Long-Term Hearing Outcome For Vestibular Schwannomas After Microsurgery And Radiotherapy: A Systematic Review and Meta-Analysis 聽力長期結果前庭神經鞘瘤微手術和放射治療：系統綜述和統合分析
Objective. Hearing loss is a common symptom associated with vestibular schwannoma (VS), either because of the tumor’s effects on the cochlear nerve or due to active treatments such as surgery or stereotactic radiosurgery (SRS). Treatment decisions for VS are based on factors including tumor size, hearing status, patient symptoms, and institutional preference. The study aimed to investigate long-term auditory outcomes in VS patients undergoing active treatments with a hearing preservation intent. 目標。聽力喪失是與前庭神經鞘瘤(VS)相關的常見症狀,或因腫瘤對蜗神經的影響,或因手術或立體定向放射手術(SRS)等主動治療。VS 的治療決策基於包括腫瘤大小、聽力狀態、患者症狀和機構偏好等因素。該研究旨在調查接受聽力保護治療的 VS 患者的長期聽力結果。
Data Sources. A systematic literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching Scopus, Pubmed, and Web of Science databases from inception to January 2024. 數據來源。進行了一項系統性文獻綜述,遵循首選報告項目系統評審和元分析指南,搜索 Scopus、Pubmed 和 Web of Science 數據庫,時間範圍從最初到 2024 年 1 月。
Review Methods. Studies meeting inclusion criteria, including a minimum 5-year follow-up and assessment of pre- and posttreatment hearing outcomes, were included. Pooled prevalence estimates for serviceable hearing after SRS and microsurgery were calculated using MetaXL software. Risk of bias assessment was performed with the Risk of Bias in Nonrandomized Studies of Interventions tool. 手術方法研究。符合納入標準的研究,包括至少 5 年的追蹤和治療前後聽力結果評估,均被納入。使用 MetaXL 軟體計算 SRS 手術和顯微手術後可用聽力的匯總盛行率估計。使用非隨機干預研究偏倚風險評估工具進行偏倚風險評估。
Results. Nine studies met the inclusion criteria, with 356 patients included for analysis. The pooled prevalence of maintaining serviceable hearing after SRS at 10 years was 18.1%18.1 \% ( 95%95 \% confidence interval [CI]: I.7%-43.3%), with wide prediction intervals indicating variability in outcomes. Microsurgery demonstrated a higher prevalence of maintaining long-term serviceable hearing, with a pooled estimate of 74.5%74.5 \% ( 95%Cl95 \% \mathrm{Cl} : 63.5%-84.1%63.5 \%-84.1 \% ). 維持可用聽力的累計盛行率低於 43.3%,存在結果的可變性,顯微手術的長期維持可用聽力的盛行率較高,為 35.3%。
Conclusion. This systematic review underscores the importance of long-term follow-up in evaluating auditory outcomes in VS treatment. Despite the biases inherent to pretreatment patients selection, hearing preservation microsurgery for sporadic VS removal demonstrated favorable and stable long-term serviceable hearing. 結論。這一系統性回顧強調了評估聽神經瘤治療中聽覺預後的長期隨訪的重要性。儘管存在預治療患者選擇固有的偏見,但用於散發性聽神經瘤切除的聽覺保留顯微手術在長期內表現良好且穩定的可用聽力。
Received March 8, 2024; accepted July 6, 2024. 收到於 2024 年 3 月 8 日;接受於 2024 年 7 月 6 日。
Vestibular schwannomas (VSs) are commonly defined as relatively rare tumors. However, recent studies demonstrated an annual incidence rate among all ages ranging between 3.0 and 5.2 VS per 100,000 person-years. ^(1,2){ }^{1,2} The incidence of VS has been increasing in recent years due to advances in modern imaging techniques, particularly, magnetic resonance imaging. VSs are benign, slow-growing tumors that originate from the vestibular portions of the eighth cranial nerves. ^(3){ }^{3} Sporadic unilateral VS accounts for approximately 90%90 \% of cases, ^(4){ }^{4} while bilateral VS is associated with neurofibromatosis Type 2. Although dizziness and tinnitus may occur, the most common presenting symptom is ipsilateral sensorineural hearing loss in more than 90%90 \% of cases. ^(4){ }^{4} Hearing loss etiology can be classified as tumorigenic or iatrogenic. The former can not only be determined by the direct compression effect of the tumor on the cochlear nerve, but also caused by the activation of inflammatory pathways, immune mechanisms, and ototoxic factors secreted by the VS. ^(5-7){ }^{5-7} The iatrogenic hearing impairment is the consequence of active tumor treatments (microsurgery or stereotactic radiosurgery [SRS]). 前庭神經鞘瘤(VS)通常被定義為相對罕見的腫瘤。然而,最近的研究表明,所有年齡段的年發病率介於 3.0 至 5.2 每 10 萬人年。VS 的發病率在最近幾年由於現代影像技術的進步,特別是磁共振成像,而有所上升。VS 是良性的,緩慢生長的腫瘤,起源於第八腦神經的前庭部分。散發性單側 VS 佔約 80%的病例,而雙側 VS 與神經纖維瘤病 2 型有關。雖然耳暈和耳鳴可能會發生,但最常見的症狀是在超過 95%的病例中出現單側感音神經性聽力損失。聽力損失的病因可分為腫瘤性的和醫源性的。前者不僅可由腫瘤對蜗神經的直接壓迫效應決定,也可由 VS 引起的炎症通路、免疫機制和耳毒性因素引起。醫源性聽力損害是由於主動腫瘤治療(顯微手術或立體定向放射手術[SRS])的結果。
Multiple treatment options as observation, SRS, and microsurgery are available to manage a VS. Several tumor- and patients’-related factors come into play in treatment selection like tumor size, hearing, facial nerve status, patient’s symptoms, age, and comorbidities. Institutional preference might also play a role, but patients’ preference and a shared decision-making represent an advisable policy of management. In cases of small VS with good hearing function, an attempt to perform hearing preservation surgery (HPS) may be considered. ^(8){ }^{8} This approach assumes that it provides the best chances of long-term hearing preservation for patients. ^(9){ }^{9} However, for short and midterm outcomes, conservative therapies such as SRS and observation may offer better results. The issue is debated, since reporting long-term results is, particularly, relevant in nonsurgical treatment, where success does not mean removal of the tumor but control of growth, and both efficacy and side effects are to be considered in later years. 有多種治療選擇,包括觀察、強烈放射治療和微創手術,可治療聽神經瘤。治療選擇需考慮腫瘤大小、聽力、面神經狀況、病人症狀、年齡和其他併發症等相關因素。機構偏好也可能會影響決定,但建議採取病人偏好並共同決定的管理政策。對於小型聽神經瘤且聽力良好的病人,可考慮進行保肝手術。但就短期和中期結果而言,保守療法如強烈放射治療和觀察可能會有更好的效果。這個問題仍存在爭議,因為非手術治療的長期效果尤其重要,成功並非意味著腫瘤切除,而是控制腫瘤生長,在隨後幾年需考慮療效和副作用。
The purpose of this study was to investigate long-term auditory outcomes in VS submitted to active treatments such as SRS or microsurgery with hearing preservation intent. A systematic literature review was conducted on this topic and a quantitative analysis of prevalence was performe for long-term maintained serviceable hearing after treatment. 聲學神經瘤已接受主動治療,如立體放射手術或顯微手術(保留聽力為目的),以探討長期聽力結果。我們進行了系統文獻回顧,並對治療後長期可使用聽力的盛行率進行了定量分析。
Materials and Methods 材料和方法
Protocol Registration 協議註冊
This systematic review protocol was registered in March 2023 before study commencement in the International Prospective Register of Systematic Reviews (PROSPERO, registry number CRD42023400669). 此系統性審查議定書於 2023 年 3 月在系統性審查國際前瞻性登記（PROSPERO，登記號碼 CRD42023400669）進行註冊，於研究開始前。
