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Current and future strategies for treatment of glioma

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Abstract

Gliomas are one of the most common types of primary brain tumors and have remained particularly challenging to treat. This review illustrates a multidisciplinary approach to the treatment of glioma and glioblastoma. We will review current advances in surgical approaches, novel imaging techniques, advanced molecular characterization of tumors and translational efforts for treatment. We will focus on current clinical trials as well as the pursuit of personalized or precision therapy. We will also comment on the importance of both quality of life of our patients and their care givers.

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Authors and Affiliations

  1. Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Nancy Ann Oberheim Bush & Susan M. Chang

  2. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Mitchel S. Berger

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  1. Nancy Ann Oberheim Bush
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  2. Susan M. Chang
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  3. Mitchel S. Berger
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Correspondence to Nancy Ann Oberheim Bush.

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Comments

Ryo Nishikawa, Saitama-ken, Japan

In the field of glioma, recent progress of molecular genetics, targeted therapy trials based on the progress of molecular genetics and biology, and, especially, most recent enthusiasm for immunotherapy are watched with keen interest. In this paper, progress of epidemiology, surgery including assistance by imaging and functional monitoring, molecular genetics and histopathology, radiotherapy, chemotherapy, targeted therapies in a separate section from chemotherapy, and immunotherapies of gliomas are summarized. Especially description of targeted therapies and immunotherapies is outstanding, timely, and useful. A brief summary of quality of life is added which makes the paper multidisciplinary indeed.

Manfred Westphal, Hamburg, Germany

Oberheim-Bush and colleagues present a comprehensive overview of the current therapeutic thinking and future strategies for the treatment of gliomas. Such contributions provide a welcome update in a field which is rapidly expanding and fast moving due to the exponentially growing interest in this complex disease, which, however, has not translated into much of a therapeutic advance yet. Some clinical trials still use lomustine which was approved in the 1970s as control arm acknowledging the fact that the extrapolation of therapeutic advances in other cancers has been disappointing at best. The reference to many clinical trials in this article illustrates the breadth of new approaches taken and the recent efforts to improve on clinical trial designs. Integrating large patient data analysis including molecular date and repurposing of drugs should be highlighted as a highly relevant strategy to advance the field. It is very important to the updated readership that with our current nomenclature, we are in the nowhere-land between the older morphological classifications and the inclusion of molecular classifiers which cross the morphological boundaries and it will only be with the much awaited revision of the WHO classification that we find a universally applied language to compare our results and allocate patients to new developments.

It also emerges that treating glioma patients successfully requires a complex infrastructure which allows for maximal data collection via a multitude of modern imaging techniques, and neuropsychological testing, allows for maximal safe resection with an array of intraoperative monitoring and visualization techniques and allows for maximal acquisition of data on the tumor tissue. Due to high degree of interdisciplinary integration and demands on complex infrastructure, this will become increasingly limited to regional centers. Of these, there should be enough so that majority of patients can be followed regularly and preferentially entered into clinical trials without having to travel too far because that impairs their quality of life. The emerging basic principles of modern GBM treatment as they get consolidated in centers of excellence are well updated in this review. The outlook on the field despite all the excitement felt in the translation of molecular insights into clinical application has to be cautionally pessimistic.

Immuno-oncology, as pointed out, offers a vast array of new technologies with CAR cells and the many permutations of vaccination but neuro-oncology has to acknowledge that riding waves as in the past with tyrosine kinase inhibition or anti-angiogenesis is burdened with the fact that gliomas come with an intrinsic neuro-biology which in the past has set frustrating limits to extrapolation.

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Bush, N.A.O., Chang, S.M. & Berger, M.S. Current and future strategies for treatment of glioma. Neurosurg Rev 40, 1–14 (2017). https://doi.org/10.1007/s10143-016-0709-8

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