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Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution

Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular... Journal of Radiation Research, 2014, 55, 351–358 doi: 10.1093/jrr/rrt121 Advance Access Publication 18 October 2013 Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution 1, 1 1 Putipun PUATAWEEPONG , Mantana DHANACHAI , Somjai DANGPRASERT , 1 1 1 Ladawan NARKWONG , Chomporn SITATHANEE , Thiti SAWANGSILPA , 3 2 Taweesak JANWITYANUJIT and Pornpan YONGVITHISATID Radiation and Oncology Unit, Department of Radiology, Faculty of Medicine, Mahidol University, Bangkok, 10400, Thailand Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand Radiosurgery Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand *Corresponding author. Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, 270 Rama VI Road, Ratchatewi, Mahidol University, Bangkok 10400, Thailand. Tel: +662-201-2295; Fax: +662-201-1191; Email: putipun.pua@mahidol.ac.th (Received 19 July 2013; revised 15 September 2013; accepted 19 September 2013) Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) have been recognized as an alternative to surgery for small to medium sized vestibular schwannoma (VS). This study analysed and com- pared the outcomes of VS treated with the first Thailand installation of a dedicated Linac-based stereotactic ra- diation machine using single-fraction radiosurgery (SRS), hypofraction stereotactic radiotherapy (HSRT) and conventional fraction stereotactic radiotherapy (CSRT). From 1997 to 2010, a total of 139 consecutive patients with 146 lesions of VS were treated with X-Knife at Ramathibodi hospital, Bangkok, Thailand. SRS was selected for 39 lesions (in patients with small tumors ≤3 cm and non-serviceable hearing function), whereas HSRT (79 lesions) and CSRT (28 lesions) were given for the remaining lesions that were not suitable for SRS. With a median follow-up time of 61 months (range, 12–143), the 5-year local control rate was 95, 100 and 95% in the SRS, HSRT and CSRT groups, respectively. Hearing preservation was observed after SRS in 75%, after HSRT in 87% and after CSRT in 63% of the patients. Cranial nerve complications were low in all groups. There were no statistically significant differences in local control, hearing preservation or complication between the treatment schedules. In view of our results, it may be preferable to use HSRT over CSRT for patients with serviceable hearing because of the shorter duration of treatment. Keywords: SRS; SRT; vestibular schwannomas; local control; hearing preservation INTRODUCTION single higher dose (14–18 Gy), have higher rates of cranial neuropathy [1–5]. This has led to a treatment modality pursu- Stereotactic radiosurgery (SRS) and radiotherapy (SRT) are ing a lower dose of single-fraction radiosurgery (12–13 Gy) techniques which administer precisely directed, high-dose ir- or fractionated stereotactic radiotherapy. The results of tumor radiation that tightly conforms to an intracranial target in control and complication were compared for the 12–13 Gy order to create a desired radiobiologic response, and to min- SRS and the SRT techniques [6]. Previous data from other imize radiation dose to the target’s surrounding normal institutions have shown a local control rate of 92–100%, a tissues. Initial radiosurgery series, using gamma knife (GK) hearing preservation rate of 58–65%, and an acceptable 1–5% therapy for vestibular schwannoma (VS), have been reported rate of treatment-related side-effects after the patients had since 1987. Further development of the Linac-based stereo- undergone SRS and SRT [7–10]. Although the use of stereo- tactic technique has allowed it to become an alternative to the tactic radiation for VS nowadays is accepted, the optimal frac- GK system. The various fractionation schemes, starting from tionation schedule is still controversial, and the practicality of © The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 352 P. Puataweepong et al. using SRS and SRT varies according to the level of experi- received SRS/SRT as the primary treatment; of the 146 ence at individual institutions. Since previous studies have lesions, 39 (27%) were treated with SRS, whereas 79 (54%) only compared two fractionation schedules (SRS vs HSRT, and 28 (19%) were treated with HSRT and CSRT, respect- or SRS vs CSRT), the objective of this report was to analyse ively. Of the 139 patients, 13 had neurofibromatosis type 2 and compare the long-term outcomes between the three com- (NF-2). Patient characteristics of each treatment group are monly used stereotactic radiation schedules, including single- detailed in Table 1. Three patients died from unrelated fraction radiosurgery (SRS), hypofraction SRT (HSRT) and causes. Two patients were lost to follow-up. conventional fraction SRT (CSRT) for VS patients treated at the same institution. Radiation technique MATERIALS AND METHODS The SRS/SRT techniques in this study were performed with the linear accelerator-based system [6 MV dedicated LINAC In 1997, the first Linac-based stereotactic radiation machine with fixed circular cone (Varian) with X-Knife planning in Thailand was opened at the Radiosurgery Center, system version 3 & 4 (Radionics}]. In the SRS technique, Ramathibodi Hospital in Bangkok. In this study, we analysed the Brown–Robert–Wells (BRW) stereotactic frame was the long-term outcomes for vestibular schwannoma patients applied with the assistance of a neurosurgeon. This differs treated at our institution. from the SRT technique in which the relocatable Gill– Thomas–Cosman (GTC) frame was applied. Individual treat- Patients ment planning was done in a work-station using an image set From December 1997 to January 2010, 139 vestibular from a contrast-enhanced CT scan, of 1.25 mm-slice thick- schwannoma patients with 146 lesions underwent Linac- ness, with or without gadolinium-enhanced MRI. Target and based SRS/SRT and were included in this study. All patients critical organ contouring was done by radiation oncologists, were followed up prospectively until death. We retrospectively and a treatment plan was generated by medical physicists. conducted a chart review of this cohort of patients after ap- The diameter of circular beams ranged from 5–50 mm. The proval by our institutional ethics committee. The median collimator size that covered at least 90% of the target volume follow-up time was 61 months (range, 12–143). Prior to treat- was selected. Multiple isocenters were used in irregularly ment, the optimal plan for management of all patients was dis- shaped targets. Arc selection was performed, and was mainly cussed and approved by our radiosurgery board. A patient non-coplanar. The target volume ratio (TVR) was usually who had a tumor large enough for brain stem compression within a range of 1.3–2. was selected to undergo a maximum safety surgical resection The selection of patients for SRS or SRT technique was and postoperative radiation for the residual tumor. For a based on pretreatment hearing function and tumor size. patient with a small to medium sized tumor, SRS or SRT was Patients who had small tumors (≤3 cm) and non-serviceable usually offered; however, for an elderly patient with