Search Strategy 搜索策略
A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. ^(10){ }^{10} The PRISMA Checklist is available as Supplemental Data S1, available online. The electronic databases Scopus, Pubmed, and Web of Science were searched from database inception to January 13, 2024. The search strategy combined various medical subject headings and text words for surgery, radiation therapy, hearing preservation, and audio-vestibular symptoms (see Supplemental Data S2, available online). The reference lists of all the included articles were thoroughly screened to find other relevant articles. References were exported to the Zotero bibliography manager (v6.0.10, Center for History and New Media, George Mason University, Fairfax, VA, USA). After duplicate removal, 2 reviewers (A.D. and D.C.) independently screened all titles and abstracts and then evaluated the full texts of the eligible articles based on the inclusion criteria. Any disagreement 依據系統性文獻回顧首選報告項目(PRISMA)建議進行了系統性文獻回顧。PRISMA 檢查單可作為補充資料 S1 線上獲得。搜索了 Scopus、Pubmed 和 Web of Science 等電子資料庫,從資料庫建立至 2024 年 1 月 13 日。搜索策略結合了各種醫學主題標題和文字詞,包括手術、放射療法、聽力保護和聽前庭症狀(見補充資料 S2,可線上獲得)。仔細篩選了所有納入文章的參考文獻,以找到其他相關文章。參考文獻導出至 Zotero 書目管理器(v6.0.10,喬治·梅森大學新媒體歷史中心,美國弗吉尼亞州費爾法克斯)。去重後,2 名審閱者(A.D.和 D.C.)獨立篩選所有標題和摘要,然後根據納入標準評估符合條件文章的全文。任何分歧
was resolved through discussion with all authors to reach a consensus. 經過與所有作者討論，達成共識。
Selection Criteria 選擇標準
Studies were deemed eligible when the following inclusion criteria were met: (i) peer-reviewed studies on sporadic VS treated either with SRS or microsurgery with a hearing preservation intent; (ii) audiological follow-up >= 5\geq 5 years for each patient included. When raw data on follow-up were not available, studies with a lower follow-up range value of >= 5\geq 5 years were selected; (iii) studies including at least 10 patients; (iv) available pretreatment and long-term posttreatment hearing outcomes, possibly assessed through either Gardner-Robertson (GR), ^(11){ }^{11} or American Academy Otolaryngology-Head and Neck Surgery (AAO-HNS) classifications. ^(12){ }^{12} Pure tone average (PTA) <= 50dB\leq 50 \mathrm{~dB} and speech discrimination score (SDS) >= 50%\geq 50 \% defined serviceable hearing, that is, GR or AAO-HNS classes A or B. We defined long-term auditory outcome as audiometric results available at least 5 years after treatment. 零星聽力保留併發症的微創手術或立體定向放射手術的隨後聽力結果
Criteria for exclusion were as follows: (i) studies dealing with neurofibromatosis type-2 patients; (ii) recurrent VS or residual tumors, treated both with SRS and/or microsurgery; (iii) lack of relevant data in terms of hearing assessment and follow-up; (iv) nonoriginal studies (ie, reviews, recommendations, letters, editorials, or book chapters); (v) non-English studies. The papers were thoroughly screened for duplicates. 排斥標準如下：(i)處理神經纖維瘤病 2 型患者的研究；(ii)經常發生的 VS 或殘留腫瘤,同時接受 SRS 和/或顯微手術治療；(iii)缺乏聽力評估和跟進的相關數據；(iv)非原創性研究(即評論、建議、信件、社論或書籍章節)；(v)非英語研究。論文經過仔細篩選,去除重複。
Data Extraction and Quality Assessment 數據提取和質量評估
Extracted data were collected in an electronic database including first author, year of publication, country of origin, study design, enrollment period, type of treatment, total sample size, number of patients with pretreatment serviceable hearing, number of patients with serviceable hearing after treatment, preoperative audiological status, posttreatment long-term audiological outcomes, follow-up. 摘录的數據收集在電子數據庫中,包括第一作者、出版年份、原產國、研究設計、入組期間、治療類型、總樣本量、治療前可聽服務人數、治療後可聽服務人數、術前聽力狀態、治療後長期聽力結果、随訪时间。
The quality of the eligible studies was categorized as Poor, Fair, and Good, in agreement with the National Institutes of Health quality assessment tool for Observational Cohorts and Cross-Sectional Studies (https://www.nhlbi.nih.gov/health-topics/ study-quality-assessment-tools, accessed on January 13, 2024). ^(13){ }^{13} Two reviewers (A.D. and D.C.) independently evaluated the papers, and any disagreement was resolved by consensus. Risk of bias assessment for nonrandomized studies was performed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. ^(14){ }^{14} Importantly, ROBINS-I bias assessments are made based on the comparison between a given study and a theoretical randomized-controlled trial with ideal design for the study question-the 合格研究的質量被歸類為差、中和好,這與美國國立衛生研究院用於橫斷面研究和隊列研究的質量評估工具一致。兩名審查員獨立評估論文,任何分歧均通過共識解決。對非隨機研究的偏差風險使用 ROBINS-I 工具進行評估。重要的是,ROBINS-I 偏差評估是基於研究與理想隨機對照試驗設計之間的比較。
latter of which represents the standard for a “low-risk” study. 後者代表"低風險"研究的標準。
Statistical Analysis 統計分析
To produce pooled estimates for the prevalence of serviceable hearing after VS treatment (SRS or microsurgery) the software MetaXL version 5.3 (EpiGear International Pty Ltd) was used. Initially, the observed prevalence for each study was transformed using the Freeman-Tukey double arcsine transformation to stabilize the variance. ^(15,16){ }^{15,16} DerSimonian-Laird model with random effects generated the overall pooled estimates with 95%95 \% confidence interval (95%CI).^(17)(95 \% \mathrm{CI}) .{ }^{17} Meta-analysis results were summarized graphically using forest plots, including the individual papers’ proportion, pooled proportions with corresponding 95%95 \% CI, and study weights. Variance in true effects was assessed by I^(2)I^{2} statistics. ^(18)95%{ }^{18} 95 \% prediction intervals ( 95%95 \% PIs) of the pooled 對於聲覺神經性耳聾手術(SRS 或顯微手術)後可聽性的盛行率,我們使用了 MetaXL 版本 5.3 軟體(由 EpiGear International Pty Ltd 開發)進行匯總估算。首先,我們對每項研究觀察到的盛行率進行 Freeman-Tukey 雙反正弦轉換,以穩定方差。隨機效應 DerSimonian-Laird 模型生成了整體匯總估計及其相應的 95%95 \% 置信區間 (95%CI).^(17)(95 \% \mathrm{CI}) .{ }^{17} 。我們使用森林圖直觀地總結了 Meta 分析結果,包括個別論文的比例、匯總比例及其相應的 95%95 \% CI,以及研究權重。通過 I^(2)I^{2} 統計量評估了真實效應的方差。我們還計算了匯總數據的 95%95 \% 預測區間。
effect size were computed as measure of index of dispersion of the true effect ^(19,20){ }^{19,20} by using the free Prediction Intervals Program (www.meta-analysis.com accessed on January 13, 2024). ^(21){ }^{21} Publication bias was graphically investigated with the Doi plot and quantified with the Luis Furuya-Kanamori (LFK) index, which was interpreted as no asymmetry for values within +-1\pm 1, minor asymmetry for values > +-1> \pm 1, and within +-2\pm 2, major asymmetry for values > +-2.^(22)> \pm 2 .{ }^{22} 效果量以真實效應的離散指數為衡量單位,運用自由預測區間計算程式（www.meta-analysis.com，於 2024 年 1 月 13 日訪問）計算。發表偏差以 Doi 圖和 Luis Furuya-Kanamori（LFK）指數圖形化探討和量化,LFK 指數值在 +-1\pm 1 範圍內屬無偏差, > +-1> \pm 1 範圍內屬輕微偏差, +-2\pm 2 範圍內屬嚴重偏差。 ^(19,20){ }^{19,20}^(21){ }^{21}> +-2.^(22)> \pm 2 .{ }^{22}
