title: Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate.
abstract: Myelosuppression may be the dose-limiting toxicity in peptide receptor radionuclide therapy (PRRT). The aim of this study was to investigate the incidence, severity, and reversibility of long-term hematotoxicity in a large cohort of patient undergoing PRRT with (177)Lu-octreotate for metastatic neuroendocrine tumors. The impact of potential risk factors, including initial cytopenia, advanced bone metastatic disease, previous chemotherapy, and cumulative administered activity, and the protective effects of splenectomy were of particular interest.
  
  
  METHODS
  A total of 632 PRRT courses were performed in 203 patients with metastatic neuroendocrine tumors. A mean activity of 7.9 GBq of (177)Lu-octreotate was administered per treatment cycle, with a goal of 4 courses at standard intervals of 3 mo. Hematologic parameters were determined before each treatment course, at 2- to 4-wk intervals between the courses, 8-12 wk after the last course of PRRT, and at 3-month intervals for further follow-up. Toxicity was recorded with Common Terminology Criteria for Adverse Events (version 3.0).
  
  
  RESULTS
  Myelodysplastic syndrome as a delayed adverse event was documented in 3 patients (1.4%). Relevant but reversible hematotoxicity (grade 3 or 4) occurred in 23 patients (11.3%) and 29 administrations (4.6%), with leukopenia in 2.7% and thrombocytopenia in 1.7%. The mean time to blood count recovery was 12 mo after the termination of PRRT (range, 3-22 mo). The only preexisting factor that contributed to hematotoxicity was initial cytopenia (P < 0.001). A high level of cumulative administered activity (>29.6 GBq) was associated with relevant leukopenia (P < 0.001). None of the patients with a history of splenectomy developed grade 3 or 4 hematotoxicity, and splenectomy was inversely associated with the incidence and degree of leukopenia (P = 0.02) and thrombocytopenia (P = 0.03).
  
  
  CONCLUSIONS
  PRRT-induced myelosuppression is almost invariably reversible and rarely requires clinical measures. Administered activity and initial cytopenia are the only factors contributing to myelosuppression, whereas splenectomy may exert a protective effect.
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Sabet
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezziddin
authors.forename: Ulrich-Frank
authors.initials: UF
authors.lastname: Pape
authors.forename: Hojjat
authors.initials: H
authors.lastname: Ahmadzadehfar
authors.forename: Karin
authors.initials: K
authors.lastname: Mayer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pöppel
authors.forename: Stefan
authors.initials: S
authors.lastname: Guhlke
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Biersack
authors.forename: Samer
authors.initials: S
authors.lastname: Ezziddin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000528:radiation effects; D004912:Erythrocytes / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D018000:Receptors, Peptide / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D013997:Time Factors
chemical_list: C554548:177Lu-octreotate; D018000:Receptors, Peptide; D015282:Octreotide
keywords: 177Lu-octreotate; NETs; PRRT; hematotoxicity