Single-fraction radiosurgery outcomes for large vestibular schwannomas in the upfront or post-surgical setting: a systematic review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines.

PURPOSE: To perform a systematic review of literature specific to single-fraction stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS), maximum diameter ≥ 2.5 cm and/or classified as Koos Grade IV, and to present consensus recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. We considered eligible prospective and retrospective studies, written in the English language, reporting treatment outcomes for large VS; SRS for large post-operative tumors were analyzed in aggregate and separately. RESULTS: 19 of the 229 studies initially identified met the final inclusion criteria. Overall crude rate of tumor control was 89% (93.7% with no prior surgery vs 87.7% with prior surgery). Rates of salvage microsurgical resection, need for shunt, and additional SRS in all series versus those with no prior surgery were 9.6% vs 3.3%, 4.7% vs 6.4% and 1% vs 0.9%, respectively. Rates of facial palsy and hearing preservation in all series versus those with no prior surgery were 1.3% vs 3.4% and 34.2% vs 40.4%, respectively. CONCLUSIONS: Upfront SRS resulted in high rates of tumor control with acceptable rates of facial palsy and hearing preservation as compared to the results in those series including patients with prior surgery (level C evidence). Therefore, although large VS are considered classic indication for microsurgical resection, upfront SRS can be considered in selected patients and we recommend a prescribed marginal dose from 11 to 13 Gy (level C evidence).

Multisession radiosurgery for grade 2 (WHO), high risk meningiomas. A phase II clinical trial.

PURPOSE: Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis. Adjuvant radiotherapy seems to be the best approach to reduce disease progression. The primary aim of this phase II explorative, monocentric, single arm study was to evaluate the safety of adjuvant multisession radiosurgery (mRS) in this group of patients; the efficacy in terms of tumour local control was the secondary endpoint. METHODS: Patients recruited from April 2017 to May 2019 were over 18 years old, had a histologically-documented intracranial recurrent or residual Grade 2 meningioma (WHO 2016) and a KPS > 70. Patients with NF2, concomitant neoplasm or pregnancy were excluded. Descriptive statistics were provided for categorical variables. Progression free survival (PFS) was modelled using the Kaplan-Meier method. RESULTS: Twenty-four patients were enrolled. All 24 patients underwent mRS: twenty-two patients received 28 Gy in 4 fractions, 2 patients received 24 Gy in 4 Treatment related adverse events (CTCAE 4.3) were limited to grade 2 in 1 patient (4.1%). At a median follow-up of 28 months, 8 patients (33.3%) had disease progression, either out-of-field or infield, compared with the planning target volume. Considering both infield and out-of-field progressions, 3-year PFS was 47% (95% confidence interval, CI, 22-69%); considering only the infield ones, 3-year PFS was 86% (95% CI 55-96%), and local control at last follow-up was 92%. CONCLUSION: mRS provides good local control of the tumour volume (TV) and is associated with a low rate of toxicity. These results call for further investigation to confirm favourable outcomes in patients with high-risk meningioma. TRIAL INFORMATION: NCT05081908, October 18, 2021, retrospectively registered.

MR-Spectroscopy and Survival in Mice with High Grade Glioma Undergoing Unrestricted Ketogenic Diet.

Glioblastoma multiforme (GBM) is considered the most malignant form of primary brain tumor. Despite multimodal treatment, prognosis remains poor. Ketogenic diet (KD) has been suggested for the treatment of GBM. In this study, the syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on the metabolic responses of the tumor using 7T magnetic resonance imaging/spectroscopy. GL261 cells were injected into the caudate nucleus of mice. Following implantation, animals were fed with standard chow or underwent a KD. 18 days after initiating the diet, mice fed with KD displayed significantly higher plasmatic levels of ketone bodies and survived longer than those fed with the standard diet. Decreased concentrations of gamma-aminobutyric acid, N-Acetyl-Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days into the KD, while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The accumulation of bHB in the tumor tissue in mice undergoing the KD, may suggest either elevated uptake/release of bHB by tumor cells, or the inability of tumor cells in this context to use it for mitochondrial metabolism.

Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma.