Results 結果
Search Results and Study Selection 搜尋結果和選取研究
A total of 3736 titles were collected from our literature search. After duplicates and non-English studies removal, 1672 records were discarded according to the inclusion/ exclusion criteria, and 35 articles relevant to the topic were retrieved and assessed for eligibility. Finally, 9 studies were included for qualitative and quantitative 從我們的文獻搜索中收集到總共 3736 個標題。經過除去重複和非英語研究後,根據納入/排除標準,1672 份記錄被丟棄,並檢索和評估了 35 篇與主題相關的文章。最終,9 項研究包括在定性和定量分析中。
Figure I. Flowchart depicting the record selection and article inclusion/exclusion process. 圖 I. 描述記錄選擇和文章包含/排除過程的流程圖。
analysis. ^(23-31){ }^{23-31} A detailed flowchart of the search process is shown in Figure I. 分析。 ^(23-31){ }^{23-31} 搜索過程的詳細流程圖如圖 I 所示。
Quality of Studies Assessment and Risk of Bias Assessment 研究質量評估和偏差風險評估
In accordance with the National Institutes of Health quality assessment tool for Observational Cohorts and CrossSectional Studies, ^(13)1{ }^{13} 1 study was deemed of Good quality ( 11.1%11.1 \% ), 7 Fair ( 77.8%77.8 \% ), and only 1 ( 11.1%11.1 \% ) were classified as Poor, due to the lack of reporting information on the series’ features (see Supplemental Data S3, available online). 根據國家衛生研究院的觀察性隊列和橫斷面研究質量評估工具， ^(13)1{ }^{13} 1 研究被評為優質( 11.1%11.1 \% )，7 項被評為一般( 77.8%77.8 \% )，只有 1 項( 11.1%11.1 \% )被評為差，原因是缺乏報告該系列特徵的資訊(請參閱在線補充資料 S3)。
Risk of bias summaries for nonrandomized studies is given in Supplemental Data S4, available online. One study was assessed as “critical risk,” 6 were scored as “serious risk,” primarily due to confounding and participants selection. Finally, 2 studies were classified as “moderate risk.” 非隨機研究的偏差風險概要載於可線上獲取的補充資料 S4。一項研究被評為「關鍵風險」,6 項研究被評為「嚴重風險」,主要由於干擾因素和參與者選擇。最後,2 項研究被歸類為「中度風險」。
Characteristics of the Included Studies 包含的研究特徵
Eight studies included in the qualitative analysis had an observational retrospective design, ^(24-31){ }^{24-31} while one had a 回顧性觀察性研究設計
prospective design. ^(23){ }^{23} Findings of the retrieved articles are discussed in dedicated sections, and data on patients’ demographics, study design, tumor treatment, and hearing results are reported in Table I. 潛在設計。 ^(23){ }^{23} 檢索文章的發現在專門的部分進行了討論,而患者的人口統計學、研究設計、腫瘤治療和聽力結果的數據則報告在表 I 中。
Studies were published between 2003 and 2021, encompassing patients treated from 1978 to 2019. Among the 965 patients of the included studies, pretreatment serviceable hearing was present in 536. Long-term posttreatment audiometric data were available for 356 patients, of which 218 received SRS and 138 were submitted to microsurgical VS resection. The audiological follow-up ranged between 60 and 264 months. The AAO-HNS classification was adopted for assessing hearing in 4 studies, ^(24,26,28,29,31){ }^{24,26,28,29,31} and the GR classification in 1.^(30)1 .{ }^{30} Two studies reported hearing status classified according to both systems, ^(25,27){ }^{25,27} while Roos et al did not adopt any specific hearing classifications. ^(23){ }^{23} 研究結果於 2003 年至 2021 年間發表,涵蓋 1978 年至 2019 年期間治療的患者。包括在內的 965 名患者中,有 536 人在接受治療前有可用的聽力。356 名患者有長期術後聽力學數據,其中 218 人接受立體定向放射治療,138 人接受顯微手術移除聲神經鞘瘤。聽力跟蹤時間介於 60 至 264 個月之間。4 項研究採用美國耳鼻喉科學院聽力分類法, ^(24,26,28,29,31){ }^{24,26,28,29,31} 1 項研究採用 GR 分類法 1.^(30)1 .{ }^{30} 。2 項研究同時報告了兩種分類系統的聽力狀態 ^(25,27){ }^{25,27} ,而 Roos 等人未採用任何特定的聽力分類。 ^(23){ }^{23}
As for SRS studies, ^(23-25,30){ }^{23-25,30} the characteristics and audiological long-term outcomes are reported in Table 2. Three of the included studies utilized the Gamma-Knife, ^(24,25,30){ }^{24,25,30} and one the linear accelerator technique, ^(23){ }^{23} with a mean margin dose ranging from 8 to 16 Gy . Two studies reported on the mean cochlear 關於 SRS 研究,表 2 報告了特徵和聽力長期結果。三項研究使用伽瑪刀技術,一項使用直線加速器技術,邊緣劑量平均在 8 到 16 Gy 之間。兩項研究報告了平均蝸牛
Table I. Characteristics of the Included Studies 表 I.納入研究的特徵
References 參考資料
Country 國家
Enrollment period 註冊期
Treatment 治療
Total number of patients 總患者人數
Patients with pretreatment serviceable hearing 患有可用治療前聽力的患者
Pretreatment hearing status according to AAO-HNS and/ or GR classifications 聽力狀態的預先處理，根據 AAO-HNS 和/或 GR 分類
{:[" Class Ab "25" (57\%) "],[" Class B "B^("b ")19(43%)]:}\begin{aligned} & \text { Class Ab } 25 \text { (57\%) } \\ & \text { Class B } B^{\text {b }} 19(43 \%) \end{aligned}
Class A 43 (32%)
Class B ^("b ")47 (35%)
GR I 44 (32%)
GR II 46 (35%)| Class A 43 (32%) |
| :--- |
| Class B ${ }^{\text {b }} 47$ (35%) |
| GR I 44 (32%) |
| GR II 46 (35%) |
NR
Park et al ^(30){ }^{30} 朴等人
Korea 韓國
1997-2004
SRS
106
56
{:[" GR Ic "32" (30.2\%) "],[" GR II "24" (22.6\%) "]:}\begin{aligned} & \text { GR Ic } 32 \text { (30.2\%) } \\ & \text { GR II } 24 \text { (22.6\%) } \end{aligned}
NR
References Country Enrollment period Treatment Total number of patients Patients with pretreatment serviceable hearing Pretreatment hearing status according to AAO-HNS and/ or GR classifications Pretreatment PTA and SDS ^("a ")
Friedman et al^(26) United States 1990-1995 MS 119 NR N^("b ") " PTA 26.3+-15.1
SDS 91+-10"
Chee et a^(31) Canada 1978-1997 MS 30 29 " Class A^(b)
I7 (56.7\%) " PTA 25+-14
Woodson et al ^(27) United States 1994-2007 MS 49 46 " Class B^(b) I2 (40%)
Class A^(b)
31(67.4%)
Class B^(b)
15(32.6%)
NR ^(c)" " SDS 88+-11.6
PTA 27+-12
SDS 89+-13"
Mazzoni et al ^(28) Italy 1985-2006 MS 200 194 NR^("b ") NR
Roos et al ^(23) Australia 1993-2000 SRS 44 28 NR NR
Carlson et al ^(24) United States 1997-2002 SRS 56 44 " Class Ab 25 (57\%)
Class B B^(b )19(43%)" " PTA 27+-11.7
(2.5-50)
SDS 88.9+-13.2
(91.5-100)"
Quist et al ^(29) "United
States" 1998-2009 MS 57 49 NR^("b ") " PTA 23 (1-50)
SDS 97 (76-100) "
Maksimoski et al^(25) United States 1998-2019 SRS 304 total 133 with available audiometric data 90 "Class A 43 (32%)
Class B ^("b ")47 (35%)
GR I 44 (32%)
GR II 46 (35%)" NR
