Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer

Abstract

Importance: Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best dictated by response to neoadjuvant therapy (as measured by CA19-9 levels and/or pathologic response), a strategy defined herein as adaptive dynamic therapy. Objective: To evaluate the association of adaptive dynamic therapy with oncologic outcomes in patients with surgically resected pancreatic cancer. Design, Setting, and Participants: This retrospective cohort study included patients with localized pancreatic cancer who were treated with either gemcitabine/nab-paclitaxel or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) preoperatively between 2010 and 2019 at a high-volume tertiary care academic center. Participants were identified from a prospectively maintained database and had a median follow-up of 49 months. Data were analyzed from October 17 to November 24, 2020. Exposures: The adaptive dynamic therapy group included 219 patients who remained on or switched to an alternative regimen as dictated by CA19-9 response and for whom the adjuvant regimen was selected based on CA19-9 and/or pathologic response. The nonadaptive dynamic therapy group included 103 patients who had their chemotherapeutic regimen selected independent of CA19-9 and/or tumoral response. Main Outcomes and Measures: Prognostic implications of dynamic perioperative therapy assessed through Kaplan-Meier analysis, Cox regression, and inverse probability weighted estimators. Results: A total of 322 consecutive patients (mean [SD] age, 65.1 [9] years; 162 [50%] women) were identified. The adaptive dynamic therapy group, compared with the nonadaptive dynamic therapy group, had a more pronounced median (IQR) decrease in CA19-9 levels (-80% [-92% to -56%] vs -45% [-81% to -13%]; P