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Radiation necrosis following treatment of high grade glioma—a review of the literature and current understanding

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Abstract

Radiation therapy is an integral part of the standard treatment paradigm for malignant gliomas, with proven efficacy in randomized control trials. Radiation treatment is not without risk however, and radiation injury occurs in a certain proportion of patients. Difficulties in differentiating recurrence from radiation injury complicate the treatment course and can compromise care. These complexities are compounded by the recent distinction of two types of radiation injury: pseudoprogression and radiation necrosis, which are likely the result of radiation injury to the tumor and normal tissue, respectively. A thorough understanding of radiation-induced injury offers insights to guide further therapies. We detail the current knowledge of the mechanisms of radiation injury, along with potential targets for therapeutic intervention. Various diagnostic modalities are also described, in addition to the multiple options for treatment within the context of their pathophysiology and clinical efficacy. Radiation therapy is an integral part of the multidisciplinary management of gliomas, and the optimal diagnosis and management of radiation injury is paramount to improving patient outcomes.

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Authors and Affiliations

  1. Department of Neurological Surgery, George Washington University Medical Center, Washington, DC, USA

    Alan Siu, Joshua J. Wind & Jonathan H. Sherman

  2. School of Medicine, Weill Cornell Medical College, New York, NY, USA

    J. Bryan Iorgulescu

  3. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Timothy A. Chan & Yoshiya Yamada

  4. Department of Neurological Surgery, The George Washington University, 2150 Pennsylvania Ave, NW Suite 7420, Washington, DC, 20037, USA

    Jonathan H. Sherman

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Comment

This review is an important read for neurosurgeons involved not only in the care of high-grade gliomas, the main point of analysis in the paper, but those who deal with radiation therapy in general. Up-to-date understanding of the biochemical mechanisms of radio necrosis is essential to interpret clinical and radiological events that develop after such therapy. With the increased use of stereotactic radiosurgical techniques in management of neurosurgical patients this review is highly topical.

Andras Kemeny

Sheffield, UK

The authors provide an impeccable and timely review of the current understanding of (a) pseudoprogression and (b) radiation necrosis that have increased with chemoradiotherapy of grade III and IV gliomas as against (c) progression that will invariably take place:

a. Pseudoprogression is early enhancement and expansion around the resection cavity seen at two to five months that will resolve in a few months. It does not require surgery - but without previous experience it may be hard to believe in the wait-and-see policy. In glioblastomas, ultraearly progression in spite of radiotherapy is a possibility but in our hands much less frequent than pseudoprogression.

b. Radiation necrosis may appear at some six months to over a year after chemoradiotherapy. A somewhat open question is whether BCNU wafers piled in the resection cavity increase the risk of radionecrosis. A question ages old is whether and how to differentiate radiation necrosis from glioma progression by various MRI sequences or PET - I find that problem somewhat academic as by definition there is always progressing glioma tissue in the area that looks like radiation necrosis. More important than a strict imaging-based distinction between the two is - in my mind - that we are prepared to re-resect lesions that produce significant brain edema. The bottom line is that radiation necrosis often requires prolonged corticosteroid therapy to alleviate symptoms from vasogenic brain edema - with a long list of side effects of corticosteroids as the price to pay.

WE MUST FIND OUT SOMETHING LESS NASTY THAN CORTICOSTEROIDS TO ALLEVIATE VASOGENIC BRAIN EDEMA CAUSED BY GRADE III-IV GLIOMAS OR RADIATION NECROSIS.

Juha E Jääskeläinen

Kuopio, Finland

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Siu, A., Wind, J.J., Iorgulescu, J.B. et al. Radiation necrosis following treatment of high grade glioma—a review of the literature and current understanding. Acta Neurochir 154, 191–201 (2012). https://doi.org/10.1007/s00701-011-1228-6

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