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ORIGINAL ARTICLE
Ahead of print publication  

Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute


1 Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
2 Department of Neurosurgery, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
3 Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzu Chi University, Hualien, Taiwan
4 Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzu Chi University, Hualien; Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan

Date of Submission16-Sep-2021
Date of Decision25-Oct-2021
Date of Acceptance14-Jan-2022
Date of Web Publication27-Jun-2022

Correspondence Address:
Hon-Yi Lin,
Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 2, Min-Sheng Road, Dalin, Chiayi
Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tcmj.tcmj_260_21

  Abstract 


Objectives: Accelerator-based stereotactic radiosurgery (SRS) is a noninvasive and effective treatment modality widely used for benign brain tumors. This study aims to report 20-year treatment outcomes in our institute. Materials and Methods: From May 2001 to December 2020, 127 patients treated with LINAC-based single-fraction SRS for their benign brain lesions were included. A neurosurgeon and two radiation oncologists retrospectively reviewed all data. Computed tomography (CT) simulation was performed after head-frame fixation under local anesthesia. All planning CT images were co-registered and fused with gadolinium-enhanced magnetic resonance imaging taken within 3 months for lesions targeting and critical organs delineation. The marginal dose was prescribed at 60%–90% isodose lines, respectively, to cover ≥95% planning target volume. Outcome evaluations included clinical tumor control rate (TCR), defined as the need for salvage therapy, and radiological response, defined as no enlargement of >2 cm in the maximal diameter. Overall survival (OS) and adverse reaction (defined according to CTCAE 5.0) were also analyzed. Results: The present study included 76 female and 51 male patients for analysis. The median age was 59 years (range, 20–88 years). Their diagnoses were vestibular schwannoma (VS, n = 54), nonvestibular cranial nerve schwannoma (n = 6), meningioma (n = 50), and pituitary adenoma (n = 17). Totally 136 lesions were treated in a single fraction, predominantly skull base tumors, accounting for 69.1%. Median and mean follow-up duration was 49 and 61 months (range, 1–214 months), Overall TCR was 92.9%. The 5-year disease-specific TCR for VS, nonvestibular schwannoma, meningioma, and pituitary adenoma were 97.4%, 91.7%, 93.8%, and 83.3%. Salvage therapy was indicated for eight patients at 4–110 months after SRS. Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 evaluable patients was 94.6% (shrinkage, 28.8%; stable, 65.8%). OS was 96.1% without treatment-related mortality. One patient with post-SRS cranial nerve injury (0.8%, involving the trigeminal nerve, grade 2 toxicities). No grade 3–4 acute or late toxicity was found. Conclusion: Our results suggested that LINAC-based SRS effectively controls tumor growth and tumor-related neurological symptoms for patients with benign brain tumors. SRS is less aggressive, associated with low neurological morbidity and no mortality. Continuous follow-up is indicated to conclude longer outcomes.

Keywords: Benign brain tumor, LINAC, Stereotactic radiosurgery, Tumor control rate



How to cite this URL:
Chew CH, Chen JC, Hung SK, Wu TH, Lee MS, Chiou WY, Chen LC, Lin HY. Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute. Tzu Chi Med J [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.tcmjmed.com/preprintarticle.asp?id=348321

Chia-Hui Chew & Jin-Cherng Chen, Both authors contributed equally to this work.





  Introduction Top


Lars Leksell, a Swedish neurosurgeon at Karolinska Institute, first introduced Stereotactic radiosurgery (SRS) in managing various intracranial benign and malignant diseases with high-dose radiation without opening the skull. The first isotope radiation machine, called the Gamma knife (GK), was built up to perform radiosurgery in 1968 [1]. The term “stereotactic” refers to a three-dimensional coordinate system that enables accurate simulation of a target. Radiosurgery is the procedure to deliver high doses of ionizing radiation to eradicate the selected target lesion. The dose is delivered through a large number of evenly distributed and precisely collimated narrow beams of ionizing radiation. In most models, there are usually 201 hemispherical arrays of collimated Cobalt-60 beams. The dose gradient is highly steep, showing rapid dose falloff and resulting in lesions sharply circumscribed by targeted radiation dose [2],[3],[4]. Adjacent normal or critical structures nearby the target receive very little radiation [5],[6]. Patients who receive GK SRS need to have head frame fixation on achieving high precision and accuracy. So, this is a minimally invasive procedure and needs to be completed in 1 day.

