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 (177)Lu-DOTATATE or (90)Y-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 (177)Lu-DOTATATE (74.78%) and 113 were treated with (90)Y-DOTATOC (25.22%). Comparing patients treated with (177)Lu-DOTATATE to those treated with (90)Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with (90)Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with (177)Lu-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 (177)Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with (90)Y-DOTATOC, but there was no difference in OS. CONCLUSION: There was no significant renal, but minor hematological toxicity, in patients treated with (177)Lu-DOTATATE compared with (90)Y-DOTATOC. Compared to (90)Y-DOTATOC, (177)Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with (177)Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.