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.
177Lu-PSMA-I&T shows a median absorbed dose to kidneys of 0.35 ± 0.10 Gy/GBq, indicating a safety profile in patients with oligorecurrent hormone-sensitive prostate cancer.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study analyzed absorbed doses of 177Lu-PSMA-I&T in 45 patients with oligorecurrent hormone-sensitive prostate cancer. The treatment involved 2 cycles at a dose of 6.8 GBq followed by stereotactic body radiotherapy. The findings indicated well-tolerated dosimetry and improved progression-free survival compared to SBRT alone.
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.
Background
This paper addresses the dosimetry of 177Lu-PSMA-I&T in patients with oligorecurrent hormone-sensitive prostate cancer, a condition where standard imaging may not detect all lesions. Previous studies have indicated that 177Lu-PSMA-I&T can improve outcomes in this patient population, but detailed dosimetry data are limited. Understanding the absorbed doses to organs at risk and lesions is crucial for assessing safety and efficacy.
Methods
This was a secondary analysis of the phase 2 LUNAR trial, which randomized 45 patients to receive 177Lu-PSMA-I&T followed by stereotactic body radiotherapy or SBRT alone. Patients received 2 cycles of 6.8 GBq. Absorbed doses were estimated using quantitative SPECT/CT images acquired at multiple time points post-injection.
Results
The median absorbed dose to the kidneys was 0.35 ± 0.10 Gy/GBq. The mean dose to lymph node lesions was 0.46 ± 0.81 Gy/GBq. There was substantial heterogeneity in absorbed dose estimates across lesions and patients.
Interpretation
The findings suggest that the absorbed doses to organs at risk are consistent with prior reports, indicating a level of safety for this treatment approach. However, the clinical significance of the observed dose variations and the implications for treatment efficacy remain uncertain. The study's limitations, including small sample size and potential imaging artifacts, may confound the results.
Key findings
- Median prostate-specific antigen was 1.10 ng/mL (range, 0.16-14.70 ng/mL).
- Median whole-body total tumor volume was 14.5 cm³ (range, 1.9-145.9 cm³).
- Median SUVmax on baseline PSMA PET/CT was 3.49 (range, 0.59-45.30).
- AD to kidneys was 0.35 ± 0.10 Gy/GBq.
- Mean dose to lymph node lesions was 0.46 ± 0.81 Gy/GBq.
Limitations
- small n=45 in the analysis
- potential for partial-volume effects in SPECT imaging
- no long-term follow-up reported
- single-site study may limit generalizability