SSAT - DECODING THE IMPACT OF NEOADJUVANT THERAPY MODALITY AND DURATION ON PROGNOSTIC FACTORS IN PANCREATIC DUCTAL ADENOCARCINOMA

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DECODING THE IMPACT OF NEOADJUVANT THERAPY MODALITY AND DURATION ON PROGNOSTIC FACTORS IN PANCREATIC DUCTAL ADENOCARCINOMA
Emily Papai^*¹, Jennifer Hwang¹, Leonard Miller², Joseph Krempa², Hal Rives², Jordan D. Fredette¹, Anthony Villano¹, Sanjay S. Reddy¹
¹Surgery, Fox Chase Cancer Center, Philadelphia, PA; ²Temple University Lewis Katz School of Medicine, Philadelphia, PA

Background
There is debate if neoadjuvant therapy (NAT) modality or duration is more important for optimal treatment of pancreatic ductal adenocarcinoma (PDAC). While the literature suggests overall survival is equivocally varied, other important prognostic factors may be impacted including gland fibrosis, margin status, and CA19-9 levels. This study aims to examine the difference between NAT modality versus duration when applied to these factors.

Methods
We conducted a retrospective single-institution analysis of patients with PDAC who underwent surgery between January 2012 and November 2024. Patients were divided by NAT modality into 4 groups: 1) surgery first (SF), 2) chemotherapy only (NACT), 3) chemoradiation only (CRT), and 4) chemotherapy & chemoradiation (TNT). Duration was defined as length of time in treatment (days). Among patients who received NACT or TNT, outcomes of fibrosis, complete pathologic response, and margins were examined using logistic regression and CA19-9 levels after NAT were examined using ordinary least square regression. Overall survival of patients who received NAT was assessed using a landmark Kaplan Meier curve and a Cox proportional hazards model with modality treated as a time varying covariate.

Results
The cohort included 213 patients: TNT (n=78), SF (n=67), NACT (n=49), CRT (n=19). Increased age (p=0.03) and ECOG of 0 (p=0.002) were found to be more frequent in the SF group. There was no difference in ECOG between groups NACT and TNT (p=0.364). Segmented logistic regression was performed among patients who received TNT to identify a cut point of diminishing returns on duration of therapy: the odds of having complete pathologic response (CR) increased significantly over the first segment which extended from 0 to 145 days [CI 0.007 � 0.065]. However, on logistic regression CR was not significantly associated with modality or duration of NAT (p=0.311 and p=0.189, respectively). Margin status was not significantly associated with modality (p=0.641) or duration (p=0.655). There was no difference in post-NAT CA19-9 levels between TNT and NACT (p=0.122) nor in the change of CA19-9 from patients� initial values (p=0.881). Similarly, duration did not have a significant effect of CA19-9 levels (p=0.975). Patients who received TNT had 4.24 times the odds of gland fibrosis compared to patients who received NACT (p=0.01) whereas duration did not have an effect (p=0.976). Neither modality nor duration were found to be associated with survival in Cox regression analysis, however overall survival differed significantly between modalities on landmark Kaplan Meier curve (p=0.0043).

Conclusion
CR, margin status, and CA19-9 values did not correlate with modality or duration of NAT. TNT significantly increased rates of gland fibrosis. Modality may confer a survival benefit that is more significant than duration of NAT.

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