title: Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.
abstract: Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China;
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, China;
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Molecular Pathology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: Anat O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: Peigen
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: ShanMin
authors.initials: S
authors.lastname: Chin
authors.affiliation: Molecular Pathology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: Martin K
authors.initials: MK
authors.lastname: Selig
authors.affiliation: Department of Neurology and Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; lei@steele.mgh.harvard.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004487:Edema / Q000150:complications / Q000473:pathology; D006801:Humans; D051379:Mice; D009133:Muscular Atrophy / Q000150:complications / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects; D016518:Neurofibromatosis 2 / Q000150:complications* / Q000503:physiopathology; D025581:Neurofibromin 2 / Q000172:deficiency / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects; D045442:Rotarod Performance Test; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000906:Antibodies; D025581:Neurofibromin 2; D042461:Vascular Endothelial Growth Factor A
keywords: NF2 schwannoma model; anti-VEGF; neurological function; radiation