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

Abstract

Introduction 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. Materials and Methods 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 (TGR0), first follow‐up (TGRfirst), and 3(±1) months of study entry (TGR3m). Results Out of 905 pts screened, 222 were eligible. Best TGRfirst (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR3m (103 pts), pts with TGR3m <0.8 (66.9%) versus TGR3m ≥ 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 TGR3m ≥ 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. TGR3m (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 TGR0 data available, 60% of pts had TGR0 < 4%/month. TGR0 ≥ 4 %/month (HR, 2.22; 95% CI, 1.15–4.31; p = .018) was also an independent factor related to shorter PFS. Conclusion TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow‐up. Implications for Practice Tumor growth rate at 3 months (TGR3m) 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 TGR3m 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.

Influence of pretreatment tumor growth rate on objective response of hepatocellular carcinoma treated with transarterial chemoembolization

“…Analyses derived from the prospective randomized CLARINET study showed that pretreatment TGR was able to predict response to Lanreotide in terms of progression-free survival in patients with NET. 31 The multicentric retrospective GREPONET study, 32 including metastatic NET patients, confirmed these results, supporting the role of pretreatment TGR as a possible predictive factor for tumor response. We hypothesized that TGR could also be a helpful predictor of patient outcome with future utility for treatment decision making and better understanding of HCC biological behavior.…”

Pre-Treatment Tumor Growth Rate Predicts Clinical Outcomes of Patients With Advanced Non-Small Cell Lung Cancer Undergoing Anti-PD-1/PD-L1 Therapy

“…A post hoc analysis from a phase II study revealed that higher pretreatment TGR tended to be associated with shorter PFS in grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) receiving lanreotide (27), and the CLARINET study further validated this finding (18). A TGR 0 < 4%/m predicted inferior PFS in G1 or G2 NET patients regardless of treatment modalities (21). Similarly, patients with higher pre-treatment tumor growth rate--measured as specific growth rate (SGR) experienced worse PFS in locally advanced NSCLC undergoing definitive chemoradiation therapy (CRT) (28).…”

“…Tumor growth rate (TGR) provides quantitative assessment of change in tumor volume over time according to RECISTdefined sum of the longest diameters of the target lesions (SLD) from two computed tomography (CT) scans and time interval between them (17). Previous studies have showed that TGR was correlated with treatment response or clinical outcomes in patients with neuroendocrine carcinoma, renal cell carcinoma, or hepatocellular carcinoma treated with angiogenesis inhibitors or transarterial chemoembolization (18)(19)(20)(21)(22)(23). These findings suggested that TGR could serve as an early radiological biomarker to predict patient's survival outcomes and to tailor radiological follow-up strategies and patients' management.…”

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

“…Combining different imaging technologies and assessment of disease with cross-sectional and molecular imaging is increasingly relevant for patients with PanNETs, not only for treatment selection following a theranostic approach, but also for assessment of response to therapy [143,144]. The development of novel radiological assessment strategies may also be of help (i.e., alternative cut-off definitions for assessment of response [145] or assessment of Tumour Growth Rate (TGR) [123,146,147].…”