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Updated: Apr 20, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Treatment of anaplastic glioma
Wolfgang Wick1, Benedikt Wiestler, Michael Platten
1Department of Neurooncology, Neurology Clinic & National Center for Tumor Diseases, University of Heidelberg and German Cancer Research Center, Neuenheimer Feld 400, 69120, Heidelberg, Germany, wolfgang.wick@med.uni-heidelberg.de.
Abstract:
Anaplastic gliomas have received increasing attention over the past years. As opposed to glioblastoma, where the focus has been on the evaluation of novel compounds (with mainly disappointing results), in anaplastic gliomas relevant progress was generated with genotoxic therapies and translational work on biomarkers. Anaplastic gliomas are classified using single biomarkers, namely isocitrate dehydrogenase (IDH) or the related CpG island methylator phenotype (CIMP), alpha-thalassemia/mental retardation syndrome X-linked (ATRX), telomerase reverse transcriptase (TERT), p53, 1p/19q, and O(6)-methylguanine DNA-methyltransferase (MGMT). With these molecular biomarkers, three main prognostically distinct groups have been defined: (i) CIMP-negative anaplastic gliomas, which have a similar prognosis as glioblastoma, (ii) CIMP-positive 1p/19q intact, and (iii) CIMP-positive 1p/19q codeleted gliomas. In the CIMP-negative, mainly IDH wild-type group, MGMT promoter methylation may be used to identify patients who benefit from alkylating chemotherapy. The mutually exclusive ATRX losses and 1p/19q codeletions are used to subcategorize anaplastic tumors with a mixed histology according to microscopic features. This eliminates the biological basis and clinical necessity for the diagnosis of mixed gliomas (anaplastic oligoastrocytomas). Retrospective long-term analysis of the EORTC 26951 and RTOG 9402 trials revealed that patients with tumors harboring 1p/19q codeletions benefit from addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to primary radiotherapy. RTOG 9402 suggests that this may be the case also for patients with 1p/19q intact tumors, but IDH mutation. Future developments in addition to the ongoing CATNON and CODEL trials, will focus on further refinement of the molecular predictors and development of treatments that not only increase survival but also maintain neurological function, cognition, and health-related quality of life.
Insights
Anaplastic gliomas are now classified by molecular biomarkers like IDH, ATRX, and 1p/19q status, defining distinct prognostic groups. These biomarkers guide treatment, showing 1p/19q codeleted tumors benefit from specific chemotherapy combinations.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genetics
Background:
- Anaplastic gliomas are increasingly recognized, with progress driven by genotoxic therapies and biomarker research, unlike glioblastoma's limited therapeutic advancements.
- Current classification relies on biomarkers such as isocitrate dehydrogenase (IDH), CpG island methylator phenotype (CIMP), alpha-thalassemia/mental retardation syndrome X-linked (ATRX), telomerase reverse transcriptase (TERT), p53, 1p/19q, and O(6)-methylguanine DNA-methyltransferase (MGMT).
Purpose of the Study:
- To define prognostically distinct groups of anaplastic gliomas using molecular biomarkers.
- To evaluate the impact of specific molecular alterations on treatment response, particularly in relation to chemotherapy and radiotherapy.
Main Methods:
- Classification of anaplastic gliomas based on molecular biomarkers: IDH, CIMP, ATRX, TERT, p53, 1p/19q, and MGMT.
- Retrospective analysis of EORTC 26951 and RTOG 9402 trials to assess treatment benefits in relation to tumor molecular profiles.
- Identification of mutually exclusive ATRX losses and 1p/19q codeletions for subcategorization.
Main Results:
- Three prognostically distinct groups identified: CIMP-negative (similar to glioblastoma prognosis), CIMP-positive 1p/19q intact, and CIMP-positive 1p/19q codeleted.
- MGMT promoter methylation identifies patients benefiting from alkylating chemotherapy in the CIMP-negative, IDH wild-type group.
- Patients with 1p/19q codeleted tumors showed benefit from adding procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (EORTC 26951 and RTOG 9402 trials).
- RTOG 9402 suggests potential benefit of PCV chemotherapy for 1p/19q intact tumors with IDH mutation.
Conclusions:
- Molecular biomarkers (IDH, CIMP, ATRX, 1p/19q) are crucial for classifying anaplastic gliomas into prognostically distinct groups.
- The findings eliminate the need for diagnosing mixed gliomas (anaplastic oligoastrocytomas) based on microscopic features alone.
- Future research will focus on refining molecular predictors and developing treatments that improve survival while preserving neurological function and quality of life.
