Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Role of gene expression in colorectal cancer: a comprehensive molecular profiling study.

Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages.

Disparities in Clinical Trial Participation: A Cross-Sectional Survey of Cancer Patients at a Midwest Academic Medical Center.

Research conducted on homogenous populations can lead to biased and misleading findings, impeding the development of effective interventions and treatments for diverse populations. Low participation among minority groups further leads to disparities in access to innovative cancer care and treatment outcomes associated with trial participation. To better understand cancer patients' attitudes and willingness to participate in clinical trials, solid tumor patients attending their clinic visits were invited to complete a survey.

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649).

Failure to Undergo Resection Following Neoadjuvant Therapy for Resectable Pancreatic Cancer: A Secondary Analysis of SWOG S1505.

Background: Neoadjuvant therapy (NT) is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC), and yet reasons for not undergoing subsequent pancreatectomy are poorly understood. Given the importance of completing multimodality therapy, we investigated factors associated with failure to undergo surgical resection following NT for PDAC.

Methods: SWOG S1505 was a multicenter phase II randomized trial of preoperative mFOLFIRINOX or gemcitabine/nab-paclitaxel prior to planned pancreatectomy for patients with potentially resectable PDAC.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

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.

First-in-Class Humanized Antibody against Alternatively Spliced Tissue Factor Augments Anti-Metastatic Efficacy of Chemotherapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma.

Alternatively spliced tissue factor (asTF) promotes the progression of pancreatic ductal adenocarcinoma (PDAC) by activating β1-integrins on PDAC cell surfaces. hRabMab1, a first-in-class humanized inhibitory anti-asTF antibody we recently developed, can suppress PDAC primary tumor growth as a single agent. Whether hRabMab1 has the potential to suppress metastases in PDAC is unknown.

Body composition measurements and clinical outcomes in patients with resectable pancreatic adenocarcinoma - analysis from SWOG S1505.

Background: Sarcopenic obesity and muscle attenuation have been associated with survival in patients with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA); however, these relationships are unknown for patients with resectable PDA. This study examined the associations between skeletal muscle and adipose tissue as measured on baseline computed tomography (CT) and the overall survival (OS) of participants with resectable PDA in a secondary analysis of the Southwest Oncology Group S1505 clinical trial (identifier: NCT02562716).

Methods: The S1505 phase II clinical trial enrolled patients with resectable PDA who were randomized to receive modified FOLFIRINOX or gemcitabine and nab-paclitaxel as perioperative chemotherapy, followed by surgical resection.

Intratumoral Cell Neighborhoods Coordinate Outcomes in Pancreatic Ductal Adenocarcinoma.

Background & Aims: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes.

Immune checkpoint inhibitors in liver transplant: a case series.

Background: Immune checkpoint inhibitors (ICIs) in the setting of liver transplant (LT) pose a risk of rejection and hold unclear benefit in both the neoadjuvant (pre-transplant) and post-transplant salvage setting. In the pre-transplant setting, neoadjuvant ICIs may serve as a bridge to LT by downstaging disease burden to fit within transplant criteria. Outcomes in this setting include patients who had successful transplants without complications to patients who suffered severe complications, including fatal hepatic necrosis and graft failure requiring re-transplant.

Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

Purpose: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT).

Methods: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation.

Microbiomic profiles of bile in patients with benign and malignant pancreaticobiliary disease.

Background: The prognostic and pathophysiologic significance of the biliary microbiota in pancreaticobiliary malignancies is little understood. Our goal was to find malignancy-related microbiomic fingerprints in bile samples taken from patients with benign and malignant pancreaticobiliary diseases.

Methods: Bile specimens were collected from consenting patients during routine endoscopic retrograde cholangiopancreatography.

Development of an artificial intelligence-derived histologic signature associated with adjuvant gemcitabine treatment outcomes in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has been left behind in the evolution of personalized medicine. Predictive markers of response to therapy are lacking in PDAC despite various histological and transcriptional classification schemes. We report an artificial intelligence (AI) approach to histologic feature examination that extracts a signature predictive of disease-specific survival (DSS) in patients with PDAC receiving adjuvant gemcitabine.

Analysis of the fecal metagenome in long-term survivors of pancreas cancer.

Background: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota.

Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study.

Background: Genomic signatures contributing to high tumour mutational burden (TMB-H) independent from mismatch-repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status are not well studied. We aimed to characterise molecular features of microsatellite stable (MSS) TMB-H gastrointestinal tumours.

Methods: Molecular alterations of 48 606 gastrointestinal tumours from Caris Life Sciences (CARIS) identified with next-generation sequencing were compared among MSS-TMB-H, dMMR/MSI-H, and MSS-TMB-low (L) tumours, using χ or Fisher's exact tests.

Pancreatic Adenocarcinoma Management.

The management of pancreatic ductal adenocarcinoma (PDAC) has evolved over the last two decades. Surgical resection remain the only potential cure for this cancer. Therefore, there is an emerging emphasis on neoadjuvant therapy to maximize the probability of resection, and identify failures early.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials.

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem.

A National Assessment of T2 Staging for Intrahepatic Cholangiocarcinoma and the Poor Prognosis Associated with Multifocality.

Background: T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors.

Methods: The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC.

Is There a Benefit to Adjuvant Chemotherapy in Resected, Early Stage Pancreatic Ductal Adenocarcinoma?

Background: The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease.

Methods: The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC.

Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma.

Objective: Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed the efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC).

Methods: We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687).