Volumetric Response of Growing Vestibular Schwannomas to Image-Guided Robotic CyberKnife Radiotherapy
--Manuscript Draft--
Manuscript Number: ANCH-D-23-00069
Full Title: Volumetric Response of Growing Vestibular Schwannomas to Image-Guided Robotic CyberKnife Radiotherapy
Article Type: Original Article
Keywords: Acoustic neuroma; CyberKnife; Stereotactic radiotherapy; Stereotactic radiosurgery;
Vestibular schwannoma
Order of Authors: Aku Lauri Kaipainen, MD
Pedram Hosseini, BM Antti Hyvärinen, MD Arto Immonen, MD, PhD Enni Kangas, BM
Jukka Huttunen, MD, PhD Tuomas Viren, PhD Janne Heikkilä, PhD Jan-Erik Palmgren, PhLic Jan Seppälä, PhD Nils Danner, MD, PhD
Olli-Pekka Kämärinen, MD, PhD Corresponding Author: Aku Lauri Kaipainen, MD
KUH: Kuopion yliopistollinen sairaala Kuopio, FINLAND
Corresponding Author Secondary Information:
Corresponding Author's Institution: KUH: Kuopion yliopistollinen sairaala Corresponding Author's Secondary
Institution:
First Author: Aku Lauri Kaipainen, MD
First Author Secondary Information:
Order of Authors Secondary Information:
Funding Information:
Abstract: Background
To evaluate the effectiveness and safety of CyberKnife (CK) radiotherapy for growing vestibular schwannomas (VSs).
Method
In total, 429 patients with VSs were identified from Kuopio University Hospital (KUH) multidisciplinary patient registry from 2005 to 2021. Sixty-seven patients with 69 VSs were treated with CK and followed up by repeated magnetic resonance imaging (MRI) with mean follow-up time of 38 months. The mean age at the time of treatment was 64
were measured. Small (Koos I–II grade) tumours were irradiated in a single treatment fraction with a marginal dose of 13 Gy. Large (Koos III–IV) tumours with brain stem compression were treated with 6 Gy in five fractions, reaching a total marginal dose of 30 Gy.
Results
During the follow-up, the tumour volume decreased in 46 (67%) of the 69 VSs after CK radiotherapy. Tumour size remained unchanged in 10 (15%) cases. Transient
enlargement was seen in 12 (17%) cases, followed by a later decrease in tumour volume in subsequent control MRI scans. In total,
98.6% of all VSs in this study with a verified growth tendency decreased or remained completely stable after the CK treatment. Clinical tumour control, defined as not requiring microsurgical or radiosurgical reintervention during post-treatment follow-up, was 100%. There were no significant adverse effects of the CK treatment. Radiation- induced symptomatic oedema was rare (1.4%).
Conclusions
CK radiotherapy is highly effective for growing VSs, regardless of tumour size. A single treatment session with a marginal dose of 13 Gy for small tumours and a
hypofractionation treatment protocol comprising 6 Gy delivered in five sessions for large VSs provides excellent tumour control, with a very low risk of serious adverse effects.
Aku L Kaipainen, MD PhD student Department of Neurosurgery Kuopio University Hospital
P.O. Box 100, FI-70029 KYS, Finland Email: aku.kaipainen@kuh.fi
Telephone: +358 50 557 81 65
Manuscript title: Volumetric Response of Growing Vestibular Schwannomas to Image- Guided Robotic CyberKnife Radiotherapy
Manuscript classification: Original article Dear Professor Tiit Mathiensen, Editor-in-Chief,
I am pleased to submit the enclosed manuscript for consideration in Acta Neurochirurgica.
In this work we analyzed the effectiveness and safety of CyberKnife (CK) radiotherapy for growing vestibular schwannomas in 67 patients from Kuopio University Hospital registry between years 2005 – 2021. In conclusion, CK radiotherapy appears to provide excellent tumour control with a minor risk of serious adverse effects.
We believe that the scope of this article is appropriate for Acta Neurochirurgica and its readership.
We confirm that this work has not been published previously and has not been submitted elsewhere. We have no financial interests or conflicts of interest, and we have adhered to all ethical standards. All authors have read and approved the manuscript, and have agreed to conditions of your journal. The ‘Methods’ section includes a statement on the regional Ethical review boards approving the conduct of this study. I, Aku Kaipainen, certify that this manuscript is a unique submission and is not being considered for publication, in part or in full, with any other source in any medium.
