Marie Blonski

Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment

Background.New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. Methods.We retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE. Results. A cohort of 39 patients was analyzed between December 2010 and April 2014. Upfront standard TMZ-based chemoradiotherapy was recused due either to tumor volume or impairment of neurological status and/or performance status. After TMZ/BEV induction (median time of 3 months), 6 (15%) patients achieved a partial response (PR), and 17 (44%) had a stable disease. 24 patients (62%) received a radical-intent chemoradiotherapy. TMZ-BEV induced median reduction of the clinical target volume (CTV) was 25.9% [-84.4%; - 4.8%]. The median PFS and OS were 8.4 months [95% CI: (6.6 - 9.9)] and 11.0 months [95% CI: (9.3 - 13.7)], respectively in the whole cohort and 10.8 [95% CI: (9.3 - 12.9)] and 15.0 [95% CI: (13.2 - 17.8)] for irradiated patients. Induction treatment led to corticosteroid dose reduction or cessation in 21 patients (54%). KPS improvement was observed in 38% of patients. Toxicity was mild with only 7/39 (18%) grade III-IV toxicity, including 1 digestive bleeding and 1 epistaxis. Conclusion.TMZ-BEV induction led to CTV reduction allowing for optimal chemoradiotherapy in a majority (62%) of patients for which radiotherapy was initially recused. A clinical benefit was obtained with improved KPS and a decrease in steroid dose.

On the relevance of two manual tumor volume estimation methods for diffuse low-grade gliomas

Management of diffuse low-grade glioma (DLGG) relies extensively on tumour volume estimation from MRI datasets. Two methods are currently clinically used to define this volume: the commonly used three-diameters solution and the more rarely used software-based volume reconstruction from the manual segmentations approach. The authors conducted an initial study of inter-practitioners’ variability of software-based manual segmentations on DLGGs MRI datasets. A panel of 13 experts from various specialties and years of experience delineated 12 DLGGs’ MRI scans. A statistical analysis on the segmented tumour volumes and pixels indicated that the individual practitioner, the years of experience and the specialty seem to have no significant impact on the segmentation of DLGGs. This is an interesting result as it had not yet been demonstrated and as it encourages cross-disciplinary collaboration. Their second study was with the three-diameters method, investigating its impact and that of the software-based volume reconstruction from manual segmentations method on tumour volume. They relied on the same dataset and on a participant from the first study. They compared the average of tumour volumes acquired by software reconstruction from manual segmentations method with tumour volumes obtained with the three-diameters method. The authors found that there is no statistically significant difference between the volumes estimated with the two approaches. These results correspond to non-operated and easily delineable DLGGs and are particularly interesting for time-consuming CUBE MRIs. Nonetheless, the three-diameters method has limitations in estimating tumour volumes for resected DLGGs, for which case the software-based manual segmentation method becomes more appropriate.