a tiny hearing were usually selected for SRS treatment. Patients lesion, we recommended an observational policy. who did not have the aforementioned criteria or were not An interview and neurological examination focusing on suitable for SRS were selected for HSRT or CSRT treatment. cranial nerve function was performed on all patients before In SRS technique, the prescribed dose might be 12–13 treatment. Hearing assessment was performed by scoring the Gy × 1 fraction for a small lesion (≤3cm) with non- ability of patients to use the telephone with the affected ear. serviceable hearing. HSRT was offered to patients with a If the patients were not able to discriminate words or could larger tumor (>3 cm) regardless of hearing levels. In general, not hear at all, they were scored as ‘non-serviceable hearing’. the prescribed dose should be 3 Gy × 10 fractions for large ir- Additionally, all patients were sent for audiograms prior to regular lesions near a critical organ, and 5 Gy × 4 fractions, SRS/SRT treatment. Hearing assessment rated according to 6 Gy × 3 fractions or 5 Gy × 5 fractions for smaller lesions the Gardner–Robertson classification was recorded, and ser- away from critical organs. However, various dose fractiona- viceable hearing was determined as Class I or Class II. tions for HSRT were selected based not only on tumor Trigeminal nerve function was assessed via asking the factors, such as tumor size, shape and location, but also on patient about facial pain or numbness according to the individual physician preference and patient expectation. CTCAE system. Facial nerve function was assessed and CSRT with the prescribed dose of 1.8–2 Gy × 25 fractions scored using the House–Brackmann facial nerve grading was preserved in very large tumors near critical organs. system [11]. Evaluation of tumor control, hearing preserva- Table 2 shows the prescribed dose, single dose equivalent, tion and cranial nerve complication were recorded according- and EQD2 value for SRS/HSRT dose schedules in our study. ly for each treated site. The patients in the SRS group received a median dose of There were 47 males and 92 females in this study. They 12 Gy (range, 12–13) prescribed at the 80% isodose line had a total of 146 lesions, of which 89 (61%) were treated (range, 80–90) to the tumor margins. The median maximum with partial tumor removal before SRS/SRT, and 57 (39%) diameter was 1.6 cm (range, 0.8–3). The median tumor SRS/SRT in vestibular schwannomas 353 Table 1. Baseline characteristics of 139 patients with 146 lesions Parameters SRS 39 (27%) HSRT 79 (54%) CSRT 28 (19%) Gender Male 6 (18%) 28 (37%) 13 (50%) Female 31 (82%) 48 (63%) 13 (50%) Surgery Yes 25 (64%) 46 (59%) 18 (64%) No 14 (36%) 33 (41%) 10 (36%) Genetic predisposition Sporadic 39 (97%) 67 (89%) 19 (75%) NF-2 2 (3%) 6 (11%) 5 (25%) Hearing function Non-serviceable 35 (90%) 46 (58%) 16 (57%) Serviceable 4 (10%) 33 (42%) 12 (43%) Age (year) 47 (16–71) 50 (14–78) 39 (18–74) Tumor size (cm) 1.6 (0.8–3) 2.5 (1–7) 4 (1.1–5) Tumor volume (cm ) 0.96 (0.08–9.2) 3.9 (0.1–34.2) 9.5 (1.7–27.5) SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction. Median follow-up time = 61 months (12–14.3). Table 2. Prescribed dose, Single dose equivalent and EQD2 for SRS and HSRT dose schedules used in our study SRS/HSRT schedule used in our study Single dose equivalent (Gy) EQD2 (Gy) Total dose (Gy) Dose/fraction No. of fractions 12 12 1 12 36 13 13 1 13 41.6 18 6 3 12 32.4 20 5 4 11 32 25 5 5 12 40 30 3 10 11 36 SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, EQD2 = equivalent dose at 2 Gy = total dose (d+ α/β)/(2+ α/β); assuming α/β =2. volume was 0.96 cm (range, 0.08–9.2), and the median The patients in the CSRT group received a median total number of isocenters was 2 (range, 1–8). dose of 50 Gy (range, 45–50) in 25 fractions (range, 20–25) The patients in the HSRT group received various hypofrac- prescribed at the 90% isodose line. The median maximum tion schedules (5 Gy × 4–5, 6 Gy × 3, and 3 Gy × 10). The diameter was 4 cm (range, 1.1–5). The median tumor median total dose of 25 Gy (range, 18–30) at the 80% isodose volume was 9.5 cm (range, 1.7–27.5). The median number line (range, 80–90) was prescribed. A median number of of isocenters was 4 (1–8). 5 fractions (range, 3–10) was used in the treatment. The median maximum diameter was 2.5 cm (range, 1–7). The Follow-up median tumor volume was 3.9 cm (range, 0.1–34.2). All patients were seen at 4–6 weeks after completing treat- The median number of isocenters was 4 (range, 1–8). ment for a first follow-up visit, then every 6 months for the 354 P. Puataweepong et al. next 2–3 years. Annual follow-up was continued thereafter. treatment-related complications were calculated using Patients were interviewed with neurological examination fo- Kaplan–Meier methods, and the survival curves were com- cusing on cranial nerve function in V, VII and VIII during pared using the log-rank test. Multivariate analysis was done each visit. If the patients had new or progressive facial numb- using the Cox proportional hazard model. All statistical ana- ness according to the CTCAE grading or an increased lyses were performed using SPSS software, version 16.0. House–Brackmann grade, this was scored as trigeminal or facial neuropathy. Regarding hearing function assessment, RESULTS for any patients who had pre-treatment serviceable hearing, audiograms were repeated every 6–12 months. However, in All patients could tolerate the treatment very well. There was patients with non-serviceable hearing before treatment, we no interruption of HSRT or CSRT treatments. Minor acute only asked about their hearing ability in the treated ear reactions occurring in this study included headaches, nausea without further audiogram. MRI was done yearly for assess- and dizziness. ment of local tumor control. Local tumor control was defined as stable (no increase in tumor diameter) or decreased Local tumor control maximum tumor diameter on follow-up MRI imaging. The LC rate in all patients was 98% and 87% at 5 and 10 Temporary symptomatic tumor necrosis (central tumor ne- years, respectively. With respect to treatment technique, the crosis on MRI with temporary increase in tumor size with or 5-year LC rates after SRS, HSRT and CSRT were 95, 100 without new or worsened neurological symptoms related to and 95%, respectively, with no statistically significant differ- the necrosis) but not requiring additional surgical treatment ence between the treatments (P = 0.46) (Fig. 1). The LC is was defined as local tumor control. Local failure was defined not statistically significantly different when other factors are as permanent progressive tumor growth with associated compared, including the presence or absence of NF-2, symptoms requiring additional surgical treatment. patient age, prior surgical intervention vs no prior surgical intervention, tumor size and tumor volume. Statistical analyses Demographic data were summarized and compared with Hearing preservation respect to the treatment group. Categorical data were In our study, 49 of 139 patients had serviceable hearing described with frequencies and percentages and compared before treatment (33.6%). Three were NF-2 and 46 were using the Fisher exact