Park et al ^(30) Korea 1997-2004 SRS 106 56 " GR Ic 32 (30.2\%)
GR II 24 (22.6\%) " NR| References | Country | Enrollment period | Treatment | Total number of patients | Patients with pretreatment serviceable hearing | Pretreatment hearing status according to AAO-HNS and/ or GR classifications | Pretreatment PTA and SDS ${ }^{\text {a }}$ |
| :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: |
| Friedman et $\mathrm{al}^{26}$ | United States | 1990-1995 | MS | 119 | NR | $N{ }^{\text {b }}$ | $\begin{gathered} \text { PTA } 26.3 \pm 15.1 \\ \text { SDS } 91 \pm 10 \end{gathered}$ |
| Chee et $\mathrm{a}^{31}$ | Canada | 1978-1997 | MS | 30 | 29 | $\begin{aligned} & \text { Class } A^{b} \\ & \text { I7 (56.7\%) } \end{aligned}$ | PTA $25 \pm 14$ |
| Woodson et al ${ }^{27}$ | United States | 1994-2007 | MS | 49 | 46 | $\begin{gathered} \text { Class } B^{\mathrm{b}} \text { I2 }(40 \%) \\ \text { Class } \mathrm{A}^{\mathrm{b}} \\ 31(67.4 \%) \\ \text { Class } \mathrm{B}^{\mathrm{b}} \\ 15(32.6 \%) \\ \text { NR }^{\mathrm{c}} \end{gathered}$ | $\begin{aligned} & \text { SDS } 88 \pm 11.6 \\ & \text { PTA } 27 \pm 12 \\ & \text { SDS } 89 \pm 13 \end{aligned}$ |
| Mazzoni et al ${ }^{28}$ | Italy | 1985-2006 | MS | 200 | 194 | $N R^{\text {b }}$ | NR |
| Roos et al ${ }^{23}$ | Australia | 1993-2000 | SRS | 44 | 28 | NR | NR |
| Carlson et al ${ }^{24}$ | United States | 1997-2002 | SRS | 56 | 44 | $\begin{aligned} & \text { Class Ab } 25 \text { (57\%) } \\ & \text { Class B } B^{\text {b }} 19(43 \%) \end{aligned}$ | $\begin{gathered} \text { PTA } 27 \pm 11.7 \\ (2.5-50) \\ \text { SDS } 88.9 \pm 13.2 \\ (91.5-100) \end{gathered}$ |
| Quist et al ${ }^{29}$ | United <br> States | 1998-2009 | MS | 57 | 49 | $N R^{\text {b }}$ | $\begin{aligned} & \text { PTA } 23 \text { (1-50) } \\ & \text { SDS } 97 \text { (76-100) } \end{aligned}$ |
| Maksimoski et $\mathrm{al}^{25}$ | United States | 1998-2019 | SRS | 304 total 133 with available audiometric data | 90 | Class A 43 (32%) <br> Class B ${ }^{\text {b }} 47$ (35%) <br> GR I 44 (32%) <br> GR II 46 (35%) | NR |
| Park et al ${ }^{30}$ | Korea | 1997-2004 | SRS | 106 | 56 | $\begin{aligned} & \text { GR Ic } 32 \text { (30.2\%) } \\ & \text { GR II } 24 \text { (22.6\%) } \end{aligned}$ | NR |
Table 2. Characteristics and Audiological Long-Term Outcomes of the SRS Studies Included 表 2. SRS 研究纳入的特征和听力长期结果
References 參考資料
SRS technique 睡眠周期技術
Mean marginal dose, Gy 平均邊緣劑量, Gy
Mean cochlear dose, Gy 平均迷路劑量，Gy
Patients with available long-term follow-up 長期跟進的病人
5 y posttreatment serviceable hearing rates 5 y 回听率
5 y actuarial serviceable hearing (95% Cl) 5 年可靠聽力服務（95%可信區間）
7 y posttreatment serviceable hearing rates 7 年後治療可用的聽力率
7 y actuarial serviceable hearing (95% CI) 7 年可用聽力(95%信賴區間)
10 y10 y posttreatment serviceable hearing rates 術後可聽性服務率
10 y actuarial serviceable hearing (95% CI) 10 年保險精算可聽度服務(95%信賴區間)
Roos et al ^(23){ }^{23} 魯斯等人
LINAC
12-14
NR
28
NR
57% (38-74)
NR
NR
29% (8/28)
24% (11-44)
Carlson et al ^(24){ }^{24} 卡爾森等人
GK
12 in 41 patients 13 in 3 patients 12 名患者中有 41 人，3 名患者中有 13 人
References SRS technique Mean marginal dose, Gy Mean cochlear dose, Gy Patients with available long-term follow-up 5 y posttreatment serviceable hearing rates 5 y actuarial serviceable hearing (95% Cl) 7 y posttreatment serviceable hearing rates 7 y actuarial serviceable hearing (95% CI) 10 y posttreatment serviceable hearing rates 10 y actuarial serviceable hearing (95% CI)
Roos et al ^(23) LINAC 12-14 NR 28 NR 57% (38-74) NR NR 29% (8/28) 24% (11-44)
Carlson et al ^(24) GK 12 in 41 patients 13 in 3 patients "5.0+-1.8
(2.0-8.3)" 44 SH 47.7% (21/44) 48% (35-65) SH 36.4% (16/44) 38% (26-56) 9.1% (4/44) 23% (13-4|)
Maksimoski et al ^(25) GK 11.0-16.0 NR 90 " SH 23.3%(21//90)
PTA 62.6
(53.5-7I.9)
SDS 39.5
(28.6-50.3)" NR " SH 13.3%(12//90)
PTA 68.1(55.2-81.0)
SDS 38.3(23.6-53-0)" NR SH 4.1% (4/90) PTA 76.9 (60.0-93.8) SDS 29.3 (12.9-45.6) NR
Park et al ^(30) GK 12.5 (8-15) 3.60+-2.60 56 NR NR NR NR SH 46.4% (26/56 patients) NR| References | SRS technique | Mean marginal dose, Gy | Mean cochlear dose, Gy | Patients with available long-term follow-up | 5 y posttreatment serviceable hearing rates | 5 y actuarial serviceable hearing (95% Cl) | 7 y posttreatment serviceable hearing rates | 7 y actuarial serviceable hearing (95% CI) | $10 y$ posttreatment serviceable hearing rates | 10 y actuarial serviceable hearing (95% CI) |
| :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: |
| Roos et al ${ }^{23}$ | LINAC | 12-14 | NR | 28 | NR | 57% (38-74) | NR | NR | 29% (8/28) | 24% (11-44) |
| Carlson et al ${ }^{24}$ | GK | 12 in 41 patients 13 in 3 patients | $\begin{gathered} 5.0 \pm 1.8 \\ (2.0-8.3) \end{gathered}$ | 44 | SH 47.7% (21/44) | 48% (35-65) | SH 36.4% (16/44) | 38% (26-56) | 9.1% (4/44) | 23% (13-4\|) |
| Maksimoski et al ${ }^{25}$ | GK | 11.0-16.0 | NR | 90 | $\begin{gathered} \text { SH } 23.3 \%(21 / 90) \\ \text { PTA 62.6 } \\ \text { (53.5-7I.9) } \\ \text { SDS 39.5 } \\ (28.6-50.3) \end{gathered}$ | NR | $\begin{gathered} \text { SH } 13.3 \%(12 / 90) \\ \text { PTA } 68.1(55.2-81.0) \\ \text { SDS } 38.3(23.6-53-0) \end{gathered}$ | NR | SH 4.1% (4/90) PTA 76.9 (60.0-93.8) SDS 29.3 $(12.9-45.6)$ | NR |
| Park et al ${ }^{30}$ | GK | 12.5 (8-15) | $3.60 \pm 2.60$ | 56 | NR | NR | NR | NR | SH 46.4% (26/56 patients) | NR |
dose. ^(24,30){ }^{24,30} As only Carlson et al, ^(24){ }^{24} reported pretreatment mean PTA and SDS for patients with serviceable hearing and long-term audiological assessment, the pooled data for the SRS study group were not calculated. All the included studies reported long-term audiological outcomes at 10 -year follow-up, and additionally, 2 studies defined outcomes at 5 - and 7 -year follow-up, as well. ^(23,25){ }^{23,25} 劑量。 ^(24,30){ }^{24,30} 僅卡爾森等人 ^(24){ }^{24} 報告瞭服務性聽力和長期聽力評估的患者的預處理平均聽力檈聲聽障(PTA)和語音辨別度(SDS),SRS 研究組的匯總數據未被計算。所有納入的研究都報告了 10 年追蹤的長期聽力結果,此外,還有 2 項研究在 5 年和 7 年的跟蹤中定義了結果。 ^(23,25){ }^{23,25}
