Tumor Growth Rate to Predict the Outcome of Patients with Neuroendocrine Tumors: Performance and Sources of Variability

Introduction: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR(3m)) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. Methods: Baseline and 3-month (+/- 1 month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden, and location of lesion on the performance of TGR(3m) to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by Lin's concordance coefficient (LCC) and kappa coefficient (KC). Results: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (= 4), tumor burden, and presence of liver metastases were significantly correlated with PFS. On multivariate analysis, >= 4 lesions (HR: 1.89 [95% CI: 1.01-3.57]), TGR(3m) >= 0.8%/month (HR: 4.01 [95% CI: 2.31-6.97]), and watch and wait correlated with shorter PFS. No correlation was found between TGR(3m) and number of lesions (rho: -0.2; p value: 0.1930). No difference in mean TGR(3m) across organs was shown (p value: 0.6). Concordance between readers was acceptable (LCC: 0.52 [95% CI: 0.38-0.65]; KC: 0.57, agreement: 81.55%). TGR(3m) remained a significant prognostic factor when data from the second reader were employed (HR: 4.35 [95% CI: 2.44-7.79]; p value <0.001) regardless his expertise (HR: 1.21 [95% CI: 0.70-2.09]; p value: 0.493). Discussion/Conclusion: TGR(3m) is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.

Automated summary

TGR(3m) as an early radiological biomarker, can predict progression-free survival in neuroendocrine tumor patients, showing good performance in both univariable and multivariable analysis. It can help identify patients who require closer radiological follow-up.