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Abstract Background The 2020 National Comprehensive Cancer Network guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab‐paclitaxel (G‐nP) for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC). Aim The purpose of our study was to compare treatment outcomes, toxicity profiles, costs, and quality‐of‐life measures between these two treatments to further inform clinical decision‐making. Methods and Results We developed a decision‐analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G‐nP over 12 years. The model inputs were estimated using clinical trial data and published literature. The primary endpoint was incremental cost‐effectiveness ratios (ICERs) with a willingness‐to‐pay threshold of $100 000 per quality‐adjusted‐life‐year (QALY). Secondary endpoints included overall (OS) and progression‐free survival (PFS), total cost of care, QALYs, PDAC resection rate, and monthly treatment‐related adverse events (TRAE) costs (USD). FOLFIRINOX was the cost‐effective strategy, with an ICER of $60856.47 per QALY when compared to G‐nP. G‐nP had an ICER of $44639.71 per QALY when compared to natural history. For clinical outcomes, more patients underwent an “R0” resection with FOLFIRINOX compared to G‐nP (84.9 vs. 81.0%), but FOLFIRINOX had higher TRAE costs than G‐nP ($10905.19 vs. $4894.11). A one‐way sensitivity analysis found that the ICER of FOLFIRINOX exceeded the threshold when TRAE costs were higher or PDAC recurrence rates were lower. Conclusion Our modeling analysis suggests that FOLFIRNOX is the cost‐effective treatment compared to G‐nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow‐up are needed to confirm our findings.

Abstract Background 16–25% of colorectal cancers (CRCs) diagnosed under age 50 are associated with hereditary cancer syndromes. Advanced adenomas are considered precursors to CRC. Although polyp removal prevents cancer, polypectomy does not change underlying genetic risk. Patients with isolated advanced polyps do not currently qualify for genetic testing unless they have a personal or family history of cancer. Aim Describe the prevalence of hereditary cancer syndromes among patients with advanced colorectal polyps. Methods We performed a single center retrospective review from 2015 to 2019 of patients who underwent germline genetic testing with indication for testing listed as colorectal polyp. We excluded patients with a personal history of CRC and those with ≥10 cumulative polyps. We collected patient demographics, polyp characteristics, family history data and genetic testing results from the medical record. Discrete variables were reported as frequency and percentages and continuous variables reported as mean with range. Results A total of 42 patients underwent genetic testing due to a personal history of advanced adenoma. 17% of patients met current genetic testing criteria. All patients underwent multi-gene panel testing. Two patients (4.8%) had a germline pathogenic mutation (one in MLH1 and one in CHEK2). The patient with an MLH1 mutation met current criteria for genetic testing (PREMM5 score 5.8), however the patient with the CHEK2 mutation did not. Both mutation carriers had a personal history of synchronous or metachronous advanced adenomas. 38% had a variant of uncertain significance. Conclusions 5% of patients with advanced adenomas in our retrospective series had a pathogenic germline mutation in a cancer predisposition gene. Though the patient with a pathogenic mutation in MLH1 met current clinical criteria for genetic testing, this was not recognized prior to referral; he was referred based on a personal history of advanced adenoma. Advanced polyps may be a red flag to identify patients who are at risk for hereditary cancer syndromes.

The article reports on results of a study of phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States. A description of the experimental set-up and measurement method is provided. The study concluded that MLH1 carriers had more colorectal cancer than MSH2 carriers. Furthermore, endometrial cancer prevalence was similar.