Your consideration of this manuscript is greatly appreciated.
Sincerely yours,
Aku Kaipainen
Department of Neurosurgery Kuopio University Hospital Kuopio, Finland
1
Volumetric Response of Growing Vestibular Schwannomas to Image-Guided Robotic CyberKnife Radiotherapy
Aku Kaipainen MD¹; Pedram Hosseini BM⁴; Antti Hyvärinen MD²; Arto Immonen MD, PhD¹; Enni Kangas BM⁴; Jukka Huttunen MD, PhD¹; Tuomas Viren PhD³; Janne Heikkilä PhD³; Jan-Erik Palmgren PhLic³; Jan Seppälä PhD³; Nils Danner MD, PhD¹; Olli-Pekka Kämärainen MD, PhD¹⁴
¹Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland
²Department of Otorhinolaryngology, Kuopio University Hospital, Kuopio, Finland
³Centre of Oncology, Kuopio University Hospital, Kuopio, Finland
⁴Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland
Aku Kaipainen and Pedram Hosseini are co-first authors.
Reprint requests to corresponding author:
Aku Kaipainen, MD, PhD student Neurosurgery of KUH NeuroCenter, Kuopio University Hospital, PB 1777, 70211 Kuopio, Finland
aku.kaipainen@kuh.fi phone +358 044 717 6093 0000-0002-3430-2969
Manuscript Click here to access/download;Manuscript;Kaipainen VS CK
16012023.pdf Click here to view linked References
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Abstract
Background: To evaluate the effectiveness and safety of CyberKnife (CK) radiotherapy for growing vestibular schwannomas (VSs).
Method: In total, 429 patients with VSs were identified from Kuopio University Hospital (KUH)
multidisciplinary patient registry from 2005 to 2021. Sixty-seven patients with 69 VSs were treated with CK and followed up by repeated magnetic resonance imaging (MRI) with mean follow-up time of 38 months. The mean age at the time of treatment was 64 years, and 61% of the patients were females. Tumour volumes pre- and post-treatment were measured. Small (Koos I–II grade) tumours were irradiated in a single treatment fraction with a marginal dose of 13 Gy. Large (Koos III–IV) tumours with brain stem compression were treated with 6 Gy in five fractions, reaching a total marginal dose of 30 Gy.
Results: During the follow-up, the tumour volume decreased in 46 (67%) of the 69 VSs after CK
radiotherapy. Tumour size remained unchanged in 10 (15%) cases. Transient enlargement was seen in 12 (17%) cases, followed by a later decrease in tumour volume in subsequent control MRI scans. In total, 98.6% of all VSs in this study with a verified growth tendency decreased or remained completely stable after the CK treatment. Clinical tumour control, defined as not requiring microsurgical or radiosurgical re-
intervention during post-treatment follow-up, was 100%. There were no significant adverse effects of the CK treatment. Radiation-induced symptomatic oedema was rare (1.4%).
Conclusions: CK radiotherapy is highly effective for growing VSs, regardless of tumour size. A single treatment session with a marginal dose of 13 Gy for small tumours and a hypofractionation treatment protocol comprising 6 Gy delivered in five sessions for large VSs provides excellent tumour control, with a very low risk of serious adverse effects.
Keywords: Acoustic neuroma, CyberKnife, Stereotactic radiotherapy, Stereotactic radiosurgery, Vestibular schwannoma
Abbreviations: CK: CyberKnife; KUH: Kuopio University Hospital; LINAC: linear accelerator; MRI: magnetic resonance imaging; NF2: neurofibromatosis 2; VS: vestibular schwannoma
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3
Introduction
A vestibular schwannoma (VS) is the most common neoplasm of the cerebellopontine angle in adults, accounting for approximately 8% of all intracranial tumours [4]. Population-based studies in the past have likely underestimated the actual prevalence of VSs. Today, due to improved detection accuracy using magnetic resonance imaging (MRI) and increased longevity, small incidental VSs are commonly diagnosed in the elderly population [15].
