Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review

Cavalcanti, Gabriela Silva Teixeira; Lemos, Andrea; Moretti, Eduarda C.; Lucena, Camilla Maria G.A.; Gomes, João Gabriel R.; Muniz, Lílian F.; Venâncio, Leonardo G.A.; Caldas, Silvio; Leal, Mariana C.

doi:10.1016/j.bjorl.2023.101300

Gabriela Silva Teixeira Cavalcanti ^**Corresponding author. E-mail:gabriela.tcavalcanti@ufpe.br (G.S. Cavalcanti).

received guidance from the authors

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0001-8061-5432

Andrea Lemos

methodological conduction of the systematic review

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0003-0631-0512

Eduarda C. Moretti

methodological conduction of the systematic review

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Alagoas, Instituto de Ciências Biológicas e da Saúde, Maceió, AL, Brazil

https://orcid.org/0000-0002-3994-8689

Camilla Maria G.A. Lucena

received guidance from the authors

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0002-6367-1376

João Gabriel R. Gomes

area of neurosurgery and radiosurgery

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Real Hospital Português, Departamento de Neurocirurgia, Recife, PE, Brazil

https://orcid.org/0000-0002-9201-2273

Lílian F. Muniz

area of audiology

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0002-0450-4148

Leonardo G.A. Venâncio

area of audiology

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0002-1971-755X

Silvio Caldas

area of otology

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências Médicas, Recife, PE, Brazil

https://orcid.org/0000-0001-5505-6093

Mariana C. Leal

area of otology

contributed in an essential way with the final result of the article

The work covers different areas of expertise

conducted independently and concomitantly all stages of the review

Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Recife, PE, Brazil

https://orcid.org/0000-0003-3358-2791

*Corresponding author. E-mail:gabriela.tcavalcanti@ufpe.br (G.S. Cavalcanti).

☆
Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.

Conflicts of interest

The authors declare no conflicts of interest.