tests. Continuous data were reported sporadic cases. Initially, we selected only patients with small with medians and ranges and compared using t-tests or tumors who had non-serviceable hearing for treatment with Wilcoxon rank-sum tests. Local tumor control (LC) and SRS. However, four patients with serviceable hearing also Fig. 1. Local control of 146 VS lesions treated with stereotactic radiation, after a median follow-up time of 61 months; local control at 5 and 10 years was 98 and 87%, respectively (A). Outcomes were not statistically significantly different after SRS, HSRT or CSRT (P = 0.46) (B). SRS/SRT in vestibular schwannomas 355 preferred the SRS and decided to be treated with this tech- statistically significantly lower in NF-2 patients (P = 0.044) nique after being informed about the risks and benefits of all (Fig. 3). Out of the three NF-2 patients with serviceable treatment alternatives. The other 33 and 12 patients with ser- hearing, two patients received CSRT, and both of them later viceable hearing were treated with HSRT and CSRT, respect- developed hearing deterioration. Another patient who ively. Table 3 shows Gardner–Robertson (GR) classification received HSRT had maintained hearing function at the time changes from GR I–II (serviceable hearing) to GR III–V of the last follow-up. (non-serviceable hearing). The probability of maintaining serviceable hearing did not differ between each radiation Trigeminal nerve function technique. With regard to pretreatment GR classification and Before SRS/SRT, 32 patients presented with mild to moder- hearing preservation, 10 out of 13 (76%) GR I patients and ate facial numbness. Nine patients (28%) were treated with 30 out of 36 (83%) GR II patients were able to maintain ser- SRS, while 16 patients (50%) and 7 patients (22%) were viceable hearing function. No GR I patients developed to treated with HSRT and CSRT, respectively. GR IV, in contrast with four patients in GR II who changed After SRS/SRT, 10 of these patients (47%) exhibited im- to GR IV hearing function. provement of facial numbness (3 in the SRS, 5 in the HSRT The overall hearing preservation rates at 1, 2 and 5 years and 2 in the CSRT groups). None of these patients showed were 90, 84 and 80%, respectively. The 5-year hearing pres- any worsening of their facial numbness. There was only one ervation rates after SRS, HSRT and CSRT were 75, 87 and patient (0.93%) in the HSRT group who developed new tri- 63%, respectively, with no statistically significant difference geminal neuropathy, characterized by mild facial numbness (P = 0.35) (Fig. 2). The only factor that affected the hearing (CTCAE Grade I). However, the symptom was spontaneously preservation was the presence of NF-2, and this was resolved without any specific treatment within 3 months. Table 3. Gardner–Robertson classification changes from GR I–II (serviceable hearing) to GR III–V (non-serviceable hearing) after SRS and SRT SRS (n = 4) HSRT (n = 33) CSRT (n = 12) Before GR I = 1 GR II = 3 GR I = 2 GR II = 31 GR I = 10 GR II = 2 After GR I = 1 GR IV = 1 GR III = 1 GR IV = 3 GR III = 2 GR III = 2 GR = Gardner–Robertson, SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction. Fig. 2. Hearing preservation rate at 1, 2 and 5 years was 90, 84 and 80%, respectively (A). Outcomes were not statistically significantly different after SRS, HSRT or CSRT (P = 0.35) (B). 356 P. Puataweepong et al. in patients with tumors sufficiently large enough to cause symptomatic brainstem compression with obstructive hydro- cephalus. SRS and SRT should be considered the best man- agement strategy for the majority of small to medium sized tumor VS patients [13]. Early radiosurgery series of SRS used to treat VS with higher dose single fraction (14–18 Gy) had higher rates of cranial nerve neuropathies (15–20% trigeminal and/or facial nerves, and 67% with decreased hearing function) [14]. This led to the practice of lowering the doses of the SRS (12–13 Gy) and the SRT technique. Both approaches have shown improved results (the local control was 92–100%, hearing preservation was 58–65%, trigeminal and facial nerve neuropathy was 1–5%) [7–10, 15–18]. Until now the standard stereotactic radiation fractionation for treatment of VS was still unknown due to a lack of published Level I evidence regarding this controversial issue. Because most previous non-randomized studies [7–10] compared only Fig. 3. Hearing preservation rate was statistically significantly single versus multiple fractionation (SRS vs HSRT, or SRS lower in NF-2 than in sporadic cases (P = 0.044). vs CSRT), the aim of this study was to compare the three commonly used stereotactic radiation schedules, i.e. SRS, Facial nerve function HSRT and CSRT, in treating VS. Before SRS/SRT, 48 patients presented with facial neur- Due to a major concern about hearing outcomes, the selec- opathy. Of these, 17 patients (35%) were treated with SRS, tion criteria for each treatment included both pretreatment 21 patients (44%) were treated with HSRT and 10 patients hearing function and tumor size. SRS was only selected to (21%) were treated with CSRT. treat patients who had non-serviceable hearing and small After SRS/SRT, five patients (10%) reported completely tumors (≤ 3cm); HSRT or CSRT was given to the remaining resolved facial palsy (one in the SRS, two in the HSRT and patients who were not suitable for SRS. By following this two in the CSRT groups). Seven patients (15%) reported im- protocol, we achieved excellent local control and hearing provement of their facial palsy. One patient in the SRS group preservation with a low complication rate. Apart from this reported worsening of facial palsy (the House–Brackmann study, there have been four reports [7–10] attempting to score changed from 2 to 3). Three patients (3.2%) developed compare the outcomes of SRS and SRT. The first study by new facial neuropathy (a House–Brackmann score of 2 in Andrews et al. [10] in 2001 reported that tumor control rates two patients and a score of 3 in one patient). Two of these for SRS (n = 63) and CSRT (n = 46) were 98% and 97% for patients were treated with HSRT and the other patient was VS patients, respectively. In 2003, the second paper by treated with SRS. All patients who had facial weakness were Meijer et al., [7] reported a series of 129 patients with VS treated with a short course of oral dexamethasone. Finally treated with Linac-based SRS vs HSRT. They also found a only one patient still had permanent facial neuropathy comparable local control rate for SRS and HSRT (100% vs (House- Brackmann score 2) at the last follow-up. 94%). In 2010, Combs et al. [8] reported the tumor control rate was 96% for both the SRS and CSRT groups, and this Noncranial nerve complication was similar to the 97.9% tumor control rate for CSRT and One patient developed hydrocephalus at 11 months after 98.5% forSRS reported by Kopp et al. [9] These tumor HSRT. Reoperation was performed at that time. This was the control rates compare well with the tumor control rates of only patient who had an operation after HSRT. 95% for RS, 100% for HSRT, and 95% for CSRT, as found in our study. DISCUSSION While the fractionation schedule seems to have no impact on local control, the impact on hearing preservation