Smoking Impairs the Effect of Neoadjuvant FOLFIRINOX on Postresection Survival in Pancreatic Cancer
Menée à partir de données portant sur 848 patients atteints d'un adénocarcinome canalaire pancréatique, cette étude évalue l'efficacité, du point de vue de la survie globale, d'une chimiothérapie néoadjuvante de type FOLFIRINOX en fonction du statut tabagique
Introduction: Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC. Methods: All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modeling was performed. Restricted cubic splines were used for linear data to define cut-off points. Results: Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median OS was 27.8 months, 36.1 months and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (HR 2.35; 95% CI 1.13-4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25 - 0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection. Conclusion: The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasizes the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.