Introduction: A key factor contributing to the poor prognosis of pancreatic cancer is a fibrotic, desmoplastic stroma which impedes drug delivery and promotes tumor growth. We examined patients who took three studied classes of stromal modulating medications (SMMs), vitamin D derivatives (vit D), angiotensin receptor blockers (ARBs), and hydroxychloroquine (HCQ) in the pre-operative setting. SMMs promote a more favorable tumor microenvironment. Conversely, smoking has been shown to promote fibrosis. We aimed to assess the effect of pre-operative SMMs on pancreatic cancer surgical outcomes of fibrosis, fistula formation, overall survival (OS), and disease-free survival (DFS). Additionally, we aimed to evaluate the effect of smoking on these outcomes.
Methods: This is a retrospective cohort study utilizing institutional data approved by the study IRB. Patients with stage 1 to 3 pancreatic ductal adenocarcinoma who underwent surgical resection from 12/2010 to 9/2023 were evaluated. Electronic medical records were reviewed for medication lists within 3 months prior to surgery. Those without this information were excluded. 157 patients met inclusion criteria. Categorical variables were compared using Fisher’s Exact Test, OS and DFS were analyzed using Kaplan Meier survival curves, and logistic regression models were used to calculate odds ratios of the fistula formation and fibrosis endpoints. Fistula was defined as grade B or C pancreatic fistulas. Fibrosis was defined at pathological examination as present or absent. 4 patients had no information regarding fistula formation and 9 no information regarding fibrosis on chart review. These patients were removed from sample for respective end point evaluations. A p<0.05 was considered statistically significant.
Results: Out of the 157 total patients, 18 were taking an ARB, 53 vit D, and 1 HCQ within 3 months prior to surgery. Fistula formation occurred in 7 out of the 153 (4.6%) patients. There was no significant difference in the frequency of fistula formation in patients taking vit D, ARBs, or HCQ. Fibrosis was present in 80 out of the 148 (54%) patients. While adjusting for smoking status, compared to those who did not have any of the three treatments, patients taking at least one of the three had a decreased odds of developing fibrosis (OR=0.71, 95% CI 0.510 to 0.996) and this was statistically significant (p=0.0474). Vit D and HCQ as individual factors were not associated with decreased frequency of fibrosis (p=0.059 and 1.000, respectively), but patients who took ARBs pre-op had decreased odds of developing fibrosis (p=0.036).
There was no significant difference in the OS or DFS between patients on any of the studied medications versus those on none.
Conclusion: SMMs are associated with decreased odds of having fibrosis. Smoking is not associated with increased fibrosis rates in patients on SMMs.
