18F-Sodium fluoride PET/CT predicts overall survival in patients with advanced genitourinary malignancies treated with cabozantinib and nivolumab with or without ipilimumab

Abstract

Purpose: We evaluated the prognostic value of ¹⁸F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab.

Methods: We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF.

Result: Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56-6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant.

Conclusion: Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population.

Keywords: Cabozantinib; Fluoride PET/CT; Genitourinary malignancy; Immune checkpoint inhibitor; NaF PET/CT.

Fig. 1

Schema of phase 1 and expansion cohorts of cabozantinib, nivolumab, and ipilimumab. Doublet, cabozantinib + nivolumab; triplet, cabozantinib + nivolumab + ipilimumab. Expansion cohorts are still accruing, NaF PET/CT no longer mandatory for protocol enrollment

Fig. 2

Quantification of SUVmax and whole body bone fluoride parameters (FTV and TLF) on NaF PET/CT. a NaF PET/CT of patient with urothelial carcinoma being treated with nivolumab 1 mg/kg, cabozantinib 40 mg, and ipilimumab 1 mg/kg. b Semi-automatic VOI is drawn in bone density contour. c With the threshold SUVmax of ≥ 10, all background activity is removed, leaving metastases and some non-metastatic VOIs with high uptake. d All non-metastatic VOIs (e.g., urine activity and brain activity) are removed. Quantitative analysis showed SUVmax of 137.1 (right pelvic bone), FTV of 719 ml, and TLF of 17,875. After 2.8 months of treatment, this patient died due to disease progression

Fig. 3

Kaplan-Meier analysis of overall survival according to TLF at baseline (a) and SUVmax at follow-up (b) using NaF PET/CT. Patients classified as higher TLF at baseline and higher SUVmax at follow-up had poorer OS. Log-rank test revealed significant differences in respective groups (p = 0.022 for TLF at baseline and p = 0.010 for SUVmax at follow-up)