Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer

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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 patients (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 535 adjuvant therapy. The median OS was 36.1 months, 23.0 months and 27.8 months after NAT, upfront resection and for the entire cohort. 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 provides evidence that neoadjuvant FOLFIRINOX is associated with excellent survival; however, active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasizes the importance of smoking cessation prior to NAT with FOLFIRINOX. Publication History Article published online: 28 August 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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