Database	Search strategy
MEDLINE	((‘‘Neuroma, Acoustic’’[mh] OR ‘‘VS’’[tiab] OR ‘‘vss’’[tiab] OR ((Acoustic[tiab] OR angle[tiab] OR vestibular[tiab]) AND Schwannoma[tiab])) AND (Radiosurgery[mh] OR Radiosurger[tiab] OR ‘‘radio-surgery’’[tiab])) AND ((Constraint[tiab] OR dose[tiab] OR fraction[tiab]) AND (Radiotherapy[mh] OR ‘‘Radiation Therapies’’[tiab] OR ‘‘Radiation Therapy’’[tiab] OR ‘‘Radiation Treatment’’[tiab] OR ‘‘Radiation Treatments’’[tiab] OR Radiotherap[tiab] OR ‘‘Therapies, Radiation’’[tiab] OR ‘‘Therapies, Targeted Radiation’’[tiab] OR ‘‘Therapy, Radiation’’[tiab] OR ‘‘Therapy, Targeted Radiation’’[tiab] OR ‘‘Treatment, Radiation’’[tiab]) AND Cochlea[mh] OR Cochlea*[tiab]) AND (Hearing[mh] OR ‘‘Hearing Disorders’’[mh] OR ‘‘Auditory Perception’’[mh] OR Hearing[tiab] OR audition[tiab] OR ‘‘Hearing, Distorted’’[tiab] OR ‘‘Hearing Disorders’’[tiab] OR ‘‘Distorted Hearing’’[tiab] OR Dysacusis[tiab] OR ‘‘Hearing Disorder’’[tiab] OR Paracousis[tiab] OR Paracusis[tiab] OR ‘‘Auditory Perceptions’’[tiab] OR ‘‘Perception, Auditory’’[tiab] OR ‘‘Perceptions, Auditory’’[tiab] OR ‘‘Gardner-Robertson’’[tiab] OR ‘‘GR’’[tiab])
EMBASE	((‘acoustic neuroma’/exp OR ‘VS’:ti,ab OR ‘vss’:ti,ab OR ((Acoustic:ti,ab OR angle:ti,ab OR vestibular:ti,ab) AND Schwannoma:ti,ab)) AND (Radiosurgery/exp OR Radiosurger:ti,ab OR ‘radio-surgery’:ti,ab)) AND ((Constraint:ti,ab OR dose:ti,ab OR fraction:ti,ab) AND (Radiotherapy/exp OR ‘Radiation Therapies’:ti,ab OR ‘Radiation Therapy’:ti,ab OR ‘Radiation Treatment’:ti,ab OR ‘Radiation Treatments’:ti,ab OR Radiotherap:ti,ab OR ‘Therapies, Radiation’:ti,ab OR ’Therapies, Targeted Radiation’:ti,ab OR ’Therapy, Radiation’:ti,ab OR ‘Therapy, Targeted Radiation’:ti,ab OR ‘Treatment, Radiation’:ti,ab) AND Cochlea/exp OR Cochlea*:ti,ab) AND (Hearing/exp OR ‘Hearing Disorder’/exp OR ‘Auditory Perception’:ti,ab OR Hearing:ti,ab OR audition:ti,ab OR ‘Hearing, Distorted’:ti,ab OR ‘Hearing Disorders’:ti,ab OR ‘Distorted Hearing’:ti,ab OR Dysacusis:ti,ab OR ‘Hearing Disorder’:ti,ab OR Paracousis:ti,ab OR Paracusis:ti,ab OR ‘Auditory Perceptions’:ti,ab OR ‘Perception, Auditory’:ti,ab OR ‘Perceptions, Auditory’:ti,ab OR ’Gardner-Robertson’:ti,ab OR ’GR’:ti,ab)
WEB OF SCIENCE	ALL = (((‘‘acoustic neuroma’’ OR ‘‘VS’’ OR ‘‘vss’’ OR ((Acoustic OR angle OR vestibular) AND Schwannoma)) AND (Radiosurger OR ‘‘radio-surgery’’ OR surger)) AND ((Constraint OR dose* OR fraction) AND (‘‘Radiation Therapies’’ OR ‘‘Radiation Therapy’’ OR ‘‘Radiation Treatment’’ OR ‘‘Radiation Treatments’’ OR Radiotherap OR ‘‘Therapies, Radiation’’ OR ‘‘Therapies, Targeted Radiation’’ OR ‘‘Therapy, Radiation’’ OR ‘‘Therapy, Targeted Radiation’’ OR ‘‘Treatment, Radiation’’) AND Cochlea*) AND (Hearing OR ‘‘Hearing Disorder’’ OR ‘‘Auditory Perception’’ OR Hearing OR audition OR ‘‘Hearing, Distorted’’ OR ‘‘Hearing Disorders’’ OR ‘‘Distorted Hearing’’ OR Dysacusis OR ‘‘Hearing Disorder’’ OR Paracousis OR Paracusis OR ‘‘Auditory Perceptions’’ OR ‘‘Perception, Auditory’’ OR ‘‘Perceptions, Auditory’’ OR ‘‘Gardner-Robertson’’ OR ‘‘GR’’))
LILACS	(mh:’’Neuroma Acústico’’ OR ‘‘Neuroma, Acoustic’’ OR ‘‘VSOR ‘‘VSS’’ OR tw:(‘‘Neuroma Acústico’’ OR ‘‘Neurinoma do Acústico’’ OR ‘‘Tumores do Ângulo Ponto-cerebelar’’ OR (Schwanoma* AND (vestibular OR acustico* OR Acoustic OR angle)))) AND (mh:Radiocirurgia OR tw:(Radiocirurgia OR Radiocirugia OR Radiosurger* OR ‘‘radio-surgery’’ OR radioterap* OR ‘‘Radia¸cão Estereotáctica’’)) AND (tw:(Constraint* OR dose* OR fraction* OR frac* OR dosag* OR dosi* OR Measurement OR medicao OR medicion OR ‘‘limite da radicao’’ OR limite)) AND (mh:Radiotherapy OR tw:(‘‘Radiation Therapies’’ OR ‘‘Radiation Therapy’’ OR ‘‘Radiation Treatment’’ OR ‘‘Radiation Treatments’’ OR Radiotherap* OR ‘‘Therapies, Radiation’’ OR ‘‘Therapies, Targeted Radiation’’ OR ‘‘Therapy, Radiation’’ OR ‘‘Therapy, Targeted Radiation’’ OR ‘‘Treatment, Radiation’’ OR radioterapia OR ‘‘Tratamento por Radia¸cão’’ OR ‘‘Tratamentos por Radiac¸ão’’ OR radiacion OR radiologico)) AND (mh:Cochlea OR tw:Cochlea OR modiolar* OR coclear) AND (mh:(Hearing OR ‘‘Hearing Disorders’’ OR ‘‘Auditory Perception’’) OR tw:(Hearing OR auditi OR Dysacusis OR Paracousis OR Paracusis OR Auditory Perceptions’’ OR Auditory OR ‘‘Gardner-Robertson’’ OR ‘‘GR’’ OR audicao OR audicion))
BDTD	((‘‘Neuroma, Acoustic’’ OR ‘‘VS’’ OR ‘‘vss’’ OR ‘‘Neuroma Acústico’’ OR ‘‘Neurinoma do Acústico’’ OR ‘‘Tumores do Ângulo Ponto-cerebelar’’) OR (Acoustic OR angle OR vestibular OR acustico OR angle)) AND (Schwannoma OR Schwanoma)