rate of Management of VS requires multidisciplinary screening to using different fractionation schedules is still controversial. select patients who are suitable for different approaches to The data from single institution reports on the effects of observation, surgery, SRS/SRT, or combinations of treat- 12–13 Gy SRS on hearing preservation rates varies from ment. Observation may be appropriate in selecting NF-2 and 32–71% [15], while the best results for hearing preservation some elderly patients, but early intervention appears to be rates have been 63–94% from CSRT with a total dose of the best strategy for long-term hearing preservation in most 40–57.6 Gy [19]. The third alternative, HSRT, using various patients [12]. Surgery appears to be the best initial treatment fractionation schedules such as 4–5 Gy × 5, 5–6 Gy × 5, or SRS/SRT in vestibular schwannomas 357 Table 4. Published studies on SRS/SRT for vestibular schwannoma 5-year hearing 5-year facial 5-year trigeminal Treatment/ 5 year LC Study preservation nerve preservation nerve preservation number of pt rate (%) rate (%) rate (%) rate (%) Andrew et al., 2004 [10] SRS/69 98 33 98 95 CSRT/56 97 81 98 93 Meijer et al., 2003 [7] SRS/49 100 75 93 92 HSRT/80 94 61 97 98 Comb et al., 2010 [8] SRS/30 96 70 83 93 CSRT/175 96 78 98 97 Kopp et al., 2010 [9] SRS/68 97.9 79 100 87 CSRT/47 98.5 85 100 100 Our study SRS/39 95 75 98 100 HSRT/79 100 87 97 99 CSRT/28 95 63 100 100 SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction, LC = local control. 3 Gy × 10, showed a hearing preservation rate of 61–100% important for hearing preservation rates. Andrews et al. [10] [7, 17]. The relationship between the fractionation schedule found a significantly greater probability of hearing preserva- and the hearing preservation rate is somewhat conflicting in tion in patients with pre-treatment GR I grading, suggesting the non-randomized comparative studies. For the example, that early intervention without observation may be a favor- Kopp et al. [9] reported an 85% hearing preservation rate able policy. Our results showed that the patients who had after SRS and 79% after CSRT, which was similar to the pre-treatment GR II deteriorated to GR IV after treatment 78% hearing preservation rate for both SRS and SRT more often than did GR I patients. We concluded that imme- reported by Combs et al. [8]. Meijer et al. [7] also reported diate treatment of GR I patients with SRT might yield the the 5-year hearing preservation probability for SRS and highest probability of functional hearing preservation. HSRT as 75% and 61%, respectively, but without any statis- Our study used various doses and fractionations such as tically significant difference. Nevertheless, a contradictory 12 Gy × 1, 6 Gy × 3, 5 Gy × 4–5, 3 Gy × 10, and 2 Gy × 25. result was reported by Andrew et al. [10], whose report was These schedules are considered to have different radiobio- 2.5 times higher for hearing preservation rate in patients who logical effects, which may make the analysis of this study received CSRT (81%) than those who received SRS (33%), difficult. Currently, there is no reliable way to use the linear- P = 0.0228). Table 4 shows a comparison of our study with quadratic (LQ) formula to extrapolate equivalent effects of the previous studies comparing SRS and SRT. high-dose single fractions to a fractionated course of RT for Based on radiobiology principles, late-responding tissue VS. The LQ model may not adequately explain dose– such as cranial nerve and brain tissue might be subject to response relationships for either tumor or normal tissue when more injury when dose fractionation exceeding a conventional stretched to include the high radiation doses used with SRS. 1.8–2 Gy dose per fraction is applied. From this knowledge, However, we hope that reliable radiobiological parameters we hypothesized that CSRT should have a higher hearing extracted from dose–response data will be available in the preservation rate than HSRT. Nevertheless, our hypothesis near future. was not correct; CSRT did not show the improved hearing The treatment technique selected for each patient in this preservation we expected. However, this finding probably study was based mainly on hearing function and tumor size. results from the larger tumor volumes and relatively small SRS was mostly reserved for patients with smaller sized number of patients in the CSRT group. tumors (<3 cm in maximal diameter) and non-serviceable The presence of NF-2 was the only factor that was asso- hearing, while SRT was reserved for those with serviceable ciated with poorer hearing preservation, but this might have hearing. One of the reasons for this is that SRS was previous- been due to the small sample size. Overall, the results ly reported as one of the potential risk factors for cranial obtained for NF-2 VS were not as good as those achieved in nerve injury in cases of relatively large tumor size [2, 24– treating sporadic unilateral [20–23]. Further studies are 25]. Although this finding has not been consistently reported needed to evaluate the techniques for improvement in local in the literature [5, 26], we believe that it was prudent for us control and hearing preservation, especially in NF-2 patients. to take this issue into account before planning the fraction- The pre-treatment Gardner–Robertson score may be ation schedule. Our strategy seems to have been suitable 358 P. Puataweepong et al. because as it turned out there was no significant difference in 10. Andrews DW, Suarez O, Goldman HW et al. Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the tumor control or adverse effect observed between the three treatment of acoustic schwannomas: comparative observations methods. However, our selection criteria were slightly differ- of 125 patients treated at one institution. Int J Radiat Oncol ent for the two techniques as well as from other studies. Biol Phys 2001;50:1265–78. 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Neurosurgery clinical results after LINAC-based single-dose radiosurgery 2003;53:75–80. versus fractionated stereotactic radiotherapy for patients with 24. Prasad D, Steiner M, Steiner L. Gamma surgery for vestibular vestibular schwannomas. Int J Radiat Oncol Biol Phys schwannoma. J Neurosurg 2000;92:745–59. 2010;76:193–200. 25. Ito K, Kurita H, Sugasawa et al. Analyses of neuro-otological 9. Kopp C, Fauser C, Muller A et al. Stereotactic fractionated complications after radiosurgery for acoustic neurinomas. Int J radiotherapy and LINAC radiosurgery in the treatment of ves- Radiat Oncol Biol Phys 1997;39:983–8. tibular schwannoma – report about both stereotactic methods 26. Flickinger JC, Kondziolka D, Niranjan A et al. Results of from a single institution. Int J Radiat Oncol Biol Phys acoustic neuroma radiosurgery: an analysis of 5 years’ experi- 2011;80:1485–91. ence using current methods. J Neurosurg 2001;94:1–6. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Radiation Research Oxford University Press

Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution

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Oxford University Press
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The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.
