Clinical value of per-treatment whole-body single-time-point automated dosimetry for [<sup>177</sup>Lu]Lu-PSMA-617 therapy in metastatic castration-resistant prostate cancer.
Single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy shows a correlation with hematological decline, but further studies are needed to establish clinical significance.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study assessed the clinical value of single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy in 59 patients with metastatic castration-resistant prostate cancer (mCRPC). The analysis focused on the correlation between absorbed doses and hematological parameters as well as PSA responses. Findings indicated a relationship between bone marrow absorbed dose and declines in red blood cells and hemoglobin.
Abstract
<h4>Purpose</h4>To assess the clinical value of single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).<h4>Methods</h4>Fifty-nine patients with progressive mCRPC expressing PSMA and previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy were retrospectively analysed. SPECT/CT imaging was performed after the first (C1) and fourth (C4) [¹⁷⁷Lu]Lu-PSMA-617 infusions on 360°-CZT camera. Automated segmentation and dosimetry protocols were applied to quantify absorbed doses in bone marrow and lesions. Dose-effect relationships were assessed using blood counts, PSA responses (PSA50 criteria), and PET imaging. Statistical analyses included Spearman correlation, Wilcoxon signed-rank test, and logistic regression.<h4>Results</h4>Bone marrow absorbed dose (BMAD) at C1 was significantly correlated with red blood cells (RBC, ρ = -0.3) and haemoglobin (ρ = -0.26) decline. A higher BMAD was associated with greater declines in RBC count (median [IQR] 0.31 [0.33] Gy vs. 0.076 [0.19], p < 0.05) and haemoglobin (0.29 [0.41] vs. 0.092 [0.20], p = 0.056). A moderate negative correlation was found between PSA variation and total metastatic tumour absorbed (TMTAD) dose at C1 (ρ = -0.35) and from C1 to C4 (ρ = -0.35). Response modelling (based on PSA50) estimated 50% and 80% probabilities of response at 8.8 Gy and 18.1 Gy for TMTAD(C1) and at 11.3 Gy and 31.7 Gy for TMTAD(C1-C4).<h4>Conclusion</h4>Single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy in mCRPC is clinically relevant, demonstrating dose-dependent haematological decline and therapeutic response. This approach has the potential to facilitate more personalised and accessible radioligand therapy.
Background
This paper addresses the clinical utility of single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Prior research has indicated the importance of dosimetry in optimizing radioligand therapies, but the specific impact of single-time-point measurements on clinical outcomes was not well established. Understanding these relationships could enhance personalized treatment approaches in mCRPC.
Methods
This retrospective analysis included 59 patients with progressive mCRPC who had previously undergone treatment with androgen receptor pathway inhibitors and taxane-based chemotherapy. SPECT/CT imaging was performed after the first (C1) and fourth (C4) infusions of [¹⁷⁷Lu]Lu-PSMA-617. Automated segmentation and dosimetry protocols quantified absorbed doses in bone marrow and lesions, with primary outcome measures including blood counts and PSA responses.
Results
The study found that the bone marrow absorbed dose (BMAD) at C1 was significantly correlated with declines in red blood cells and hemoglobin. Specifically, higher BMAD was associated with a median RBC decline of 0.31 Gy compared to 0.076 Gy in lower doses (p < 0.05). The correlation between PSA variation and total metastatic tumor absorbed dose (TMTAD) was moderate, with ρ = -0.35 for both C1 and C4.
Interpretation
These findings suggest a relationship between dosimetry and hematological outcomes, which aligns with previous literature indicating the importance of dose management in radioligand therapies. However, the effect sizes reported, while statistically significant, may not be clinically meaningful given the small sample size and retrospective nature of the study. The potential confounds include the lack of randomization and the reliance on historical controls, which may limit the reliability of the conclusions drawn.
Key findings
- Bone marrow absorbed dose (BMAD) at C1 was significantly correlated with red blood cells (RBC, ρ = -0.3) and hemoglobin (ρ = -0.26) decline.
- Higher BMAD was associated with greater declines in RBC count (median [IQR] 0.31 [0.33] Gy vs. 0.076 [0.19], p < 0.05).
- Higher BMAD was associated with greater declines in hemoglobin (0.29 [0.41] vs. 0.092 [0.20], p = 0.056).
- Response modelling estimated 50% and 80% probabilities of response at 8.8 Gy and 18.1 Gy for TMTAD(C1).
- Response modelling estimated 50% and 80% probabilities of response at 11.3 Gy and 31.7 Gy for TMTAD(C1-C4).
Limitations
- Retrospective analysis may introduce bias.
- Sample size of 59 patients may limit generalizability.
- No randomization in study design.
- Reliance on historical controls.