Authors, year (country)	Type of study	Sample characteristics	Exposition	Outcomes	Results
Paek et al., 2005¹¹11 Paek SH, Chung H-T, Jeong SS, Park C-K, Kim C-Y, Kim JE, et al. Hearing preservation after gamma knife stereotactic radiosurgery of vestibular schwannoma. Cancer. 2005;104: 580-90. (Korea)	Retrospective cohort	Sample: 25 7 women and 18 men. Age: median 47 (22-65) years. Tumor size: 3.62 (0.16-9.1)cm³. Median follow-up: 49 (26-77) months. Previous microsurgery: 1 patient. GR classification at cohort start: 13 class I and 12 class II patients. PTA at cohort start: 28.64 (8-48) dB. GR classification at cohort end: 13 preserved GR I or II PTA at cohort end: mean 47.12 (20-80) dB. Maximum cochlear dose: mean 8.1 ±3.1 Gy. Radiation therapy dose: mean 12 (11-14) Gy.	Maximum cochlear dose	Hearing preservation (pre- and post-radiosurgery PTA difference <20dB). No hearing preservation (preand post-radiosurgery PTA difference ≥20dB). Sample dichotomization: with or without hearing preservation
Brown et al., 2011¹⁶16 Brown M, Ruckenstein M, Bigelow D, Judy K, Wilson V, Alonso-Basanta M, et al. Predictors of hearing loss after gamma knife radiosurgery for vestibular schwannomas: age, cochlear dose, and tumor coverage. Neurosurgery. 2011;69: 605-13. (United States)	Retrospective cohort	Sample: 53. 31 women and 22 men. Age: mean 56 (36-87) years. Tumor size: 1.11 (0.043-4) cm³. Left side: 28. Right side: 25. Follow-up: mean 15.43 (0.77-36.2) months. Previous microsurgery: 1 patient. GR classification at cohort start: 31 class I and II patients. PTA at cohort start: mean 42.9 (15-88.3)dB. GR classification at cohort end: 19 preserved GR I or II PTA at cohort end: mean 54.3 (13.3-121.6)dB. Mean cochlear dose: mean 5.3 (2.5-10.5)Gy. Radiation therapy dose: median 12.5 (12-13) Gy.	Mean and maximum cochlear dose	Hearing preservation (pre- and post-radiosurgery PTA difference <20dB). No hearing preservation (pre-and post-radiosurgery PTA difference ≥20dB). Sample dichotomization: with or without hearing preservation
Yomo et al., 2012²⁵25 Yomo S, Carron R, Thomassin JM, Roche PEH, Régis J. Longitudinal analysis of hearing before and after radiosurgery for vestibular schwannoma. J Neurosurg. 2012; 117:877-85. (France)	Retrospective cohort	Sample: 154 77 women and 77 men. Age: mean 54.1 (24-76) years. Tumor size: 0,73 (0.03-5.37) cm³. Follow-up: mean 52 (7-123) months. Previous microsurgery: 0. GR classification at cohort start: 50 class I, 55 class II, 47 class III and 2 class IV patients. PTA at cohort start: mean 40.4± 18.2 dB. GR classification at cohort end: 64 preserved GR I or II. PTA at cohort end: mean 55.4±22.8dB. Radiation therapy dose: mean 12.1 (9-14) Gy.	Maximum cochlear dose Sample dichotomization: ≤4 Gy vs. >4 Gy	AHDR: PTA change in dB divided by the number of years
Page et al., 2013²⁷27 PageMJ, McKenzie JE, Bossuyt PM, BoutronI, Hoffmann TC, Mulrow CD, etal. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. (United States)	Prospective cohort	Sample: 40. Age: median 49 (26-80) years. Tumor size: 0.23 (0.05-4.3) cm³. Follow-up: mean 34.5 (6.1-57.8) months. Previous microsurgery: 1 patient. GR classification at cohort start: 28 class I and 12 class II patients. PTA at cohort start: (3-48) dB. GR classification at cohort end: 30 preserved GR I or II. Maximum cochlear dose: median 6.9 (1.6-16) Gy. Mean cochlear dose: median 2.7 (0.7-5) Gy. Radiation therapy dose: 12.5 Gy on 38 patients and 13Gy on 2.	Mean cochlear dose Sample dichotomization: ≥3 Gy vs. <3 Gy	Usable hearing preservation (GR I or II class maintenance). Usable hearing loss (change to GR class III, IV or V).	Usable hearing loss in the mean cochlear dose group: ≥3Gy = 41% <3Gy = 9%