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Oncology
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0449-3060
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10.1093/jrr/rrt121
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Abstract

Journal of Radiation Research, 2014, 55, 351–358 doi: 10.1093/jrr/rrt121 Advance Access Publication 18 October 2013 Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution 1, 1 1 Putipun PUATAWEEPONG , Mantana DHANACHAI , Somjai DANGPRASERT , 1 1 1 Ladawan NARKWONG , Chomporn SITATHANEE , Thiti SAWANGSILPA , 3 2 Taweesak JANWITYANUJIT and Pornpan YONGVITHISATID Radiation and Oncology Unit, Department of Radiology, Faculty of Medicine, Mahidol University, Bangkok, 10400, Thailand Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand Radiosurgery Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand *Corresponding author. Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, 270 Rama VI Road, Ratchatewi, Mahidol University, Bangkok 10400, Thailand. Tel: +662-201-2295; Fax: +662-201-1191; Email: putipun.pua@mahidol.ac.th (Received 19 July 2013; revised 15 September 2013; accepted 19 September 2013) Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) have been recognized as an alternative to surgery for small to medium sized vestibular schwannoma (VS). This study analysed and com- pared the outcomes of VS treated with the first Thailand installation of a dedicated Linac-based stereotactic ra- diation machine using single-fraction radiosurgery (SRS), hypofraction stereotactic radiotherapy (HSRT) and conventional fraction stereotactic radiotherapy (CSRT). From 1997 to 2010, a total of 139 consecutive patients with 146 lesions of VS were treated with X-Knife at Ramathibodi hospital, Bangkok, Thailand. SRS was selected for 39 lesions (in patients with small tumors ≤3 cm and non-serviceable hearing function), whereas HSRT (79 lesions) and CSRT (28 lesions) were given for the remaining lesions that were not suitable for SRS. With a median follow-up time of 61 months (range, 12–143), the 5-year local control rate was 95, 100 and 95% in the SRS, HSRT and CSRT groups, respectively. Hearing preservation was observed after SRS in 75%, after HSRT in 87% and after CSRT in 63% of the patients. Cranial nerve complications were low in all groups. There were no statistically significant differences in local control, hearing preservation or complication between the treatment schedules. In view of our results, it may be preferable to use HSRT over CSRT for patients with serviceable hearing because of the shorter duration of treatment. Keywords: SRS; SRT; vestibular schwannomas; local control; hearing preservation INTRODUCTION single higher dose (14–18 Gy), have higher rates of cranial neuropathy [1–5]. This has led to a treatment modality pursu- Stereotactic radiosurgery (SRS) and radiotherapy (SRT) are ing a lower dose of single-fraction radiosurgery (12–13 Gy) techniques which administer precisely directed, high-dose ir- or fractionated stereotactic radiotherapy. The results of tumor radiation that tightly conforms to an intracranial target in control and complication were compared for the 12–13 Gy order to create a desired radiobiologic response, and to min- SRS and the SRT techniques [6]. Previous data from other imize radiation dose to the target’s surrounding normal institutions have shown a local control rate of 92–100%, a tissues. Initial radiosurgery series, using gamma knife (GK) hearing preservation rate of 58–65%, and an acceptable 1–5% therapy for vestibular schwannoma (VS), have been reported rate of treatment-related side-effects after the patients had since 1987. Further development of the Linac-based stereo- undergone SRS and SRT [7–10]. Although the use of stereo- tactic technique has allowed it to become an alternative to the tactic radiation for VS nowadays is accepted, the optimal frac- GK system. The various fractionation schemes, starting from tionation schedule is still controversial, and the practicality of © The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 352 P. Puataweepong et al. using SRS and SRT varies according to the level of experi- received SRS/SRT as the primary treatment; of the 146 ence at individual institutions. Since previous studies have lesions, 39 (27%) were treated with SRS, whereas 79 (54%) only compared two fractionation schedules (SRS vs HSRT, and 28 (19%) were treated with HSRT and CSRT, respect- or SRS vs CSRT), the objective of this report was to analyse ively. Of the 139 patients, 13 had neurofibromatosis type 2 and compare the long-term outcomes between the three com- (NF-2). Patient characteristics of each treatment group are monly used stereotactic radiation schedules, including single- detailed in Table 1. Three patients died from unrelated fraction radiosurgery (SRS), hypofraction SRT (HSRT) and causes. Two patients were lost to follow-up. conventional fraction SRT (CSRT) for VS patients treated at the same institution. Radiation technique MATERIALS AND METHODS The SRS/SRT techniques in this study were performed with the linear accelerator-based system [6 MV dedicated LINAC In 1997, the first Linac-based stereotactic radiation machine with fixed circular cone (Varian) with X-Knife planning in Thailand was opened at the Radiosurgery Center, system version 3 & 4 (Radionics}]. In the SRS technique, Ramathibodi Hospital in Bangkok. In this study, we analysed the Brown–Robert–Wells (BRW) stereotactic frame was the long-term outcomes for vestibular schwannoma patients applied with the assistance of a neurosurgeon. This differs treated at our institution. from the SRT technique in which the relocatable Gill– Thomas–Cosman (GTC) frame was applied. Individual treat- Patients ment planning was done in a work-station using an image set From December 1997 to January 2010, 139 vestibular from a contrast-enhanced CT scan, of 1.25 mm-slice thick- schwannoma patients with 146 lesions underwent Linac- ness, with or without gadolinium-enhanced MRI. Target and based SRS/SRT and were included in this study. All patients critical organ contouring was done by radiation oncologists, were followed up prospectively until death. We retrospectively and a treatment plan was generated by medical physicists. conducted a chart review of this cohort of patients after ap- The diameter of circular beams ranged from 5–50 mm. The proval by our institutional ethics committee. The median collimator size that covered at least 90% of the target volume follow-up time was 61 months (range, 12–143). Prior to treat- was selected. Multiple isocenters were used in irregularly ment, the optimal plan for management of all patients was dis- shaped targets. Arc selection was performed, and was mainly cussed and approved by our radiosurgery board. A patient non-coplanar. The target volume ratio (TVR) was usually who had a tumor large enough for brain stem compression within a range of 1.3–2. was selected to undergo a maximum safety surgical resection The selection of patients for SRS or SRT technique was and postoperative radiation for the residual tumor. For a based on pretreatment hearing function and tumor size. patient with a small to medium sized tumor, SRS or SRT was Patients who had small tumors (≤3 cm) and non-serviceable