Impact of Positive Resection Margins on Recurrence and Survival Following Resection and Adjuvant Chemotherapy in Pancreatic Cancer: Results of the PRODIGE 24-CCTG PA-6 Randomized Controlled Trial.

Objective: This study investigated the correlation between positive resection margins and outcomes in patients with pancreatic ductal adenocarcinoma who underwent surgery and adjuvant chemotherapy according to the pivotal trial PRODIGE 24-CCTG PA-6.

Background: The primary focus is on elucidating the prognostic significance of specific resection margins, including those associated with the superior-mesenteric vein (SMV), medial, and posterior pancreas.

Methods: The analysis involved 400 patients across multiple centers in France and Canada.

Development and validation of AI-assisted transcriptomic signatures to personalize adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma.

Background: After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine (GEM)-based regimens or the modified FOLFIRINOX (mFFX) regimen. While mFFX regimen has been shown to be more effective than GEM-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor.

Adjuvant Chemotherapy and Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Clinical Practice Guideline.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC).

Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma.

Background: Systemic inflammatory scores may aid prognostication and patient selection for trials. We compared five scores in advanced pancreatic adenocarcinoma (PDAC).

Methods: Unresectable/metastatic PDAC patients enrolled in the Comprehensive Molecular Characterisation of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection trial (NCT02750657) were included.

Comparative Effectiveness of FOLFIRINOX Versus Gemcitabine and Nab-paclitaxel in Initially Unresectable Locally Advanced Pancreatic Cancer: A Population-based Study to Assess Subsequent Surgical Resection and Overall Survival.

Aims: First-line FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan, and OXaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have been publicly funded for patients with unresectable locally advanced pancreatic cancer (uLAPC) in Ontario, Canada. We examined the overall survival and surgical resection rate after first-line FOLFIRINOX or GnP and determined the association between resection and overall survival in patients with uLAPC.

Materials And Methods: We conducted a retrospective population-based study including patients with uLAPC who received first-line treatment FOLFIRINOX or GnP from April 2015 to March 2019.

Impact of an Accelerated Diagnostic Assessment Program on the Timeliness of Cancer Diagnosis and Treatment.

Purpose: The Accelerated Diagnostic Assessment Program (ADAP) manages patients with imaging abnormalities, with or without concomitant symptoms, where cancer is suspected. The ADAP is offered to primary care practitioners and emergency departments with cases triaged by a medical oncologist.

Methods: We performed a retrospective patient chart review of electronic medical records from January 2019 until June 2021 to validate the program.

Outcomes Following Treatment with FOLFOX for Patients with Resectable or Potentially Resectable Metastatic Colorectal Cancer: A Population-based Cohort Study.

Aims: To evaluate the safety and effectiveness of oxaliplatin-based combination chemotherapy for patients with metastatic colorectal cancer (mCRC) to extrahepatic sites.

Materials And Methods: We conducted a population-based retrospective study examining the safety and effectiveness of perioperative oxaliplatin for resectable or potentially resectable colorectal metastases in Ontario, Canada. Outcomes were also compared with patients with liver-only metastases.

hENT1 Expression Predicts Response to Gemcitabine and Nab-Paclitaxel in Advanced Pancreatic Ductal Adenocarcinoma.

Purpose: Modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel (GnP) remain standard first-line options for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Human equilibrative nucleoside transporter 1 (hENT1) was hypothesized to be a biomarker of gemcitabine in the adjuvant setting, with conflicting results. In this study, we explore hENT1 mRNA expression as a predictive biomarker in advanced PDAC.

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial.

Importance: Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available.

Objective: To report 5-year outcomes and explore prognostic factors for overall survival.

Design, Setting, And Participants: This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization.

Preneoplastic Lesions in Surgical Specimens Do Not Worsen the Prognosis of Patients Who Underwent Surgery for Pancreatic Adenocarcinoma: Post-Hoc Analysis of the PRODIGE 24-CCTG PA 6 Trial.

Objective: The prognosis of pancreatic cancer after curative surgery is burdened by frequent recurrence. The aim of this study was to evaluate the impact of dysplasia in the surgical specimen on disease-free survival (DFS).

Methods: A post-hoc analysis of the phase III PRODIGE 24-CCTG PA 6 trial was performed.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

Background: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada.

Factor quinolinone inhibitors disrupt spindles and multiple LSF (TFCP2)-protein interactions in mitosis, including with microtubule-associated proteins.

Factor quinolinone inhibitors (FQIs), a first-in-class set of small molecule inhibitors targeted to the transcription factor LSF (TFCP2), exhibit promising cancer chemotherapeutic properties. FQI1, the initial lead compound identified, unexpectedly induced a concentration-dependent delay in mitotic progression. Here, we show that FQI1 can rapidly and reversibly lead to mitotic arrest, even when added directly to mitotic cells, implying that FQI1-mediated mitotic defects are not transcriptionally based.

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap.

Mass spectrometry imaging is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an atmospheric pressure (AP-) matrix-assisted laser desorption ionization (MALDI) source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices CHCA, norharmane, DHB, DHAP, THAP, and DAN in combination with tissue washing and matrix additives to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials.

Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit.

Design, Setting, And Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database.

A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination-deficient Pancreatic Cancer.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline or (g) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on g mutational status alone is associated with heterogeneous responses.

Experimental Design: We performed a seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which nine were g mutated.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline.

Objective: The purpose of the present review was to provide evidence-based guidance about the provision of cytoreductive surgery (crs) with hyperthermic intraperitoneal chemotherapy (hipec) in the treatment of peritoneal cancers.

Methods: The guideline was developed by the Program in Evidence-Based Care together with the Surgical Oncology Program at Ontario Health (Cancer Care Ontario) through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews.

Results: For patients with newly diagnosed stage iii primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, hipec should be considered for those with at least stable disease after neoadjuvant chemotherapy at the time that interval crs (if complete) or optimal cytoreduction is achieved.

GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer.

Purpose: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker.

Experimental Design: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review.

The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs.

Anterior segment optical coherence tomographic characterisation of keratic precipitates.

Background/objectives: Anterior segment optical coherence tomography (AS-OCT) can be used to visualise keratic precipitates (KPs) on the corneal endothelium. However, there has been no correlation between characteristic clinical appearances of KPs and AS-OCT morphology. We wished to assess the potential diagnostic role of AS-OCT in patients presenting with inflammatory eye disease and KPs.

Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis.

Background: In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.

Methods: Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database.

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer.

Background: Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.

Methods: We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks.