Epidemiology, treatment and outcomes of gastroenteropancreatic neuroendocrine neoplasms.

To investigate incidence, treatment patterns and outcomes of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) in the United States. The 2019 National Cancer Database was searched for adult GEP-NEN patients. Main outcomes included overall and site-specific incidence, treatment patterns, and overall survival (OS).

Tumor response assessment in hepatocellular carcinoma treated with immunotherapy: imaging biomarkers for clinical decision-making.

Objective: To compare the performance of 1D and 3D tumor response assessment for predicting median overall survival (mOS) in patients who underwent immunotherapy for hepatocellular carcinoma (HCC).

Methods: Patients with HCC who underwent immunotherapy between 2017 and 2023 and received multi-phasic contrast-enhanced MRIs pre- and post-treatment were included in this retrospective study. Tumor response was measured using 1D, RECIST 1.

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer.

Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital.

Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection.

Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival.

Design, Setting, And Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021.

NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.

Background: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.

Patients And Methods: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment.

Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer.

Background: For patients with operable locally advanced esophageal carcinoma (LA-EC), we hypothesized that pre-operative induction chemotherapy followed by chemoradiotherapy (IC-CRT) would improve progression-free survival (PFS) and overall survival (OS) when compared to chemoradiotherapy (CRT).

Methods: This was a single institution retrospective cohort study including patients with LA-EC who received preoperative-intent IC-CRT CRT between 2013-2019. The Kaplan-Meier method was used to estimate OS and PFS.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies.

Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer.

Purpose: O-methylguanine DNA methyltransferase ()-silenced tumors reveal sensitivity to temozolomide (TMZ), which may be enhanced by PARP inhibitors. Approximately 40% of colorectal cancer has silencing and we aimed to measure antitumoral and immunomodulatory effects from TMZ and olaparib in colorectal cancer.

Experimental Design: Patients with advanced colorectal cancer were screened for promoter hypermethylation using methylation-specific PCR of archival tumor.

Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer.

Background And Purpose: Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC.

Clinical care in hepatocellular carcinoma: A mixed methods assessment of experiences and challenges of oncology professionals.

Introduction: Healthcare providers (HCPs) may face numerous dilemmas in optimally screening, diagnosing, and treating patients with, and/or at risk for, hepatocellular carcinoma (HCC). This study aimed to achieve a greater understanding of the challenges in HCC care which in turn could delineate HCP educational opportunities within this oncologic sub-specialty.

Methods: A mixed-methods approach was used to identify practice gaps and clinical barriers experienced by US-based medical oncologists, hepatologists, oncology physician assistants, oncology nurse practitioners, and interventional radiologists involved in HCC care.

PD-1 targeted immunotherapy for advanced hepatocellular carcinoma: current utilization and outcomes in the USA.

To evaluate the utilization and outcomes of PD-1-directed immunotherapy (PD-1 IMT) for advanced hepatocellular carcinoma. Patients with advanced hepatocellular carcinoma receiving systemic therapy and PD-1 IMT (nivolumab/pembrolizumab) were included from the Flatiron database. Overall survival (OS) was evaluated using multivariable Cox models with the following subgroup analyses: patients with data on clinical performance and liver function and patients receiving tyrosine kinase inhibitors.

Clinical outcomes of first line FOLFIRINOX gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System.

Background: FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GN) are established first line therapies for metastatic pancreatic cancer (MPC). There are, however, no randomized controlled trials comparing FFX and GN in the first line setting and real-world data on their comparative effectiveness is limited. We aimed to evaluate the outcomes of patients with MPC who were treated with first line FFX and GN and to further characterize dose modifications, discontinuation rates due to treatment toxicity, and rates of hospitalizations while on treatment.

Safety, Efficacy, and Biomarker Results from a Phase Ib Study of the Anti-DKK1 Antibody DKN-01 in Combination with Pembrolizumab in Advanced Esophagogastric Cancers.