Regarding MS studies (Table 3), ^(26-29,31)3{ }^{26-29,31} 3 studies treated patients via a middle cranial fossa (MCF) approach, ^(26,27,29){ }^{26,27,29} and 2 via a retrosigmoid (RS) corridor. ^(28,31){ }^{28,31} When the data were available, 318 patients presented with preoperative serviceable hearing, and 188(59.1%)188(59.1 \%) retained serviceable hearing in the early postoperative period. According to the inclusion criteria, 138 patients with early postoperative serviceable hearing and long-term follow-up were considered for quantitative analysis. Pooled preoperative mean PTA and SDS were 24.9 dB (range: 1-501-50 ) and 91.9%91.9 \% (range: 56-10056-100 ), respectively. These results were calculated based on the line data available in the studies. ^(27,29,31){ }^{27,29,31} 關於 MS 研究(表 3)， ^(26-29,31)3{ }^{26-29,31} 3 研究通過中顱窩(MCF)接近方式治療患者， ^(26,27,29){ }^{26,27,29} 和 2 通過後乳突(RS)走廊。 ^(28,31){ }^{28,31} 當數據可用時，318 名患者術前存在可服務聽力， 188(59.1%)188(59.1 \%) 在早期術後期間保留可服務聽力。根據納入標準，138 名早期術後可服務聽力並長期隨訪的患者被列為定量分析。預術前平均 PTA 和 SDS 分別為 24.9 dB(範圍: 1-501-50 )和 91.9%91.9 \% (範圍: 56-10056-100 )。這些結果是根據研究中可用的線性數據計算得出的。 ^(27,29,31){ }^{27,29,31}
Two studies reported minimum follow-up as >= 60\geq 60 months, ^(26,29){ }^{26,29} and the mean follow-up for the other 3 studies was 124.8 months (range: 62-264)…^(27,28,31)^{27,28,31} The pooled mean postoperative PTA and SDS calculated in the early postoperative period were 35.8 dB (range: 27.5-48.7) and 87.7%87.7 \% (range: 80.2-95.4), respectively. At last follow-up available, pooled mean PTA was 45.9 dB (range: 41-48.6) and SDS 81.9%81.9 \% (range: 71-93). 最小追蹤 >= 60\geq 60 個月, ^(26,29){ }^{26,29} 其他 3 個研究的平均追蹤期為 124.8 個月(範圍:62-264)。手術後早期的綜合平均 PTA 和 SDS 分別為 35.8 分貝(範圍:27.5-48.7)和 87.7%87.7 \% (範圍:80.2-95.4)。最後追蹤時,綜合平均 PTA 為 45.9 分貝(範圍:41-48.6),SDS 為 81.9%81.9 \% (範圍:71-93)。
Long-Term Prevalence of Serviceable Hearing After SRS 長期可用聽力盛行率後 SRS
The pooled prevalence of serviceable hearing after SRS for VS is represented as a forest plot in Figure 2. The random-effects pooled estimated prevalence of maintaining serviceable hearing 10 years after SRS was 18.1%18.1 \% ( 95%95 \% CI: 1.7%-43.3%1.7 \%-43.3 \% ) with a wide range of 95%95 \% PI between 1.0%1.0 \% and 88.0%88.0 \% (Supplemental Data S5, available online). Calculated variance in true effects was I^(2)=93%I^{2}=93 \%. Doi plot for publication bias showed minor asymmetry, as confirmed by LFK index =1.85=1.85 (Supplemental Data S6, available online). At 5- and 7year follow-up after SRS, the pooled prevalences of serviceable hearing were 33.7%33.7 \% ( 95%CI95 \% \mathrm{CI} : 11.5%-60.0%11.5 \%-60.0 \% ), and 22.0%quad(95%22.0 \% \quad(95 \% CI: 3.1%-48.9%)3.1 \%-48.9 \%), respectively. Corresponding 95%95 \% PIs were not calculated for these pooled proportions, as the number of included studies was less than 3 (forest plots are shown in Figure 2). 腫瘤切除術後可維護性聽力的綜合患病率以森林圖表示於圖 2。隨機效應模型估計的腫瘤切除術後 10 年可維護性聽力的綜合患病率為 18.1%18.1 \% （ 95%95 \% CI： 1.7%-43.3%1.7 \%-43.3 \% ），其範圍寬廣為 95%95 \% PI，介於 1.0%1.0 \% 和 88.0%88.0 \% 之間（見網上補充資料 S5）。實際效應的計算變異為 I^(2)=93%I^{2}=93 \% 。發表偏差的 Doi 圖呈現輕微不對稱，並由 LFK 指數 =1.85=1.85 確認（見網上補充資料 S6）。腫瘤切除術後 5 年和 7 年的可維護性聽力綜合患病率分別為 33.7%33.7 \% （ 95%CI95 \% \mathrm{CI} ： 11.5%-60.0%11.5 \%-60.0 \% ）和 22.0%quad(95%22.0 \% \quad(95 \% CI: 3.1%-48.9%)3.1 \%-48.9 \%) 。由於納入的研究數量少於 3 篇，故未計算這些綜合比率的相應 PI（詳見圖 2）。
Long-Term Prevalence of Serviceable Hearing After Microsurgery 長期可服務性聽力的常見性
The pooled prevalence of serviceable hearing after microsurgery for VS is represented as a forest plot in Figure 3. The random-effects pooled estimated prevalence of maintaining serviceable hearing at last follow-up was 74.5%(95%74.5 \%(95 \% CI: 63.5%-84.1%)63.5 \%-84.1 \%), with a range of 95%95 \% PI between 49.0%49.0 \% and 90.0%90.0 \% (Supplemental 中文：
微神經手術治療聽神經瘤後可維持可用聽力的匯整盛行率,以林地圖表示於圖 3。以隨機效果模型估算,最後一次隨訪時可維持可用聽力的匯整估計盛行率為 74.5%(95%74.5 \%(95 \% (CI: 63.5%-84.1%)63.5 \%-84.1 \%) ),介於 95%95 \% 及 49.0%49.0 \% (參閱補充資料)。
Data S5, available online). Calculated variance in true effects was I^(2)=46.4%I^{2}=46.4 \%. Doi plot for publication bias showed no asymmetry, as confirmed by LFK index == -0.70 (Supplemental Data S6, available online). 數據 S5，可在線獲取）。真實效應的計算方差為 I^(2)=46.4%I^{2}=46.4 \% 。出版偏差的 Doi 圖顯示無不對稱性，如 LFK 指數 == -0.70（補充數據 S6，可在線獲取）所確認。
Discussion 討論
Summary of Findings 調查結果摘要
In this study, we aimed to investigate the long-term prevalence of serviceable hearing following SRS and microsurgery. The meta-analysis revealed that the prevalence of maintaining serviceable hearing after SRS for VS was 18.1%18.1 \% at the 10 -year mark, indicating that most patients do not maintain posttreatment functional long-term hearing. Notably, the wide 95%95 \% PI ranging from 1.0%1.0 \% to 88.0%88.0 \% underscores the considerable variability in hearing outcomes observed across studies. At the 5- and 7-year follow-up intervals, the pooled prevalences of serviceable hearing were 33.7%33.7 \% and 22.0%22.0 \%, respectively. While these proportions suggest a higher likelihood of hearing preservation compared to the 10 -year mark, the wide 95%95 \% CI reflected the limited number of the included studies. 本研究旨在調查微創手術和 SRS 後長期維持聽力的 prevalence。meta 分析顯示 SRS 治療 VS 患者 10 年後有效聽力的 prevalence 18.1%18.1 \% ，表明大多數患者無法長期維持治療後的聽力功能。值得注意的是,從 1.0%1.0 \% 到 88.0%88.0 \% 的廣泛 95%95 \% PI 反映了各研究中聽力結果存在較大差異。在 5 年和 7 年追蹤中,有效聽力的綜合 prevalence 分別為 33.7%33.7 \% 和 22.0%22.0 \% 。儘管這些比例表明聽力保留的可能性高於 10 年時間點,但廣泛的 95%95 \% CI 反映了納入研究的數量有限。
In contrast to what observed after SRS, long-term audiological outcomes after microsurgery demonstrated a substantially higher long-term prevalence of maintaining serviceable hearing. The pooled estimate of 74.5%74.5 \% suggests that a significant majority of patients who underwent successful microsurgical VS removal with hearing preservation, retained long-term functional hearing. The narrower 95%95 \% PI between 49.0%49.0 \% and 90.0%90.0 \% indicates less variability in outcomes compared to SRS. Furthermore, analyses for publication bias and sensitivity revealed no significant asymmetry or variation, indicating robustness and consistency in the findings across studies. 與 SRS 觀察所得相比,微手術後長期聽力結果顯示維持可用聽力的長期盛行率顯著較高。已彙總估計 74.5%74.5 \% 表明,成功進行聽力保護的聽神經瘤微手術切除術的患者中,有重大多數人保留了長期功能性聽力。 95%95 \% PI 與 49.0%49.0 \% 和 90.0%90.0 \% 之間的範圍更窄,表明結果比 SRS 的變異性更低。此外,發表偏差和敏感性分析未發現重大不對稱或變異,表明研究結果在各個研究中表現出穩健性和一致性。
