Impact of biologically effective dose on tremor decrease after stereotactic radiosurgical thalamotomy for essential tremor: a retrospective longitudinal analysis.

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BEDGy2.47) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36-88). Mean follow-up period was 14 months (median 12, 3-36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy2.47 (median 4612, 4022.1-4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8-98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED (p = 0.04; beta coefficient - 0.029) and beam-on time (p = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED (p = 0.02; beta coefficient 0.038) and beam-on time (p = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy2.47 (median 4650, range 4466-4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy2.47. Tremor improvement was correlated with BED Gy2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300-4500 Gy2.47. ARE appeared for a BED of more than 4500 Gy2.47. Such finding should be validated in larger cohorts.

Stereotactic radio-neurosurgery for jugular foramen schwannomas.

BACKGROUND: Stereotactic radiosurgery (SRS) represents a minimally invasive and valuable alternative for jugular foramen schwannomas (JFS), both as upfront and/or adjuvant treatment (in hybrid approaches). METHODS: We conducted a retrospective review of our cases treated at the Lausanne University Hospital (CHUV) from June 2010 to October 2023. Eleven patients underwent SRS, among whom three had prior surgery, two in our center in the frame of a planned combined approach and one in another center. Two patients received "volume-staged" SRS. The mean age at SRS was 60 years (median 68; range 29-83). Cranial nerve (CN) symptoms were present in six patients, while five were asymptomatic. The mean tumor volume at SRS was 2.1 cc (median 1.2; range 0.068-7.3 cc), with a 12 Gy marginal dose prescribed in all cases. RESULTS: The mean follow-up period was 3.9 years (median 2, range 1-7). Cranial nerve function improved after SRS in six patients, while five remained stable. At the last follow-up, all tumors showed a decrease in volume, except for one patient, who underwent surgery at 18 months after SRS, for volumetric increase at 6 and 12 months, with further XII-th CN palsy and medulla oblongata compression. Although tumor decreased at 18 months, such patient needed microsurgical resection for symptom persistence and was further controlled. The mean tumor volume at 1 year post-SRS was 1.6 cc (median 0.55; range 0.028-7.77 cc), at 2 years was 1.31 cc (median 0.76; range 0.19-5), and at 3 years was 1.32 cc (median 0.59; range 0.23-4.8). No adverse radiation events were observed. CONCLUSIONS: Stereotactic radiosurgery is considered a safe and effective treatment for jugular foramen schwannomas, ensuring high rates of tumor control in all patients over the long term. The cranial nerve function improved after SRS in the 6 patients who had deficits and the other 5 patients who had no deficits remained asymptomatic. For larger tumors, combined/hybrid approaches can be a valuable alternative, to obtain tumor control and to preserve neurological function.

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).

Successful MRI-Guided Focused Ultrasound Thalamotomy after Ipsilateral Gamma Knife Radiosurgery for Essential Tremor: A Case Report with Video.

We report the case of a 67-year-old left-handed female patient with disabling medically refractory essential tremor who underwent successful right-sided magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus after ipsilateral gamma knife radiosurgery (GKRS) thalamotomy performed 3 years earlier. The GKRS had a partial effect on her postural tremor without side effects, but there was no reduction of her kinetic tremor or improvement in her quality of life (QoL). The patient subsequently underwent a MRgFUS thalamotomy, which induced an immediate and marked reduction in both the postural and kinetic tremor components, with minor complications (left upper lip hypesthesia, dysmetria in her left hand, and slight gait ataxia). The MRgFUS-induced lesion was centered more medially than the GKRS-induced lesion and extended more posteriorly and inferiorly. The MRgFUS-induced lesion interrupted remaining fibers of the dentatorubrothalamic tract (DRTT). The functional improvement 1-year post-MRgFUS was significant due to a marked reduction of the patient's kinetic tremor. The QoL score (Quality of Life in Essential Tremor) improved by 88% and her Clinical Rating Scale for Tremor left hand score by 62%. The side effects persisted but were minor, with no impact on her QoL. The explanation for the superior efficacy of MRgFUS compared to GKRS in our patient could be due to either a poor response to the GKRS or to a better localization of the MRgFUS lesion with a more extensive interruption of DRTT fibers. In conclusion, MRgFUS can be a valuable therapeutic option after unsatisfactory GKRS, especially because MRgFUS has immediate clinical effectiveness, allowing intra-procedural test lesions and possible readjustment of the target if necessary.

