Single Fraction Stereotactic Radiosurgery (SRS) versus Fractionated Stereotactic Radiotherapy (FSRT) for Vestibular Schwannoma (VS)

Vestibular schwannoma (VS), formerly referred to as acoustic neuroma, is one of the common benign intracranial tumors with rising incidence due to improved and more frequent neuroimaging [1-3]. These common tumors of the cerebellopontine angle arise from the Schwann cells of vestibulocochlear nerve, and management with main therapeutic modalities of surgery and radiation therapy (RT) may be considered while observation is also an option for selected patients [4-8]. Several studies have also addressed multimodality management of VS to improve the toxicity profi le of treatment [9-11]. Intervention may be required for VS although these slow growing tumors may follow an indolent disease course. Affected patients may suffer from a plethora of symptoms including headache, dizziness, tinnitus, vertigo, hearing loss, incoordination or instability with gait disturbancess, cranial nerve symptoms as a result of facial or trigeminal nerve involvement, facial dysesthesia or spasms, dysphagia, dysarthria, cerebellar seizures, symptoms of increased intracranial pressure and respiratory distress [11,12]. Typical location for VS is the internal auricular canal or cerebellopontine angle. Tumors may be in intricate association with critical neurovascular structures, and symptomatology may occur due to compression with the mass effect which may result in substantial quality of life deterioration [12]. Abstract


Introduction
Vestibular schwannoma (VS), formerly referred to as acoustic neuroma, is one of the common benign intracranial tumors with rising incidence due to improved and more frequent neuroimaging [1][2][3]. These common tumors of the cerebellopontine angle arise from the Schwann cells of vestibulocochlear nerve, and management with main therapeutic modalities of surgery and radiation therapy (RT) may be considered while observation is also an option for selected patients [4][5][6][7][8]. Several studies have also addressed multimodality management of VS to improve the toxicity profi le of treatment [9][10][11]. Intervention may be required for VS although these slow growing tumors may follow an indolent disease course. Affected patients may suffer from a plethora of symptoms including headache, dizziness, tinnitus, vertigo, hearing loss, incoordination or instability with gait disturbancess, cranial nerve symptoms as a result of facial or trigeminal nerve involvement, facial dysesthesia or spasms, dysphagia, dysarthria, cerebellar seizures, symptoms of increased intracranial pressure and respiratory distress [11,12]. Typical location for VS is the internal auricular canal or cerebellopontine angle. Tumors may be in intricate association with critical neurovascular structures, and symptomatology may occur due to compression with the mass effect which may result in substantial quality of life deterioration [12].

Abstract
Vestibular schwannoma (VS), also referred to as acoustic neuroma, is one of the common benign intracranial tumors with rising incidence due to improved and more frequent neuroimaging. These common tumors of the cerebellopontine angle arise from the Schwann cells of vestibulocochlear nerve, and management with main therapeutic modalities of surgery and radiation therapy (RT) may be considered while observation is also an option for selected patients. Intervention may be required for VS although these slow growing tumors may follow an indolent disease course. Decision for management with a given modality should take into account several factors including lesion location, size, and closeness to critical structures, age, symptomatology, patient preferences, and logistical issues. RT has traditionally served as a viable treatment modality for VS management and radiosurgical applications in the forms of single fraction Stereotactic Radiosurgery (SRS) or Fractionated Stereotactic Radiotherapy (FSRT) have been utilized for treatment of patients. Selection of dose and fractionation is critical for safe and effective radiosurgical treatment of VS. Studies of SRS and FSRT for VS management consistently reported high tumor control rates with both modalities. It appears that smallerVS lesions are well suited for single dose SRS while FSRT may serve as an excellent treatment alternative for management of larger VS lesions particularly for improving the toxicity profi le of treatment. Herein, we assess the use of single fraction SRS versus FSRT for management of VS in light of the literature with focus on recent trends and future perspectives.

