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Published on: September 12, 2019
Metabolic Switch in Hepatocellular Carcinoma Patients Treated with Sorafenib: a Proof-of-Concept Trial
Angelo Castello1, Lorenza Rimassa2,3, Nicola Personeni2,3
1Department of Nuclear Medicine, Humanitas Clinical and Research Hospital-IRCCS, Via Manzoni 56, CAP, 20089, Rozzano, Milano, Italy.
Background:
Sorafenib is a multikinase inhibitor used to treat advanced hepatocellular carcinoma (HCC). Recently, a preclinical trial has shown that response to sorafenib is associated with a metabolic shift towards aerobic glycolysis. To test this observation in humans, we decided to conduct a proof-of-concept trial investigating the role of metabolic shift detected on [18F]FDG PET/CT in predicting survival and tumor response in HCC patients treated with sorafenib.
Methods:
We prospectively enrolled advanced HCC patients candidate to sorafenib and undergoing [18F]FDG PET/CT at baseline, at 24 h, and at day 7 following treatment start. Response evaluation was obtained after 8 weeks according to Response Evaluation Criteria in Solid Tumors (RECIST). All clinical variables and metabolic parameters (i.e., SUVmax; metabolic tumor volume, MTV; total lesion glycolysis, TLG; and their variations, Δ) were compared with those of treatment response and correlated to progression-free (PFS) and overall survival (OS).
Results:
For this proof-of-concept trial, between August 2016 and August 2018, 13 patients (10 male, 3 female, median age 69) were enrolled. Considering the entire cohort, we demonstrated a significant negative correlation between ΔSUVmax at 24 h and 1 week (rho = - 0.733, p = 0.016). The metabolic shift, as expected, demonstrated median SUVmax, MTV, and TLG after 1 week lower in patients with a stable disease than a progressive disease (p = 0.019). Metabolic parameters and ECOG performance status (PS) resulted significantly correlated to PFS and OS at univariate analysis. On multivariate analysis, only median MTV at 1 week resulted as an independent prognostic factor for PFS (p = 0.033).
Conclusions:
As hypothesized, [18F]FDG PET/CT resulted in able to evaluate metabolic shift at 24 h and early treatment response already 1 week after treatment start. Moreover, metabolic parameters and ECOG PS resulted in predictive and prognostic factors to PFS and OS, with MTV at 1 week appearing as an independent predictive factor for PFS.
Insights
Early [18F]FDG PET/CT scans can predict treatment response in advanced hepatocellular carcinoma (HCC) patients receiving sorafenib. Metabolic changes detected by PET/CT, particularly metabolic tumor volume (MTV), are linked to progression-free survival (PFS).
Area of Science:
- Oncology
- Nuclear Medicine
- Radiomics
Background:
- Sorafenib is a key treatment for advanced hepatocellular carcinoma (HCC).
- Preclinical studies suggest sorafenib response correlates with a metabolic shift to aerobic glycolysis.
- This study investigates this metabolic shift in HCC patients treated with sorafenib.
Purpose of the Study:
- To assess if [18F]FDG PET/CT can detect metabolic shifts in HCC patients treated with sorafenib.
- To determine if these metabolic changes predict tumor response and patient survival.
- To evaluate the role of early metabolic changes in predicting progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Prospective enrollment of advanced HCC patients receiving sorafenib.
- [18F]FDG PET/CT scans performed at baseline, 24 hours, and 7 days post-treatment initiation.
- Tumor response assessed by RECIST criteria after 8 weeks; correlation of metabolic parameters (SUVmax, MTV, TLG) and clinical variables with response and survival.
Main Results:
- A significant negative correlation was found between the change in SUVmax at 24h and 1 week (rho = -0.733, p = 0.016).
- Patients with stable disease showed lower median SUVmax, MTV, and TLG at 1 week compared to progressive disease (p = 0.019).
- Metabolic parameters and ECOG performance status (PS) were significant predictors of PFS and OS on univariate analysis; MTV at 1 week was an independent prognostic factor for PFS on multivariate analysis (p = 0.033).
Conclusions:
- [18F]FDG PET/CT effectively detects metabolic shifts within 24 hours and early treatment response by 1 week.
- Metabolic parameters and ECOG PS are predictive and prognostic factors for PFS and OS.
- MTV at 1 week emerged as an independent predictive factor for PFS in HCC patients treated with sorafenib.
