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Rachel C. Kim*, Kara A. Allen, Alexandra M. Roch, James Butler, Eugene P. Ceppa, Michael G. House, Nicholas J. Zyromski, Attila Nakeeb, C. Max Schmidt, Trang Nguyen
Surgery, Indiana University School of Medicine, Indianapolis, IN

Introduction: The advantages of neoadjuvant chemotherapy (NAC) over upfront surgery in patients with resectable pancreatic adenocarcinoma (PDAC) remain under debate. In this study, we aim to evaluate the impact of NAC and its dependence on receiving adjuvant therapy on the oncologic and survival outcomes of patients with resectable PDAC.

Methods: All patients with resectable PDAC (defined by AHPBA/SSO/SSAT consensus guidelines) who underwent oncologic resection at a single, high-volume institution between Jan 2017 and Feb 2020 were retrospectively reviewed. Groups were compared using chi-squared or Mann-Whitney U-test. Kaplan-Meier and Cox proportional-hazards regression were used for survival analysis.

Results: Out of 228 patients with resectable PDAC, 93 (40.8%) had neoadjuvant chemotherapy and 135 (59.2%) underwent upfront surgery (US). Patients who received NAC were younger (NAC vs US, med[IQR]: 67.5[12.7] vs. 80.0[13.7] yrs). Groups were similar in comorbidities except for COPD (3.2% vs 10.4%, p=0.04). Patients with NAC had larger tumors at diagnosis (T2 disease: 58.7% vs 39.0%, T3 disease: 16.3% vs 11.4%, p<0.01), but similar clinical nodal staging (p=0.89). The med[IQR] duration of NAC was 2.30[0.96] mos. Surgery type, approach, duration, and EBL were similar between groups. NAC was associated with more node negative disease on pathology (56.7% vs 43.3%, p<0.01) and lower 30-d readmission rates (5.4% vs 13.3%, p=0.05). Groups were comparable in postoperative complications such as pancreatic fistula, DGE, and organ space infection, as well as 90-d mortality (4.3% vs 9.6%, p=0.13), and similar proportions went on to reach adjuvant chemotherapy (77.5% vs 75.0%, p=0.70). NAC was associated with higher rates of one-year survival (88.5% vs 58.3%, p<0.01) and better overall survival (med (95% CI): 31.7 (24.2 – 39.3) vs 15.3 (11.5 – 19.0) mos, p<0.01). When considering patients with adequate records on the course of systemic therapy (n=174), the survival benefit of NAC is lost in patients who do not receive adjuvant chemotherapy (Figure, p<0.01). This difference remained significant after adjusting for differences between groups, clinical stage, and other factors (NAC w/ vs w/o adjuvant, HR (95% CI): 0.36 (0.15 – 0.86), p=0.02).

Conclusion: In resectable PDAC, neoadjuvant chemotherapy was associated with improved overall survival and more node negative disease after surgery. However, the survival benefit is lost if patients do not receive adjuvant chemotherapy. This supports further investigating the potential role of total neoadjuvant chemotherapy in resectable pancreatic cancer.

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