Microsurgical resection of gliomas of the cingulate gyrus: a systematic review and meta-analysis.

Cingulate gyrus gliomas are rare among adult, hemispheric diffuse gliomas. Surgical reports are scarce. We performed a systematic review of the literature and meta-analysis, with the aim of focusing on the extent of resection (EOR), WHO grade, and morbidity and mortality, after microsurgical resection of gliomas of the cingulate gyrus. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1996 and December 2022 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies of microsurgical series reporting resection of gliomas of the cingulate gyrus. Primary outcome was EOR, classified as gross total (GTR) versus subtotal (STR) resection. Five studies reporting 295 patients were included. Overall GTR was 79.4% (range 64.1-94.7; I2= 88.13; p heterogeneity and p < 0.001), while STR was done in 20.6% (range 5.3-35.9; I2= 88.13; p heterogeneity < 0.001 and p= 0.008). The most common WHO grade was II, with an overall rate of 42.7% (24-61.5; I2= 90.9; p heterogeneity, p< 0.001). Postoperative SMA syndrome was seen in 18.6% of patients (10.4-26.8; I2= 70.8; p heterogeneity= 0.008, p< 0.001), postoperative motor deficit in 11% (3.9-18; I2= 18; p heterogeneity= 0.003, p= 0.002). This review found that while a GTR was achieved in a high number of patients with a cingulate glioma, nearly half of such patients have a postoperative deficit. This finding calls for a cautious approach in recommending and doing surgery for patients with cingulate gliomas and for consideration of new surgical and management approaches.

Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome-a systematic review and meta-analysis.

Independently, both 5-aminolevulinic acid (5-ALA) and intraoperative neuromonitoring (IONM) have been shown to improve outcomes with high-grade gliomas (HGG). The interplay and overlap of both techniques are scarcely reported in the literature. We performed a systematic review and meta-analysis focusing on the concomitant use of 5-ALA and intraoperative mapping for HGG located within eloquent cortex. Using PRISMA guidelines, we reviewed articles published between May 2006 and December 2022 for patients with HGG in eloquent cortex who underwent microsurgical resection using intraoperative mapping and 5-ALA fluorescence guidance. Extent of resection was the primary outcome. The secondary outcome was new neurological deficit at day 1 after surgery and persistent at day 90 after surgery. Overall rate of complete resection of the enhancing tumor (CRET) was 73.3% (range: 61.9-84.8%, p < .001). Complete 5-ALA resection was performed in 62.4% (range: 28.1-96.7%, p < .001). Surgery was stopped due to mapping findings in 20.5% (range: 15.6-25.4%, p < .001). Neurological decline at day 1 after surgery was 29.2% (range: 9.8-48.5%, p = 0.003). Persistent neurological decline at day 90 after surgery was 4.6% (range: 0.4-8.7%, p = 0.03). Maximal safe resection guided by IONM and 5-ALA for high-grade gliomas in eloquent areas is achievable in a high percentage of cases (73.3% CRET and 62.4% complete 5-ALA resection). Persistent neurological decline at postoperative day 90 is as low as 4.6%. A balance between 5-ALA and IONM should be maintained for a better quality of life while maximizing oncological control.

Single fraction and hypofractionated radiosurgery for perioptic meningiomas-tumor control and visual outcomes: a systematic review and meta-analysis.

Perioptic meningiomas, defined as those that are less than 3 mm from the optic apparatus, are challenging to treat with stereotactic radiosurgery (SRS). Tumor control must be weighed against the risk of radiation-induced optic neuropathy (RION), as both tumor progression and RION can lead to visual decline. We performed a systematic review and meta-analysis of single fraction SRS and hypofractionated radiosurgery (hfRS) for perioptic meningiomas, evaluating tumor control and visual preservation rates. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed articles published between 1968 and December 8, 2022. We retained 5 studies reporting 865 patients, 438 cases treated in single fraction, while 427 with hfRS. For single fraction SRS, the overall rate of tumor control was 95.1%, with actuarial rates at 5 and 10 years of 96% and 89%, respectively; tumor progression was 7.7%. The rate of visual stability was 90.4%, including visual improvement in 29.3%. The rate of visual decline was 9.6%, including blindness in 1.2%. For hfRS, the overall rate of tumor control was 95.6% (range 92.1-99.1, p < 0.001); tumor progression was 4.4% (range 0.9-7.9, p = 0.01). Overall rate of visual stability was 94.9% (range 90.9-98.9, p < 0.001), including visual improvement in 22.7% (range 5.0-40.3, p = 0.01); visual decline was 5.1% (range 1.1-9.1, p = 0.013). SRS is an effective and safe treatment option for perioptic meningiomas. Both hypofractionated regimens and single fraction SRS can be considered.