Management options for newly diagnosed VSs include observation, microsurgical resection, stereotactic radiotherapy or a combination of the latter two therapies. There are no randomized trials to guide the management of patients with VSs [2], and treatment strategies of centres vary substantially [3]. A wait-and- scan approach is the most commonly recommended initial management in the U.S. and several European countries for small non-growing VSs that are less than 1.5 cm in diameter [5]. Microsurgical resection is the gold standard for large tumours presenting with brain stem compression, hydrocephalus, cranial nerve deficiencies or long tract signs. However, surgical strategies are the subject of controversy [28], with debate surrounding whether the aim should be complete tumour removal or near-total removal, followed by
radiosurgery when necessary [24]. In general, the treatment trend has shifted towards a less aggressive approach, with the aim of long-term tumour control while maintaining maximal quality of life.
CyberKnife (CK) (Accuray Inc., Sunnyvale, CA) is a linear accelerator (LINAC)-based robotic system that can deliver stereotactic radiotherapy with 6 degrees of freedom according to a single or multi-fraction program, without stereotactic frame fixation [1]. CK radiotherapy does not require invasive head fixation, and the treatment may be performed as an outpatient procedure. Although the safety and efficacy of CK treatment in terms of long-term VS growth control have been demonstrated in the literature, there is substantial variability in the radiation regimens of different centres [14]. In most studies, tumour dimensions (mediolateral,
anteroposterior or craniocaudal) have been used to calculate tumour size and to evaluate growth control after CK treatment [29]. This method leads to an approximation of the treatment effect on tumour volume and is affected by inter- and intra-reporter variability [29]. Thus far, although the results of CK treatment, in general, have been excellent, most studies have included only non-growing VSs, making the evaluation of the treatment effect on growing tumours difficult. Furthermore, the optimal treatment strategy in terms of the best possible tumour response, with minimal adverse effects has yet to be determined.
In this study, we evaluated the effectiveness and safety of CK radiotherapy for growing VSs in an Eastern Finnish population treated with CK after radiographically documented tumour growth. The outcomes of a treatment regime comprising a single radiation dose for small VSs and fractionated treatment for large VSs are presented and discussed. The findings add to the literature on VS treatment with CK.
Materials and Methods
Kuopio University Hospital (KUH) VS management protocol in Eastern Finland
KUH is one of the five university hospitals in Finland. It is an academic, non-profit publicly funded tertiary centre, which provides neurosurgical and otorhinolaryngological services for a geographically defined population of approximately 800,000 people in Eastern Finland. All VS cases in the catchment area are referred to KUH for evaluation by a multidisciplinary team, which is specialized in tumours of the
cerebellopontine angle. This team consists of a skull base neurosurgeon, an otorhinolaryngologist and a 1
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stereotactic radiation specialist. All referred patients are reviewed, followed by treatment and/or follow-up recommendations based on individual patient- and tumour-specific factors.
Study cohort
We identified 429 patients from the KUH patient registry who were admitted for multidisciplinary consultation for VSs between 2005 and 2021. Nearly half the patients (n = 188, 44%) were managed conservatively with a wait-and-scan protocol, without any intervention. Microsurgical resection was the only treatment for 145 (34%) patients who presented with a large VS causing brain stem compression. Microsurgical resection was followed by stereotactic radiotherapy in 45 (10%) cases where there was documented post-operative tumour growth. Stereotactic radiotherapy was the only treatment modality in 51 (12%) cases. After 2012, CK was the exclusive method of stereotactic radiotherapy for VSs. In 33 patients, CK treatment was administered after surgery and in 34 patients as the only treatment. Of these 67 patients two had bilateral growing VSs thus constituting the final study population of 69 VSs altogether (Fig. 1).
Microsurgical treatment protocol
The KUH surgical treatment protocol for VSs has been described in detail elsewhere [24]. The main indication for surgical treatment is a large schwannoma with brain stem compression and fourth ventricle deformation. All patients are operated via the retrosigmoid approach under neurophysiological monitoring.
Prior to 2012, when CK treatment was not available, the aim of VS surgery was gross total resection of the tumour, with drilling of the internal acoustic channel to remove all the intra-meatal part of the tumour.