Comparison to Other Studies 與其他研究相比
Considering the different treatment options for VS, observation, SRS, and microsurgery diverge in the longterm durability of preserved hearing. Observation provides good short- and mid-term results, but predictably poor long-term hearing preservation rates. ^(32){ }^{32} SRS is unlikely to cause immediate hearing loss, yet many patients experience progressive hearing loss over time. ^(33){ }^{33} The reported SRS hearing preservation rates are heterogeneous between studies. Many systematic reviews have been published on this topic, showing at mid-term followup hearing preservation rates ranging between 41%41 \% and 88%88 \%. ^(34-36){ }^{34-36} Analogously, Tsao et al ^(37){ }^{37} reported 5 -year actuarial hearing preservation rates ranging between 41%41 \% and 79%79 \%. However, overall long-term follow-up data shows a decline in hearing preservation over time of 49%49 \%, 24%24 \%, and 12%12 \% at 5 -, 10 - and 15 -year postradiation, 考慮 VS 的不同治療選擇,觀察、立體定向放射手術(SRS)和微手術在長期保留聽力方面有所不同。觀察能提供良好的短期和中期效果,但長期保留聽力的預測效果較差。立體定向放射手術不太可能立即造成聽力損失,但許多患者隨時間會出現逐漸惡化的聽力損失。有關立體定向放射手術聽力保留率的報告在研究之間存在差異。許多系統性評論已發表在這一主題上,顯示中期隨訪聽力保留率在 41%41 \%
Table 3. Characteristics Audiological Long-Term Outcomes of the Microsurgery Studies Included 表 3.微手術研究的聽力長期結果的特徵
References 參考資料
Microsurgical approach 顯微外科手術
Patients with preserved postoperative hearing 術後保留聽力的患者
Patients with early postoperative serviceable hearing and available longterm follow-up 術後早期聽力良好並長期跟蹤的患者
Follow-up for the included patients, mo 跟進所包括的病人，mo
Early postoperative hearing assessment ^("a "){ }^{\text {a }} 術後早期聽力評估
Last postoperative serviceable hearing rates 最后手術後可聽服務率
Last postoperative hearing assessment ^("a "){ }^{\text {a }} 最後術後聽力評估
Figure 3. Forest Plot for microsurgery-effects estimates on long-term hearing. Cl , confidence interval. 圖 3. 顯示微手術效果對長期聽力的森林圖。CI，置信區間。
respectively, in Watanabe et al^(38)\mathrm{al}^{38} and 59.4%59.4 \% at median follow-up of 6.7 years (2-23 years) in Ballosier et al. ^(33){ }^{33} 分別在 Watanabe 等人的研究和 Ballosier 等人的研究中,在 6.7 年（2-23 年）的中位随访期间。
Microsurgery has the highest risk of hearing loss in the early posttreatment period. Sughrue et al^(39)\mathrm{al}^{39} sought to evaluate the rates of hearing preservation at any point after microsurgical resection, finding an overall postoperative hearing preservation rate of 52%52 \%. In their meta-analysis, Ahsan et al ^(40){ }^{40} attempted to evaluate longterm hearing preservation following HPS and showed hearing durability rates between 60%60 \% and 92%92 \% at last follow-up (mean follow-up 104.3 months, range: 14-264). Hunt et al^(41)\mathrm{al}^{41} evidenced that 58%58 \% of patients with preoperative serviceable hearing retained it at last audiological assessment (mean follow-up for the included studies was 52.5 months). Furthermore, they stated that, conversely to SRS, prolonged follow-up was not associated with worsened hearing preservation in microsurgery. Considering the importance of long-term follow-up to define the evolution of hearing in VS treatment, Golfinos et al^(42)\mathrm{al}^{42} outlined that SRS was superior to microsurgery in preserving hearing due to the shorter follow-up time of the SRS patients’ group. 顯微手術在早期術後期間有最高的聽力損失風險。Sughrue 等人尋求評估顯微手術切除後任何時間點的聽力保留率,發現總體術後聽力保留率為。Ahsan 等人在他們的 meta 分析中試圖評估 HPS 後長期聽力保留,發現最後一次 follow-up 時聽力持久率在 和 之間(平均 follow-up 104.3 個月,範圍:14-264)。Hunt 等人得出證據,即有 的術前有效聽力患者在最後一次聽力評估時保持這種聽力(納入研究的平均 follow-up 時間為 52.5 個月)。此外,他們表示,與 SRS 相反,長期 follow-up 與微創手術中聽力保留的惡化沒有關聯。考慮到長期 follow-up 對定義聽力損害治療演變的重要性,Golfinos 等人指出,與接受 SRS 的患者組相比,微創手術在保護聽力方面表現更優,這是由於 SRS 患者組的 follow-up 時間較短。
To date, few studies have compared the outcomes of different VS management strategies. In 2000, a metaanalysis by Kaylie et al^(43)\mathrm{al}^{43} comparing microsurgery and SRS reported no significant difference ( P=.82P=.82 ) in hearing preservation, with rates of 44%44 \% in both groups. Different results were reported by Maniakas and Saliba ^(44){ }^{44} who observed overall useful hearing preservation rates in SRS and microsurgery patients of 70.2%70.2 \% and 50.3%50.3 \%, respectively. Finally, a systematic review by Aman et al ^(45){ }^{45} evidenced that in all the studies included, SRS was superior to microsurgery in preserving hearing function. The following considerations must be addressed, though. In Kaylie et al,^(43)VS\mathrm{al},{ }^{43} \mathrm{VS} of up to 4 cm in diameter were included in the analysis, whereas the other 2 comparative studies focused on smaller-size tumors excluding all VS larger than 2 and 2.5 cm , respectively. ^(44,45)In{ }^{44,45} \mathrm{In} fact, tumor size has a considerable impact on HPS rates. ^(9,46,47){ }^{9,46,47} 迄今為止,很少有研究比較不同的聽覺神經管理策略的結果。2000 年,凱利等人的 meta 分析比較了顯微手術和 SRS,報告聽力保存率沒有顯著差異,兩組均為 44%44 \% 。Maniakas 和 Saliba 報告的結果則不同,他們觀察到 SRS 和顯微手術患者的實用聽力保存率分別為 70.2%70.2 \% 和 50.3%50.3 \% 。最後,Aman 等人的系統評述顯示,所有包含的研究中,SRS 優於顯微手術在保護聽力功能方面。然而,必須解決以下考慮因素:凱利等人的研究包括直徑最大 4 公分的腫瘤,而其他 2 項比較研究則集中在較小尺寸(2 公分和 2.5 公分以下)的腫瘤。事實上,腫瘤大小對聽力保存率有很大影響。
Clinical Impact 臨床影響
Data comparison considering hearing preservation after microsurgery and SRS is challenging to address. A detailed description of possibly homogeneous ways of tumor measurement and reporting outcomes is essential, considering the current heterogeneous methodologies in reporting hearing status. Several methods of PTA assessment, and different hearing evaluation scores are provided by the diverse hearing classifications available worldwide (to cite some of the mostly widespread: GR, ^(11){ }^{11} AAOHNS, ^(12){ }^{12} Tokyo, ^(48){ }^{48} Sanna, ^(49){ }^{49} and Word Recognition Score classifications ^(50){ }^{50} ). 聽力保護微手術與放射手術後的數據比較具有挑戰性。詳細描述可能均一的腫瘤測量方式和報告結果至關重要,考慮目前衡量聽力狀況的異質方法。全球各地提供了多種 PTA 評估方法和不同的聽力評估評分(例如 GR、AAOHNS、Tokyo、Sanna 和語音識別評分分類)。
The identification of the best hearing-preservation treatment between SRS and surgical options is influenced by case-specific, tumors’, and patients’ factors. Hearing status and the possibility of hearing preservation with 聽力保護治療方案最佳化選擇,受個案腫瘤及患者因素影響,在立體放射手術(SRS)和手術治療選項間。聽力狀態及聽力保護可能性
