Abstract
Our objective was to investigate direct voxel-wise relationship between dose and early MR biomarker changes both within and in the high-dose region surrounding brain metastases following stereotactic radiosurgery (SRS). Specifically, we examined the apparent diffusion coefficient (ADC) from diffusion-weighted imaging and the contrast transfer coefficient (Ktrans) and volume of extracellular extravascular space (ve) derived from dynamic contrast-enhanced (DCE) MRI data. We investigated 29 brain metastases in 18 patients using 3 T MRI to collect imaging data at day 0, day 3 and day 20 following SRS. The ADC maps were generated by the scanner and Ktrans and ve maps were generated using in-house software for dynamic tracer-kinetic analysis. To enable spatially-correlated voxel-wise analysis, we developed a registration pipeline to register all ADC, Ktrans and ve maps to the planning MRI scan. To interrogate longitudinal changes, we computed absolute ΔADC, ΔKtrans and Δve for day 3 and 20 post-SRS relative to day 0. We performed a Kruskall-Wallice test on each biomarker between time points and investigated dose correlations within the gross tumour volume (GTV) and surrounding high dose region > 12 Gy via Spearman’s rho. Only ve exhibited significant differences between day 0 and 20 (p < 0.005) and day 3 and 20 (p < 0.05) within the GTV following SRS. Strongest dose correlations were observed for ADC within the GTV (rho = 0.17 to 0.20) and weak correlations were observed for ADC and Ktrans in the surrounding > 12 Gy region. Both ΔKtrans and Δve showed a trend with dose at day 20 within the GTV and > 12 Gy region (rho = -0.04 to -0.16). Weak dose-related decreases in Ktrans and ve within the GTV and high dose region at day 20 most likely reflect underlying vascular responses to radiation. Our study also provides a voxel-wise analysis schema for future MR biomarker studies with the goal of elucidating surrogates for radionecrosis.
Highlights
Stereotactic radiosurgery (SRS) is a well established treatment for patients with brain metastases [1]
Four patients had a single lesion with evidence of radionecrosis, and one patient had two lesions with radionecrosis, only one of which was within the imaging slice coverage
Post-hoc Kruskall-Wallis tests for ve within the gross tumour volume (GTV) showed a significant decrease in ve at day 20 compared with day 0 (p
Summary
Stereotactic radiosurgery (SRS) is a well established treatment for patients with brain metastases [1]. Patients with brain metastases typically present with 1–4 lesions, and many exhibit hallmarks of oligiometastatic disease. Utilizing SRS to ablate these brain lesions in patients with well-controlled primary disease and further systemic therapy options has the potential to improve patient-related outcomes, including overall survival (OS) [2]. Recent evidence suggests that SRS alone reduces cognitive deterioration at 3 months without significant differences in OS compared with whole brain irradiation [3]. With ablative SRS dose prescriptions; local target control (LC) must be balanced with the potential for radiation-induced necrosis (radionecrosis). Distinguishing local tumour progression from radionecrosis is a key challenge for evaluation and clinical management of patients with treated brain metastases [4]. Biopsy following SRS provides histologic confirmation of radionecrosis, it is invasive, only applicable to accessible lesions, and has inherent surgical morbidities [5]
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