Kim et al., 2013¹⁴14 Kim Y-H, Kim DG, Han JH, Chung H-T, Kim IK, Song SW, et al. Hearing outcomes after stereotactic radiosurgery for unilateral intracanalicular vestibular schwannomas: implication of transient volume expansion. Int J Radiat Oncol Biol Phys. 2013;85:61-7. (Korea)	Retrospective cohort	Sample: 60 37 women and 23 men. Age: mean 49.6 (21-69) years. Tumor size: 0.34 (0.03-1)cm³. Follow-up: mean 61.5 (36-141) months. Previous microsurgery: 1 patient. GR classification at cohort start: 35 class I and 25 class II patients. PTA at cohort start: mean 28.4 (6-50) dB. GR classification at cohort end: 34 preserved GR I or II PTA at cohort end: mean 42.1 (8-80) dB. Maximum cochlear dose: mean 8.2 (2.7-16.6)Gy. Mean cochlear dose: mean 4.2 (1.6-8.9)Gy. Radiation therapy dose: mean 12.2 (11,5-13) Gy.	Mean and maximum cochlear dose	Usable hearing preservation (GR I or II class maintenance). Usable hearing loss (change to GR class III, IV or V). Sample dichotomization: loss or preservation of usable hearing	Mean maximum cochlear dose in the usable hearing preservation group (n = 34): 7.7Gy vs. mean maximum cochlear dose in the usable hearing loss group (n = 26): 8.8Gy. Average mean cochlear dose in the usable hearing preservation group: 3.9 Gy vs. average mean cochlear dose in the usable hearing loss group: 4.7 Gy.
Jacob et al., 2014¹³13 Jacob JT, Carlson ML, Schiefer TK, Pollock BE, Driscoll CL, Link MJ. Significance of cochlear dose in the radiosurgical treatment of vestibular schwannoma: controversies and unanswered questions. Neurosurgery. 2014;74: 466-74, discussion 474. (United States)	Retrospective cohort	Sample: 59 32 women and 27 homens. Age: mean 58.9 (33-79) years. Left side: 27. Right side: 32. Follow-up: mean 25.2 (6-46) months. Previous microsurgery: 1 patient. GR classification at cohort start: 59 class I and II patients. PTA at cohort start: mean 32.3 (8-50) dB. GR classification at cohort end: 38 preserved GR I or II Maximum cochlear dose: mean 11.8 (3.7-19.2) Gy. Mean cochlear dose: mean 4.9 (1.9-8.3) Gy. Radiation therapy dose: 12Gy on 38 patients and 13 Gy on 21.	Mean cochlear dose Sample dichotomization: >5 Gy vs. <5 Gy	Usable hearing preservation (GR I or II class maintenance). Usable hearing loss (change to GR class III, IV or V).	Usable hearing loss at 1-3 years, respectively, in the mean cochlear dose group: >5Gy = 7%, 29% and 63% <5Gy = 0%, 4% and 24%
Prabhuraj et al., 2019¹⁵15 Prabhuraj AR, Yeole U, Arimappamagan A, Narasinga Rao KVL, Bhat DI, Dwarakanath S, et al. Effect of gamma knife radiosurgery on vestibular schwannoma with serviceable hearing: a single-center Indian study. World Neurosurg. 2019;127: e114-23. (India)	Retrospective cohort	Sample: 77 39 women and 38 men. Age: mean 39.46 (22-67) years. Tumor size: 4.28 (0.4-10.5)cm³. Follow-up: mean 30 (24-80) months. Previous microsurgery: 1 patient. GR classification at cohort start: 42 class I and 35 class II patients. PTA at cohort start: mean 28.71 (8.3-50) dB. GR classification at cohort end: 61 preserved GR I or II PTA at cohort end: mean 39.76 (5-71.6) dB. Maximum cochlear dose: mean 5.9 (3.8-10) Gy. Mean cochlear dose: mean 3.74 (2.3-6.5) Gy. Radiation therapy dose: mean 12 (11.5-14) Gy.	Mean cochlear dose Sample dichotomization: >4 Gy vs. <4 Gy	Usable hearing preservation (GR I or II class maintenance). Usable hearing loss (change to GR class III, IV or V).	Usable hearing loss in the mean cochlear dose group: >4Gy = 7/27 <4Gy = 9/50