Following the initiation of CK radiotherapy for VSs, the emphasis of the surgery shifted towards even more careful preservation of the facial nerve function and quality of life of the patients. This led to the current treatment strategy of near-total resection of the tumour, where a thin layer of tumour tissue or capsule is intentionally left on the adherent parts of the facial nerve when it cannot all be safely removed. In the current treatment strategy, the internal acoustic meatus is not drilled. In cases of residual tumour regrowth during subsequent follow-up, CK radiosurgery is used as second-line treatment [24]. The popularity of this
treatment strategy has growth, and it is recognized as a viable option for patients with larger VSs to maintain the best possible functional outcome [4, 17].
CK treatment protocol
In Finland, stereotactic radiotherapy utilizes LINAC systems. To date, there are no Gamma Knife platforms in use. Thus far, the only CK system in Scandinavia is at KUH, where it was installed in 2012 and stereotactic CK radiosurgery was adapted as part of the treatment protocol for VSs. Since then, stereotactic radiosurgery has been the first-line treatment modality for growing Koos I–III VSs that do not cause significant brainstem compression [11]. The following treatment indications for CK radiotherapy were in use during the whole study period from 2012 to 2021: 1) tumour growth verified with consecutive MRI follow-up and 2) residual tumour growth after microsurgical resection. Preventive CK treatment for non-growing tumours is
controversial due to its presumed association with hearing decline [21]. Such preventive treatment is not in use in our institute.
Treatment planning and radiation delivery
Prior to treatment, a CT image (slice thickness: 1 mm) with a custom-made thermoplastic mask was acquired for each patient. Subsequently, MRI with T1, T2, CISS and contrast-enhanced T1-weighted images were 1
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5 scanned and registered on the CT images. The tumour and adjacent critical structures (e.g. brain stem and cochlea) were outlined on the contrast-enhanced T1-weighted sequence by an experienced neurosurgeon.
The T2-weighted sequences and gradient echo were used to ensure anatomic accuracy. MultiPlan software (Accuray Inc., Sunnyvale, CA) or MIM software (MIM Software Inc., Cleveland, OH) were used for image registrations and contouring. The treatment plan was generated by radiation physicists using MultiPlan or Precision Treatment Planning software (Accuray Inc., Sunnyvale, CA), and plans were verified by a neurosurgeon specialized in stereotactic radiotherapy. Possible concerns relating to individual treatment planning were reviewed by a multidisciplinary team. Prior to treatment commencement, the patients were immobilized on the RoboCouch (Accuray Inc., Sunnyvale, California) of the CK system using a custom-made thermoplastic mask. Koos I–II grade tumours were irradiated in a single treatment fraction with a marginal dose of 13 Gy. Koos III–IV tumours with larger volumes and brain stem compression were treated with a hypofractionated protocol delivering 6 Gy in five fractions in at least 48 hour intervals, reaching a total marginal dose of 30 Gy. Details on the treatment parameters are presented in Table 2.
Tumour control
Precise volumetric measurements of tumours were obtained from each patient during the follow-up. The tumours were outlined on each T1-weighted contrast-enhanced image (thickness: 1–3 mm), and the MIM software was used to calculate the tumour volume on all follow-up magnetic resonance images. Volumetric changes in tumour size after the CK treatment were categorized as follows, as suggested in previous studies [16, 19]: 1) enlargement, 2) transient enlargement, 3) stable and 4) shrinkage. Clinical tumour control was defined as a lack of need for microsurgical or radiosurgical re-intervention during post-treatment follow-up [19, 20, 27].
Statistical methods
Continuous variables were reported as means with standard deviations. Normally distributed continuous variables were tested using a one-way analysis of variance. Categorical variables were evaluated by the χ2- test and reported as frequencies and percentages. IBM SPSS 27.0 (SPSS Inc., Chicago, IL) was used to carry out the statistical analyses. In all analyses, p-values under 0.05 were considered statistically significant.
Ethical aspects
This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the research ethics committee of KUH.
Results
Between 2005 and 2021, of 429 patients with VSs who underwent evaluations, 67 patients received CK treatment. Eight (12%) patients had been diagnosed with neurofibromatosis 2 (NF2). Two patients with NF2 received treatment separately for both bilateral growing VSs, giving a total of 69 CK-treated VSs. The volumetric outcomes of these two bilateral cases were analysed separately. The mean age at the time of treatment was 64 years, and 61% of the patients were females. Thirty-four (51%) patients had no
serviceable hearing in the ipsilateral ear at the time of treatment. In terms of demographics and tumour size, the patients who underwent microsurgical tumour resection prior to the CK treatment did not differ from those who received only stereotactic radiotherapy. However, the majority (n = 28, 85%) of the patients who had 1
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received previous microsurgical treatment had ipsilateral deafness, whereas 82% of the previously untreated patients had some serviceable hearing (Table 1).
