Response heterogeneity as a new biomarker of treatment response in patients with neuroendocrine tumors.

Abstract

Aim: The RAISE project aimed to find a surrogate end point to predict treatment response early in patients with enteropancreatic neuroendocrine tumors (NET). Response heterogeneity, defined as the coexistence of responding and non-responding lesions, has been proposed as a predictive marker for progression-free survival (PFS) in patients with NETs. Patients & methods: Computerized tomography scans were analyzed from patients with multiple lesions in CLARINET (NCT00353496; n=148/204). Cox regression analyses evaluated association between response heterogeneity, estimated using the standard deviation of the longest diameter ratio of target lesions, and NET progression. Results: Greater response heterogeneity at a given visit was associated with earlier progression thereafter: week 12 hazard ratio (HR;95% confidence interval): 1.48 (1.20-1.82);p< 0.001;n=148; week 36: 1.72 (1.32-2.24);p<0.001;n=108. HRs controlled for sum of longest diameter ratio: week 12: 1.28 (1.04-1.59);p=0.020 and week 36: 1.81 (1.20-2.72);p=0.005. Conclusion: Response heterogeneity independently predicts PFS in patients with enteropancreatic NETs. Further validation is required.