SRS versus FSRT for VS management
Since its inception, radiosurgery has been judiciously utilized for precisely focused irradiation of various central nervous system disorders and tumors throughout the human body with promising treatment results . Radiosurgery  [52]. Local control rates were found to be comparable with both treatment schemes, and SRS with a single dose of ≤ 13 Gy was found to be a safe alternative to FSRT [52]. The authors concluded that FSRT could be safely administered for management of VS of all sizes while SRS should be reserved for smaller VS lesions [52].
In the study by Collen et al. comparatively evaluating outcomes of SRS and FSRT for linear accelerator based VS management, overall 5-year local control rate was 95% at a median follow-up of 62 months [53]. Mean largest tumor diameter was 16.6 mm in the single fraction SRS group and 24.6 mm for the FSRT group [53]. Median single dose for single fraction SRS was 12.5 Gy prescribed to the 80% isodose line encompassing the target volume [53]. FSRT group received either 10 x 3-4 Gy or 25 x 2 Gy prescribed to the 100% isodose line and 95% isodose line encompassed the planning target volumes for these patients [53]. Four year probability of preservation of useful hearing was 59% with SRS and 82% with FSRT [53]. The authors concluded that linac-based RT resulted in good local control and acceptable clinical outcome for small to medium sized VS, however, radiosurgery remained to be a challenge for large VS with Koos grade of 3 or more given the increased risk of facial nerve neuropathy [53]. In the study by Anderson et al. assessing long term outcomes of SRS and FSRT for linear accelerator based VS, median tumor maximum dimension was 1.5 cm for the SRS group and 1.7 cm for the FSRT group [54]. Median tumor volume was 0.66 cc for SRS group and 1.35 cc for FSRT group [54]. Single fraction SRS median peripheral dose was 12.5 Gy. FSRT group received either 45 to 50.4 Gy in 25 to 28 fractions with conventional fractionation or 5 x 4 Gy with a once weekly hypofractionated schedule [54]. Five year progression free rates were equivalent with no differences in 5-year rates of trigeminal and facial nerve toxicity, vestibular dysfunction, or tinnitus [54]. Gy in 5 fractions, respectively [55]. Excellent tumor control rates were achieved by all modalities [56]. However, relatively increased incidence and shorter time to hearing deterioration was reported in the SRS cohort compared to the FSRT and hypoFSRT cohorts [56].
A recent study comparatively evaluating linear accelerator based SRS versus hypoFSRT delivered in 3 or 5 fractions for VS reported high rate of local control with no signifi cant differences between treatment schedules [57]. Median tumor volume was 1 cc for the whole patient group. Single session SRS dose was 12 Gy while patients in hypoFSRT group received either 18-21 Gy in 3 fractions or 25 Gy in 5 fractions. Overall local control rate was 93.4% for the whole group while local control rates for SRS and hypoFSRT groups were 89.2% and 94.7% -97.4% respectively [57].
Overall, studies of SRS and FSRT for VS management consistently reported high tumor control rates with both modalities [49][50][51][52][53][54][55][56][57]. It appears that smallerVS lesions are well suited for single dose SRS while FSRT may serve as an excellent treatment alternative for management of larger VS lesions particularly for improving the toxicity profi le of treatment.
Future randomized trials are needed to shed light on optimal management of patients with VS.

Conclusion and future perspectives
There have been unprecedented advances and substantial improvements in the radiation oncology discipline such as contemporary irradiation technologies such as Intensity Modulated Radiation Therapy (IMRT), Image Guided Radiation Therapy (IGRT), Breathing Adapted Radiation Therapy (BART), Adaptive Radiation Therapy (ART) as well as radiosurgical applications along with automatic segmentation techniques and incorporation of molecular imaging for improved staging and target defi nition of several cancers . State of the art radiosurgical applications along with improved neuroimaging technologies have paved the way for widespread adoption of radiosurgery to serve as the primary therapeutic modality for several intracranial disorders and tumors. In the context of VS radiosurgery, studies of SRS and FSRT consistently reported high tumor control rates with both modalities. It appears that smallerVS lesions are well suited for single dose SRS while FSRT may serve as an excellent treatment alternative for management of larger VS lesions particularly for improving the toxicity profi le of treatment. Future randomized trials are needed to shed light on optimal management of patients with VS.