Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study

Vascular changes in spine metastases treated with SBRT

Abstract

Objectives The primary objective is to quantify changes in vascular micro-environment in spinal metastases(SM) patients treated with SBRT with multi-parametric dynamic contrast enhanced(DCE) magnetic resonance imaging (MRI). The secondary objective is to study plasma biomarkers related to endothelial apoptosis.

Methods

Patients were imaged with DCE-MRI at baseline/1-week/12-weeks post-SBRT. Metrics including normalised time-dependent leakage(Ktrans), permeability surface product(PS), fractional plasma volume(Vp), extracellular volume(Ve) and perfusion(F) were estimated using distributed parameter model. Serum acid sphingomyelinase(ASM) and sphingosine-1-phosphate(S1P) were quantified using ELISA. Clinical outcomes including physician-scored and patient-reported toxicity were collected.

Results

Twelve patients (with varying primary histology) were recruited, of whom 10 underwent SBRT. Nine patients (with 10 lesions) completed all 3 imaging assessment timepoints. One patient died due to pneumonia (unrelated) before follow-up scans were performed. Median SBRT dose 27 Gy(range:24–27) over 3 fractions(range:2–3). Median follow-up for alive patients was 42-months(range:22.3–54.3), with a local control of 90% and one grade 2 or higher toxicity (vertebral compression fracture). In general, we found an overall trend of reduction at 12-weeks in all parameters(Ktrans/PS/Vp/Ve/F). Ktrans and PS showed a reduction as early as 1-week. Ve/Vp/F exhibited a slight rise 1-week post-SBRT before reducing below the baseline value. There were no significant changes, post-SBRT, in plasma biomarkers(ASM/S1P).

Conclusion

Tumour vascular micro-environment (measured by various metrics) showed a general trend towards downregulation post-SBRT. It is likely that vascular-mediated cell killing contributes to excellent local control rates seen with SBRT. Future studies should evaluate the effect of SBRT on primary-specific spinal metastases (e.g., renal cell carcinoma).