Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.

Integrated Capecitabine-Temozolomide with Radioembolization for Liver-Dominant G2 NETs: Long-Term Outcomes of a Single-Institution Retrospective Study.

Purpose: Capecitabine-Temozolomide (CapTem) is an oral chemotherapy regimen for NETs. Both drugs are radiosensitizers. Integrating CapTem and Y90 transarterial radioembolization (TARE) in patients with grade 2 neuroendocrine tumor (NET) liver metastases achieved an encouraging objective response rate (ORR) and progression-free survival (PFS) in a feasibility study.

The Clinical Implications of Reversions in Patients with Advanced Pancreatic Cancer and Pathogenic Variants in BRCA1, BRCA2, or PALB2 after Progression on Rucaparib.

Purpose: PARP inhibitors (PARPi) provide an effective maintenance option for patients with BRCA- or PALB2-mutated pancreatic cancer. However, mechanisms of PARPi resistance and optimal post-PARPi therapeutic strategies are poorly characterized.

Experimental Design: We collected paired cell-free DNA samples and post-PARPi clinical data on 42 patients with advanced, platinum-sensitive pancreatic cancer who were treated with maintenance rucaparib on NCT03140670, of whom 32 developed progressive disease.

Multianalyte Prognostic Signature Including Circulating Tumor DNA and Circulating Tumor Cells in Patients With Advanced Pancreatic Adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Multianalyte signatures, including liquid biopsy and traditional clinical variables, have shown promise for improving prognostication in other solid tumors but have not yet been rigorously assessed for PDAC.

Materials And Methods: We performed a prospective cohort study of patients with newly diagnosed locally advanced pancreatic cancer (LAPC) or metastatic PDAC (mPDAC) who were planned to undergo systemic therapy.

Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI): Study Protocol for a Pragmatic Implementation Trial for Establishing and Screening to Guide Chemotherapy Dosing.

Background: Fluoropyrimidines (fluorouracil [5-FU], capecitabine) and irinotecan are commonly prescribed chemotherapy agents for gastrointestinal (GI) malignancies. Pharmacogenetic (PGx) testing for germline and variants associated with reduced enzyme activity holds the potential to identify patients at high risk for severe chemotherapy-induced toxicity. Slow adoption of PGx testing in routine clinical care is due to implementation barriers, including long test turnaround times, lack of integration in the electronic health record (EHR), and ambiguity in test cost coverage.

Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial.

Background: Establishing alternatives to lifelong chemotherapy for patients with advanced pancreatic cancer has been proposed to address chemotherapy resistance and cumulative toxicity. Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in this setting, and concurrent immune checkpoint blockade could offer synergistic tumour control. The aim of this study was to test the safety and antitumour activity of maintenance with PARP inhibition combined with immune checkpoint blockade in patients with advanced pancreatic cancer who had a stable response to platinum-based chemotherapy.

Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer.

Background: The antiangiogenic tyrosine kinase inhibitor regorafenib provides a survival benefit in patients with previously treated metastatic colorectal cancer (CRC). Antiangiogenic therapy causes hypoxic stress within tumor cells, which activates autophagy as a survival mechanism. The histone deacetylase inhibitor (HDAC) entinostat increases dependence on autophagy through epigenetic mechanisms.

Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation.

Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice.

Methods: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies.

Concurrent Nab-paclitaxel and Radiotherapy: Novel Radiosensitization for Borderline Resectable or Unresectable Pancreatic Cancer.

Purpose: This study evaluates the toxicity and tumor response with concurrent nab-paclitaxel chemoradiotherapy (CRT) compared with standard (5-fluorouracil or gemcitabine) CRT.

Materials And Methods: Fifty patients with borderline resectable or unresectable pancreatic adenocarcinoma from 2014 to 2017 were divided into 2 groups: concurrent nab-paclitaxel (100 to 125 mg/m2 weekly) CRT (median: 2.1 Gy fraction size and 52.

Quantifying the impact of the COVID-19 pandemic on gastrointestinal cancer care delivery.

Background And Aim: This study quantifies how changes in healthcare utilization and delivery during the first months of the COVID-19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system.

Methods And Results: Patients diagnosed with a GI malignancy (ICD10: C15-C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre-pandemic (weeks 1-10) and early pandemic (weeks 11-20) study periods.

Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in , , or .

Purpose: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline or pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in , , or .

Patients And Methods: Eligible patients had advanced PC; germline (g) or somatic (s) PVs in , , or , and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance.

DPYD and UGT1A1 Pharmacogenetic Testing in Patients with Gastrointestinal Malignancies: An Overview of the Evidence and Considerations for Clinical Implementation.

Gastrointestinal (GI) malignancies are among the most commonly diagnosed cancers worldwide. Despite the introduction of targeted and immunotherapy agents in the treatment landscape, cytotoxic agents, such as fluoropyrimidines and irinotecan, remain as the cornerstone of chemotherapy for many of these tumors. Pharmacogenetics (PGx) is a rapidly evolving field that accounts for interpatient variability in drug metabolism to predict therapeutic response and toxicity.

