Examination for the Presence of an Oligo-Metastatic State in Patients with Newly Diagnosed Metastatic Pancreatic Adenocarcinoma Undergoing Systemic Chemotherapy.

Abstract

PURPOSE/OBJECTIVE(S)\nMore than 50% of patients with PDAC will present with distant metastatic disease. Outcomes are known to be heterogenous amongst this patient cohort. By identifying clinical and disease burden characteristics that are associated with increased durations of OS, we can better apply non-systemic therapies/interventions on- or off-trial.\n\n\nMATERIALS/METHODS\nWe identified patients who presented with newly diagnosed metastatic PDAC that received treatment with FOLFIRINOX or gemcitabine-based chemotherapies between 8/01/2011-09/01/2017 at our institution. Patients with localized disease at diagnosis that progressed to metastatic disease were excluded. Metastatic disease burden was comprehensively characterized radiologically via imaging segmentation; locations, number, and volume of metastatic disease (when able) using commercially available image annotation software (MIM Inc, Ohio). Survival curves were estimated using the Kaplan-Meier method, and compared between groups via the log-rank test. ECOG performance status was obtained via chart review and Charlson Comorbidity Index (CCI) was calculated for all patients using publicly available online tools.\n\n\nRESULTS\n121 patients were evaluated, median age was 62 (37-86), 40% were female, 25% were ECOG 0 at presentation, 7.5% had a CCI of 0 at presentation. Of the 121 total patients included, 33% (n\u202f=\u202f41) were alive at 12 months, and 25% (n\u202f=\u202f31) were alive at 18 months. Landmark analysis was performed at 18 months and demonstrated a significant difference between patients surviving < 18 months and > /\u202f=\u202f18 months regarding the presence of lung metastases (36% vs 16% P\u202f=\u202f0.04), number of organs with metastases (> /\u202f=\u202f2 vs 1 P\u202f=\u202f0.04), and disease volume (mean of 19.1cc vs 1.4cc P\u202f=\u202f0.04). At year 1, predictors for OS were: ECOG status at diagnosis (ECOG 0 vs ECOG 1 P\u202f=\u202f0.04), metastatic disease volume at diagnosis (< /\u202f=\u202f0.1cc vs > 60 cc P\u202f=\u202f0.004), metastasis only in the liver (P\u202f=\u202f0.04), and normalization of CA 19-9 (P < 0.001). At year 2, the only predictor of OS was normalization of the CA 19-9 (P\u202f=\u202f0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months. Total number of metastatic lesions, presence of lymph nodes, and location of the pancreatic primary tumor were not significant predictors for OS.\n\n\nCONCLUSION\nWe present a detailed characterization of metastatic disease outcomes using segmented diagnostic imaging at the time of diagnosis. Patients with normalization of CA-19-9, or limited volumetric disease burden, demonstrated OS approaching that of patients with non-metastatic disease. These metrics identify potential selection criteria for clinical trials evaluating local interventions for patients with metastatic PDAC.