Weight gain during neoadjuvant therapy is associated with improved recurrence-free survival for patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma

Abstract

Presenter: Jonathan Hue MD | Case Western Reserve University School of Medicine Background: Weight loss commonly precedes the diagnosis of pancreatic ductal adenocarcinoma (PDAC). There is growing emphasis on neoadjuvant treatment for patients with localized disease. The severity and impact of weight loss during neoadjuvant therapy is not well studied. We hypothesized that weight loss during neoadjuvant chemotherapy would be associated with poor short- and long-term outcomes. Methods: We performed a single institution retrospective cohort study of patients with histologically confirmed PDAC who received neoadjuvant chemotherapy (with or without radiotherapy) and underwent a pancreatectomy between 2009-2021. We abstracted patient weights within 1 year preceding diagnosis, as well as at diagnosis, chemotherapy start, and before pancreatectomy. Patients were categorized based on weight change from start of chemotherapy to surgery: weight gain (≥5%), stable ( < 5% gain to < 5% loss), and weight loss (≥5%). The association between weight change and pathologic, perioperative, and long-term outcomes was analyzed. Results: A total of 127 patients received neoadjuvant therapy followed by pancreatectomy during the study period, of whom 95 had raw weights recorded at the specified time points and were included in the analysis. The median weight loss prior to diagnosis was 7.9% (range: 0.5% gain to 24.1% loss). Thirty patients (31.6%) lost weight during neoadjuvant chemotherapy, 56 (59.0%) had stable weight, and nine (9.5%) gained weight. Patients who lost weight were more likely to have locally advanced disease compared to patients with stable weight or weight gain (26.7% vs 8.9% vs 11.1%, p=0.12). CA19-9 levels were similar at the time of diagnosis and prior to pancreatectomy across groups. There was no difference between the three groups in the number of chemotherapy cycles administered, chemotherapeutic regimens, rate of neoadjuvant radiotherapy, or the time from initiation of chemotherapy to surgery. There was no difference in pathologic (tumor size, lymph node positivity, margin positivity, pathologic response to therapy) or perioperative (in-hospital complication rate, length of stay, discharge disposition) outcomes based on degree of weight loss during therapy. Utilization of adjuvant chemotherapy and adjuvant radiotherapy was also similar between groups. Median overall survival of patients who gained weight during neoadjuvant therapy was longer than that of patients with stable weight or weight loss (38.4 vs 25.8 vs 26.7 months, p=0.58), but this did not reach statistical significance. Median recurrence-free survival of patients who gained weight during neoadjuvant therapy was longer than that of patients with stable weight or weight loss (29.5 vs 9.6 vs 14.0 months, p=0.07, Figure). After controlling for clinical and treatment factors as well anatomic stage, weight gain was associated with improved recurrence-free survival benefit compared to weight loss (HR=0.15, 95% CI 0.03-0.81). A similar association was not identified when analyzing overall survival (HR=1.17, 95% CI 0.28-4.80). Conclusion: Weight trends during neoadjuvant therapy are variable, but the majority of patients maintain weight or lose weight. Patients who gain weight during neoadjuvant therapy may have improved recurrence-free survival. The association between weight and overall survival is less clear. Future studies may validate weight as a predictor of survival among patients receiving neoadjuvant therapy for localized PDAC.