The mean target volume of the tumour at the time of treatment was 3.7 cm³. The tumour volumes of the patients who received single fraction or fractionated radiosurgery as the only treatment modality were significantly smaller than those of the patients who received the CK treatment after microsurgical tumour resection (2.7 cm³ and 4.9 cm³, respectively). The majority of patients (n = 57, 83%) were treated in a single session with a marginal dose of 13 Gy. A hypofractionated treatment plan with five fractions of 6 Gy marginal doses up to a total dose of 30 Gy was delivered to 12 (17%) patients due to large tumour volumes (cut-off:
6.6 cm³) and significant brain stem compression. Only four large (Koos III–IV: > 6.6 cm³) tumours were treated with CK without prior surgery due to old age or other patient-related factors. The mean treatment coverage of the tumour volume in all patients was 95.0%. The mean prescription dose coverage of the tumour volume in all patients was 95.0%. The dose coverage among the CK-only group was 96.5%, whereas the dose coverage among the microsurgical resection plus CK treatment group was 93.7% (Table 2).
Follow-up
The first MRI follow-up post-CK treatment was performed after 1 year (median 12 months), the second after 3 years (median 34 months) and the third after 5 years (median 60 months). The mean follow-up time for the whole study population was 38 months (Table 3). The follow-up was terminated after clear continuous tumour shrinkage was verified by MRI or after sufficiently long tumour stability in elderly patients.
Volumetric tumour response to CK treatment
During the MRI follow-up, we detected shrinkage in 46 of the 69 (67%) CK-treated VSs. The tumour
remained completely stable in 10 (15%) cases. Transient enlargement in primary follow-up MRI was seen in 12 (17%) cases, followed by a decrease in tumour volume in subsequent control imaging. At the last follow- up, the tumour volume had decreased in all 12 patients in this group. Nevertheless, in most cases, the volume was larger than before the CK treatment. Only one VS showed slow progressive growth, despite CK treatment, increasing from 2.8 cm³ to 4.4 cm³ during the 60-month follow-up period. However, this slowly growing VS required no further intervention in this 84-year-old patient. We did not detect significant differences in the volumetric tumour response between patients treated with a single dose of 13 Gy compared to those treated with hypofractionated doses (χ2=3.244, p=0.197). The follow-up times were similar in these groups (Table 3). Changes in individual tumour volumes after the CK treatment are grouped by 1) prior microsurgical resection and no microsurgery, 2) single and hypofractionation and 3) tumour response and presented as a function of time in Figures 2-4.
Adverse effects of the CK treatment
In our cohort, 50 (73%) of the CK-treated patients did not report any acute adverse effects immediately after the treatment or later during the post-treatment follow-up. Sixteen (23%) patients reported mild transient side effects, including headaches, vertigo, nausea, fatigue and numbness, but these required no further
intervention, besides symptom-specific medication. One patient reported diplopia, with worsening vertigo 2 months after a single session of CK treatment. In this case, transient tumour enlargement and necrosis inside the tumour capsule occurred in response to the treatment. The symptoms resolved during the 1
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7 following months without any treatment, and the tumour remained stable. No other adverse effects related to transient tumour enlargement were reported. There was only one case (1.4%) of radiation-induced
symptomatic brain oedema in our cohort. This case was detected one year after the CK treatment, and it resolved with corticosteroids (Table 3).
In this study, 34 (51%) of 67 patients had no serviceable hearing in the ipsilateral ear at the time of
treatment. Thus, the effect of the CK treatment on hearing preservation was analysed only in the remaining 33 (49%) patients in the cohort. Among those who received only CK treatment without previous
microsurgery, there were only 13 patients with serviceable hearing for whom we were able to retrieve reliable long-term follow-up data on hearing. Thus, our data are insufficient to analyse the treatment effect on
hearing. Nevertheless, we detected no permanent severe hearing deficits associated with the CK treatment.
