Textbook Neoadjuvant Experience: Defining a Novel Composite Outcomes Measure for Patients with Pancreatic Cancer Undergoing Neoadjuvant Therapy.

Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC). Disease progression, toxicity, and failure to undergo surgical resection are common during NT, yet little research has focused on efforts to optimize care delivery. We sought to define and validate a novel composite outcomes metric that characterizes the successful delivery of NT.

Study Design: All patients with localized PDAC receiving NT in intention-to-treat fashion between 2018-2023 were retrospectively evaluated. A textbook neoadjuvant experience (TNE) was defined as the absence of mortality, disease progression, or hospital admission during NT as well as the completion of all intended NT and successful surgical resection.

Results: Among 306 patients with localized PDAC, median age was 66 and 58.5% were male. Overall, only 85 (28%) experienced a TNE which was more common among patients with potentially resectable (45/96, 47%) than borderline resectable (33/112, 29%) or locally advanced (7/98, 7%) disease. Patients with a TNE experienced greater overall survival (OS) than those individuals without a TNE (median not reached vs 16.4 months (95%CI: 14.9-17.9 months), p<0.001). On multivariable Cox regression analysis, a TNE was the strongest predictor of improved OS (HR 0.33; 95%CI: 0.20-0.54, p<0.001).

Conclusion: A TNE is infrequently achieved among patients with PDAC undergoing NT but is significantly associated with improved long-term outcomes. Future research aimed at optimizing outcomes of NT delivery should incorporate this novel composite metric that may more accurately reflect patient and provider expectations of treatment.