Phase II Trial of Palbociclib in Patients with Advanced Esophageal or Gastric Cancer.

Lessons Learned: Palbociclib monotherapy demonstrated minimal clinical activity in patients with previously treated gastroesophageal cancers. Further clinical evaluation of palbociclib monotherapy is not warranted in gastroesophageal cancers, but improved understanding of resistance mechanisms may permit rational combination approaches.

Background: Dysregulation of the cell cycle is a hallmark of cancer.

Retrospective Survival Analysis of Patients With Resected Pancreatic Ductal Adenocarcinoma and a Germline or Mutation.

Purpose: Germline mutations in the homologous recombination genes , , and confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in homologous recombination genes are sensitive to DNA-damaging agents. We retrospectively studied patients with resected PDAC and a pathogenic germline mutation in one of these three genes.

Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Autophagy is a mechanism of treatment resistance to chemotherapy that has a role in the maintenance of pancreatic cancer. Hydroxychloroquine sulfate (HCQ) is an inhibitor of autophagy that inhibits the fusion of the autophagosome to the lysosome.

Objective: To determine whether HCQ improves overall survival at 1 year in combination with gemcitabine hydrochloride and nab-paclitaxel (GA) among patients with metastatic pancreatic cancer.

Efficacy of Oral Cryotherapy During Oxaliplatin Infusion in Preventing Oral Thermal Hyperalgesia: A Randomized Trial.

Background: Chemotherapy-induced oral thermal hyperalgesia (OTH) is a common and debilitating side effect of platinum-based anticancer agents. This study evaluated the efficacy of oral cryotherapy in preventing OTH during oxaliplatin chemotherapy infusion.

Methods: Patients with gastrointestinal cancer treated with biweekly oxaliplatin (85 mg/m2 over 120 minutes) at Abramson Cancer Center at the University of Pennsylvania were randomized to receive oral cryotherapy (ice chips) during oxaliplatin infusion or standard-of-care treatment.

Safety and Feasibility of Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 Liver-Dominant Metastatic Neuroendocrine Tumors.

Objectives: An integrated protocol combining capecitibine-temozolomide with yttrium-90 radioembolization (CapTemY90) for liver-dominant grade 2 neuroendocrine tumors (NETs) was designed in the hope of achieving synergistic improvement in liver disease control with no more than additive toxicities. This report describes the feasibility and safety of this regimen.

Methods: Twenty-one patients with unresectable grade 2 NET liver-dominant metastases without contraindications to radioembolization or to CapTem initiated therapy with capecitabine 600 mg/m twice daily for 14 days and temozolomide 150 to 200 mg/m in 2 divided doses on days 10 to 14, with 14 days between cycles.

E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors.

Lessons Learned: Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer.

Purpose: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine.

Fluoropyrimidine-induced cardiac toxicity: challenging the current paradigm.

Background: Fluoropyrimidine chemotherapy [5-fluorouracil (5-FU) and capecitabine] are commonly used agents in the treatment of various solid malignancies. However, their use has been limited by cardiac toxicity, presenting as a wide spectrum of asymptomatic (e.g.

Efficacy of Peptide Receptor Radionuclide Therapy in a United States-Based Cohort of Metastatic Neuroendocrine Tumor Patients: Single-Institution Retrospective Analysis.

Objectives: The aim of this study was to analyze in a retrospective cohort study the outcomes of a United States-based group of metastatic neuroendocrine tumor (NET) patients who underwent peptide receptor radionuclide therapy (PRRT).

Methods: Twenty-eight patients from a single US NET Center were treated with PRRT. Toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.

Proton beam reirradiation for locally recurrent pancreatic adenocarcinoma.

Background: Local recurrence following definitive treatment for pancreatic adenocarcinoma is common and can be associated with significant morbidity and mortality. Retreatment options for these patients are limited. Proton beam reirradiation (PRT) may limit dose and toxicity to previously irradiated normal tissues in patients without evidence of metastatic disease.

Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment.

Purpose: For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 μmol/L) depending upon the regimen.

Imaging Tests for the Diagnosis and Staging of Pancreatic Adenocarcinoma: A Meta-Analysis.

Imaging tests are central to the diagnosis and staging of pancreatic adenocarcinoma. We performed a systematic review and meta-analysis of the pertinent evidence on 5 imaging tests (computed tomography (CT), magnetic resonance imaging, CT angiography, endoscopic ultrasound with fine-needle aspiration, and combined positron emission tomography with CT). Searches of several databases up to March 1, 2014, yielded 9776 articles, and 24 provided comparative effectiveness of 2 or more imaging tests.

The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN).

Background: The literature investigating pancreatic invasive intraductal papillary mucinous neoplasm (IPMN) has largely come from small institutional studies, preventing adequately powered comparisons of adjuvant therapy versus surgery alone (SA) within specific patient subgroups.

Methods: Patients with resected, stage I through IV, invasive IPMN and conventional pancreatic ductal adenocarcinoma (PDAC) were identified in the National Cancer Data Base (1998-2010). Cox modeling of patients with invasive IPMN was used to compare overall survival (OS) between patients who received adjuvant therapy and those who underwent SA.