title: Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate.
abstract: The kidneys are critical organs in peptide receptor radiation therapy (PRRT). Renal function loss may become apparent many years after PRRT. We analyzed the time course of decline in creatinine clearance (CLR) in patients during a follow-up of at least 18 mo after the start of PRRT with (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA),Tyr(3)-octreotide ((90)Y-DOTATOC) or (177)Lu-DOTA(0),Tyr(3)-octreotate ((177)Lu-DOTATATE).
  
  
  METHODS
  Twenty-eight patients with metastasized neuroendocrine tumors received 1-5 cycles of (90)Y-DOTATOC, leading to renal radiation doses of 5.9-26.9 Gy per cycle and a total of 18.3-38.7 Gy. Median follow-up was 2.9 y (range, 1.5-5.4 y), with a median of 16 measurements (range, 5-53) per patient. Thirty-seven patients with metastasized neuroendocrine tumors received 3-7 cycles of (177)Lu-DOTATATE, leading to renal radiation doses of 1.8-7.8 Gy per cycle and a total of 7.3-26.7 Gy. Median follow-up was 2.4 y (range, 1.7-4.0 y), with a median of 10 (range, 6-27) measurements per patient. All renal dose estimates were calculated with the MIRDOSE3 model. All patients were infused with renoprotective amino acids during the administration of the radioactive peptides. The time trend of CLR was determined by fitting a monoexponential function through the data of individual patients, yielding the decline in CLR in terms of percentage change per year.
  
  
  RESULTS
  The median decline in CLR was 7.3% per y in patients treated with (90)Y-DOTATOC and 3.8% per y in patients treated with (177)Lu-DOTATATE (P = 0.06). The time trend of decline in CLR was sustained during the follow-up period. Eleven patients had a >15% per y decline in CLR. Cumulative renal radiation dose, per-cycle renal radiation dose, age, hypertension, and diabetes are probable contributing factors to the rate of decline in CLR after PRRT.
  
  
  CONCLUSIONS
  This study showed that the time course of CLR after PRRT was compatible with the pattern of sustained CLR loss in progressive chronic kidney disease.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. r.valkema@erasmusmc.nl
authors.forename: Roelf
authors.initials: R
authors.lastname: Valkema
authors.forename: Stanislas A
authors.initials: SA
authors.lastname: Pauwels
authors.forename: Larry K
authors.initials: LK
authors.lastname: Kvols
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
authors.forename: Francois
authors.initials: F
authors.lastname: Jamar
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
authors.forename: Raffaella
authors.initials: R
authors.lastname: Barone
authors.forename: Stephan
authors.initials: S
authors.lastname: Walrand
authors.forename: Peter P M
authors.initials: PP
authors.lastname: Kooij
authors.forename: Willem H
authors.initials: WH
authors.lastname: Bakker
authors.forename: Janet
authors.initials: J
authors.lastname: Lasher
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000528:radiation effects; D007677:Kidney Function Tests; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000378:metabolism; D020127:Recovery of Function / Q000528:radiation effects; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C496730:90Y-octreotide, DOTA-Tyr(3)-; C447941:lutetium Lu 177 dotatate; D015282:Octreotide