Anti-VEGF Treatment Plus Radiation For Schwannoma Control

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Dr. Lei Xu

MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital

Medical Research: What is the background for this study?

Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.

Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.

Medical Research: What are the main findings?

Dr. Lei Xu: Treatment with an anti-angiogenesis drug may improve the effectiveness of radiation treatment of nervous system tumors that interfere with the hearing of patients with the genetic disorder neurofibromatosis 2 (NF2). Furthermore, we found that anti-angiogenic treatment improves neurologic function in our mouse model by alleviating tissue edema, which may further improve neurologic function by decreasing muscle atrophy and increasing nerve regeneration.

Medical Research: What should clinicians and patients take away from your report?

Dr. Lei Xu: Combining anti-VEGF with radiation therapy allows use of a lower radiation dose, which can achieve better tumor control and minimize radiation-related neurological damage.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Lei Xu: On the bench side, studies in animal models that would permit testing of the vestibular nerve function and hearing response for Vestibular Schwannomas is needed for translational studies.

On the bedside, our study provides compelling rationale and paves the road for testing of the combined therapy in human Vestibular Schwannoma. Clinical studies of relative vessel size and permeability, tumor contrast enhancement, and edema-associated parameters are needed to fully elucidate the normalization effect of bevacizumab in NF2 patients.

Citation:

Gao, Y. Zhao, A. O. Stemmer-Rachamimov, H. Liu, P. Huang, S. Chin, M. K. Selig, S. R. Plotkin, R. K. Jain, L. Xu. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model. Proceedings of the National Academy of Sciences, 2015; DOI: 10.1073/pnas.1512570112

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Lei Xu, MD, PhD (2015). Anti-VEGF Treatment Plus Radiation For Schwannoma Control MedicalResearch.com;

Last Updated on November 12, 2015 by Marie Benz MD FAAD

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