BACKGROUND: Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown. METHODS: We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma. Patients were randomly assigned to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide. RESULTS: A total of 562 patients underwent randomization, 281 to each group. The median age was 73 years (range, 65 to 90). The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone (9.3 months vs. 7.6 months; hazard ratio for death, 0.67; 95% confidence interval [CI], 0.56 to 0.80; P<0.001), as was the median progression-free survival (5.3 months vs. 3.9 months; hazard ratio for disease progression or death, 0.50; 95% CI, 0.41 to 0.60; P<0.001). Among 165 patients with methylated O6-methylguanine-DNA methyltransferase (MGMT) status, the median overall survival was 13.5 months with radiotherapy plus temozolomide and 7.7 months with radiotherapy alone (hazard ratio for death, 0.53; 95% CI, 0.38 to 0.73; P<0.001). Among 189 patients with unmethylated MGMT status, the median overall survival was 10.0 months with radiotherapy plus temozolomide and 7.9 months with radiotherapy alone (hazard ratio for death, 0.75; 95% CI, 0.56 to 1.01; P=0.055; P=0.08 for interaction). Quality of life was similar in the two trial groups. CONCLUSIONS: In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00482677 .).

Multisession radiosurgery for perioptic meningiomas: medium-to-long term results from a CyberKnife cooperative study.

PURPOSE: Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery (mRS) can be the solution. The best treatment schedule for mRS, however, is not well established. The aim of the present retrospective study is to validate the effectiveness of one approach, 25 Gy delivered in 5 fractions in 5 consecutive days, to treat skull base meningiomas. METHODS: This is a retrospective multicenter study. Patients with an anterior or a medium skull base meningioma that could not be treated by sRS due to large volume or proximity to the anterior optic pathways (AOPs) underwent 5-fraction mRS. Only patients with at least 36 months follow-up were included in the analysis. Local control and visual outcomes were investigated. RESULTS: One-hundred-sixty-seven patients were included in the analysis. One-hundred-one patients underwent RS as a primary indication and 66 were treated after a previous surgery. The median follow-up period was 51 months (range 36-129 months). Progression-free survival at 3, 5 and 8 years were, respectively, 98%, 94% and 90%. Excluding the progressive disease patients, the visual worsening rate was 3.7%. The 42% of the patients with a pre-treatment visual deficit experienced improvement in vision. CONCLUSION: 25 Gy delivered in 5 fractions is an effective modality for meningiomas that are near the AOP or are too large to be treated by sRS. The treatment schedule controlled the tumors while sparing visual function.

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

INTRODUCTION: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. METHODS: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months. RESULTS: Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p  ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. CONCLUSION: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

Radiosurgery for trigeminal neuralgia: the state of art.

The trigeminal neuralgia (TN) is a chronic, episodic, and disabling facial pain syndrome. It is a relatively rare disorder. Despite this, because of the intensity of the pain, TN may have a dramatic impact for many patients. Fortunately, most of the patients may obtain a good pain relief simply by taking drugs. Historically, the surgical approaches represent a true treatment paradigm for all the drug-resistant TN. In this context, radiosurgery (RS) is a relatively new treatment modality. The effectiveness and safety of radiosurgery are today widely accepted and the technique can be proposed to many patients which suffer from a drug-resistant TN. This is true especially when the patients are less than ideal candidates for an open surgery, or for elderly ones, when a clear neuro-vascular conflict is not evident. The present review provides a concise analysis of the actual indications for radiosurgery, as well as the most acknowledged prognostic factors. The pathogenesis of TN and the rationale for the RS efficacy are also investigated and described. Some technical aspects including the target selection and the prescription doses, which have widely changed in time, are depicted. In conclusion, the present review supports the idea that TN is a complex disease and radiosurgery represents an effective and relatively new treatment modality, which enriches the treatment armamentarium for these unfortunate patients. To optimize the RS results, a correct patient selection has to be performed.

The role of radiosurgery in trigeminal neuralgia.

A short review of clinical use of radiosurgery in trigeminal neuralgia is offered.

Treatments of glossopharyngeal neuralgia: towards standard procedures.