microsurgery or SRS are crucial considerations in the decision-making process for patients. Among the factors influencing HPS outcomes, such as preoperative candidates’ selection in terms of preoperative hearing and tumor size, ^(9){ }^{9} the surgical technique plays a paramount role. 微創手術或性別重置手術是患者決策過程中的關鍵考慮因素。在影響聽力保存手術(HPS)結果的因素中,如術前候選人的聽力和腫瘤大小的篩選,手術技術在其中發揮至關重要的作用。
Considering microsurgery, MCF, and RS approaches are invariably contemplated for patients with preoperative serviceable hearing and small tumors. They provide exposure of the entire internal auditory canal up to the fundus and offer the possibility of hearing preservation. ^(51){ }^{51} Several studies suggest that smaller tumors are easier to dissect from the nerves, being tumor size a prognostic factor for hearing preservation. ^(9,52){ }^{9,52} RS and MCF surgical approaches demonstrated comparable results in terms of hearing. In a 2012 retrospective study by Mazzoni et al, ^(28){ }^{28} involving sporadic VS of any size treated with the RS approach and retrolabyrinthine meatotomy, overall hearing preservation was achieved in 97 out of 200 cases ( 48.5%48.5 \% ). Notably, 87%87 \% of postoperative classes A + B (AAO-HNS classification) cases demonstrated high long-term hearing stability, with a deterioration rate of 13%13 \%. Similarly, in Chee et al^(31)a\mathrm{al}^{31} \mathrm{a} retrospective analysis of 30 cases surgically treated by RS approach evidenced a hearing preservation rate of 65.4%65.4 \% in patients with audiological follow-up of >= 5\geq 5 years. A 5-year follow-up study by Quist et al ^(29){ }^{29} investigated patients undergoing MCF approach, focusing on 49 patients with AAO-HNS Class A or B hearing preoperatively. Initial results showed 55%55 \% maintaining Class A//B\mathrm{A} / \mathrm{B} hearing postsurgery, of which 75%75 \% maintained it over 5 years. Woodson et al ^(27){ }^{27} demonstrated a 57%57 \% long-term hearing preservation rate in small tumor removal through MCF surgery with a minimum 5 -year follow-up. Friedman et al ^(26){ }^{26} reviewed MCF surgeries from 1990 to 1995, reporting 61%61 \% of cases with postoperative preserved hearing, of which 70%70 \% maintained it for more than 5 years. 考慮到顯微手術、MCF 和 RS 方法不可避免地被用於術前有功能性聽力和小腫瘤的患者。它們可以暴露整個內耳道直到底部,並提供保護聽力的可能性。研究表明,較小的腫瘤更容易與神經分離,腫瘤大小是聽力保留的預後因素。RS 和 MCF 手術方法在聽力方面的結果是可比的。在 2012 年 Mazzoni 等人的回顧性研究中,使用 RS 方法和迴聲室順行性小切口治療的散發性聽神經瘤患者中,97 例中有 97 例（48.5%）達到了整體聽力保留。值得注意的是,術後 A + B 級（AAO-HNS 分類）病例中有很高的長期聽力穩定性,惡化率為 14.3%。同樣,在 Chee 等人對 30 例使用 RS 方法手術治療的回顧性分析中,有聽力随访的患者聽力保留率為 96.7%。Quist 等人 5 年随访研究的 49 例 MCF 手術患者中,初步結果顯示有 83.7%維持術前 A 級或 B 級聽力,其中有 65.3%在 5 年內保持。Woodson 等人證明通過 MCF 手術切除小腫瘤,至少 5 年随访的長期聽力保留率為 90%。Friedman 等人回顧了 1990 年至 1995 年 MCF 手術,其中 50%的患者術後保留聽力,其中 87.5%維持超過 5 年。
SRS has been identified as a potential alternative to microsurgery for patients with VS. Reported tumor control rates exceed 90%90 \% in some series. ^(33,53,54){ }^{33,53,54} However, pretreatment tumor growth is a crucial factor to be defined before SRS commencement, especially in small VS that typically demonstrates no-or very slow growth. This might affect treatment outcomes in the literature, as demonstrated by Marston et al ^(55){ }^{55} that evidenced a different tumor control rate according to pretreatment fast and slow growth ( 69%69 \% vs 97%97 \%, respectively). If the long-term period evaluation is crucial to assess hearing stability after microsurgery, this becomes more evident considering nonsurgical treatments like SRS, where the effects of irradiation on hearing over time add up to that given by the natural history of the tumor. SRS demonstrated excellent short- and mid-term results on hearing preservation. Nevertheless, at 10-year follow-up, reported rates ranged from 4.1%4.1 \% to 46.4%46.4 \%. ^(25,30){ }^{25,30} Pretreatment hearing status, ^(24,25,56,57){ }^{24,25,56,57} and tumor size ^(24,56,57){ }^{24,56,57} have been identified as prognosticators for hearing 全身性紅皮症(SRS)被認為是微創手術患者一個潛在的替代方案。在某些研究中報告的腫瘤控制率超過 90%90 \% 。 ^(33,53,54){ }^{33,53,54} 然而,治療前腫瘤生長是一個至關重要的因素,尤其是對於那些通常沒有或非常緩慢生長的小型聽神經瘤(VS)。這可能會影響文獻中的治療結果,正如 Marston 等人 ^(55){ }^{55} 所證明的那樣,根據治療前快速和緩慢生長得出不同的腫瘤控制率( 69%69 \% 對 97%97 \% )。如果長期評估對於評估微創手術後聽力穩定性至關重要,那麼在考慮非手術性治療(如 SRS)時,這一點就變得更加明顯,因為輻射對聽力的影響隨時間的累積會加上腫瘤自然病史所造成的影響。SRS 在短期和中期內對聽力保護方面展現出優秀的結果。然而,在 10 年的追蹤中,報告的保留率從 4.1%4.1 \% 到 46.4%46.4 \% 不等。 ^(25,30){ }^{25,30} 治療前聽力狀態、 ^(24,25,56,57){ }^{24,25,56,57} 和腫瘤大小 ^(24,56,57){ }^{24,56,57} 已被確認為聽力預後的預測因子。
preservation after SRS. Brainstem contact, ^(24){ }^{24} and age under 60^(57)60{ }^{57} emerged as factors increasing the risk of developing nonserviceable hearing after SRS. Postattinic hearing decline mechanisms may include inner ear ischemia, posttreatment tumor expansion, and cochlear nerve demyelination. ^(56){ }^{56} 放射手術後的保護。腦幹接觸、 ^(24){ }^{24} 和年齡在 60^(57)60{ }^{57} 以下出現為增加放射手術後失聰風險的因素。放射誘發性聽力下降機制可能包括內耳缺血、術後腫瘤擴大和蜗神經去髓鞘化。 ^(56){ }^{56}
Of note, in the mid-term, favorable audiological outcomes tend to favor SRS, while in the long-term, the surgical option appears more advantageous. However, these conclusions are burdened by 2 fundamental biases: pretreatment patients’ selection (considering hearing and tumor size) and surgical experience. Long-term follow-up beyond 10 years is crucial to better understand the durability of treatment effects, and the onset of late complications. Comparative studies evaluating the outcomes of active VS treatments as microsurgery and SRS in a well-defined patient population would help in supporting clinical decision-making. 中期而言，有利的聽力結果往往有利於立體定向放射外科手術,而長期而言,手術選項似乎更有優勢。然而,這些結論受到兩種基本偏見的束縛:治療前患者的選擇(考慮聽力和腫瘤大小)和手術經驗。10 年以上的長期隨訪對於更好地理解治療效果的持久性以及晚期並發症的發生至關重要。評估微創手術和立體定向放射外科手術在特定患者群體中的活動 VS 治療結果的比較研究將有助於支持臨床決策。
Strengths and Limitations 優勢與局限
