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

Background: Monitoring of pancreatic neuroendocrine tumors (PanNET) undergoing peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE depends on changes in tumor size, which often occur late. Tumor growth rate (TGR) allows for quantitative assessment of the tumor kinetics expressed as %/month. We explored how TGR changes before and during/after PRRT and evaluated TGR as a biomarker for progression-free survival (PFS). Methods: In PanNET patients undergoing PRRT with Lu-177-DOTATATE from 2006 to 2018, contrast-enhanced CT or MRI was performed before and during the therapy. Patients with at least one hypervascular liver metastasis were included. TGR was calculated for the period preceding treatment and for two intervals during/after PRRT. Cox regression was used for the survival analysis. Results: Sixty-seven patients (43 men, 24 women), median age 60 years (range 29-77), median Ki-67 10% (range 1-30) were included. TGR before baseline (n = 57) (TGR(0)) was mean (s.d.) 6.0%/month (S.D. = 8.7). TGR at 4.5 months (n = 56) (TGR(4)) from baseline was -3.4 (s.d. = 4.2) %/month. TGR at 9.9 months (n = 57) (TGR(10)) from baseline was -3.0 (S.D. = 2.9) %/month. TGR(4) and TGR(10) were lower than TGR(0) (TGR(4) vs TGR(0), P < 0.001 and TGR(10) vs TGR(0), P < 0.001). In the survival analysis, patients with TGR(10) >= 0.5%/month (vs <0.5%/month) had shorter PFS (median = 16.0 months vs 31.5 months, hazard ratio 2.82; 95% CI 1.05-7.57, P = 0.040). Discussion: TGR in PanNET patients decreases considerably during PRRT with Lu-177-DOTATATE. TGR may be useful as a biomarker to identify patients with the shortest PFS.