The degree of disability due to glossopharyngeal neuralgia (GN) refractory to conservative treatments justifies surgical procedures as second-line treatments. Since the first description of this facial pain disorders, many surgical options have been described either via a percutaneous or an open surgical way. Actually, when a neurovascular conflict on root entry zone (REZ) or cisternal portion of the ninth and tenth cranial nerves is identified, microvascular decompression (MVD) is the first surgical option to consider. Many studies have demonstrated its efficacy and safety for the treatment of GN. Recently, stereotactic radiosurgery has gained space in the treatment of selected cases of GN. We provide an overview of the surgical procedures for the treatment of GN and of our own experience.

Sum signal dosimetry: A new approach for high dose quality assurance with Gafchromic EBT3.

Gafchromic EBT3 film dosimetry in radiosurgery (RS) and hypofractionated radiotherapy (HRT) is complicated by the limited film accuracy at high fractional doses. The aim of this study is to develop and evaluate sum signal (SS) film dosimetry to increase dose resolution at high fractional doses, thus allowing for use of EBT3 for dose distribution verification of RS/HRT treatments. To characterize EBT3 dose-response, a calibration was performed in the dose range 0.44-26.43 Gy. Red (RC) and green (GC) channel net optical densities were linearly added to produce the SS. Dose resolution and overall accuracy of the dosimetric protocol were estimated and compared for SS,RC, and GC. A homemade Matlab software was developed to compare, in terms of gamma analysis, dose distributions delivered by a Cyberknife on EBT3 films to dose distributions calculated by the treatment planning system. The new SS and conventional single channel (SC) methods were compared, using 3%/1 and 4%/1 mm acceptance criteria, for 20 patient plans. Our analysis shows that the SS dose-response curve is characterized by a steeper trend in comparison with SC, with SS providing a higher dose resolution in the whole dose range investigated. Gamma analysis confirms that the percentage of points satisfying the agreement criteria is significantly higher for SS compared to SC: 95.03% vs. 88.41% (P = 0.014) for 3%/1 mm acceptance criteria and 97.24% vs. 93.58% (P = 0.048) for 4%/1 mm acceptance criteria. This study demonstrates that the SS approach is a new and effective method to improve dosimetric accuracy in the framework of the RS-HRT patient-specific quality assurance protocol.

Spontaneous resolution of visual loss due to optic pathway meningioma: A case report and a review of the literature.

BACKGROUND/AIM: Meningiomas of the anterior cranial fossa are often diagnosed after impaired visual function occurrence. Some epidemiologic studies suggest an association between exogenous or endogenous hormones and meningioma risk. The aim of this study is to briefly review the literature and relate a case report. PATIENT AND METHODS: This study presents a case of a 51-year-old woman with a moderate visual loss of 6/10 and markedly constricted visual field in the right eye. A normal visual acuity and peripheral reduction of visual field in the left eye was documented. During medical interview, she reported a prolonged assumption of oral contraceptive. Her visual deterioration had progressed over the previous 3 months and was associated with occasional headache. MRI scanning showed a small optic pathway meningioma. RESULTS: After various examinations, it was decided to 'wait and see' and no therapy was administered. The patient noticed a progressive improvement in the vision in her right eye, with corresponding improvement in the bilateral visual field. CONCLUSION: The case reports on the spontaneous resolution of visual loss due to the volume reduction of the anterior visual pathway compressive intracranial meningioma after interruption of prolonged assumption of oral contraceptive and focuses on the correlation between sexual hormone pathway and intracranial meningioma.

The cavernous sinus meningiomas' dilemma: Surgery or stereotactic radiosurgery?

Despite the advances in techniques and technologies, the management of cavernous sinus (CS) meningiomas still remains a challenge for both neurosurgeons and radiation oncologists. On the other hand, the improvement of the anatomical knowledge and the microsurgical techniques together with diffusion of radiosurgery are currently changing the treatment strategy, opening new perspectives to the patients which are suffering from such lesions. The authors reviewed here the literature data. A multidisciplinary treatment algorithm is also proposed.

Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

Management of sporadic intracanalicular vestibular schwannomas: A critical review and International Stereotactic Radiosurgery Society (ISRS) practice guidelines.

BACKGROUND: The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect. RESULTS: Forty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01). CONCLUSIONS: SRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.

