July 27, 2023
Future Oncology

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


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.


Response heterogeneity independently predicts PFS in patients with enteropancreatic NETs. Further validation is required.

Clarisse Dromain
Marianne Pavel
Maxime Ronot
Niklaus Schaefer
Dalvinder Mandair
Delphine Gueguen
Catherine Cheng
Olivier Dehaene
Kathryn Schutte
David Cahané
Simon Jegou
Felix Balazard