SRS can be performed with GK utilizing Cobolt-60 source or X-knife generated from a linear accelerator (LINAC, CyberKnife) or heavy particles (proton therapy, heavy carbon ion) [7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19]. GK is exclusively designed for intracranial lesions, in maximal size <3 cm, such as meningioma, vestibular schwannoma (VS), trigeminal neuralgia, arteriovenous malformation, and pituitary adenoma. In contrast, LINAC can be used to deliver fractionated radiotherapy (FRT) to all parts of the body. In some instances, we deliver conventional radiation dose (1.8–2.0 Gy per fraction), known as FRT, to treat intracranial lesions close to a critical organ with less tolerance to a single-fraction high radiation dose [20],[21],[22],[23]. LINAC-based SRS was developed in early 1980 [24]. After a series of modifications, SRS-capable LINAC is increasingly utilized for both primary and metastatic brain tumors because of its cost-effectiveness and ease of use. Solitary and multiple lesions can be treated simultaneously. Literature showed that advanced and well-equipped linear accelerators have the same effectiveness and safety profiles compatible with the GK. Improvement of multi-leaflet collimator technology, delivery technology (e.g., volumetric modulated arc therapy [VMAT]), guiding devices, and treatment planning system, LINAC SRS was proven to have similarly acceptable precision, accuracy, and mechanical stability. Here, we present the long-term results of benign tumors treated with single fraction frame-based LINAC SRS in a single institute.


  Materials and Methods Top


Research ethics and data collection

This study had been approved by the Institutional Review Board of Buddist Dalin Tzu Chi Hospital (approval number: B11003015) on September 12, 2021. Informed written consent was waived because the study was a retrospective data analysis. We retrospectively retrieved and analyzed data from medical records and our prospective departmental database, the Integrated Radiotherapy Oncology Information Platform [25],[26]. From May 2001 to December 2020, 127 patients who received single-fraction SRS for their benign brain tumors were analyzed. Indications of treatment included all symptomatic or progressive tumors that had either tumor-rated locally inoperable or bearing a high surgical risk for permanent neurologic deficits; residual or recurrent tumors after previous surgery; refused surgery, or increased risk of surgery due to comorbidity. A single lesion with maximal diameter <5 cm or two to three separated lesions with each maximal diameter <3 cm was illegible. In general, treatment decisions were made by an interdisciplinary discussion between neurosurgeon and radiation oncologist.

Patients who had no complete clinical information and radiotherapy record were excluded. Patient data were retrieved from chart review and digital patient information (Hospital Information System and Integrated Radiotherapy Oncology Information Platform). Documented data included patient profiles, tumor-specific profiles, and treatment parameters. Radiation parameters, including tumor volume, marginal dose, and the number of noncoplanar arches, were evaluated on a radiotherapy treatment planning system. Duration of treatment could be retrieved for patients who received treatment utilizing the current planning system. Treatment time was between the first cone-beam computed tomography (CBCT) acquisition and the last radiation beam completed. Beam-on time was the time that the radiation source delivered radiation.

Equipment and radiosurgery technique

All patients were co-reviewed by a neurosurgeon and a radiation oncologist before SRS. Gadolinium-enhanced brain magnetic resonance imaging (MRI) with standardized MRI protocol, including 1-mm or 3-mm T1-weight contrast-enhanced sequences, were performed within 3 months before treatment. On treatment day, 123 (96.9%) patients received head-frame fixation under local anesthesia, and 4 (3.1%) patients used bite block and intensified-thermoplastic mask immobilization. Then, a high-resolution contrast-enhanced brain computed tomography (CT) scan (i.e., 1-mm slice thickness) simulation was obtained for treatment planning. The planning CT images were co-registered and fused with MRI images to aid the delineation of the target, defined as gross tumor volume (GTV). Critical organs, including the optic nerve, optic chiasm, brainstem, cochlear, and adjacent cranial nerves, were also contoured. No margin expansion was added from GTV to generate planning target volume (PTV). Radiotherapy planning was done using FastPlan 5.5.1 (2002–2009) or Eclipse™ after 2010 (Varian Medical System, Palo Alto, CA, USA).

