Current Management of Large Vestibular Schwannomas for NF2 Patients in a National Reference Center

Abstract

Objective Recently, treatment decision making for large vestibular schwannomas (VS) in patients with neurofibromatosis type 2 (NF2) has become increasingly challenging due to the availability of multiple therapeutic options including surgery, bevacizumab (an anti‐VEGF), radiosurgery, and observation; and it often remains an arbitrary decision based on local practices without firm recommendations. Our objective is to discuss the multimodal treatment options for Koos IV VS in a national reference center for NF2. Study Design Single‐institution retrospective cohort study. Methods All NF2 patients with Koos IV VS who visited our center, the National Reference Center for NF2 Rare Disease in Pitié‐Salpétrière Hospital of Paris, between January 2016 and December 2018 were included. Clinical charts, radiology, operative reports, and audiograms were reviewed. Results Among 54 NF2 patients with Koos IV VS (mean maximum extrameatal diameter: 34 mm; range:17–62 mm), 27 were operated on for 28 VS; 21 were treated with bevacizumab; and six were observed. In the surgical group, VS resections were gross total, near‐total, subtotal, or partial in 32%, 25%, 32%, and 11%, respectively; and a good (House‐Brackmann grades I–II) facial nerve function was achieved in 81.5% at 1 year. Hearing was preserved in 14%, 78%, and 66% of the surgical (n = 7), bevacizumab (n = 9), and observation (n = 3) patients, respectively. Conclusion All therapeutic options, including surgery and/or bevacizumab and occasionally observation, should be proposed to NF2 patients with large VS in the setting of dedicated centers. A decision‐making tree is proposed for Koos IV VS management based on tumor evolution, hearing and clinical status of the patient, and contralateral VS size. Level of Evidence 4, case series study, historically controlled study Laryngoscope, 131:E98–E107, 2021

Cochlear Implantation in Neurofibromatosis Type 2‐Related Schwannomatosis: Long‐Term Hearing Outcomes

“…The mean duration of follow-up was 6 ± 5 years [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Ten patients had more than 5 years of follow-up and 4 had more than 10 years of follow-up.…”

“…VS in the context of NF2 differs from sporadic schwannoma in its multifocality and polyclonality (73% of cases), infiltration of adjacent nerve and bone structures, frequent infiltration of the cochlear fossa and labyrinth (88%), frequent involvement of the cochlear nerve (24%), and the high frequency of facial schwannoma. 6 These factors account for the higher recurrence rates and difficulties preserving hearing or even facial function after surgery. Moreover, the natural course of the disease appears to be different from that of sporadic VS, with tumor growth observed at 3 years in 79% of 1 ENT Department, La Pitié-Salpêtrière, APHP, Sorbonne University, Paris, France 2 Technologies and Gene Therapy for Deafness, Hearing Institute, Pasteur Institute/Inserm /Université Paris Cité, Paris, France patients, and rapid tumor growth (>3 mm/y) in 25%, with no correlation between this growth and hearing deterioration.…”

“…Moreover, the natural course of the disease appears to be different from that of sporadic VS, with tumor growth observed at 3 years in 79% of 1 ENT Department, La Pitié-Salpêtrière, APHP, Sorbonne University, Paris, France 2 Technologies and Gene Therapy for Deafness, Hearing Institute, Pasteur Institute/Inserm /Université Paris Cité, Paris, France patients, and rapid tumor growth (>3 mm/y) in 25%, with no correlation between this growth and hearing deterioration. 6,7 The therapeutic management of NF2 patients is therefore challenging, and must take into account the patient's symptoms, including HL, tumor size and progression, illness severity, and surgical risk. [7][8][9][10][11] For small tumors that are not growing aggressively, a "waitand-scan" strategy is recommended.…”

Simultaneous inhibition of PI3K and PAK in preclinical models of neurofibromatosis type 2-related schwannomatosis

“…Pathogenic variants in NF2 inactivate the merlin tumor suppressor, a scaffold protein controlling downstream signaling from numerous cell surface receptors that stimulate Schwann cell proliferation and/or survival [ 3 , 4 ]. Individuals with NF2 undergo regular monitoring and tumors are treated, when necessary, with surgery, radiation, or experimental drug therapies [ 5 – 7 ]. There is a great need for an effective and well-tolerated drug therapy for this patient population.…”

Simultaneous Inhibition of PI3K and PAK in Preclinical Models of Neurofibromatosis Type 2-related Schwannomatosis

“…Pathogenic variants in NF2 inactivate the merlin tumor suppressor, a scaffold protein controlling downstream signaling from numerous cell surface receptors that stimulate Schwann cell proliferation and/or survival (3,4). Individuals with NF2 undergo regular monitoring and tumors are treated, when necessary, with surgery, radiation, or experimental drug therapies (5)(6)(7). There is a great need for an effective and well-tolerated drug therapy for this patient population.…”