Discussion
Stereotactic radiotherapy delivered either in a single session or divided into multiple fractions has established a solid foundation as the standard primary treatment for small growing VSs. Nevertheless, microsurgery is needed in cases of large tumours presenting with significant brain stem compression and/or cranial nerve symptoms. The outcomes of the 69 progressive vestibular schwannomas in our series treated with a robotic image-guided CK system were excellent in terms of tumour control and lack of serious adverse effects. In this study cohort, in the presence of a verified tumour growth tendency, up to 98.6% of all tumours decreased in size or remained completely stable after the CK treatment as shown by a comparison of the treatment planning MRI scans with the last follow-up MRI scans. Furthermore, clinical tumour control, defined as a lack of need for microsurgical or radiosurgical re-intervention during the post-treatment follow- up, was 100%.
Although the high efficacy of stereotactic radiotherapy for benign neoplasms with a slow cell division rate is recognized, the optimal treatment scheme concerning the marginal dose and number of treatment fractions remains unclear. However, data that can address this issue are accumulating from different centres that use image-guided robotic treatment platforms to treat patients with VSs. Most previous CK studies have reported a hypofractionated treatment paradigm with 18–21 Gy delivered in three to five sessions [7, 14, 21, 25].
Although many of the reported cohorts are substantially smaller than that in the current study, the reported tumour control rates have been generally excellent [6, 9, 10, 12, 13, 18, 25]. To our knowledge, there are only three significantly larger CK cohorts than the cohort in the current study [7, 8, 21]. However, these studies either did not report the number of patients treated after verified tumour growth [8] or stated that a significant proportion (up to 73%) of possibly non-growing VSs were treated preventively, which means an evaluation of the radiological treatment effect on actual tumour growth was not feasible [7, 21]. However, these previous cohorts can shed light on possible auditory and non-auditory adverse effects of radiation.
Dosimetric details of VS radiotherapy studies are heterogenic [23]. Our treatment strategy was based on the literature and previous results of large Gamma Knife studies [26], with the aim of achieving an effective response in terms of VS growth, with minimal adverse effects.
Based on the current cohort, it seems that CK is as effective in preventing further tumour growth when given in a single dose or in a fractionated dose. It is also notable that it may take up to 3 years, as demonstrated in this study, to see a treatment effect (i.e. a decrease in tumour volume) during the follow-up. Thus, patience on the part of the clinical treatment team is warranted when planning and making decisions based on follow- 1
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up images of VSs post-CK treatment. It is also noteworthy that none of the CK-treated patients in our series needed further surgical intervention.
In our study, some of the microsurgically operated VSs decreased rapidly, whereas others remained stable after the CK treatment. Histopathological and molecular genetic differences between these tumours could be investigated to determine which operated tumours are likely to decrease after CK treatment. This information could be valuable when considering surgical risks and the required level of resection.
This study has considerable strengths as compared to previous reports. Most previous studies have used standard cuboidal measuring method to determine tumour dimensions after stereotactic radiotherapy.
However, this method overestimates tumour size [22]. In this study, we ensured the accuracy of volumetric measurements by using contouring software. In addition, our study sample was relatively large, and only tumours that increased in size were treated with CK. This allowed us to analyse the effectiveness of image- guided robotic radiotherapy for active tumour growth. Furthermore, our study cohort was derived from a geographically determined population-based sample of over 400 VS patients, with complete information on the previous growth history of the VS, treatment interventions and follow-up. A weakness of our study was that we were not able to determine possible adverse effects of the treatment on hearing, as a significant number of the patients did not have serviceable hearing and the follow-up data concerning hearing was not entirely available for this study. However, this issue was addressed in a recent large VS cohort study, which reported hearing declines over time after stereotactic radiotherapy in a high proportion of cases. Thus, prophylactic radiation for small tumours in patients with normal/serviceable hearing with undetermined growth behaviour does not seem to be justified [21]. As the natural history of VSs also leads to a decline in hearing, estimation of the true effect of radiation on hearing is difficult. In the future, more cohorts similar to that in the present study are needed for improved pooled data analyses to optimize treatment outcomes for patients with VSs.
Conclusions
CK radiotherapy is highly effective against growing VSs and provides excellent tumour control, with a very low risk of serious adverse effects. Treatment paradigm of a single 13 Gy marginal dose for small (< 6.5 cm³) tumours and 30 Gy marginal dose in five fractions for large tumours is highly effective against further tumour growth. The risk of non-auditory adverse effects is very low with this treatment strategy.
