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

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 (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 Dromain et al.

Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE

“…This is well in line with several studies reporting a high cytoreductive potential of PRRT in PanNET patients (7,22,27,28). Moreover, the in-treatment cut-off for TGR in the present study was slightly lower than in previous reports (0.5 %/month as opposed to 0.8 %/month) (18)(19)(20). This is a consequence of the lower intreatment TGR in the present study, again reflecting the high cytoreductive potential of PRRT with 177 Lu-DOTATATE in PanNET patients.…”

“…The aim of the study was primarily to calculate TGR before and during/after PRRT with 177 Lu-DOTATATE, to shed some light on the dynamics of TGR in this quite unique cohort of NET-patients, with PanNET patients exclusively that underwent PRRT. This is in contrast to the previous reports including various NET types undergoing different types of systemic therapies and watch and wait ( 18 , 19 , 20 ).…”

“…Attempts to mathematically discern tumor growth patterns has for long been in the scope of oncological research (16). Calculation of tumor growth rate (TGR) is based on changes in the sum of lesion diameters and allows for quantitative assessment of tumor kinetics (17)(18)(19)(20).…”

“…Recent data indicate that TGR can be useful as an early biomarker in patients with small intestinal neuroendocrine tumors (SI-NET) and PanNETs undergoing a range of systemic therapies and watch-and-wait (18)(19)(20). Data also indicate that Ki-67 index at baseline may be associated with progression-free survival (PFS) (20).…”

“…Attempts to mathematically discern tumor growth patterns has for long been in the scope of oncological research ( 16 ). Calculation of tumor growth rate (TGR) is based on changes in the sum of lesion diameters and allows for quantitative assessment of tumor kinetics ( 17 , 18 , 19 , 20 ). Recent data indicate that TGR can be useful as an early biomarker in patients with small intestinal neuroendocrine tumors (SI-NET) and PanNETs undergoing a range of systemic therapies and watch and wait ( 18 , 19 , 20 ).…”