Abstract
BackgroundThe aim of the present analysis was to evaluate the recurrence pattern in patients with recurrent malignant glioma after re-irradiation in combination with bevacizumab as there is limited data on how to optimally choose dose, fractionation and delineation margins.MethodsThirty-one patients with recurrent malignant glioma treated with re-irradiation and bevacizumab after previous chemoradiotherapy (concurrent temozolomide 75 mg/m2/d according to the EORTC/NCIC trial) and [18 F]FET-PET and/or MRI confirmed recurrence were retrospectively analyzed. Bevacizumab was applied twice during fractionated re-irradiation (10 mg/kg, d1 + d15, median 36 Gy, conventionally fractionated). Recurrence patterns were assessed by means of [18 F]FET-PET and/or MRI.ResultsMedian follow-up was 34.0 months for all patients [95%-CI, 27.7-40.3] and median post-recurrence survival 10.8 months [95%-CI, 9.2-12.4]. Concerning the recurrence patterns, 61.3% of these were located in-field (19 patients), 22.6% were marginal (7 patients) and 16.1% ex-field (5 patients). No influence on the recurrence pattern was observed according to sex, WHO grade, maintenance chemotherapy or MGMT methylation status whereas planning target volume (PTV) size had a significant influence on the recurrence pattern (p = 0.032). PTV sizes > 75 ml were associated with a higher in-field recurrence rate and lower median post-recurrence progression-free survival (8.5 vs. 4.9 months, p = 0.016).ConclusionsAfter the administration of re-irradiation with bevacizumab the recurrence pattern seems to be mainly centrally located. The PTV size was the main predictor for a marginal/ex-field recurrence.
Highlights
In patients with high-grade glioma (HGG) a high rate of local failures has been observed after multimodal therapy [1]
Various groups have investigated the use of bevacizumab – a humanised monoclonal antibody against VEGF-A with an already established role in metastatic colon, breast, and lung cancer [11] – for patients with recurrent HGG [12] and several trials have documented its efficacy [13,14,15,16,17] which may be due to the presence of pronounced hypoxia as well as high levels of tumor driven angiogenesis in HGG [18]
In a previous retrospective study on 30 recurrent malignant glioma patients undergoing re-irradiation, 20 treated with bevacizumab and 10 without bevacizumab we showed that PFS-6 within the bevacizumab-treated cohort was 72% and survival was significantly enhanced [21]
Summary
In patients with high-grade glioma (HGG) a high rate of local failures has been observed after multimodal therapy [1]. Since the efficacy of radiation-based re-treatment is limited, it is reasonable to test how far the addition of a putative radiation response modulator would impact on the efficacy of re-treatment. In this regard, one group tested the sequential use of radiosurgery and bevacizumab with. The aim of the present analysis was to evaluate the recurrence pattern in patients with recurrent malignant glioma after re-irradiation in combination with bevacizumab as there is limited data on how to optimally choose dose, fractionation and delineation margins
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