Prescription dose for meningioma followed the NCCN guideline. The planning and dose prescription for Schwannoma was referred to RTOG studies. In cases of pituitary adenoma, the prescription dose was based on the recommendation of large-scale studies. Marginal doses were prescribed at 60%–90% isodose line to cover at least 95% of the PTV. The marginal dose was tailored regarding the patient's condition, tumor characteristics, tolerance of adjacent normal organs, and existing neurological functions. Therefore, the marginal doses we used for schwannoma, meningioma, and pituitary adenoma were 8–13, 8–15, and 12–16, respectively. Constraints of normal organs were brainstem (<12 Gy), cochlear (<9 Gy), optic nerve (<8 Gy), and chiasm (<8 Gy). We used multiple noncoplanar arcs of beam converging on one to three isocenter(s). After an experienced medical physicist generated the SRS plan, quality assurance for the treatment system and dry run were carried out before treatment.

SRS was delivered using 6MV LINAC equipped with VMAT technique. We used Varian Clinic 2300IX (80 multileaf collimators) system before February 2010 (n = 15). Then, the treatment system was upgraded to Varian Trilogy® after April 2010 (n = 112), which had strengths of increased dose rate and whole 360°C arc of delivery to shorten treatment duration, 2D-and 3D-image guidance for better target visualization and targeting, and dynamic high-resolution 120 multileaf collimators for precise treatment. All patients received dexamethasone 4 mg, metoclopramide 10 mg, and ranitidine 50 mg injection within 1 h before SRS. Patients were treated in a supine position. The headframe and CT localizer or intensified-thermoplastic mask were fixed on a treatment couch. Precise localization was achieved by the sensitive optical guidance platform monitoring system detecting variation in 0.1 mm and CBCT for image-guided radiotherapy. The accuracy for the whole treatment was limited to <1 mm. After treatment, the head frame was removed. Patients were discharged on the following day after dexamethasone 4 mg injection.

Outcome evaluations

Contrast-enhanced T1-weighted MRI was performed in 1 year for 5 years, then at least 2 years subsequently, depending on the clinical status and physician's judgment. The follow-up schedule was 2 weeks after the procedure, then at 6 and 12 months after SRS, followed by per year subsequently. Physical and neurological examinations were evaluated on each visit.

Tumor control rate (TCR) was defined as the percentage of patients who had no requirement for salvage therapy, including re-irradiation and surgery. The period was calculated from the date of SRS to the date of salvage therapy, defined as events. Follow-up was censored at last evaluation or death. On evaluating the cumulative risk of salvage therapy, the date of the first salvage therapy after SRS was recorded. Ventriculoperitoneal shunt (VP shunt) procedure was counted as a complication. We also evaluated overall survival (OS); the period of survival was calculated from the day of SRS to the date of death. If no events happened, follow-up was censored at the last evaluation.

To determine radiologic tumor control, we measured the largest axial tumor diameter in the anteroposterior and lateral extension on T1-weighted MRIs. The interval change of the tumor size was evaluated on the latest MRI, compared with the image before SRS. Radiologic tumor control was classified into three groups, control (tumor diameter reduced by ≥2 mm), stable (the diameter reduced by <2 mm), and progression (tumor growth by >2 mm). Volumetric quantification on series MRIs was analyzed to study volumetric change patterns after SRS.

At each clinical follow-up, the development of symptoms was classified either as symptoms improved, stable, or worse. Toxicity of SRS was assumed when new, permanent, objectified symptoms developed after SRS. Symptoms were classified according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).

Statistics and data analysis

Accordingly, the data were analyzed using SAS (version 9.2; SAS Institute, Inc., Cary, NC, USA) and IBM SPSS (version 26, SPSS Inc., Chicago, IL, USA). Survival and local control rates were analyzed using the Kaplan-Meier method with the log-rank test. A P < 0.05 was considered significant statistically.


