Bevacizumab-induced tumor calcifications as a surrogate marker of outcome in patients with glioblastoma. Neuro Oncol

Dr. Senckenberg Institute of Neurooncology, Goethe-University Hospital Frankfurt, Frankfurt, Germany.
Neuro-Oncology (Impact Factor: 5.56). 09/2011; 13(9):1020-9. DOI: 10.1093/neuonc/nor099
Source: PubMed


Therapy-induced calcifications in glioblastoma are rarely recognized. They may represent regressive changes in the tumor tissue, but their occurrence and possible predictive or prognostic value have not been systematically assessed. The observation of hyperintense lesions on precontrast T1-weighted magnetic resonance images (MRIs) in 2 index patients with glioblastoma after therapy with bevacizumab, subsequently identified as calcifications on computed tomographs (CTs), prompted us to prospectively screen for these radiographic changes. Therefore, 36 patients with recurrent glioblastoma prospectively treated with bevacizumab in an observational trial were examined every 8 weeks by MRI and, if clinically necessary, by CT. In 22 patients (61.1%), T1 hyperintense lesions became apparent after bevacizumab treatment. The median time to detection of these lesions was 55 days. In 14 (63.6%) of 22 patients, CTs were available and confirmed the existence of tumor calcifications. No substantial changes in T1 hyperintense lesions or calcifications were recognized on additional MRI or CT scans. Interestingly, the patients with therapy-induced T1 hyperintense lesions had better durations of progression-free survival than patients without these changes (median, 5.8 vs 3.5 months; P< .001), and the duration of overall survival was also superior (median, 9.7 vs 5.0 months; P= .006). There was a striking correlation between the appearance of therapy-induced T1 hyperintense lesions and overall response to bevacizumab. Therefore, this phenomenon is a rather early and time-limited event during the first weeks of treatment and appears to be response related. In summary, T1 hyperintense lesions are common in patients with glioblastoma who have been exposed to bevacizumab, may represent a novel biomarker of response and outcome, and seem to correspond to tumor calcifications.

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Available from: Oliver Bähr, Apr 17, 2014
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    • "Initial results suggest that glioblastoma patients with oligodendroglial components have prolonged survival and show better response to temozolomide [20], [21], [22], [23]. Furthermore, a recent report suggests that formation of calcifications in patients with glioblastoma after therapy with bevacizumab is associated with the response to therapy and improved outcome [24]. Therefore, the presence of calcifications in glioblastoma may represent an important biomarker for therapy decision, treatment response, and outcome. "
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    ABSTRACT: The application of susceptibility weighted imaging (SWI) in brain tumor imaging is mainly used to assess tumor-related "susceptibility based signals" (SBS). The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM), is able to distinguish between both entities reliably. SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication). Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of calcification in the context of different therapy regimes.
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    • "Herein it should be raised that there is no imaging ‘gold standard’ to detect tumor infiltration and even the FLAIR sequence may fail to show histopathological paths of tumor invasion. FLAIR is influenced by T1- and T2-relaxation times and both may be changed especially under therapy [52]. On the other hand the sensitivity of MRS to detect pathologies in normal appearing brain tissue has been shown for brain tumors [53], [54]. "
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    Full-text · Article · Mar 2013 · PLoS ONE
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    No preview · Chapter · Jan 2013
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