Patient-specific dosimetry in predicting renal toxicity with (90)Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship.
Nephrotoxicity is the major limiting factor during therapy with the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). Pretherapeutic assessment of kidney absorbed dose could help to minimize the risk of renal toxicity. The aim of this study was to evaluate the contribution of patient-specific adjustments to the standard dosimetric models, such as the renal volume and dose rate, for estimating renal absorbed dose during therapy with (90)Y-DOTATOC. In particular, we investigated the correlation between dose estimates and effect on renal function after therapy.


METHODS
Eighteen patients with neuroendocrine tumors (9 men and 9 women; median age, 59 y) underwent treatment with (90)Y-DOTATOC (8.1-22.9 GBq) after pretherapeutic biodistribution study with (86)Y-DOTATOC. Kidney uptake and residence times were measured and the absorbed dose (KAD) was computed using either the MIRDOSE3.1 software assuming a standard kidney volume (KAD(StdVol)) or the MIRD Pamphlet 19 values and the actual kidney cortex volume determined by pretherapeutic CT (KAD(CTVol)). For each patient, the biologic effective dose (BED) was calculated according to the linear quadratic model to take into account the effect of dose rate and fractionation. Renal function was evaluated every 6 mo by serum creatinine and creatinine clearance (CLR) during a median follow-up of 35.5 mo (range, 18-65 mo). The individual rate of decline of renal function was expressed as CLR loss per year.


RESULTS
KAD(CTVol) ranged between 19.4 and 39.6 Gy (mean, 28.9 +/- 5.34 Gy). BED, obtained from KAD(CTVol), ranged between 27.7 and 59.3 Gy (mean, 40.4 +/- 10.6 Gy). The CLR loss per year ranged from 0% to 56.4%. In 12 of 18 patients, CLR loss per year was <20%. No correlation was observed between CLR loss per year and the KAD(StdVol) or the KAD(CTVol). In contrast, BED strongly correlated with CLR loss per year (r = 0.93; P < 0.0001). All 5 patients with CLR loss per year >20% received a BED >45 Gy. Patients who were treated with low fractionation were those with the highest rate of renal function impairment.


CONCLUSIONS
Radiation nephrotoxicity after (90)Y-DOTATOC therapy is dose dependent. Individual renal volume, dose rate, and fractionation play important roles in an accurate dosimetry estimation that enables prediction of risk of renal function impairment.
Barone
Raffaella
R
Centre of Nuclear Medicine and Laboratory of Positron Emission Tomography; Université Catholique de Louvain, Brussels, Belgium.
Borson-Chazot
Françoise
F
Valkema
Roelf
R
Walrand
Stéphan
S
Chauvin
Franck
F
Gogou
Lida
L
Kvols
Larry K
LK
Krenning
Eric P
EP
Jamar
François
F
Pauwels
Stanislas
S
D000328:Adult; D000368:Aged; D000465:Algorithms; D001822:Body Burden; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000532:radiotherapy; D006801:Humans; D007668:Kidney / Q000528:radiation effects; D007674:Kidney Diseases / Q000175:diagnosis* / Q000209:etiology* / Q000517:prevention & control; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000532:radiotherapy; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016896:Treatment Outcome
D019275:Radiopharmaceuticals; D015282:Octreotide; C106246:Edotreotide