  Results Top


Patients

We identified 127 patients who received SRS within 20 years. There were 76 (59.8%) female and 51 (40.2%) male patients, at median age 60 years (range: 11–88 years). Lesion diagnoses for SRS were VS (n = 54, 42.5%), nonvestibular cranial nerve schwannoma (NVCNS) (n = 6, 4.7%), benign meningioma (n = 50, 39.4%), and pituitary adenoma (n = 17, 13.4%). The median duration between the date of diagnosis and SRS was 2 months (range: 0–149 months); 99 patients (78.0%) were treated within 1 year after a confirmed brain tumor. Indications for SRS were symptomatic tumor in 80 (63.0%), progressive asymptomatic tumor growth in eight (6.3%), and adjuvant after surgical resection in 24 (18.8%) patients. Sixteen patients (11.7%) received salvage SRS because the follow-up MRI showed tumor enlargement after previous treatment (surgery, n = 15; surgery and FRT, n = 1). Seventy-eight patients (61.4%) had a tumor with cranial nerve involvement, and seven of them had two cranial nerves involvement. All VS patients were considered as vestibulocochlear nerve involvement. Dizziness (31.5%) was the most common presentation, followed by headache and tinnitus.

Seven patients had cancer before SRS (three breast cancers, three colorectal cancers, and one hypopharyngeal cancer), as shown in [Table 1]. Half of them had at least one comorbidity (n = 64), one third had more than two comorbidities. Two patients were neurofibromatosis type II, presented with bilateral VS.
Table 1: Patient characteristics, n=127

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Tumor characteristics and radiation parameters

Total 136 lesions were treated. The number of patients who received SRS for one, two, and three lesions in a single session was 119 (93.7%), 7 (5.5%), and 1 (0.8%). Brain tumors were predominantly located at the skull base (69.1%), followed by supratentorial (19.9%) and infratentorial lesions (10.3%). The median tumor volume was 2.6 cm3 (range 0.1–36.6 cm3).

The median marginal doses for VS, NVCNS, meningioma, functional and nonfunctional pituitary adenoma were 12 Gy, 13 Gy, 14 Gy, 13 Gy, and 12 Gy, respectively. We prescribed marginal doses at 60% to 90% isodose lines cover ≥95% of the PTV. LINAC systemic delivered radiation dose utilizing four to ten noncoplanar arcs (median, five arcs). Duration of treatment was available for 78 patients; median treatment time and beam on time were 25 min 52 s and 4 min 12 s, respectively [Table 2].
Table 2: Tumor characteristics of the 136 lesions treated with stereotactic radiosurgery and radiotherapy parameters (n=127)

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Tumor control rate

The median and mean duration of follow-up were 49 and 61 months (range 1–214 months). Fifty patients (39.3%) had a duration of follow-up for more than five years; 14 patients were more than 10 years (11%). The crude rate of tumor control after SRS was 93.4%. Eight patients required salvage therapy after SRS, five received surgical resection, and three had salvage radiotherapy (one conventional radiotherapy, one hypo FRT, and one re-SRS). The indications for salvage therapy were associated with deteriorated symptoms in all patients; five of them had radiological tumor enlargement, another three had a residual tumor. Overall, the 1-year, 2-year, 5-year, and 10-year TCR were 98.3%, 97.5%, 95.3%, and 82.8%, respectively [Figure 1]a. The 5-year disease-specific TCR s for VS, NVCNS, meningioma, and pituitary adenoma were 97.4%, 83.3%, 91.7%, and 93.8%, respectively [Figure 1]b.
Figure 1: Tumor control rate. Kaplan-Meier plot shows the 5-year tumor control rate of 92.9% for all included patients (a). By histological grouping, 5-year Tumor control rates for vestibular schwannoma, meningioma, pituitary adenoma, and nonvestibular schwannoma were 97.4%, 91.7%, 93.8%, and 83.3%, respectively (b)

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Clinical outcome

Before SRS, 115 patients had tumor-related symptoms; the other 12 patients were asymptomatic. All asymptomatic patients remained symptom-free after treatment. Among symptomatic patients, symptom improvement, stable, and worse were 76 (66.1%), 27 (23.5%), and 4 (3.5%), respectively [Table 3].
Table 3: Clinical improvement after stereotactic radiosurgery