usually offered; however, for an elderly patient with a tiny hearing were usually selected for SRS treatment. Patients lesion, we recommended an observational policy. who did not have the aforementioned criteria or were not An interview and neurological examination focusing on suitable for SRS were selected for HSRT or CSRT treatment. cranial nerve function was performed on all patients before In SRS technique, the prescribed dose might be 12–13 treatment. Hearing assessment was performed by scoring the Gy × 1 fraction for a small lesion (≤3cm) with non- ability of patients to use the telephone with the affected ear. serviceable hearing. HSRT was offered to patients with a If the patients were not able to discriminate words or could larger tumor (>3 cm) regardless of hearing levels. In general, not hear at all, they were scored as ‘non-serviceable hearing’. the prescribed dose should be 3 Gy × 10 fractions for large ir- Additionally, all patients were sent for audiograms prior to regular lesions near a critical organ, and 5 Gy × 4 fractions, SRS/SRT treatment. Hearing assessment rated according to 6 Gy × 3 fractions or 5 Gy × 5 fractions for smaller lesions the Gardner–Robertson classification was recorded, and ser- away from critical organs. However, various dose fractiona- viceable hearing was determined as Class I or Class II. tions for HSRT were selected based not only on tumor Trigeminal nerve function was assessed via asking the factors, such as tumor size, shape and location, but also on patient about facial pain or numbness according to the individual physician preference and patient expectation. CTCAE system. Facial nerve function was assessed and CSRT with the prescribed dose of 1.8–2 Gy × 25 fractions scored using the House–Brackmann facial nerve grading was preserved in very large tumors near critical organs. system [11]. Evaluation of tumor control, hearing preserva- Table 2 shows the prescribed dose, single dose equivalent, tion and cranial nerve complication were recorded according- and EQD2 value for SRS/HSRT dose schedules in our study. ly for each treated site. The patients in the SRS group received a median dose of There were 47 males and 92 females in this study. They 12 Gy (range, 12–13) prescribed at the 80% isodose line had a total of 146 lesions, of which 89 (61%) were treated (range, 80–90) to the tumor margins. The median maximum with partial tumor removal before SRS/SRT, and 57 (39%) diameter was 1.6 cm (range, 0.8–3). The median tumor SRS/SRT in vestibular schwannomas 353 Table 1. Baseline characteristics of 139 patients with 146 lesions Parameters SRS 39 (27%) HSRT 79 (54%) CSRT 28 (19%) Gender Male 6 (18%) 28 (37%) 13 (50%) Female 31 (82%) 48 (63%) 13 (50%) Surgery Yes 25 (64%) 46 (59%) 18 (64%) No 14 (36%) 33 (41%) 10 (36%) Genetic predisposition Sporadic 39 (97%) 67 (89%) 19 (75%) NF-2 2 (3%) 6 (11%) 5 (25%) Hearing function Non-serviceable 35 (90%) 46 (58%) 16 (57%) Serviceable 4 (10%) 33 (42%) 12 (43%) Age (year) 47 (16–71) 50 (14–78) 39 (18–74) Tumor size (cm) 1.6 (0.8–3) 2.5 (1–7) 4 (1.1–5) Tumor volume (cm ) 0.96 (0.08–9.2) 3.9 (0.1–34.2) 9.5 (1.7–27.5) SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction. Median follow-up time = 61 months (12–14.3). Table 2. Prescribed dose, Single dose equivalent and EQD2 for SRS and HSRT dose schedules used in our study SRS/HSRT schedule used in our study Single dose equivalent (Gy) EQD2 (Gy) Total dose (Gy) Dose/fraction No. of fractions 12 12 1 12 36 13 13 1 13 41.6 18 6 3 12 32.4 20 5 4 11 32 25 5 5 12 40 30 3 10 11 36 SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, EQD2 = equivalent dose at 2 Gy = total dose (d+ α/β)/(2+ α/β); assuming α/β =2. volume was 0.96 cm (range, 0.08–9.2), and the median The patients in the CSRT group received a median total number of isocenters was 2 (range, 1–8). dose of 50 Gy (range, 45–50) in 25 fractions (range, 20–25) The patients in the HSRT group received various hypofrac- prescribed at the 90% isodose line. The median maximum tion schedules (5 Gy × 4–5, 6 Gy × 3, and 3 Gy × 10). The diameter was 4 cm (range, 1.1–5). The median tumor median total dose of 25 Gy (range, 18–30) at the 80% isodose volume was 9.5 cm (range, 1.7–27.5). The median number line (range, 80–90) was prescribed. A median number of of isocenters was 4 (1–8). 5 fractions (range, 3–10) was used in the treatment. The median maximum diameter was 2.5 cm (range, 1–7). The Follow-up median tumor volume was 3.9 cm (range, 0.1–34.2). All patients were seen at 4–6 weeks after completing treat- The median number of isocenters was 4 (range, 1–8). ment for a first follow-up visit, then every 6 months for the 354 P. Puataweepong et al. next 2–3 years. Annual follow-up was continued thereafter. treatment-related complications were calculated using Patients were interviewed with neurological examination fo- Kaplan–Meier methods, and the survival curves were com- cusing on cranial nerve function in V, VII and VIII during pared using the log-rank test. Multivariate analysis was done each visit. If the patients had new or progressive facial numb- using the Cox proportional hazard model. All statistical ana- ness according to the CTCAE grading or an increased lyses were performed using SPSS software, version 16.0. House–Brackmann grade, this was scored as trigeminal or facial neuropathy. Regarding hearing function assessment, RESULTS for any patients who had pre-treatment serviceable hearing, audiograms were repeated every 6–12 months. However, in All patients could tolerate the treatment very well. There was patients with non-serviceable hearing before treatment, we no interruption of HSRT or CSRT treatments. Minor acute only asked about their hearing ability in the treated ear reactions occurring in this study included headaches, nausea without further audiogram. MRI was done yearly for assess- and dizziness. ment of local tumor control. Local tumor control was defined as stable (no increase in tumor diameter) or decreased Local tumor control maximum tumor diameter on follow-up MRI imaging. The LC rate in all patients was 98% and 87% at 5 and 10 Temporary symptomatic tumor necrosis (central tumor ne- years, respectively. With respect to treatment technique, the crosis on MRI with temporary increase in tumor size with or 5-year LC rates after SRS, HSRT and CSRT were 95, 100 without new or worsened neurological symptoms related to and 95%, respectively, with no statistically significant differ- the necrosis) but not requiring additional surgical treatment ence between the treatments (P = 0.46) (Fig. 1). The LC is was defined as local tumor control. Local failure was defined not statistically significantly different when other factors are as permanent progressive tumor growth with associated compared, including the presence or absence of NF-2, symptoms requiring additional surgical treatment. patient age, prior surgical intervention vs no prior surgical intervention, tumor size and tumor volume. Statistical analyses Demographic data were summarized and compared with Hearing preservation respect to the treatment group. Categorical data were In our study, 49 of 139 patients had serviceable hearing described with frequencies and percentages and compared before treatment (33.6%). Three were NF-2 and 46 were