ABSTRACT
BACKGROUND: Differential responses to neoadjuvant therapy (NAT) exist in pancreatic ductal adenocarcinoma (PDAC); however, contributing factors are poorly understood. Tobacco smoke is a common risk factor for PDAC, with nicotine-induced chemoresistance observed in other cancers. This study aimed to explore the potential association between tobacco use and NAT efficacy in PDAC. METHODS: A single-center, retrospective analysis was conducted that included all consecutive patients with PDAC who underwent surgical resection after NAT with a documented smoking history (N = 208). NAT response was measured as percentage fibrosis in the surgical specimen. Multivariable models controlled for covariates and survival were modeled using the Kaplan-Meier method. RESULTS: Postoperatively, major responses to NAT (>95% fibrosis) were less frequently observed in smokers than in nonsmokers (13.7% vs 30.4%, respectively; P = .021). Pathologic complete responses were similarly less frequent in smokers than in nonsmokers (2.1% vs 9.9%, respectively; P = .023). On multivariate analysis controlling for covariates, smoking history remained independently associated with lower odds of major fibrosis (odds ratio [OR], 0.25; 95% CI, 0.10-0.59; P = .002) and pathologic complete response (OR, 0.21; 95% CI, 0.03-0.84; P = .05). The median overall survival was significantly longer in nonsmokers than in smokers (39.1 vs 26.6 months, respectively; P = .05). CONCLUSION: Tobacco use was associated with diminished pathologic responses to NAT. Future research to understand the biology underlying this observation is warranted and may inform differential NAT approaches or counseling among these populations.
Subject(s)
Carcinoma, Pancreatic Ductal , Neoadjuvant Therapy , Pancreatic Neoplasms , Smoking , Humans , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Male , Female , Retrospective Studies , Middle Aged , Aged , Smoking/adverse effects , Smoking/epidemiology , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Treatment Outcome , Fibrosis , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Risk Factors , Kaplan-Meier EstimateABSTRACT
BACKGROUND: Tumor fibrosis after neoadjuvant treatment (NAT) for pancreatic ductal adenocarcinoma (PDAC) correlates with treatment response. Herein we assessed how different NAT strategies influence pathologic responses and survival. METHODS: Patients with surgically resected PDAC who received NAT (1991-2020) were included. Descriptive statistics compared outcomes amongst fibrosis groups (none, minor <50 â%, partial 51%-94 â%, major ≥95 â%) and NAT (chemotherapy alone, chemoradiation, or chemotherapy â+ âchemoradiation (total neoadjuvant therapy, TNT)). RESULTS: Patients with major fibrosis most often received TNT (65.8 â%, p â< â0.001). Major fibrosis was associated with the greatest rate of downstaging (77.8 â%, p â< â0.001), highest R0 margin rate (100 â%, p â< â0.01), and lowest mean positive lymph node ratio (0.80, p â< â0.01). Amongst complete responders, 11/14 (78.6 â%) received TNT. Median overall (66.3 months, p â= â0.003) and disease-free (54.7months, p â= â0.05) survival were highest with major fibrosis. CONCLUSIONS: Major fibrosis and complete pathologic responses after NAT are most frequent with a TNT strategy and are associated with improved outcomes.
