Individualised 177Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry

Abstract

PurposeTo present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED).MethodTreatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 ± 2 Gy (α/β = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 ± 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR).ResultsFifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function.ConclusionsIndividualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3678-4) contains supplementary material, which is available to authorized users.

The conflict between treatment optimization and registration of radiopharmaceuticals with fixed activity posology in oncological nuclear medicine therapy

“…In the ongoing ILUMINET clinical study based on 177 Lu-DOTATATE, the number of cycles is tailored to the absorbed dose to the kidneys in the individual patient, and in an interim analysis the number of delivered cycles was found to vary between three and eight [15]. In the group of patients in whom treatment was terminated because they had reached the protocol-specified dose limit, 73% received more and 9% received fewer than four cycles.…”

Technical Note: Optimal sampling schedules for kidney dosimetry based on the hybrid planar/SPECT method in 177Lu‐PSMA therapy

“…The simulated time‐activity data for planar imaging were fitted with a mono‐exponential function. The TIAC was then determined with the area under the TAC scaled with the simulated activity value of the quantitative SPECT/CT measurement according towhere A SPECT is the activity value of the simulated SPECT/CT measurement, A planar is the mono‐exponential biokinetic determined by fitting the simulated planar activity data, and A 0 is the injected activity . Furthermore, the TIACs estimated without a SPECT/CT measurement, that is, only with planar imaging, were also calculated.…”

“…where A SPECT is the activity value of the simulated SPECT/ CT measurement, A planar is the mono-exponential biokinetic determined by fitting the simulated planar activity data, and A 0 is the injected activity. 6,10,11,13,25 Furthermore, the TIACs estimated without a SPECT/CT measurement, that is, only with planar imaging, were also calculated. As noise was implemented in the simulation routine, 1000 replications were performed for each sampling schedule and virtual patient, that is, 13 9 1000 TIACs were simulated for each sampling schedule.…”

“…This study focuses on the determination of OSS for renal dosimetry for 177 Lu‐PSMA I&T patients using the hybrid planar/SPECT method . This approach is recommended for dosimetry if quantitative SPECT scans cannot be acquired at multiple time points .…”

“…This study focuses on the determination of OSS for renal dosimetry for 177 Lu-PSMA I&T patients using the hybrid planar/SPECT method. 6,[10][11][12][13][14][15] This approach is recommended for dosimetry if quantitative SPECT scans cannot be acquired at multiple time points. 12,14 As the SPECT/CT measurement basically corrects the planar activity data for systematic errors, an enhanced noise model incorporating systematic and stochastic errors was used.…”