Re-Irradiation, Chemotherapy, New Drugs for the (Re)-Treatment of Recurrent Gliomas

Dear Colleagues,

Gliomas account for ca. 70% of all primary brain tumors. Malignant glioma include all glioma with a WHO grade III and IV where the glioblastoma multiforme (WHO IV) is the most malignant and common tumour (ca. 60%). For glioblastoma, combined postoperative chemoradiotherapy with temozolomide is the current standard medical practice after results of the joint EORTC-NCIC phase III study randomizing between radiotherapy alone and combined chemoradiotherapy with temozolomide showed a significant improvement in 2-years survival from 8% to 24% for the combined treatment arm and is associated with 5 year survival estimates in the region of 10% [1,2]. It was shown, that survival favoured combined primary treatment despite salvage treatments given. However, a large proportion of patients relapse within 18 months after first treatment. Also many patients harbouring an anaplastic glioma experience either a transformation of the glioma into a higher grade or a local recurrence after primary treatment. Currently, there is no standard salvage treatment at recurrence defined. Re-treatments considered are  re-resection, second line chemotherapy or novel agents or re-irradiation.

Challenges for second line chemotherapy are fact that many patients have reduced bone marrow capacity after first line chemotherapy as well as the fact that in a subgroup of patients who responded well to temozolomide at first line treatment, developed resistance mechanisms to temozolomide at relapse. (Re)-resection cannot be curable due to the highly invasive nature of glioma cells into surrounding normal tissue. Re-irradiation carries concerns of late toxicity. New drugs with anti-angiogenic characteristsics for example of other targeted drugs open new doors for potential treatment combinations.

Future treatment approaches point into the direction of combined multi-disciplinary treatment approaches like in the primary situation. Recurrent glioma also open the possibility to testing new treatments and new treatment techniques within prospective controlled trials also as these patients are best treated within clinical trials.

These edition shall collect and present the current available knowledge on re-treatment options as well as potential future developments and current research.

For this issue and in regard to the malignant glioma, possible topics of interest may include:

Retreatment approaches either with a single treatment option like second line chemotherapy, re-operation, re-irradiation or new targeted drugs or new combined multi-disciplinary approaches combining for example, targeted drugs with irradiation or vaccination with operation, application of new imaging techniques like PET imaging or new functional MRI imaging (perfusion, diffusion) etc.

Regarding new treatment techniques, stereotactic radiotherapy, brachytherapy, proton therapy, carbion therapy, new neurosurgical techniques or current reserach on new targeted drugs, vaccination or immunotherapy for example, are of interest.

Regarding cancer biology, possible topics of interest may include cancer stem cells, resistance to MGMT, new potential targets in malignant glioma.

Regarding clinical outcome survival, local control either clincally or radiologically, toxicity, morbidity, and efficay are topics of interest.

Dr. Brigitta Baumert PhD
Guest Editor

References:

1. Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R.C.; Ludwin, S.K.; Gorlia, T.; Allgeier, A.; Lacombe, D.; Cairncross, J.G.; Eisenhauer, E.; Mirimanoff, R.O.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987-996.

2. Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.B.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; et al. on behalf of the European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groupsthe National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10, 459-466.

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• malignant glioma
• recurrence
• re-irradiation
• re-treatment
• re-operation
• targeted drugs