Therapeutic combinations targeting innate and adaptive immunity and predictive biomarkers of response in esophagogastric cancer (EGC) are needed. We assessed safety and clinical utility of DKN-01 (a novel DKK1-neutralizing IgG4 antibody) combined with pembrolizumab and retrospectively determined DKK1 tumoral expression as a biomarker. Patients with advanced EGC received intravenous DKN-01 (150 or 300 mg) on days 1 and 15 with pembrolizumab 200 mg on day 1 in 21-day cycles.

Real-world association of HER2/ concordance with trastuzumab clinical benefit in advanced esophagogastric cancer.

To assess concordance between HER2 status measured by traditional methods and amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Retrospective analysis of HER2/ concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2 advanced esophagogastric cancer who received first-line trastuzumab.

The effect of chronic viral hepatitis on prognostic value of inflammatory biomarkers in hepatocellular carcinoma.

Background: Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis.

Methods: Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution.

Moving Beyond the Momentum: Innovative Approaches to Clinical Trial Implementation.

Despite efforts to enhance enrollment and the merger of national cooperative groups, < 5% of patients with cancer will enroll into a clinical trial. Additionally, clinical trials are affected by a lack of diversity inclusive of minority patients, rural residents, or low-income individuals. COVID-19 further exacerbated known barriers of reduced physician-patient interaction, physician availability, trial activation and enrollment, financial resources, and capacity for conducting research.

Microsatellite Instability and KRAS Mutation in Stage IV Colorectal Cancer: Prevalence, Geographic Discrepancies, and Outcomes From the National Cancer Database.

Background: This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC).

Materials And Methods: The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability-high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed.

Evaluation of the Cost-effectiveness of Doublet Therapy in Metastatic BRAF Variant Colorectal Cancer.

Importance: The BEACON trial showed that combination therapy with encorafenib (BRAF inhibitor) and cetuximab (EGFR inhibitor) was associated with prolonged overall survival compared with standard chemotherapy in patients with metastatic BRAF variant colorectal cancer. However, the cost-effectiveness of using these agents in this clinical setting is unknown.

Objective: To create a cost-effectiveness model to compare doublet therapy (encorafenib plus cetuximab) with standard chemotherapy (cetuximab plus irinotecan or cetuximab plus folinic acid, fluorouracil, and irinotecan) in treating patients with metastatic BRAF variant colorectal cancer.

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis.

Purpose: Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown.

A phase 1b expansion study of TAS-102 with oxaliplatin for refractory metastatic colorectal cancer.

Background: TAS-102, a novel antimetabolite, is approved for treatment of refractory metastatic colorectal cancer (CRC). This study sought to determine whether the addition of TAS-102 to oxaliplatin (TAS-OX) was safe and effective in metastatic CRC previously treated with oxaliplatin.

Methods: This investigator-initiated, open-label, single-arm phase 1b study enrolled patients with metastatic CRC previously treated with 5-fluorouracil, irinotecan, and oxaliplatin.

Reliable prediction of survival in advanced-stage hepatocellular carcinoma treated with sorafenib: comparing 1D and 3D quantitative tumor response criteria on MRI.

Objectives: To compare 1D and 3D quantitative tumor response criteria applied to DCE-MRI in patients with advanced-stage HCC undergoing sorafenib therapy to predict overall survival (OS) early during treatment.

Methods: This retrospective analysis included 29 patients with advanced-stage HCC who received sorafenib for at least 60 days. All patients underwent baseline and follow-up DCE-MRI at 81.

Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer.

Purpose: Dickkopf-1 (DKK1) modulates Wnt signaling, promoting tumor growth, metastasis, and immunosuppression. High DKK1 expression has been detected in various tumor types-including biliary tract cancer (BTC)-and is associated with poor prognosis. DKN-01-a humanized mAb targeting DKK1-was evaluated in a phase I multicenter study in combination with gemcitabine and cisplatin in patients with unresectable or metastatic BTC with no prior systemic therapy for advanced disease.

A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer.

Objectives: In the 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) era, the benefit of surgery versus definitive radiation for borderline resectable (BR) and locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC) is not well defined. Our primary objective was to identify the survival impact of surgery for BR and LA unresectable PDAC treated with induction FOLFIRINOX.

Methods: We performed a single-center retrospective review of BR and LA PDAC treated with FOLFIRINOX from 2010 to 2018.