1419P - Radiobiological parameters for the assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

Background

The lack of robust radiobiological data hampers the further optimization of emerging ¹⁷⁷Lu-PSMA-directed radioligand therapy (RLT). This study aims to explore several conventional radiobiological parameters in the assessment of outcomes in tumor and normal organs at risk (OARs) for castration-resistant prostate cancer (CRPC) patients.

Methods

20 patients received a median of 3 (range 1–6, a totally of 86 cycles) ¹⁷⁷Lu-PSMA-617 RLT were retrospectively included. Hematological status, renal and liver function, and serum PSA test before and within two weeks post-therapy were documented. Pre-therapy PSMA-PET/CT image dates were collected to establish CT-based organ segmentation. The post-therapy dosimetry of each patient was measured using at least 3-time-points SPECT/CT imaging. PSA was used to determine therapy response, and the related adverse events were documented. Dose parameters including conventional radiobiological such as absorbed dose, integral dose (D10/50/90), biologically effective doses (BED) and cumulated BEDs (cBED) were tested.

Results

All patients are well-tolerated and 19/20 patients received a partial response post-therapy. The dosimetry evaluation demonstrated a high absorbed dose in tumors compared to OARs (p<.0001). The Dose_mean/max/sum of target organs decreases as the treatment cycle increases. The absorbed dose in non-tumor-bearing bones is significantly correlated with hematological AEs (G2-4) (p<.05). The patients with larger PET-based tumor volumes present higher absorbed doses in tumor and OARs (also when normalized to the administered activity). The highest D10/50/90 was received by tumor-bearing bone, the whole-body tumor and lymph/visceral regions respectively compared to OARs. BED_1.5 (AUROC: 0.633) and cBED_1.5 (AUROC: 0.714) demonstrated aggregable diagnostic accuracy in detecting better post-treatment PSA outcomes.

Conclusions

Despite the limited number of patients in this study, the preliminary results encourage the exploration of radiobiological models in the assessment of PSMA-RLT. In-depth analysis and interpretation of these radiobiological parameters are still ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.