Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases

Abstract

Background Context Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. Purpose To identify early MRI biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. Study Design/Setting Retrospective case series at a large tertiary cancer center. Patient Sample From 2011 to 2014, nine consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with DCE-MRI both pre- and post-SBRT. Outcome Measure Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multi-parametric MRI (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. Methods All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t-tests were used to compare groups. P<0.05 was deemed statistically significant. Results The median time from SBRT until post-treatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared to pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <0.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of “worsening,” “no change,” or “improvement,” respectively, by both radiologists’ graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2 = 0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared to the mpMRI score change post-SBRT (R2 = 0.026). Conclusions We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at two months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

A Pilot Study Evaluating the Use of Dynamic Contrast-Enhanced Perfusion MRI to Predict Local Recurrence After Radiosurgery on Spinal Metastases

“…Recent studies have demonstrated that DCE-MRI can detect tumor response to high-dose RT in spinal bone metastases through changes in perfusion parameters shortly after treatment. 10 , 16 Here, we show that in addition to evaluating tumor response to treatment, DCE-MRI can predict local tumor recurrence following high-dose RT. Specifically, average change in perfusion parameters V p and K trans differed significantly from the LC group compared with the LR group ( P < .01).…”

“… 14 , 15 Furthermore, DCE-MRI has been used to assess treatment response in patients with spinal metastases treated with high-dose radiation therapy (RT). 10 , 16 It has been demonstrated that changes in perfusion parameters, particularly V p , reflect tumor response to RT in spinal bone metastases. 10 …”

DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR

“…A recent early stage breast cancer study [13] found significant increases in the initial area under an enhancement curve for the entire GTV at one-week post-single dose SABR. However, when assessing response at later times (>1month) in other cancer sites, decreases in K trans were associated with pathologically complete response [39][40][41]. Two of these reports [39,41] also indicated that decreases in rK trans was indicative of response.…”

Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery

“…Multiparametric MRI utilizing DCE information outperformed clinical radiologists' anatomical impressions of treatment outcomes. 43 In both radiation and specifically antiangiogenic systemic therapy, vascular changes quantified by DCE-MRI may show predictive changes earlier than morphological changes seen in standard MRI or CT. 5,41 Based on these results from Spratt et al, the use of multiparametric MRI appears to be the most sensitive imaging technique at detecting response to SSRS and is considered by many to now be the gold standard for monitoring response to treatment. There is currently (at the time of this writing) an ongoing prospective trial evaluating the use of DCE-MRI in the assessment of patients with spinal metastases (NCT02376127; www.…”

“…Local control rates of SSRS approach 90% up to 2 years after treatment, 16,60,61 although the accuracy of what is deemed "control" is controversial, given the inability of conventional metrics of tumor size to accurately assess the volume of viable disease and correlate with ultimate tumor progression. 43 There are no standardized consensus guidelines for tumor imaging after SSRS. There are also few studies evaluating the utility of different imaging modalities after SSRS, none of which use histopathological correlation.…”