to Checkpoint Inhibitors.

Hepatocellular carcinoma (HCC) is a leading cause of mortality. Checkpoint inhibitors of programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown great efficacy, but lack biomarkers that predict response. Circulating tumor cells (CTCs) have promise as a liquid-biopsy biomarker; however, data on HCC CTCs expressing PD-L1 have not been reported.

Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells.

Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling.

A Prognostic Scoring System for the Prediction of Metastatic Recurrence Following Curative Resection of Pancreatic Neuroendocrine Tumors.

Background: Patients with early-stage pancreatic neuroendocrine tumors (PNETs) may develop metastatic recurrences despite undergoing potentially curative pancreas resections. We sought to identify factors predictive of metastatic recurrences and develop a prognostication strategy to predict recurrence-free survival (RFS) in resected PNETs.

Methods: Patients with localized PNETs undergoing surgical resection between 1989 and 2015 were identified.

Pancreatic cancer circulating tumor cells: applications for personalized oncology.

Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC. Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs.

A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma.

Current clinicopathologic staging systems and serum biomarkers poorly discriminate tumor biology in hepatocellular carcinoma (HCC), with high recurrence rates following curative-intent surgical resection and liver transplantation (LT). Identification of accurate biomarkers for improved prognostication and treatment selection is a critical unmet need. We sought to develop a novel "liquid-biopsy" assay capable of detecting HCC circulating tumor cells (CTCs) and characterizing phenotypic subpopulations with prognostic significance.

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

Background: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients.

Experimental Design: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay.

A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.

Background And Objectives: Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence.

Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection.

Precision oncology using a limited number of cells: optimization of whole genome amplification products for sequencing applications.

Background: Sequencing analysis of circulating tumor cells (CTCs) enables "liquid biopsy" to guide precision oncology strategies. However, this requires low-template whole genome amplification (WGA) that is prone to errors and biases from uneven amplifications. Currently, quality control (QC) methods for WGA products, as well as the number of CTCs needed for reliable downstream sequencing, remain poorly defined.

Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens.

Applications of precision oncology strategies rely on accurate tumor genotyping from clinically available specimens. Fine needle aspirations (FNA) are frequently obtained in cancer management and often represent the only source of tumor tissues for patients with metastatic or locally advanced diseases. However, FNAs obtained from pancreas ductal adenocarcinoma (PDAC) are often limited in cellularity and/or tumor cell purity, precluding accurate tumor genotyping in many cases.

Reality of Single Circulating Tumor Cell Sequencing for Molecular Diagnostics in Pancreatic Cancer.

To understand the potential and limitations of circulating tumor cell (CTC) sequencing for molecular diagnostics, we investigated the feasibility of identifying the ubiquitous KRAS mutation in single CTCs from pancreatic cancer (PC) patients. We used the NanoVelcro/laser capture microdissection CTC platform, combined with whole genome amplification and KRAS Sanger sequencing. We assessed both KRAS codon-12 coverage and the degree that allele dropout during whole genome amplification affected the detection of KRAS mutations from single CTCs.