Proton beam radiation therapy for vestibular schwannomas-tumor control and hearing preservation rates: a systematic review and meta-analysis.

OBJECTIVE: Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and meta-analysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation. METHODS: We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients. RESULTS: Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5-97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8-6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5-97.7%, I2 = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6-97.7%, I2 = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4-51.8%, I2 = 43.36%, p heterogeneity= 0.1, p<0.001). CONCLUSION: Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not offer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.

Stereotactic Therapies for Meningiomas.

Although surgery remains the mainstay of treatment for most meningiomas, radiotherapy, specifically stereotactic radiosurgery, has become more commonplace as first-line therapy for select meningioma cases, particularly small meningiomas in challenging or high-risk anatomic locations. Radiosurgery for specific groups of meningiomas have been found to provide local control rates comparable to surgery alone. In this chapter stereotactic techniques for the treatment of meningiomas such as stereotactic radiosurgery by using Gamma knife or Linear Accelerator-based techniques (modified LINAC, Cyberknife, etc.) as well as stereotactically guided implantation or radioactive seeds for brachytherapy are introduced.

Surgery for clinoidal meningiomas with cavernous sinus extension: Near-total excision and chiasmopexy.

BACKGROUND: The main factors limiting the extent of resection for clinoidal meningiomas are cavernous sinus extension and vessel adventitia involvement. The proximity to the optic apparatus and the risk of radiation-induced optic neuropathy often prevents many surgeons from proposing adjuvant radiosurgery. METHOD: We describe a simple technical solution that is to place a fat graft between the optic apparatus and the residual tumor to maintain the distance gained at surgery and facilitates the identification of anatomic structures. CONCLUSION: This technique allows to deliver optimal therapeutic doses to the residue reduces the dose received by the optic nerve below 8 Gy.

[Management of brain metastases in 2022]. / Prise en charge des métastases cérébrales en 2022.

Brain metastases (BM) are a common occurrence of systemic cancers. Technical improvements in neuroimaging offer additional tools for an early detection of BM, to target them precisely and differentiate these lesions from other cerebral pathologies. The therapeutic tools have also evolved from neurosurgery and whole brain therapy to include stereotactic radiosurgery, targeted and immune therapies. Given the numerous treatment options available, a multidisciplinary approach is essential to offer the patient a personalized approach to optimize the sequence and combination of treatments to offer the best outcome possible. This article aims to review key elements of diagnosis, risk stratification and modern treatment paradigms in the diagnosis and management of BM.

Les métastases cérébrales (MC) sont une manifestation fréquente des cancers systémiques. Les améliorations des techniques de radiologie offrent des options supplémentaires pour détecter de manière précoce les MC, les cibler avec précision et les différencier d'autres pathologies. Les outils thérapeutiques se sont également élargis pour inclure des techniques de radiothérapie stéréotaxiques, des thérapies ciblées et des immunothérapies. Au vu des nombreuses options de traitement pour les patients souffrant de MC, une approche multidisciplinaire doit impérativement être favorisée pour personnaliser le traitement de chaque patient et améliorer le pronostic. Cet article décrit les éléments clés du diagnostic, de la stratification du risque et les paradigmes modernes de la prise en charge et des traitements des patients avec MC.

Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a valuable treatment option for persistent and/or recurrent acromegaly secondary to growth hormone (GH) secreting pituitary adenoma (PA). Here, we assess the role of biological effective dose (BED) received by PA treated with SRS in relation with endocrine remission. METHODS: Forty-two patients (minimum 6 months follow-up) were included. Mean marginal dose was 27.7 (median 28, 20-35), and mean BED received by tumour was 193.1 Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients in high tumour BED group (H-BEDtm, 199.7-237.1 Gy2.47, n = 12) and low BED one (L- BEDtm, 64.1-199.7 Gy2.47 , n = 10). The two groups did not differ by pretherapeutic IGF-1 levels (p = .1) or by the prescribed dose (p = .6). RESULTS: Mean follow-up period was 62.5 months (median 60.5, 9-127). Probability of IGF-1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogues. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during follow-up course. In univariate analysis, only statistically significant parameter was pretherapeutic serum IGF-1 and IGF-1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05). CONCLUSION: Our study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pretherapeutic serum levels of IGF-1 were only statistically significant parameter for endocrine remission.

Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial.

PURPOSE: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection. METHODS: Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death. RESULTS: There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months). CONCLUSIONS: This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

Trigeminal Neuralgia Secondary to Meningiomas and Vestibular Schwannoma Is Improved after Stereotactic Radiosurgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TN) secondary to tumors is encountered in up to 6% of patients with facial pain syndromes and is considered to be associated with tumors affecting the trigeminal nerve pathways. The most frequent are meningiomas and vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has emerged as a valuable treatment, with heterogeneity of clinical results. We sought to review the medical literature on TN treated with SRS for meningiomas and VS and investigate the rates of improvement of TN symptoms. METHODS: We reviewed articles published between January 1990 and December 2019 in PubMed. Pain relief after SRS, the maintenance of pain relief, and TN recurrence and complications were evaluated with separate meta-analyses, taking into account the data on individual patients. RESULTS: Pain relief after SRS was reported as Barrow Neurological Institute (BNI) pain intensity scores of BNI I in 50.5% (range 36-65.1%) of patients and BNI I-IIIb in 83.8% (range 77.8-89.8%). There was no significant difference in series discussing outcomes for tumor targeting versus tumor and nerve targeting. Recurrences were described in 34.7% (range 21.7-47.6; tumor targeting). Maintenance of BNI I was reported in 36.4% (range 20.1-52.7) and BNI I-IIIb in 41.2% (range 29.8-52.7; tumor targeting series). When both the nerve and the tumor were targeted, only 1 series reported 86.7% with BNI I-IIIb at last follow-up. Complications were encountered in 12.6% (range 6.3-18.8; tumor targeting series) of patients; however, they were much higher, as high as 26.7%, in the only study reporting them after targeting both the nerve and the tumor. The most common complication was facial numbness. CONCLUSION: SRS for TNB secondary to benign tumors, such as meningiomas and VS, is associated with favorable clinical course, but less favorable than in idiopathic TN. There was, however, heterogeneity among reports and targeting approaches. Although targeting both the nerve and the tumor seemed to achieve better long-term results, the rate of complications was much higher and the number of patients treated was limited. Future clinical studies should focus on the standard reporting of clinical outcomes and randomization of targeting methods.

The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol.

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot's targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim's circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas.

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1-73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3-9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

Tumor control and trigeminal dysfunction improvement after stereotactic radiosurgery for trigeminal schwannomas: a systematic review and meta-analysis.

Trigeminal nerve schwannomas (TS) are uncommon intracranial tumors, frequently presenting with debilitating trigeminal and/or oculomotor nerve dysfunction. While surgical resection has been described, its morbidity and mortality rates are non-negligible. Stereotactic radiosurgery (SRS) has emerged with variable results as a valuable alternative. Here, we aimed at reviewing the medical literature on TS treated with SRS so as to investigate rates of tumor control and symptomatic improvement. We reviewed manuscripts published between January 1990 and December 2019 on PubMed. Tumor control and symptomatic improvement rates were evaluated with separate meta-analyses. This meta-analysis included 18 studies comprising a total of 564 patients. Among them, only one reported the outcomes of linear accelerators (Linac), while the others of GK. Tumor control rates after SRS were 92.3% (range 90.1-94.5; p < 0.001), and tumor decrease rates were 62.7% (range 54.3-71, p < 0.001). Tumor progression rates were 9.4% (range 6.8-11.9, p < 0.001). Clinical improvement rates of trigeminal neuralgia were 63.5% (52.9-74.1, p < 0.001) and of oculomotor nerves were 48.2% (range 36-60.5, p < 0.001). Clinical worsening rate was 10.7% (range 7.6-13.8, p < 0.001). Stereotactic radiosurgery for TS is associated with high tumor control rates and favorable clinical outcomes, especially for trigeminal neuralgia and oculomotor nerves. However, patients should be correctly advised about the risk of tumor progression and potential clinical worsening. Future clinical studies should focus on standard reporting of clinical outcomes.

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis.

Vestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2-3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44-64). The median marginal dose prescribed at first SRS was 12 Gy (range 8-24) and at second SRS was 12 Gy (range 9.8-19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2-39%, I2 = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7-75.1%, I2 = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5-29.7%, I2 = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4-18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4-7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8-83.8%, I2 = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.

Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis.

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8-7.9). The intraoperative seizure rate was 3.7% (range 1.4-6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7-44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8-52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5-65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2-39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3-6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections.