Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone

Matthew S Robertson; Yating Wang; SuChun Cheng; Hyesun Park; Shahar Glomski; Lauren C Harshman; Amanda Pace; Jacqueline Kilar; Meredith Flynn; Lauren Gilbert; Atish D Choudhury; Heather Jacene

doi:10.1007/s11547-024-01931-7

Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone

Radiol Med. 2024 Nov 20. doi: 10.1007/s11547-024-01931-7. Online ahead of print.

Authors

Matthew S Robertson¹, Yating Wang², SuChun Cheng², Hyesun Park^{3

4}, Shahar Glomski^{3

5}, Lauren C Harshman⁶, Amanda Pace⁶, Jacqueline Kilar⁶, Meredith Flynn⁶, Lauren Gilbert³, Atish D Choudhury⁶, Heather Jacene³

Affiliations

¹ Department of Imaging, Dana-Farber Cancer Institute, Department of Radiology Brigham and Women's Hospital, Boston, MA, 02115, USA. mrobertson@bwh.harvard.edu.
² Division of Biostatistics, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Imaging, Dana-Farber Cancer Institute, Department of Radiology Brigham and Women's Hospital, Boston, MA, 02115, USA.
⁴ Lahey Hospital, Burlington, MA, USA.
⁵ Midstate Radiology Associates, Meriden, CT, USA.
⁶ Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

PMID: 39565570
DOI: 10.1007/s11547-024-01931-7

Abstract

Objective: The purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUV_max) in normal bone, to provide the reference value of metastatic lesions, and to evaluate the clinical implication of SUV_max changes of osseous metastasis during treatment.

Material and methods: This prospective imaging sub-study was performed as part of a phase 2 clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to the combination of pembrolizumab plus radium-223 or to radium-223 alone (NCT03093428). The maximum standardized uptake value (SUV_max) and mean Hounsfield Unit (HU_mean) of normal bone as well as metastases were measured using a 1.5 cm region of interest (ROI) on CT and xSPECT Quant reconstruction on the baseline study (S₀) and restaging scans. The most tracer-avid metastatic lesion in each patient on S₀ was selected as a target lesion, and changes of SUV_max and HU_mean of the target lesion were compared on the first restaging scan (S₁). Correlations between the percentage changes of SUV_max of the target lesion with alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were assessed.

Results: Twenty-one patients were enrolled on the imaging sub-study of which 15 had paired baseline S₀ and S₁ data. On S₀, the median SUV_max and HU_mean of normal bone was 5.85 g/mL (0.42-14.98) and 133.03 (range, 28.47-461.91), respectively. The median SUV_max and HU_mean of metastasis were 42.2 g/mL (range, 17.96-143.36) and 549.58 (177.87-1107.64), respectively. There was significant reduction in SUV_max (- 40.1%, range - 86.2 to + 23.5%), p < 0.001) and increase in HU_mean (+ 8.3%, range - 11.3 to + 61.7%, p = 0.0479, Wilcoxon signed-rank test) of target lesions between S₀ and S₁. Spearman correlation between the percentage changes of SUV_max of a target lesion and both serum PSA (r = 0.33, p = 0.226) and ALP (r = 0.45, p = 0.094) were not statistically significant.

Conclusion: Quantitative SPECT/CT provides consistent and objective imaging parameters, which can help monitor tumor burden. The median SUVmax of metastasis at baseline was roughly 7.2-fold higher than normal bone. Quantitative SPECT/CT may help visualize the early osteoblastic treatment response in prostate cancer patients treated with radium-223 alone or combined with pembrolizumab.

Keywords: Quantitative; Radiotherapy; SPECT/CT.