Fractionated Proton Radiation Therapy and Hearing Preservation for Vestibular Schwannoma: Preliminary Analysis of a Prospective Phase 2 Clinical Trial

Abstract

BACKGROUND:Local management for vestibular schwannoma (VS) is associated with excellent local control with focus on preserving long-term serviceable hearing. Fractionated proton radiation therapy (FPRT) may be associated with greater hearing preservation because of unique dosimetric properties of proton radiotherapy.OBJECTIVE:To investigate hearing preservation rates of FPRT in adults with VS and secondarily assess local control and treatment-related toxicity.METHODS:A prospective, single-arm, phase 2 clinical trial was conducted of patients with VS from 2010 to 2019. All patients had serviceable hearing at baseline and received FPRT to a total dose of 50.4 to 54 Gy relative biological effectiveness (RBE) over 28 to 30 fractions. Serviceable hearing preservation was defined as a Gardner–Robertson score of 1 to 2, measured by a pure tone average (PTA) of ≤50 dB and a word recognition score (WRS) of ≥50%.RESULTS:Twenty patients had a median follow-up of 4.0 years (range 1.0-5.0 years). Local control at 4 years was 100%. Serviceable hearing preservation at 1 year was 53% (95% CI 29%-76%), and primary end point was not yet reached. Median PTA and median WRS both worsened 1 year after FPRT (P < .0001). WRS plateaued after 6 months, whereas PTA continued to worsen up to 1 year after FPRT. Median cochlea D90 was lower in patients with serviceable hearing at 1 year (40.6 Gy [RBE] vs 46.9 Gy [RBE]), trending toward Wilcoxon rank-sum test statistical significance (P = .0863). Treatment was well-tolerated, with one grade 1 cranial nerve V dysfunction and no grade 2+ cranial nerve dysfunction.CONCLUSION:FPRT for VS did not meet the goal of serviceable hearing preservation. Higher cochlea doses trended to worsening hearing preservation, suggesting that dose to cochlea correlates with hearing preservation independent of treatment modality.

Hearing preservation surgery for vestibular schwannoma: a systematic review and meta-analysis

“…The male to female ratio was not reported in all studies; for this reason, these data were not included in the analysis. The individual studies used different hearing classifications: some authors 14 , 26-27 , 29 used the AAO-HNS classification, while others 15 , 28 , 30-33 used the GR classification. Similarly, when ambiguity over the concept of ‘serviceable hearing preservation’ was found, these data were standardised by including under this definition only Class A and B according to the AAO-HNS classification, and Class I and II according to the GR classification (pure tone audiometry average threshold lower or equal to 50 dB and word recognition at speech audiometry greater or equal to 50%).…”

“…Fractioned proton radiosurgery was administered by Saraf et al 30 to 20 patients with smaller VSs (median volume, 0.81 cm 3 ) with a good hearing preservation at the short- (53% at 1 year) and long-term (57% at 3 years).…”

The Recent Management of Vestibular Schwannoma Radiotherapy: A Narrative Review of the Literature

“…Protons achieve greater avoidance of normal tissue radiation dose than photon-based techniques based on the characteristic of the proton beam, which deposes energy at the end of a linear track, beyond which there is a rapid fall-off in dose. In a prospective study [ 33 ], 20 patients received between 50.4 and 54 Gy proton RT from 2010 to 2019. They showed a local control rate of 100% at 1 year but did not meet the primary endpoint with a serviceable hearing preservation of 53%.…”

Cochlear-optimized treatment planning in photon and proton radiosurgery for vestibular schwannoma patients

“…Previous research on the use of photon or proton therapy for treating vestibular schwannomas has not fully explored the potential of cochlear sparing strategies, for example by not specifically focusing on cochlea optimization during treatment planning or by utilizing passive scattering techniques (in proton therapy) [13] , [14] , [15] . Thus, there could be a potential to reduce the dose to the cochlea and surrounding tissues with current advanced radiation therapy technologies such as robotic radiosurgery with CyberKnife and intensity-modulated proton therapy (IMPT).…”