Predictive role of temporal changes in intratumoral metabolic heterogeneity during palliative chemotherapy in advanced pancreatic cancer patients: A prospective cohort study.

Abstract

311 Background: Metabolic intratumoral heterogeneity (ITH) is known to be related with cancer treatment outcome. However, information on the temporal changes in metabolic ITH during chemotherapy and the correlations between metabolic changes and treatment outcomes in patients with pancreatic cancer (PC) is sparse. We aimed to analyze the temporal changes in metabolic ITH and the predictive role of its changes in advanced PC patients who underwent palliative chemotherapy. Methods: We prospectively enrolled unresectable locally advanced or metastatic PC patients before initiation of first-line palliative chemotherapy. 18F-fluorodeoxyglucose positron emission tomography was performed at baseline (T1) and at the first response follow-up (T2). Standardized uptake values (SUVs), volumetric parameters, and textural features of the primary pancreatic tumor were analyzed. Relationships between the parameters at T1, T2, and changes in the parameters with response to therapy, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Among 63 enrolled patients, the best objective response rate was 25.8% (95% confidence interval [CI], 14.6% to 37.0%). Sixteen (25.8%) patients who obtained partial response were classified as responders and 46 (74.2%) as nonresponders. The median PFS and OS were 7.1 months (95% CI, 5.1 to 9.7 months) and 10.1 months (95% CI, 8.6 to 12.7 months), respectively. Most of the parameters changed significantly during the first-line chemotherapy, in a way of reducing ITH. Metabolic ITH was more profoundly reduced in responders than in nonresponders. Multiple Cox regression analysis identified high baseline compacity ( P = 0.023) and smaller decreases in SUVpeak ( P = 0.007) and entropyGLCM ( P = 0.033) to be independently associated with poor PFS. Patients with a high CA 19-9 ( P = 0.042), high pretreatment SUVpeak ( P = 0.008), and high coefficient of variance at T2 ( P = 0.04) showed worse OS. Conclusions: Reduction in metabolic ITH during palliative chemotherapy in advanced PC patients is associated with response to therapy and might be predictive of PFS and OS.