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Radiological response rate

We evaluated the radiological response for 111 patients with a median radiological follow-up interval of 38 months. The overall radiological control rate was 94.6%. Thirty-two patients (28.8%) achieved tumor control with a size reduction of at least 2 mm in diameter, and 73 patients (65.8%) had stable disease. Tumor enlargement was found in six patients (four meningiomas, one VS, and one NVCNS). Salvage intervention was performed for five patients because the enlarged tumor demonstrated neurological symptoms. Only one meningioma patient had an enlarged tumor on MRI took 1 year after SRS followed by stability; no salvage intervention was introduced because he was asymptomatic. On the analysis of the patterns of tumor volume change, eight patients with VS had increased in tumor size, followed by continuous shrinkage, during a period of 13 months (range, 6–31 months). There was no need to offer salvage treatment for them [Table 4].
Table 4: Radiological response rate and patterns of tumor response of the 111 patients with evaluable contrast-enhanced magnetic resonance imaging

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Overall survival

The OS rate was 96.1%, with five deaths (mean age of 72 years). Of these, three patients died due to underlying disease and old age. Two patients had advanced malignant diseases. One patient was colon cancer diagnosed 6 years before SRS and progressed to terminal stage 4 years after SRS. Another patient had multiple myeloma diagnosed 2 years after SRS [Figure 2].
Fig]ure 2: Overall survival. Kaplan-Meier curve of overall survival shows 96.1%

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Evaluation of adverse events

All patients were well tolerated to SRS. No CTCAE grade 2 or higher acute toxicity was reported. No early cranial nerve injury occurred 6 months after SRS. Four patients developed transient adverse events, and two meningioma patients had Grade 1 headaches. A trigeminal schwannoma patient and a VS patient had transient dizziness. Gait disturbance related to hydrocephalus was diagnosed 5 months later for one VS patient who improved after VP shunt placement.

No severe late adverse events greater than Grade 2 occurred during long-term follow-up. A VS patient (0.8%) had a new-onset trigeminal injury and hydrocephalus treated with VP shunt. The other two patients with meningioma developed post-SRS hydrocephalus and were then managed by VP shunt. One left VS patient developed persistent dizziness 7 years after SRS, also associated with chronic otitis media. After local surgery, the patient continued medications for symptomatic control. There was no evidence of radionecrosis on MRIs [Table 5].
Table 5: Overview of early and late onset of adverse events after stereotactic radiosurgery according to the common terminology criteria for adverse events 5.0 criteria

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  Discussion Top


In the present study, the indications for SRS were schwannoma, meningioma, and pituitary adenoma. Predominantly, these tumors are located at the skull base. Meningioma, pituitary adenoma, and schwannoma were the three most common benign brain tumors, composing 36.4%, 15.5%, and 8.1%–11.5% of all primary intracranial tumors [27],[28]. Managements for these benign tumors include observation, microsurgery, and radiation therapy. The TCR s after microsurgery correlate with the extension of tumor removal. In managing meningioma, if total or near-total, i.e., Simpson grade I/II, resection is achieved, TCR is up to 97% [29],[30],[31]. However, the TCR decreases to 29% [32],[33]. If safety and functional preservation are the primary concern, it is technically challenging to perform complete tumor resection. Surgical morbidity is high for tumors located in high-risk regions of the skull base [34],[35],[36],[37],[38],[39],[40],[41],[42],[43]. In this regard, SRS plays a crucial role in managing tumors located at the skull base or adjacent to critical neurovascular structures. Therefore, most neurosurgeons may prefer to manage high-risk and deep-location tumors less aggressively unless these tumors cause mass effect, mechanical compression, and bleeding. Remarkably, observation is reasonable for elderly and vulnerable patients, especially when tumor-related symptoms are mild [44],[45],[46]. Managing brain tumors is challenging; interdisciplinary decision-making between neurosurgeons and radiation oncologists is critical.