Repeat Single-Session Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Systematic Review, Meta-Analysis, and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND AND OBJECTIVES: Repeat stereotactic radiosurgery (SRS) for residual arteriovenous malformations (AVMs) can be considered as a salvage approach after failure of initial SRS. There are no published guidelines regarding patient selection, timing, or SRS parameters to guide clinical practice. This systematic review aimed to review outcomes and complications from the published literature to inform practice recommendations provided on behalf of the International Stereotactic Radiosurgery Society. METHODS: We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of MEDLINE, Scopus, Web of Science, and Embase was conducted. Fourteen studies with 925 patients met the inclusion criteria. Patients were treated between 1985 and 2022. All studies were retrospective, except for one prospective cohort. RESULTS: The median patient age at repeat SRS ranged from 32 to 60 years. Four studies (630 patients) reported detailed information on Spetzler-Martin grade at the time of repeat SRS; 12.54% of patients had Spetzler-Martin grade I AVMs (79/630 patients), 46.51% had grade II (293/630), 34.92% had grade III (220/630), 5.08% had grade IV (32/630), and 0.95% had grade V (6/630). The median prescription doses varied between 15 and 25 Gy (mean, 13.06-22.8 Gy). The pooled overall obliteration rate at the last follow-up after repeat SRS was 59% (95% CI 51%-67%) with a median follow-up between 21 and 50 months. The pooled hemorrhage incidence at the last follow-up was 5% (95% CI 4%-7%), and the pooled overall radiation-induced change incidence was 12% (95% CI 7%-20%). CONCLUSION: For an incompletely obliterated AVM, repeat radiosurgery after 3 to 5 years of follow-up from the first SRS provides a reasonable benefit to the risk profile. After repeat SRS, obliteration is achieved in the majority of patients. The risk of hemorrhage or radiation-induced change appears low, and International Stereotactic Radiosurgery Society recommendations are presented.

Stereotactic Radiosurgery for Intermediate (III) or High (IV-V) Spetzler-Martin Grade Arteriovenous Malformations: International Stereotactic Radiosurgery Society Practice Guideline.

BACKGROUND AND OBJECTIVES: Consensus guidelines do not exist to guide the role of stereotactic radiosurgery (SRS) in the management of patients with Spetzler-Martin Grade III-V arteriovenous malformations (AVMs). We sought to establish SRS practice guidelines for Grade III-V AVMs based on a critical systematic review of the published literature. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant search of Medline, Embase, and Scopus, 1986 to 2023, for publications reporting post-SRS outcomes in ≥10 Grade III-V AVMs with the median follow-up ≥24 months was performed. Primary end points were AVM obliteration and post-SRS hemorrhage. Secondary end points included dosimetric variables, Spetzler-Martin parameters, and neurological outcome. RESULTS: : In total, 2463 abstracts were screened, 196 manuscripts were reviewed, and 9 met the strict inclusion criteria. The overall sample of 1634 AVMs consisted of 1431 Grade III (88%), 186 Grade IV (11%), and 11 Grade V lesions (1%). Total median post-SRS follow-up was 53 months for Grade III and 43 months for Grade IV-V AVMs (ranges, 2-290; 12-262). For Grade III AVMs, the crude obliteration rate was 72%, and among Grade IV-V lesions, the crude obliteration rate was 46%. Post-SRS hemorrhage was observed in 7% of Grade III compared with 17% of Grade IV-V lesions. Major permanent deficits or death from hemorrhage or radiation-induced complications occurred in 86 Grade III (6%) and 22 Grade IV-V AVMs (12%). CONCLUSION: Most patients with Spetzler-Martin Grade III AVMs have favorable SRS treatment outcomes; however, the obliteration rate for Grade IV-V AVMs is less than 50%. The available studies are heterogenous and lack nuanced, long-term, grade-specific outcomes.

Circulating T regulatory cells migration and phenotype in glioblastoma patients: an in vitro study.