Several constraints are evident in the present investigation. First, the included studies consisted of retrospective case series, lacking in randomized clinical trials. Data reporting in the included studies was also extremely heterogeneous and often incomplete, specifically considering pretreatment tumor size or the accurate quantification of PTA and SDS. This aspect prevented us from conducting further subgroup analyses or pooled analysis of data. Additionally, the division of studies into subgroups based on treatment, although essential for comparing similar interventions, resulted in restricted sample sizes within each subgroup, some of which had a limited number of studies and cases. Despite these limitations in size, a comprehensive statistical analysis was conducted, recognizing that our findings could be bolstered by subsequent studies with larger sample sizes. 現有調查中存在幾個明顯的限制。首先,納入的研究包括回顧性病例系列,缺乏隨機對照臨床試驗。納入研究中的數據報告也極為異質和經常不完整,特別是考慮治療前腫瘤大小或 PTA 和 SDS 的準確定量。這一方面阻止了我們進行進一步的亞組分析或數據的匯總分析。此外,雖然基於治療將研究分組對於比較類似的干預措施至關重要,但這導致了每個亞組中的樣本量較小,有些亞組僅有少數研究和病例。儘管存在這些樣本量限制,但我們進行了全面的統計分析,認識到我們的發現可能會被更大樣本量的後續研究所支持。
It is crucial to interpret the results with caution, given that many of the included studies exhibit a high risk of bias, as demonstrated by our formal risk of bias assessment using the ROBINS-I tool. ^(14){ }^{14} This assessment revealed significant heterogeneity among the studies, with variations in study design, patient populations, and outcome measures. Such heterogeneity, coupled with potential selection bias, substantially limits the robustness and generalizability of our findings. Specifically, the lack of detailed preoperative audiologic data and tumor size information further complicates the ability to draw definitive conclusions. While our study provides valuable insights into the long-term hearing outcomes of microsurgery, these results should be interpreted within the context of the abovementioned limitations. Consequently, although short- and medium-term data may support SRS, long-term audiological results highlight a different trend. 解釋結果時務須謹慎,因為納入的許多研究存在高風險偏差,這由我們使用 ROBINS-I 工具進行的正式偏差風險評估所證實。這項評估揭示了各項研究之間存在顯著異質性,在研究設計、患者群體和結果指標方面各有不同。這種異質性加上潛在的選擇偏差,嚴重限制了我們發現的穩健性和概括性。具體而言,缺乏詳細的術前聽力學數據和腫瘤大小資訊,使得我們難以得出明確的結論。儘管我們的研究為顯微手術的長期聽力結果提供了寶貴見解,但這些結果應該在上述局限性的背景下解釋。因此,儘管短期和中期數據可能支持體外放射手術,但長期聽力結果卻呈現不同趨勢。
To enhance our understanding of how each treatment modality compares to others, designing a multi-institutional, prospective, randomized, controlled trial of primary SRS versus primary microsurgery approaches (ie, via MCF or RS approaches) is advocated. 增強我們對不同治療方式相互比較的理解,設計一項多機構、前瞻性、隨機對照的初級 SRS 與初級顯微手術方式(即通過 MCF 或 RS 方式)的試驗是值得提倡的。
Conclusions 結論
In conclusion, this systematic review and metaanalysis highlighted the importance of long-term follow-up in evaluating the audiological outcomes of patients with sporadic VS treated either with microsurgery or SRS. The availability of data on long-term hearing preservation rates following VS treatment is crucial in providing effective counseling for patients facing the possibilities of HPS, SRS, or observation. Despite the above-mentioned biases inherent to the included studies, hearing preservation microsurgery for sporadic VS removal demonstrated favorable and stable long-term serviceable hearing. 在此總結,本系統性回顧和元分析強調了對患有散發性聲神經瘤的患者接受顯微手術或立體定向放射手術進行長期隨訪的重要性。有關聲神經瘤治療後長期聽力保存率的數據可以提供有效的諮詢,幫助患者面對保留聽力手術、立體放射手術或觀察等可能性。儘管包括的研究存在上述固有偏差,但用於散發性聲神經瘤切除的聽力保存顯微手術仍表現出有利且穩定的長期有用聽力。
Acknowledgments 致謝
The authors thank Alison Garside for correcting the English version of this paper and Rosalinda Russo for the literature search. Open access publishing facilitated by Universita degli Studi di Padova, as part of the Wiley - CRUI-CARE agreement. 作者感謝 Alison Garside 修正本文的英文版本,並感謝 Rosalinda Russo 進行文獻搜索。Universita degli Studi di Padova 作為 Wiley - CRUI-CARE 協議的一部分,使開放接入出版成為可能。
Author Contributions 作者貢獻
Antonio Daloiso, conceptualization, methodology, data curation, writing-original draft preparation, writing-review and editing; Diego Cazzador, conceptualization, methodology, data curation, writing-original draft preparation, writing-review and editing; Stefano Concheri, writing-review and editing, visualization; Giulia Tealdo, writing-review and editing, visualization; Elisabetta Zanoletti, conceptualization, writingreview and editing, supervision; All authors have read and agreed to the published version of the manuscript. 安東尼奧·達羅伊索、概念化、方法論、數據管理、原創草稿撰寫、審閱及編輯；迭戈·卡薩多爾、概念化、方法論、數據管理、原創草稿撰寫、審閱及編輯；斯特凡諾·孔切利、審閱及編輯、視覺化；朱莉亞·泰爾多、審閱及編輯、視覺化；伊莎貝拉·薩諾萊蒂、概念化、審閱及編輯、監督；所有作者均已閱讀並同意本手稿的已發表版本。
Disclosures 披露
Competing interests: The authors declare that they have no conflict of interest. 利益競爭：作者聲明他們沒有利益衝突。
Funding source: Not applicable. 資金來源：不適用。
Supplemental Material 補充材料
Additional supporting information is available in the online version of the article. 本文線上版本中有提供更多補充資訊。
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Department of Neuroscience DNS, Otolaryngology Section, University of Padova, Padova, Italy 帕多瓦大學神經科學系耳鼻喉科部門,帕多瓦,義大利
*These authors contributed equally to this article. 這些作者對本文做出了同等貢獻。
Corresponding Author: 對應作者:
Diego Cazzador, MD, Department of Neuroscience DNS, Otolaryngology Section, University of Padova, Via Giustiniani 2, Padova 35I28, Italy. 帕多瓦大學,耳鼻喉科部門,神經科學部,迭戈·卡佐多,醫學博士,吉斯蒂尼亞尼大街 2 號,帕多瓦 35I28,意大利。
Email: diego.cazzador@unipd.it 迭戈·卡薩多爾@unipd.it
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 這是根據創意共享署名許可條款授權的開放存取文章,允許在任何媒體中使用、分發和複製原始作品,但必須適當引用。
PTA is calculated in dB,SDS\mathrm{dB}, \mathrm{SDS} as percentage. 百分比。
Abbreviations: AAO-HNS, American Academy Otolaryngology-Head and Neck Surgery; GR, Gardner-Robertson; MS, microsurgery; NR, not reported; PTA, pure tone average; SDS, speech discrimination score; SRS, stereotactic radiosurgery. 美國耳鼻喉頭頸外科學會;Gardner-Robertson;顯微手術;未報告;純音平均聽力;語音辨別評分;立體定向放射外科手術。 ^("a "){ }^{\text {a }} Mean +-\pm standard deviation (range). Calculated for patients with pretreatment serviceable hearing. ^("a "){ }^{\text {a }} 平均值 +-\pm 標準差 (範圍)。針對服務性聽力預治療的患者計算所得。 ^(b){ }^{\mathrm{b}} AAO-HNS classification. 美國耳鼻喉頭頸外科學會分類。 ^(c)GR{ }^{\mathrm{c}} \mathrm{GR} classification. <代碼 0> 分類。
PTA is calculated in dB, SDS as percentage. 聲壓水平以分貝計，語音清晰度以百分比計。
Abbreviations: HPS, hearing preservation surgery; MCF, middle cranial fossa; MS, microsurgery; NR, not reported; PTA, pure tone average; RS, retrosigmoid; SDS, speech discrimination score; SH, serviceable hearing. 聽力保留手術；中顱窩；顯微手術；未報告；純音平均聽力；後乳突；語言辨識得分；可用聽力。 ^("a "){ }^{\text {a }} Mean +-\pm standard deviation (range). ^("a "){ }^{\text {a }} 標準差 (範圍)。