using the Fisher exact tests. Continuous data were reported sporadic cases. Initially, we selected only patients with small with medians and ranges and compared using t-tests or tumors who had non-serviceable hearing for treatment with Wilcoxon rank-sum tests. Local tumor control (LC) and SRS. However, four patients with serviceable hearing also Fig. 1. Local control of 146 VS lesions treated with stereotactic radiation, after a median follow-up time of 61 months; local control at 5 and 10 years was 98 and 87%, respectively (A). Outcomes were not statistically significantly different after SRS, HSRT or CSRT (P = 0.46) (B). SRS/SRT in vestibular schwannomas 355 preferred the SRS and decided to be treated with this tech- statistically significantly lower in NF-2 patients (P = 0.044) nique after being informed about the risks and benefits of all (Fig. 3). Out of the three NF-2 patients with serviceable treatment alternatives. The other 33 and 12 patients with ser- hearing, two patients received CSRT, and both of them later viceable hearing were treated with HSRT and CSRT, respect- developed hearing deterioration. Another patient who ively. Table 3 shows Gardner–Robertson (GR) classification received HSRT had maintained hearing function at the time changes from GR I–II (serviceable hearing) to GR III–V of the last follow-up. (non-serviceable hearing). The probability of maintaining serviceable hearing did not differ between each radiation Trigeminal nerve function technique. With regard to pretreatment GR classification and Before SRS/SRT, 32 patients presented with mild to moder- hearing preservation, 10 out of 13 (76%) GR I patients and ate facial numbness. Nine patients (28%) were treated with 30 out of 36 (83%) GR II patients were able to maintain ser- SRS, while 16 patients (50%) and 7 patients (22%) were viceable hearing function. No GR I patients developed to treated with HSRT and CSRT, respectively. GR IV, in contrast with four patients in GR II who changed After SRS/SRT, 10 of these patients (47%) exhibited im- to GR IV hearing function. provement of facial numbness (3 in the SRS, 5 in the HSRT The overall hearing preservation rates at 1, 2 and 5 years and 2 in the CSRT groups). None of these patients showed were 90, 84 and 80%, respectively. The 5-year hearing pres- any worsening of their facial numbness. There was only one ervation rates after SRS, HSRT and CSRT were 75, 87 and patient (0.93%) in the HSRT group who developed new tri- 63%, respectively, with no statistically significant difference geminal neuropathy, characterized by mild facial numbness (P = 0.35) (Fig. 2). The only factor that affected the hearing (CTCAE Grade I). However, the symptom was spontaneously preservation was the presence of NF-2, and this was resolved without any specific treatment within 3 months. Table 3. Gardner–Robertson classification changes from GR I–II (serviceable hearing) to GR III–V (non-serviceable hearing) after SRS and SRT SRS (n = 4) HSRT (n = 33) CSRT (n = 12) Before GR I = 1 GR II = 3 GR I = 2 GR II = 31 GR I = 10 GR II = 2 After GR I = 1 GR IV = 1 GR III = 1 GR IV = 3 GR III = 2 GR III = 2 GR = Gardner–Robertson, SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction. Fig. 2. Hearing preservation rate at 1, 2 and 5 years was 90, 84 and 80%, respectively (A). Outcomes were not statistically significantly different after SRS, HSRT or CSRT (P = 0.35) (B). 356 P. Puataweepong et al. in patients with tumors sufficiently large enough to cause symptomatic brainstem compression with obstructive hydro- cephalus. SRS and SRT should be considered the best man- agement strategy for the majority of small to medium sized tumor VS patients [13]. Early radiosurgery series of SRS used to treat VS with higher dose single fraction (14–18 Gy) had higher rates of cranial nerve neuropathies (15–20% trigeminal and/or facial nerves, and 67% with decreased hearing function) [14]. This led to the practice of lowering the doses of the SRS (12–13 Gy) and the SRT technique. Both approaches have shown improved results (the local control was 92–100%, hearing preservation was 58–65%, trigeminal and facial nerve neuropathy was 1–5%) [7–10, 15–18]. Until now the standard stereotactic radiation fractionation for treatment of VS was still unknown due to a lack of published Level I evidence regarding this controversial issue. Because most previous non-randomized studies [7–10] compared only Fig. 3. Hearing preservation rate was statistically significantly single versus multiple fractionation (SRS vs HSRT, or SRS lower in NF-2 than in sporadic cases (P = 0.044). vs CSRT), the aim of this study was to compare the three commonly used stereotactic radiation schedules, i.e. SRS, Facial nerve function HSRT and CSRT, in treating VS. Before SRS/SRT, 48 patients presented with facial neur- Due to a major concern about hearing outcomes, the selec- opathy. Of these, 17 patients (35%) were treated with SRS, tion criteria for each treatment included both pretreatment 21 patients (44%) were treated with HSRT and 10 patients hearing function and tumor size. SRS was only selected to (21%) were treated with CSRT. treat patients who had non-serviceable hearing and small After SRS/SRT, five patients (10%) reported completely tumors (≤ 3cm); HSRT or CSRT was given to the remaining resolved facial palsy (one in the SRS, two in the HSRT and patients who were not suitable for SRS. By following this two in the CSRT groups). Seven patients (15%) reported im- protocol, we achieved excellent local control and hearing provement of their facial palsy. One patient in the SRS group preservation with a low complication rate. Apart from this reported worsening of facial palsy (the House–Brackmann study, there have been four reports [7–10] attempting to score changed from 2 to 3). Three patients (3.2%) developed compare the outcomes of SRS and SRT. The first study by new facial neuropathy (a House–Brackmann score of 2 in Andrews et al. [10] in 2001 reported that tumor control rates two patients and a score of 3 in one patient). Two of these for SRS (n = 63) and CSRT (n = 46) were 98% and 97% for patients were treated with HSRT and the other patient was VS patients, respectively. In 2003, the second paper by treated with SRS. All patients who had facial weakness were Meijer et al., [7] reported a series of 129 patients with VS treated with a short course of oral dexamethasone. Finally treated with Linac-based SRS vs HSRT. They also found a only one patient still had permanent facial neuropathy comparable local control rate for SRS and HSRT (100% vs (House- Brackmann score 2) at the last follow-up. 94%). In 2010, Combs et al. [8] reported the tumor control rate was 96% for both the SRS and CSRT groups, and this Noncranial nerve complication was similar to the 97.9% tumor control rate for CSRT and One patient developed hydrocephalus at 11 months after 98.5% forSRS reported by Kopp et al. [9] These tumor HSRT. Reoperation was performed at that time. This was the control rates compare well with the tumor control rates of only patient who had an operation after HSRT. 95% for RS, 100% for HSRT, and 95% for CSRT, as found in our study. DISCUSSION While the fractionation schedule seems to have no impact on local control, the impact on hearing