Tumour growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumours; the GREPONET-2 study

Abstract

PURPOSE: TGR represents the percentage change in tumour volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR3m) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in NETs.

EXPERIMENTAL DESIGN: Pts from7 centres with advanced grade(G) 1/2 NETs from the pancreas(P)/small bowel(SB) initiating ST/WW were eligible. Computed tomography (CT) / magnetic resonance imaging (MRI) performed at pre-baseline, baseline and 3(+/-1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (?TGR3m-BL) (paired T-test) and Aim-2: validate TGR3m (<0.8%/m vs ?0.8%/m) as an early biomarker in an independent cohort (Kaplan-Meier/Cox Regression).

RESULTS: Out of 785 pts screened, 127 were eligible. Mean (SD) TGR0 and TGR3m were 5.4%/m (14.9) and -1.4%/m (11.8), respectively. Mean(SD) ?TGR3m-BL paired-difference was -6.8%/m(19.3) (p<0.001). Most marked ?TGR3m-BL (mean (SD);p) were identified with targeted therapies (-11.3%/m(4.7);0.0237) and chemotherapy (-7.9%/m(3.4);0.0261). Multivariable analysis confirmed the absence of previous treatment (Odds Ratio (OR) 4.65 (95%CI 1.31-16.52); p-value0.018) and low TGR3m (continuous variable; OR 1.09 (95%CI 1.01-1.19); p-value0.042) to be independent predictors of radiological objective response. When the multivariable Cox Regression was adjusted to grade (p-value 0.004) and stage (p-value0.017), TGR3m?0.8 (vs.<0.8) maintained its significance (p<0.001), while TGR0 and ?TGR3m-BL did not. TGR3m was confirmed as an independent prognosis factor for PFS (external validation; Aim-2) (multivariable HR 2.21 (95%CI 1.21-3.70); p-value0.003).

CONCLUSIONS: TGR has a role as biomarker for monitoring response to therapy for early prediction of PFS and radiological objective response.