BACKGROUND. Imaging biomarkers of response to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDA) are needed to optimize treatment decisions and long-term outcomes. OBJECTIVE. The purpose of this study was to investigate metrics from PET/MRI and CT to assess pathologic response of PDA to NAT and to predict overall survival (OS). METHODS. This retrospective study included 44 patients with ¹⁸F-FDG-avid borderline resectable or locally advanced PDA on pretreatment PET/MRI who also underwent post-NAT PET/MRI before surgery between August 2016 and February 2019. Carbohydrate antigen 19-9 (CA 19-9) level, metabolic metrics from PET/MRI, and morphologic metrics from CT (n = 34) were compared between pathologic responders (College of American Pathologists scores 0 and 1) and nonresponders (scores 2 and 3). AUCs were measured for metrics significantly associated with pathologic response. Relation to OS was evaluated with Cox proportional hazards models. RESULTS. Among 44 patients (22 men, 22 women; mean age, 62 ± 11.6 years), 19 (43%) were responders, and 25 (57%) were nonresponders. Median OS was 24 months (range, 6-42 months). Before treatment, responders and nonresponders did not differ in CA 19-9 level, metabolic metrics, or CT metrics (p > .05). After treatment, responders and nonresponders differed in complete metabolic response (CMR) (responders, 89% [17/19]; nonresponders, 40% [10/25]; p = .04], mean change in SUV_max (ΔSUV_max; responders, -70% ± 13%; nonresponders, -37% ± 42%; p < .001), mean change in SUV_max corrected to serum glucose level (ΔSUV_gluc) (responders, -74% ± 12%; nonresponders, -30% ± 58%; p < .001), RECIST response on CT (responders, 93% [13/14]; nonresponders, 50% [10/20]; p = .02)], and mean change in tumor volume on CT (ΔTvol) (responders, -85% ± 21%; nonresponders, 57% ± 400%; p < .001). The AUC of CMR for pathologic response was 0.75; ΔSUV_max, 0.83; ΔSUV_gluc, 0.87; RECIST, 0.71; and ΔTvol 0.86. The AUCs of bivariable PET/MRI and CT models were 0.83 (CMR and ΔSUV_max), 0.87 (CMR and ΔSUV_gluc), and 0.87 (RECIST and ΔTvol). OS was associated with CMR (p = .03), ΔSUV_max (p = .003), ΔSUV_gluc (p = .003), and RECIST (p = .046). CONCLUSION. Unlike CA 19-9 level, changes in metabolic metrics from PET/MRI and morphologic metrics from CT after NAT were associated with pathologic response and OS in patients with PDA, warranting prospective validation. CLINICAL IMPACT. Imaging metrics associated with pathologic response and OS in PDA could help guide clinical management and outcomes for patients with PDA who undergo emergency therapeutic interventions.

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