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

Neuroendocrinology. 2021;111(9):831-839. doi: 10.1159/000510445. Epub 2020 Jul 27.

Abstract

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 (TGR3m) 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 TGR3m 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]), TGR3m ≥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 TGR3m and number of lesions (rho: -0.2; p value: 0.1930). No difference in mean TGR3m 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%). TGR3m 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: TGR3m 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.

Keywords: Biomarkers; Neuroendocrine tumors; Prognosis; Reproducibility of results.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / diagnostic imaging
  • Neuroendocrine Tumors / pathology*
  • Outcome Assessment, Health Care*
  • Progression-Free Survival*
  • Retrospective Studies
  • Tumor Burden*
  • Young Adult