Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers.

Abstract

Purpose: Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.

Methods: A retrospective cohort of 448 NET patients treated with either ¹⁷⁷Lu-DOTATATE or ⁹⁰Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.

Results: Of the 448 PRRT treated patients, 335 received ¹⁷⁷Lu-DOTATATE (74.78%) and 113 were treated with ⁹⁰Y-DOTATOC (25.22%). Comparing patients treated with ¹⁷⁷Lu-DOTATATE to those treated with ⁹⁰Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with ⁹⁰Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with ¹⁷⁷Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received ¹⁷⁷Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with ⁹⁰Y-DOTATOC, but there was no difference in OS.

Conclusion: There was no significant renal, but minor hematological toxicity, in patients treated with ¹⁷⁷Lu-DOTATATE compared with ⁹⁰Y-DOTATOC. Compared to ⁹⁰Y-DOTATOC, ¹⁷⁷Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with ¹⁷⁷Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.