Value of Tumor Growth Rate (TGR) as an Early Biomarker Predictor of Patients’ Outcome in Neuroendocrine Tumors (NET)—The GREPONET Study

Abstract

Gastroenteropancreatic neuroendocrine tumors are rare, and advanced disease cannot be cured. This article explores the role of tumor growth rate as a novel radiological biomarker in patients with advanced neuroendocrine tumors. Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications. Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible. Baseline and follow‐up scans were retrospectively reviewed to calculate TGR at pretreatment (TGR 0 ), first follow‐up (TGR first ), and 3(±1) months of study entry (TGR 3m ). Out of 905 pts screened, 222 were eligible. Best TGR first (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR 3m (103 pts), pts with TGR 3m <0.8 (66.9%) versus TGR 3m ≥ 0.8 (33.1%) had longer median progression‐free survival (PFS; 26.3 m; 95% confidence interval [CI] 19.5–32.4 vs. 9.3 m; 95% CI, 6.1–22.9) and lower progression rate at 12 months (7.3% vs. 56.8%; p = .001). WW (vs. ST) and TGR 3m ≥ 0.8 (hazard ratio [HR], 3.75; 95% CI, 2.21–6.34; p < .001) were retained as factors associated with a shorter PFS in multivariable Cox regression. TGR 3m (HR, 3.62; 95% CI, 1.97–6.64; p < .001) was also an independent factor related to shorter PFS when analysis was limited to pts with stable disease (81 pts). Out of the 60 pts with TGR 0 data available, 60% of pts had TGR 0 < 4%/month. TGR 0 ≥ 4 %/month (HR, 2.22; 95% CI, 1.15–4.31; p = .018) was also an independent factor related to shorter PFS. TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow‐up. Tumor growth rate at 3 months (TGR 3m ) is an early radiological biomarker able to predict progression‐free survival and to identify patients with advanced neuroendocrine tumors who may require closer radiological follow‐up. It is feasible to calculate TGR 3m in clinical practice and it could be a useful tool for guiding patient management. This biomarker could also be implemented in future clinical trials to assess response to therapy.