Dosimetry Analysis of <sup>177</sup>Lu-PSMA-I&T in Patients with Low-Volume Oligometastatic Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the LUNAR Trial.
Authors
Affiliations (5)
Affiliations (5)
- Department of Nuclear Medicine and Theranostics, Ahmanson Translational Theranostics Division, David Geffen School of Medicine, UCLA, Los Angeles, California; [email protected].
- Department of Nuclear Medicine and Theranostics, Ahmanson Translational Theranostics Division, David Geffen School of Medicine, UCLA, Los Angeles, California.
- Department of Medicine Statistical Core, UCLA, Los Angeles, California.
- Department of Radiation Oncology, UCLA, Los Angeles, California; and.
- Department of Nuclear Medicine, TUM Klinikum, Rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany.
Abstract
The phase 2 LUNAR trial randomized (1:1) patients with oligorecurrent hormone-sensitive prostate cancer to neoadjuvant [<sup>177</sup>Lu]Lu-PSMA-I&T (2 cycles, 6.8 GBq) followed by stereotactic body radiotherapy (SBRT) versus SBRT alone. [<sup>177</sup>Lu]Lu-PSMA-I&T before SBRT was well tolerated and significantly improved PSMA PET/CT-based progression-free survival compared with SBRT alone. Here, we report the estimated absorbed doses (AD) of [<sup>177</sup>Lu]Lu-PSMA-I&T to organs at risk and lesions. <b>Methods:</b> This analysis was conducted on all 45 patients randomized to the investigational arm. Quantitative SPECT/CT images were acquired at 4, 24, and 72-96 h postinjection of cycle 1. Kidneys, salivary and lacrimal glands, and liver were delineated with deep learning-assisted segmentation, whereas lumbar vertebrae were manually segmented as a surrogate for bone marrow. Planned target volumes were transferred from the SBRT plans to the SPECT/CT series. Registration between time points was manually verified for each segmentation. ADs were estimated using a multiple-time-point voxel-based schema. Time-activity data were fit using a monoexponential function. Partial-volume effects were corrected using volume-specific phantom-based recovery coefficients. <b>Results:</b> In the 45 patients included, the median prostate-specific antigen was 1.10 ng/mL (range, 0.16-14.70 ng/mL). In total, 123 lesions total were identified, with a median per patient of 2 (range, 1-9). Median whole-body total tumor volume was 14.5 cm<sup>3</sup> (range, 1.9-145.9 cm<sup>3</sup>). Median SUV<sub>max</sub> on baseline PSMA PET/CT and 24-h SPECT/CT was 3.49 (range, 0.59-45.30) and 0.72 (range, 0.02-34.24), respectively. The AD to the kidneys, parotids, submandibulars, lacrimals, liver, and bone marrow were 0.35 ± 0.10, 0.20 ± 0.10, 0.24 ± 0.10, 0.70 ± 0.49, 0.03 ± 0.01, and 0.005 ± 0.002 Gy/GBq, respectively. The mean dose to bone (<i>n</i> = 38), lymph node (<i>n</i> = 82), and soft tissue (<i>n</i> = 3) lesions were 0.19 ± 0.42, 0.46 ± 0.81, and 0.30 ± 0.38 Gy/GBq, respectively. <b>Conclusion:</b> The ADs from [<sup>177</sup>Lu]Lu-PSMA-I&T to organs at risk were consistent with prior reports, supporting the safety in patients with oligorecurrent hormone-sensitive prostate cancer. There was substantial heterogeneity in lesion AD estimates on both inter- and intrapatient levels. Because of the limited spatial resolution of SPECT, partial-volume effects can underestimate the AD in small volumes. Nevertheless, 2 neoadjuvant cycles of [<sup>177</sup>Lu]Lu-PSMA-I&T before SBRT prolonged progression-free survival, consistent with effective treatment of occult disease beyond imaging detectability.