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Abstract
BackgroundCranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified.MethodsSWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4 years after chemoradiotherapy to 60 Gy. The median age at the time of treatment was 41 years (range 25 – 74 years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (<30 Gy), median (30–45 Gy), and high (>45 Gy) dose regions was computed.ResultsTwelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (>3 years from treatment) compared to early (<3 years) timepoints (early median 6 CMBs; late median 27 CMBs; p = 0.001), and there were proportionally more CMBs at lower doses for late scans (p = 0.006). 88% of all CMBs were observed in regions receiving at least 30 Gy, but the CMB density within medium and high dose regions was not significantly different (p = 0.33 and p = 0.9, respectively, for early and late time points).ConclusionsCMBs predominantly form in regions receiving at least 30 Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose–response relationship at doses above 30 Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation.
Highlights
Radiotherapy plays an integral role in the management of gliomas
The number of Cerebral microbleeds (CMB) was observed to increase with time, with patients scanned after 3 years demonstrating significantly more CMBs than those scanned at or before 3 years
The three patients who underwent scans at both timepoints all demonstrated substantially increased CMB counts with the later scan (25, 25 and 71 vs 4, 2 and 21). For both early and late timepoints, CMB count was not associated with patient age or the use of antiangiogenic therapy
Summary
Radiotherapy plays an integral role in the management of gliomas. Combined adjuvant chemoradiotherapy (CRT) constitutes the standard of care after maximal safe resection in malignant glioma [1], and is gaining acceptance as adjuvant treatment for high-risk, low-grade gliomas [2]. Given the amount of normal irradiated brain tissue, late toxicity from radiotherapy for gliomas is of significant concern, for patients with lower-grade gliomas for whom survival can extend well over 10 years [2]. Cognitive testing of long-term glioma survivors has shown significant decline across multiple cognitive domains [7], evidence exists for tumor progression as a driver of cognitive decline in glioma patients [8]. Reliable markers of late radiation toxicity are needed to better characterize the mechanism of white matter damage as well as patient, tumor, and treatment factors that influence the risk of late cognitive decline. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified
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