Glioblastoma multiforme (GBM) is the most aggressive primary human brain tumor. The relatively high amount of T regulatory lymphocytes present in the tumor, contributes to the establishment of an immunosuppressive microenvironment. Samples of peripheral blood were collected from GBM patients and healthy controls and a purified population of Treg (CD4(+)/CD25(bright)) was isolated using flow cytometric cell sorting. Treg migrating capacities toward human glioma cell line conditioned medium were evaluated through an in vitro migration test. Our data show that supernatants collected from GBM cell lines were more attractant to Treg when compared to complete standard medium. The addition of an anti-CCL2 antibody to conditioned medium decreased conditioned medium-depending Treg migration, suggesting that CCL2 (also known as Monocyte Chemoattractant Protein, MCP-1) is implicated in the process. The number of circulating CD4(+)/µL or Treg/µL was similar in GBM patients and controls. Specific Treg markers (FOXP3; CD127; Helios; GITR; CTLA4; CD95; CCR2, CCR4; CCR7) were screened in peripheral blood and no differences could be detected between the two populations. These data confirm that the tumor microenvironment is attractive to Treg, which tend to migrate toward the tumor region changing the immunological response. Though we provide evidence that CCL2 is implicated in Treg migration, other factors are needed as well to provide such effect.

Intradural extramedullary benign spinal lesions radiosurgery. Medium- to long-term results from a single institution experience.

BACKGROUND: Surgery represents the first-choice treatment for spinal intradural tumours. On the other hand, whether it is most appropriate in the setting of recurrences, residual or multiple lesions remains an open question. Moreover, some patients are less than ideal candidates for surgery. In this study we report about our own radiosurgery experience in the treatment of benign intradural extramedullary tumours of the spine. METHODS: In our study we analyzed the outcomes for 18 patients (21 lesions) treated for benign intradural extramedullary lesions, with a minimum follow-up period of 32 months. The lesions included 11 meningiomas, 9 schwannomas and 1 neurofibroma. RESULTS: The mean follow-up was 43 months (32-73 months). The median tumour volume was 2 cc (0.2-17.7 cc). Eleven lesions underwent single-fraction treatment (mean prescribed dose ranging from 10 to 13 Gy). The others received a multisession radiosurgery treatment (4-6 fractions) with a mean prescription dose ranging from 18.5 to 25 Gy. The maximum dose to the spinal cord ranged from 9.2 to 26 Gy. During the follow-up period, none of the lesions showed radiological evidence of progression. Neurological status was preserved or improved and no permanent sequelae were observed. Significant and durable pain relief was observed. CONCLUSIONS: Although surgical excision remains the primary treatment option for most intradural tumours, radiosurgery offers a real alternative therapeutic modality, especially in case of recurrent and residual lesions or when surgery is contraindicated.

Hypofractionated Radiosurgery for Large or in Critical-Site Intracranial Meningioma: Results of a Phase 2 Prospective Study.

PURPOSE: Radiosurgery is a well-known, safe, and effective technique used in the treatment of intracranial meningiomas. However, single-fraction radiosurgery can lead to high toxicity rates when large-volume or critically located lesions are targeted. Multisession-also called hypofractionated-radiosurgery (hypo-RS) might overcome these limitations. Accordingly, we carried out a prospective phase 2 trial, aiming to establish whether a fractionated RS schedule of 25 Gy in 5 fractions would be safe and effective in treating large (≥ 3 cm) and/or critically located (<3 mm from critical structures) grade 1 intracranial meningiomas. The main aim was to evaluate the safety of hypo-RS in terms of absence of adverse events. The secondary aim was to evaluate tumor response in terms of local control, defined as stability or reduction of lesion volume. METHODS AND MATERIALS: We prospectively enrolled patients with diagnoses of grade 1 meningiomas, large size and/or critically located lesions, either histologically diagnosed or imaging defined. Additional inclusion criteria were signed informed consent, an age of ≥18 years, and Karnofsky Performance Status ≥70. RESULTS: Between 2011 and 2016, 178 patients were consecutively enrolled. The median follow-up was 53 months (range, 4-101 months). Overall, the toxicity rate was 12.7% (21 of 166 patients). At a 5-year minimum follow-up, the patients' toxicity rates were 11.7 % (9 of 77 patients). Symptom evaluation at both 3-year and last follow-up showed an improvement in most of the patients. Five-year local tumor control was 97% (95% confidence interval, 92%-99%). CONCLUSIONS: Hypo-RS schedule of 25 Gy in 5 fractions is a well-tolerated option in the treatment of large-volume and/or critically located benign meningiomas. Early results suggest favorable local control, although longer-term follow-up is needed.