Quantifying the changes in the tumour vascular micro-environment in spinal metastases treated with stereotactic body radiotherapy - a single arm prospective study
Article Category: Research Article
Publicado en línea: 13 dic 2022
Páginas: 525 - 534
Recibido: 24 ago 2022
Aceptado: 29 sept 2022
DOI: https://doi.org/10.2478/raon-2022-0046
© 2022 Balamurugan Vellayappan, Dennis Cheong, Salil Singbal, Jeremy Tey, Yu Yang Soon, Cheng Nang Leong, Alvin Wong, Sein Lwin, Chau Hung Lee, Pravin Periasamy, Simon Lo, Naresh Kumar, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Background
The primary objective was to quantify changes in vascular micro-environment in spinal metastases (SM) patients treated with stereotactic body radiotherapy (SBRT) with multi-parametric dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The secondary objective was to study plasma biomarkers related to endothelial apoptosis.
Patients and 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 was 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 local control rate 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).
Conclusions
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).