preservation rate of Management of VS requires multidisciplinary screening to using different fractionation schedules is still controversial. select patients who are suitable for different approaches to The data from single institution reports on the effects of observation, surgery, SRS/SRT, or combinations of treat- 12–13 Gy SRS on hearing preservation rates varies from ment. Observation may be appropriate in selecting NF-2 and 32–71% [15], while the best results for hearing preservation some elderly patients, but early intervention appears to be rates have been 63–94% from CSRT with a total dose of the best strategy for long-term hearing preservation in most 40–57.6 Gy [19]. The third alternative, HSRT, using various patients [12]. Surgery appears to be the best initial treatment fractionation schedules such as 4–5 Gy × 5, 5–6 Gy × 5, or SRS/SRT in vestibular schwannomas 357 Table 4. Published studies on SRS/SRT for vestibular schwannoma 5-year hearing 5-year facial 5-year trigeminal Treatment/ 5 year LC Study preservation nerve preservation nerve preservation number of pt rate (%) rate (%) rate (%) rate (%) Andrew et al., 2004 [10] SRS/69 98 33 98 95 CSRT/56 97 81 98 93 Meijer et al., 2003 [7] SRS/49 100 75 93 92 HSRT/80 94 61 97 98 Comb et al., 2010 [8] SRS/30 96 70 83 93 CSRT/175 96 78 98 97 Kopp et al., 2010 [9] SRS/68 97.9 79 100 87 CSRT/47 98.5 85 100 100 Our study SRS/39 95 75 98 100 HSRT/79 100 87 97 99 CSRT/28 95 63 100 100 SRS = stereotactic radiosurgery, HSRT = stereotactic radiotherapy, hypofraction, CSRT = stereotactic radiotherapy, conventional fraction, LC = local control. 3 Gy × 10, showed a hearing preservation rate of 61–100% important for hearing preservation rates. Andrews et al. [10] [7, 17]. The relationship between the fractionation schedule found a significantly greater probability of hearing preserva- and the hearing preservation rate is somewhat conflicting in tion in patients with pre-treatment GR I grading, suggesting the non-randomized comparative studies. For the example, that early intervention without observation may be a favor- Kopp et al. [9] reported an 85% hearing preservation rate able policy. Our results showed that the patients who had after SRS and 79% after CSRT, which was similar to the pre-treatment GR II deteriorated to GR IV after treatment 78% hearing preservation rate for both SRS and SRT more often than did GR I patients. We concluded that imme- reported by Combs et al. [8]. Meijer et al. [7] also reported diate treatment of GR I patients with SRT might yield the the 5-year hearing preservation probability for SRS and highest probability of functional hearing preservation. HSRT as 75% and 61%, respectively, but without any statis- Our study used various doses and fractionations such as tically significant difference. Nevertheless, a contradictory 12 Gy × 1, 6 Gy × 3, 5 Gy × 4–5, 3 Gy × 10, and 2 Gy × 25. result was reported by Andrew et al. [10], whose report was These schedules are considered to have different radiobio- 2.5 times higher for hearing preservation rate in patients who logical effects, which may make the analysis of this study received CSRT (81%) than those who received SRS (33%), difficult. Currently, there is no reliable way to use the linear- P = 0.0228). Table 4 shows a comparison of our study with quadratic (LQ) formula to extrapolate equivalent effects of the previous studies comparing SRS and SRT. high-dose single fractions to a fractionated course of RT for Based on radiobiology principles, late-responding tissue VS. The LQ model may not adequately explain dose– such as cranial nerve and brain tissue might be subject to response relationships for either tumor or normal tissue when more injury when dose fractionation exceeding a conventional stretched to include the high radiation doses used with SRS. 1.8–2 Gy dose per fraction is applied. From this knowledge, However, we hope that reliable radiobiological parameters we hypothesized that CSRT should have a higher hearing extracted from dose–response data will be available in the preservation rate than HSRT. Nevertheless, our hypothesis near future. was not correct; CSRT did not show the improved hearing The treatment technique selected for each patient in this preservation we expected. However, this finding probably study was based mainly on hearing function and tumor size. results from the larger tumor volumes and relatively small SRS was mostly reserved for patients with smaller sized number of patients in the CSRT group. tumors (<3 cm in maximal diameter) and non-serviceable The presence of NF-2 was the only factor that was asso- hearing, while SRT was reserved for those with serviceable ciated with poorer hearing preservation, but this might have hearing. One of the reasons for this is that SRS was previous- been due to the small sample size. Overall, the results ly reported as one of the potential risk factors for cranial obtained for NF-2 VS were not as good as those achieved in nerve injury in cases of relatively large tumor size [2, 24– treating sporadic unilateral [20–23]. Further studies are 25]. Although this finding has not been consistently reported needed to evaluate the techniques for improvement in local in the literature [5, 26], we believe that it was prudent for us control and hearing preservation, especially in NF-2 patients. to take this issue into account before planning the fraction- The pre-treatment Gardner–Robertson score may be ation schedule. Our strategy seems to have been suitable 358 P. Puataweepong et al. because as it turned out there was no significant difference in 10. Andrews DW, Suarez O, Goldman HW et al. Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the tumor control or adverse effect observed between the three treatment of acoustic schwannomas: comparative observations methods. However, our selection criteria were slightly differ- of 125 patients treated at one institution. Int J Radiat Oncol ent for the two techniques as well as from other studies. Biol Phys 2001;50:1265–78. Therefore, it is difficult to conclude that SRS is not as good 11. Vrabec JT, Backous DD, Djalilian HR et al. Facial Nerve Grading as SRT for medium or large sized VS tumors. System 2.0. Otolaryngol Head Neck Surg 2009;140:445–50. 12. Sakamoto T, Shirato H, Takeichi N et al. Annual rate of CONCLUSION hearing loss falls after fractionated stereotactic irradiation for vestibular schwannoma. Radiother Oncol 2001;60:45–8. 13. Pollock BE. Vestibular schwannoma management: an In summary, this study showed excellent outcomes for 139 evidence-based comparison of stereotactic radiosurgery and VS patients treated with either SRS or SRT, without signifi- microsurgical resection. Prog Neurol Surg 2008;21:222–7. cant difference with respect to local control, hearing preser- 14. Kondziolka D, Subach BR, Lunsford LD et al. Outcomes after vation, or complication rate. HSRT may be preferable to gamma knife radiosurgery in solitary acoustic tumors and CSRT because it has a shorter treatment duration. 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Journal

Journal of Radiation ResearchOxford University Press

Published: Mar 18, 2014

Keywords: SRS SRT vestibular schwannomas local control hearing preservation

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