SRS is widely used to treat benign brain tumors because it is less invasive and offers high long-term effectiveness. In our study with a mean follow-up period of 5 years, TCR s are high and comparable with previous studies, being 90%–99% [47],[48],[49],[50]. Although responses to SRS for different histology types demonstrate some variation, the differences are not largely significant. Five-year and 10-year local TCR s for VS treated with SRS were 90%–100% and 92%–98% [51],[52],[53],[54],[55],[56],[57]. In meningioma, 5-year and 10-year TCR s were 86%–99%, and 69%–97%, respectively [43],[58],[59],[60],[61],[62],[63]. The main purpose of delivering SRS for pituitary adenoma is to prevent tumor progression, but it shows a relatively slow response for hypersecretion of functional adenoma. The tumor growth-control rate for pituitary adenoma was around 90%–93% at 5–10 years [64],[65],[66],[67],[68],[69]. A comprehensive review of the long-term outcome of a large population treated with SRS was summarized [Table 6]. Our analysis revealed that clinical tumor control was within this range after 5 and 10 years.
Table 6: Summary of selected studies for benign tumors treated with stereotactic radiosurgery

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The VS subgroup achieved the highest and durable TCR in the present study. The median marginal dose we prescribed was 12 Gy. According to current practice guidelines, including ASTRO Quantec, AANS and CNS association, and ESTRO Guidelines, a marginal dose of less than 13 Gy is recommended [44],[46],[70]. Compared with higher doses, 12–13 Gy showed no clinical and radiological control difference. It was proven beneficial for hearing preservation, increased from 20%–26% to 32%–68% and minimized trigeminal and facial nerve complications from >90% to 14%–60% [52],[53],[54],[56],[57],[71],[72]. Notably, 31% of our patients who received lower marginal doses with 8–11 Gy obtained favorable TCR during the long-term follow-up period. Our patients had no cranial nerve injury or deterioration of hearing.

With an advanced skull base endoscopic approach, surgical resection is the mainstay of treatment. In the surgical series, 67%–90% of patients achieved total tumor removal, but the newly developed morbidity rates were 5%–62%, and mortality rates were 0%–3% [73]. The morbidity of resection is still relatively high, depending on the size and location of the tumor. Patients with NVCNS demonstrate a higher rate of salvage therapy after SRS. SRS technique possesses safety advantages and reduces the rates of symptoms deterioration to 0-16% [74],[75],[76],[77],[78]. Unlike VS, NVCNS had a lower 5-year tumor growth control rate when treated with SRS alone, being around 80% [73],[79],[80],[81]. Among our six NVCNS patients, one patient showed tumor growth with deterioration of neurological symptoms and required microsurgery at 8 months after SRS. The other two patients required salvage surgery at 86 months and conventional radiotherapy at 110 months after SRS due to neurological symptoms. The latter patient had tumor enlargement. All patients were stable after salvage management. The patient number in our study is too small to conclude the effectiveness of SRS. Long-term follow-up is crucial to monitor late recurrence. Salvage therapy, either surgical or radiation therapy, can provide the opportunity to improve or at least preserve neurological function.

In the present study, tumor control failure was defined as the requirement for salvage radiotherapy, surgery, or a combination of these procedures. This endpoint is also presented in many large population studies for meningiomas and VS [74],[82],[83],[84]. Surgery for VP shunt was considered a complication but not treatment failure. Besides, radiological tumor response is defined by the variation of maximal tumor diameter, and volumetric quantification is considered a sensitive indicator for tumor progression [85],[86],[87],[88]. On evaluating maximal tumor diameter, we selected the stricter threshold of the change of diameter, 2 mm, which was used in large population studies [51],[89],[90]. In meningioma and VS, a temporary enlargement of tumor size may occur within 6–18 months after SRS, followed by long-term stability or regression. This enlargement pattern followed by volumetric regression was found in nine patients (eight VS and one meningioma). As a result, it was essential to have regular neuroimaging in the first 3 years after treatment. Close observation was advised if the tumor enlargement do not associate with aggravated neurological symptoms and signs in this period [91],[92],[93]. Such a pattern of pseudoprogression did not occur in our cases of pituitary adenoma or NVCNS.

This study reported our 20-year experience of performing LINAC-based SRS, which showed similar results as previous studies for meningioma [43],[90],[94],[95],[96],[97], schwannoma [56],[89], and pituitary adenoma [64],[65]. The 5-year TCR s were comparable with GK series, and the neurological toxicities were not increased. The measured radiological accuracy for GK is down to 0.15–0.3 mm [98],[99] compared with about 0.5–1.00 mm for LINAC system [100],[101],[102]. However, advancement of the treatment planning system, incorporated with MRI guidance (MR-LINAC), and smart frameless stereotactic navigation devices are under development to minimize the differences between these two systems.

