The incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear.
A nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ???30 g/day for men and ???16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs.
A total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ???3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity (P = .011).
Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.
Interesting study that quantifies the risk of Venous Thromboembolism (VTE) in patients undergoing neo(adjuvant) treatment. Risk was about 9% overall, underscoring the need to be aware and potentially provide prophylaxis where appropriate.
PAXG (capecitabine 1250 mg/m² total daily dose administered as 625 mg/m² twice daily, plus intravenous cisplatin 30 mg/m², nab-paclitaxel 150 mg/m², and gemcitabine 800 mg/m² every 14 days) significantly improved event-free survival (EFS) compared with modified FOLFIRINOX (mFOLFIRINOX) in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) (16.0 months vs 10.2 months).
The GENERATE/JCOG1611 trial in Japanese patients with metastatic or recurrent PDAC found that neither mFOLFIRINOX nor S-IROX improved overall survival (OS) versus nab-paclitaxel/gemcitabine (median OS 14.0 vs 13.6 vs 17.0 months; hazard ratio (HR) ≈1.29), and the study was stopped early for futility. Progression-free survival (PFS) was similar across arms (≈5.8–6.7 months) but nab-paclitaxel/gemcitabine had fewer grade 3–4 GI toxicities and less febrile neutropenia, supporting its continued use in this population. The OS difference likely reflects more effective second-line sequencing after nab-paclitaxel/gemcitabine, including liposomal irinotecan, rather than intrinsic superiority. In Western studies, NALIRIFOX outperformed Nab-P/Gem, but in the Japanese trial, Nab-P/Gem remained at least as effective as triplet regimens, likely due to differences in patient population, sequencing, and access to second-line therapies.
Japanese studies, which included S-1 with oxaliplatin and irinotecan—both 5-FU–based regimens—showed no superiority to gemcitabine/nab-paclitaxel in first- or second-line therapy. The trial was terminated for futility. So, what is your regimen du jour?
I recall this trial well, in node-negative pancreatic cancer GemCap is a better option than gemcitabine alone in patients who can’t be treated with mFOLFIRINOX with improved five-year overall survival (OS) 59 vs 53%, hazard ratio (HR) 0.63.