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9 Statements and Declarations
Ethics approval and consent to participate
The Research Ethics Committee of the Kuopio University Hospital approved the study.
Consent for publication Not applicable
Availability of data and material
The datasets generated and/or analysed during the present study are not publicly available, but they are available from the corresponding author on reasonable request.
Competing interests
The authors declare that they have no competing interests.
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and single arm meta-analysis. Am J Otolaryngol 43(2):103337
27. Tsai JT, Lin JW, Lin CM, Chen YH, Ma HI, Jen YM, Chen YH, Ju DT (2013) Clinical Evaluation of CyberKnife in the Treatment of Vestibular Schwannomas. Biomed Res Int. doi: 10.1155/2013/297093 28. Tuleasca C, Daniel RT LM (2021) Vestibular Schwannomas. Reply. N Engl J Med 385(4):381–382 29. Vivas EX, Wegner R, Conley G, Torok J, Heron DE, Kabolizadeh P, Burton S, Ozhasoglu C, Quinn A,
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13 Display items
Fig. 1 The flowchart of vestibular schwannoma (VS) patients from Kuopio University Hospital (KUH) multidisciplinary patient registry from 2005 to 2021.
Fig. 2 Changes in individual vestibular schwannoma volumes grouped by prior microsurgical tumour resection and CyberKnife combined and only CyberKnife treatment without prior resection
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Fig. 3 Changes in vestibular schwannoma volumes between single and hypofractionated radiotherapy
Fig 4. Changes in vestibular scwannoman volumes grouped by tumour response 1
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15
Table 1 Demographic data of vestibular schwannoma patients treated with CyberKnife
Total
(n=67)
Resection and CK (n=33)
Only CK
(n=34) Significance Mean age in years (SD) 63.5 (14.6) 61.7 (15.0) 65.3 (14.1) p=0.316
Sex
Male 26 (38.8 %) 15 (45.5 %) 11 (32.4 %) p=0.271
Female 41 (61.2 %) 18 (54.5 %) 23 (67.6 %)
Neurofibromatosis 2 8 (11.9 %) 4 (11.8 %) 4 (12.1 %) p=0.964
Deafness 34 (50.7 %) 28 (84.8 %) 6 (17.6 %) p<0.001
Table 2 Treatment data of vestibular schwannoma cases treated with CyberKnife
Total
(n=69)
Resection and CK (n=33)
Only CK
(n=36) Significance Mean planning target
volume cm³ (range) 3.7 (0.1-21.0) 4.9 (0.6-21.0) 2.7 (0.1-8.7) p=0.037
Treatment protocol
1 x 13 Gy 57 (82.6 %) 25 (75.8 %) 32 (88.9 %) p=0.151
5 x 6 Gy 12 (17.4 %) 8 (24.2 %) 4 (11.1 %)
Dose
Dmin 12.0 (4.7) 12.6 (4.9) 11.5 (4.6) p=0.312
Dmax 20.7 (8.3) 21.9 (9.5) 19.6 (7.0) p=0.245
Coverage (%) 95.0 (4.4) 93.7 (5.2) 96.5 (2.6) p=0.008
Table 3 Volumetric tumour control and adverse effects of the CyberKnife treatment
Total
(n=69)
Resection and CK (n=33)
Only CK
(n=36) Significance Mean follow-up time in
months (SD) 37.7 (20.3) 37.7 (18.4) 37.8 (22.2) p=0.987
Tumour control
Shrinkage 46 (66.7 %) 23 (69.7 %) 23 (63.9 %) p=0.480
Stable 10 (14.5 %) 3 (9.1 %) 7 (19.4 %)
Transient enlargement 12 (17.4 %) 6 (18.2 %) 6 (16.7 %)
Enlargement 1 (1.4 %) 1 (3.0 %) 0 (0.0 %)
Adverse effects
None 50 (72.5 %) 23 (69.7 %) 27 (75.0 %) p=0.328
Mild e.g. transient nausea, headache,
vertigo, numbness
16 (23.2 %) 9 (27.3 %) 7 (19.4 %)
Severe e.g. sudden deafness, transient
diplopia
2 (2.9 %) 0 (0.0 %) 2 (5.6 %)
Radiation necrosis 1 (1.4 %) 1 (3.0 %) 0 (0.0 %)
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