There are three advantages of LINAC-based SRS. First, LINAC-based SRS can perform FRT. Fractionation radiotherapy delivered a lower dose per fraction to allow a higher accumulative dose to the target. This benefit can improve tumor control while sparing radiosensitive normal tissue to high radiation doses. The center nervous system is susceptible to radiation, especially the optic nerve, chiasm, and brainstem. High concern to limit radiation dose exposure to these critical structures is the mainstay to avoid irreversible neurological complications. Therefore, tumors in proximity to the optic chiasm, such as pituitary adenoma, AVM, and meningioma at cavernous sinus, are preferred to be treated with fractionated stereotactic radiotherapy. Second, the immobilization and localization of LINAC-based SRS can apply head-frame fixation for single-use (similar to GK) or noninvasive methods, such as thermoplastic, upper-jaw fixation mold, or vacuum-formed masks, incorporated with precise treatment couch and highly stable treatment isocenters identified by CBCT for targeting and optical tracking system. Third, the LINAC system is relatively easy to use, low-cost, and wide-range indicated. SRS-capable LINAC offers radiotherapy for intra- and extracranial lesions, while indications of GK are limited to small intracranial or upper cervical spine lesions. It is also difficult for GK to treat peripherally or laterally located lesions due to collision of the head or the head frame with the helmet. These lesions are generally can be approached by LINAC. Furthermore, the Cobalt-based GK system required additional maintenance and replacing the decaying cobalt sources. Therefore, LINAC-based SRS is more flexible and financially feasible for a smaller community hospital.[103],[104]. Patients in our regional hospital find it more accessible to receive LINAC-based SRS than referral for GK SRS in another farther center.

Benign brain tumors seldom lead to mortality. No patients in our cohort had SRS-related mortality. The causes of death were mainly due to comorbidities and aging. The two patients died of terminal cancer; they were diagnosed with colon cancer and multiple myeloma, not at the treatment fields. The risk of radiation-induced tumors is rare. A retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign brain tumors found that no patients had radiation-induced tumors at 5 and 10 years [105].

Most of the patients who suffered from treatment-related toxicities had skull base tumors, including VS and NVCNS. Most acute adverse reactions were mild and transient. The incidence of late toxicity was low, and all could be managed medically. Four patients with skull base tumors required VP shunt placement after SRS due to new or worsening hydrocephalus. Previous results showed that the incidence of VP procedure after SRS was around 1%–5% [56],[72],[97]. All patients improved after the procedure without long-term sequelae. Older studies showed high cranial nerve complications after SRS because the higher marginal dose was prescribed. After dose reduction, recent studies suggested that the cranial nerve injuries to trigeminal or facial after SRS for VS of skull base tumors was reported as low as 5% at 10 years [57]. Our cranial nerve complication was <1% because our marginal dose prescriptions followed the dose reduction strategy. More notably, critical organ delineations were guided by using MRI, and dose constraints strictly adhered to our brain irradiation principle.

Limitations

The present study has some limitations. First, the study's retrospective nature is the reason for incomplete data, particularly regarding late toxic effects. Second, tumor-contouring images were based on one treating radiation oncologist; thus, there would be some variations on tumor volume. However, gadolinium-enhanced MRIs were obtained for all patients to define the target lesions accurately. Two experienced radiation oncologists reviewed all contours well to avoid the variation or target miss. Third, about 5% of patients lost follow-up at our institute because they returned to their original hospital to continue treatment. Our nurses record their status by using the telephone for these patients, which accounted for about 1% of cases. Finally, the cohort has mixed histologic tumor subtypes; however, it represents a real-world scenario and, therefore, probably represents the best data available to answer the clinical questions.


  Conclusion Top


LINAC-based SRS is an effective treatment modality for benign brain tumors, including VS, meningioma, and pituitary schwannoma. In patients with NVCNS, more prolonged surveillance is indicated because late progression may occur, which can be salvaged with aggressive intervention. High clinical and radiological control rates can be achieved with this minimally invasive and safe procedure. The most concern toxicity is neurological deficit caused by high radiation dose; the complication rate is <1%. Disease-specific analysis showed that VS achieved the highest benefit, although the prescription dose was lower (<12 Gy).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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