Nephrotoxicity and Hematotoxicity One Year after Four Cycles of Peptide Receptor Radionuclide Therapy (PRRT)

Purpose: Renal and hematologic long-term side effects after PRRT have been described in heterogeneous studies using various cumulative activities, number of treatments or radiolabeled peptides. We analyzed long-term side effects for a homogenous treatment schedule in PRRT-patients.

Methods: From our database 89/384 patients receiving the same PRRT (177Lu-DOTATATE or 90Y-DOTATOC) within a 10 to 12 week-interval and who had a follow-up at 12 months after the fourth cycle, were analyzed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to the chronic kidney disease classification (CKD), grading of hematotoxicity according to CTCAE. Impact of subgroups (age, gender, cumulative activity, type of PRRT) on long-term-toxicity was assessed.

Results: Prior to therapy eGFR Grade 1-2 dropped from 87/102 to 71 cases one year after the fourth therapy cycle (p<0.001). Before treatment Grade 3a was found in 13, Grade 3b in 2 cases, and one year after the fourth treatment cycle Grade 3a in 25, Grade 3b in 5, and Grade 4 in 1 case. Anemia prior to PRRT and one year after was Grade 0 in 63 versus 48 (p<0.001), Grade 1 in 36 versus 48, and Grade 2 in three versus six cases. WBC Grade 0 in 89 versus 83 (p=0.071), Grade 1 in 12 versus 13, and Grade 2 in 1 versus 6. Platelets were Grade 0 in 92 versus 84 (p=0.033), Grade 1 in 10 versus 18, and none Grade 2 or higher. The subgroup analysis revealed that an age above 65 years shows a higher incidence for anemia Grade 0 in 31/102 cases initially versus 18 after PRRT (p=0.006).

Conclusions: In roughly 20% of cases a deterioration in grading of nephrotoxicity or hematotoxicity is observed. In all patients, except in one, toxicity findings were mild or moderate one year after completion of four cycles of PRRT with either 90Y- or 177Lu-SST-analogues. In terms of safety, PRRT, including re-PRRT, has no critical impact on further oncologic treatment options in case of disease progression.

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