title: Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic factors, incidence and course.
abstract: OBJECTIVE
  In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from (131)I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with (177)Lu-DOTA(0)-Tyr(3)-octreotate ((177)Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.
  
  
  METHODS
  The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.
  
  
  RESULTS
  Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 × 10(9)/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq (177)Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.
  
  
  CONCLUSIONS
  The incidence of subacute haematological toxicity after PRRT with (177)Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from (131)I, seems not to be valid for PRRT with (177)Lu-DOTATATE.
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. bergsmahb@gmail.com.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bergsma
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Konijnenberg
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Boen L R
authors.initials: BL
authors.lastname: Kam
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Jaap J M
authors.initials: JJ
authors.lastname: Teunissen
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Kooij
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.affiliation: Department of Surgery, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Gaston J H
authors.initials: GJ
authors.lastname: Franssen
authors.affiliation: Department of Surgery, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Casper H J
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006801:Humans; D007455:Iodine / Q000737:chemistry; D008187:Lutetium / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D009942:Organometallic Compounds / Q000009:adverse effects / Q000737:chemistry*; D011379:Prognosis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D011868:Radioisotopes / Q000009:adverse effects / Q000737:chemistry*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000737:chemistry*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; D008187:Lutetium; D007455:Iodine; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
keywords: 177Lu-DOTATATE; Bone marrow; Dosimetry; PRRT; Toxicity