Author, year (country)	Selection				Comparability	Outcome
Author, year (country)	1	2	3	4	1	1	2	3
Paek, 2005 (Korea)	D	A*	A*	A*	X	A*	A*	D
Brown, 2010 (United States)	A*	A*	A*	B	X	A*	B	D
Yomo, 2012 (France)	A*	A*	A*	B	X	B*	B	D
Baschnagel, 2013 (United States)	A*	A*	A*	A*	X	B*	B	D
Kim, 2013 (Korea)	A*	A*	A*	A*	X	B*	A*	D
Jacob, 2014 (United States)	A*	A*	A*	A*	X	A*	B	D
Prabhuraj, 2019 (India)	A*	A*	A*	A*	X	A*	A*	D
Selection 1) Representativeness of the exposed cohort a) Truly representative of the average VS patients treated with SRS in the community * b) Somewhat representative of the average VS patients treated with SRS in the community * c) Selected group of users e.g. nurses, volunteers d) No description of the derivation of the cohort 2) Selection of the non exposed cohort a) Drawn from the same community as the exposed cohort * b) Drawn from a different source c) No description of the derivation of the non exposed cohort 3) Ascertainment of exposure a) Secure record (e.g. surgical records) * b) Structured interview * c) Written self report d) No description 4) Demonstration that outcome of interest was not present at start of study a) Yes * b) No Comparability 1) Comparability of cohorts on the basis of the design or analysis a) Study controls for pretreatment hearing level (select the most important factor) * b) Study controls for any additional factor * Outcome 1) Assessment of outcome a) Independent blind assessment* b) Record linkage * c) Self report d) No description 2) Was follow-up long enough for outcomes to occur a) Yes (>12 months) * b) No 3) Adequacy of follow up of cohorts a) Complete follow up – all subjects accounted for* b) Subjects lost to follow up unlikely to introduce bias – small number lost - ≥>90% follow up, or description provided of those lost * c) Follow up rate <90% and no description of those lost d) No statement

[1] *Corresponding author. E-mail:gabriela.tcavalcanti@ufpe.br (G.S. Cavalcanti).

Patient or population: adults with vestibular schwannoma undergoing radiosurgery
Intervention: mean cochlear dose >4Gy
Comparison: mean cochlear dose <4Gy
Outcomes	Potential absolute effects^* * The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). (95% CI)		Relative effect (95% CI)	Nº of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with mean cochlear dose <4Gy	Risk with mean cochlear dose >4 Gy
Loss of usable hearing with: Gardner-Robertson classification (decline from class I or II to III, IV or V) follow-up: 24-80 months	18-100	26 per 100 (11-62)	RR 1.44 (0.60-3.44)	77 (1 observational study)	(+)◯◯◯ Very low^a a Risk of bias: serious. ,^b b Inconsistency: serious. ,^c c Imprecision: very serious.

Brasil

Brasil

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review^☆ ☆ Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.

Abstract

Objectives:

Methods:

Results:

Conclusion:

Highlights

Brasil

Brasil

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review☆ ☆ Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.

Abstract

Objectives:

Methods:

Results:

Conclusion:

Highlights

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review^☆ ☆ Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.