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Won-Gun Yun*, Youngmin Han, Mirang Lee, Young Jae Cho, Hye-Sol Jung, Wooil Kwon, Jin-Young Jang
Department of surgery, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Objective: To compare the effectiveness of radiologic and biochemical response evaluation after neoadjuvant FOLFIRINOX chemotherapy to predict survival outcome and investigate the efficacy of adjuvant chemotherapy in patients with non-metastatic pancreatic ductal adenocarcinoma.
Summary Background Data: To maximize the effect of surgery, the treatment paradigm is shifting from upfront surgery to neoadjuvant chemotherapy with advances in chemotherapy. Therefore, neoadjuvant FOLFIRINOX chemotherapy has been increasingly used, however, the response evaluation methods are still inconsistent and the benefits of adjuvant chemotherapy are also unclear.
Methods: 160 non-metastatic pancreatic ductal adenocarcinoma patients who underwent curative-intent pancreatectomy after at least 4 cycles of neoadjuvant FOLFIRINOX chemotherapy between 2012 and 2020 were identified. Patients with a normalized CA 19-9 level after neoadjuvant chemotherapy were defined as biochemical responders. Patients with complete or partial response according to Response Evaluation Criteria in Solid Tumors were defined as radiologic responders. Survival analysis was performed using Kaplan-Meier estimates.
Results: Of 160 patients, 58 (36.3%) were identified as biochemical and radiologic responder (BR+/RR+), 31 (19.4%) as only biochemical responder (BR+/RR-), 17 (10.6%) as only radiologic responder (BR-/RR+), 44 (27.5%) as non-responder (BR-/RR-). The 2-year overall survival rates were 82.0%, 77.3%, 64.7%, 45.5% for BR+/RR+, BR+/RR-, BR-/RR+, and BR-/RR-, respectively (P = 0.008). The differences of 2-year overall survival rates between patients who completed adjuvant chemotherapy and those who stopped or did not receive adjuvant chemotherapy were 20.4% (88.8% vs. 68.4%, P < 0.001), 53.6% (91.1% vs. 37.5%, P < 0.001), 58.3% (83.3% vs. 25.0%, P = 0.002), 49.4% (62.7% vs. 13.3%, P < 0.001) in BR+/RR+, BR+/RR-, BR-/RR+, and BR-/RR-, respectively.
Conclusions: Biochemical response to neoadjuvant FOLFIRINOX chemotherapy has a greater impact on prognosis than radiologic response, and radiologic response plays an important role only in biochemical non-responders. Completion of adjuvant chemotherapy is important in all patients regardless of response to neoadjuvant FOLFIRINOX chemotherapy, especially except for BR+/RR+, the efficacy was greater.

Overall survival according to the biological and radiological response to neoadjuvant FOLFIRINOX

Overall survival according to the completion of adjuvant chemotherapy
A. Biochemical and radiologic responders
B. Biochemical only responders
C. Radiologic only responders
D. Non-responders

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