Publications by authors named "Abou-Alfa G"

Background: Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers; however, subset analyses of intrahepatic cholangiocarcinoma (IHC) show limited survival benefit. This study evaluated the impact of adjuvant chemotherapy on recurrence patterns and overall survival (OS) in patients with resected IHC.

Methods: Patients who underwent curative-intent resection for IHC were identified within a bi-institutional dataset and the National Cancer Database (NCDB).

View Article and Find Full Text PDF

Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events.

View Article and Find Full Text PDF

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.

View Article and Find Full Text PDF
Article Synopsis
  • - This study investigates how specific genetic variants affect survival and recurrence in patients with different types of biliary tract cancers (BTCs), focusing on intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder adenocarcinoma (GB).
  • - Out of 985 patients analyzed, 15% had significant mutations, with IHC and EHC showing the highest mutation rates (38% and 37%, respectively). Patients with mutations in IHC had a notably worse survival rate compared to those with wild-type tumors.
  • - The findings highlight that G12 mutations in IHC are particularly detrimental to patient outcomes, underscoring the need for tailored therapies
View Article and Find Full Text PDF

Background: This article aims to present the single-institution outcomes of patients with Fibrolamellar Carcinoma (FLC) treated with liver-directed therapies (LDT).

Methods: In this single-center retrospective study, all patients diagnosed with FLC who underwent LDT were identified. Between July 2012 and July 2023, six patients were identified.

View Article and Find Full Text PDF
Article Synopsis
  • Adjuvant mFOLFIRINOX (mFFX) is a standard treatment for patients with resected pancreatic ductal adenocarcinoma (PDAC), but there is limited information on its effectiveness outside of clinical trials.
  • A study of 147 patients showed a median recurrence-free survival (RFS) of 26 months, with some patients over 70 years experiencing a median overall survival (OS) of 51 months.
  • Starting mFFX treatment within 8 weeks of surgery was linked to better survival outcomes, while certain genetic factors like KRAS mutations suggested poorer RFS and OS.
View Article and Find Full Text PDF
Article Synopsis
  • Advanced biliary tract cancer (BTC) patients may benefit from fluoropyrimidine-based chemotherapy, but no direct comparisons between different regimens had been previously conducted.
  • An individual patient-level meta-analysis was performed using data from two clinical trials to evaluate overall survival (OS) across different chemotherapy regimens, including nal-IRI plus 5-FU/LV, mFOLFOX, and mFOLFIRI.
  • Results showed that nal-IRI plus 5-FU/LV significantly improved OS compared to both mFOLFOX and mFOLFIRI, with notable side effects differing among regimens; thus, considering both effectiveness and safety is essential in treatment decisions.
View Article and Find Full Text PDF
Article Synopsis
  • Gallbladder cancer (GBC) is a highly lethal cancer with low overall incidence but higher prevalence in specific regions like Chile; this study compares clinical and molecular features of GBC patients from Chile and the US.
  • The study involved 260 patients, revealing a significantly higher rate of gallstones in the Chilean cohort and similar genetic alteration prevalence between the two groups, with overall alterations found in 14% of patients.
  • Patients with GBC having genetic alterations showed better overall survival rates, suggesting they may benefit from targeted therapies, highlighting the necessity for broader genomic analysis in regions with high GBC rates.
View Article and Find Full Text PDF
Article Synopsis
  • Hepatic artery infusion (HAI) chemotherapy combined with systemic treatment shows promising long-term results for patients with intrahepatic cholangiocarcinoma (IHC), suggesting improved disease control and overall survival rates.
  • A phase II clinical trial and a retrospective analysis revealed a median progression-free survival (PFS) of 11.8 months and overall survival (OS) of 26.8 months among a subset of patients, with particular genomic alterations indicating worse outcomes.
  • The study indicates that HAI with floxuridine (FUDR) alongside systemic therapies can provide durable disease control in locally advanced IHC, while molecular changes, particularly in the TP53 pathway, might help predict patient response to treatment.
View Article and Find Full Text PDF

Background & Aims: In the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was non-inferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs.

View Article and Find Full Text PDF

Background: Management of intrahepatic cholangiocarcinoma (IHC) has advanced in recent decades, including randomized trial evidence supporting systemic therapy in the palliative and adjuvant setting. Mounting observational evidence suggests resection of IHC with multifocal disease (IHC-MF) or lymph node metastasis (IHC-LNM) should be limited. It is unknown how real-world practice has evolved in light of research advances.

View Article and Find Full Text PDF

Purpose: This study aimed to define genomic differences between perihilar cholangiocarcinoma (PCA) and distal cholangiocarcinoma (DCA) and identify genomic determinants of survival.

Materials And Methods: Consecutive patients with ECA with tissue for targeted next-generation sequencing were analyzed, stratified by anatomic site (PCA/DCA), disease extent, and treatment. Associations between genomic alterations, clinicopathologic features, and outcomes were analyzed using Cox proportional hazards regression to compare survival.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Introduction: Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the neurosensory retina. In this report, we outline 3 cases of a rarely documented toxicity, MEK inhibitor-associated ocular hypertension.

View Article and Find Full Text PDF

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.

View Article and Find Full Text PDF

Purpose: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.

View Article and Find Full Text PDF

Introduction: Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy.

Methods: This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment.

View Article and Find Full Text PDF

Purpose: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC).

Methods: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations.

View Article and Find Full Text PDF

Background: Oncologists are prescribing checkpoint inhibitors with greater frequency, and an awareness of and ability to recognize immune-related adverse events (irAEs) is a key part of the safe administration of these drugs.

Case Description: Herein, we report the case of a 26-year-old male diagnosed with metastatic right-sided colon cancer to the liver, with tumor immunohistochemistry demonstrating loss of and , and a pathogenic mutation in identified on germline testing, consistent with Lynch Syndrome. The patient received first-line treatment with pembrolizumab.

View Article and Find Full Text PDF

Biliary tract cancers continue to increase in incidence and have a high mortality rate. Most of the patients present with advanced-stage disease. The discovery of targetable genomic alterations addressing IDH, FGFR, HER2, BRAFV600 E, and others has led to the identification and validation of novel therapies in biliary cancer.

View Article and Find Full Text PDF