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.
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.
Valkema
Roelf
R
Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. r.valkema@erasmusmc.nl
Pauwels
Stanislas A
SA
Kvols
Larry K
LK
Kwekkeboom
Dik J
DJ
Jamar
Francois
F
de Jong
Marion
M
Barone
Raffaella
R
Walrand
Stephan
S
Kooij
Peter P M
PP
Bakker
Willem H
WH
Lasher
Janet
J
Krenning
Eric P
EP
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
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C496730:90Y-octreotide, DOTA-Tyr(3)-; C447941:lutetium Lu 177 dotatate; D015282:Octreotide