Tumour growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumours; the GREPONET-2 study
de Mestier, L
AffiliationMedical Oncology, The Christie NHS Foundation Trust, Manchester
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AbstractPURPOSE: 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.
CitationLamarca A, Ronot M, Moalla S, Crona J, Opalinska M, Lopez Lopez C, et al. Tumour growth rate as a validated early radiological biomarker able to reflect treatment-induced changes in neuroendocrine tumours; the GREPONET-2 study. Clin Cancer Res. 2019 Aug 2.
JournalClinical Cancer Research