Single-session Stereotactic Radiosurgery Research Articles

Up-front single-session radiosurgery for large brain metastases-volumetric responses and outcomes.

Patients presenting with large brain metastases (LBM) pose a management challenge to the multidisciplinary neuro-oncologic team. Treatment options include surgery, whole-brain or large-field radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these. To determine if corticosteroid therapy followed by SRS allows for efficient minimally invasive care in patients with LBMs not compromised by mass effect. We analyzed the change in tumor volume to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Twenty-nine patients with systemic cancer and brain metastasis (≥ 2.7cm in greatest diameter) who underwent single-session SRS were included. Among 29 patients, 69% of patients had either lung, melanoma, or breast cancer. The median initial tumor size (maximal diameter) was 32mm (range 28-43), and the median initial tumor volume was 9.56 cm3 (range 1.56-25.31). The median margin dose was 16Gy (range 12-18). The average percent decrease in tumor volume compared to pre-SRS volume was 55% on imaging at 1-2months, 58% at 3-5months, 64% at 6-8months, and 57% at > 8months. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21days. Median survival after radiosurgery was 15months. Initial high-dose corticosteroid therapy followed by prompt single-stage SRS is a safe and efficacious method to manage patients with LBMs (defined as ≥ 2.7cm).

Growth dynamics of brain metastases differentiate radiation necrosis from recurrence.

Radiation necrosis (RN) is a frequent adverse event after fractionated stereotactic radiotherapy (FSRT) or single-session stereotactic radiosurgery (SRS) treatment of brain metastases (BMs). It is difficult to distinguish RN from progressive disease (PD) due to their similarities in the magnetic resonance images. Previous theoretical studies have hypothesized that RN could have faster, although transient, growth dynamics after FSRT/SRS, but no study has proven that hypothesis using patient data. Thus, we hypothesized that lesion size time dynamics obtained from growth laws fitted with data from sequential volumetric measurements on magnetic resonance images may help in discriminating recurrent BMs from RN events. A total of 101 BMs from different institutions, growing after FSRT/SRS (60 PDs and 41 RNs) in 86 patients, displaying growth for at least 3 consecutive MRI follow-ups were selected for the study from a database of 1031 BMs. The 3 parameters of the Von Bertalanffy growth law were determined for each BM and used to discriminate statistically PDs from RNs. Growth exponents in patients with RNs were found to be substantially larger than those of PD, due to the faster, although transient, dynamics of inflammatory processes. Statistically significant differences (P < .001) were found between both groups. The receiver operating characteristic curve (AUC = 0.76) supported the ability of the growth law exponent to classify the events. Growth law exponents obtained from sequential longitudinal magnetic resonance images after FSRT/SRS can be used as a complementary tool in the differential diagnosis between RN and PD.

CTNI-40. PHASE I TRIAL OF SULFASALAZINE COMBINED WITH STEREOTACTIC RADIOSURGERY FOR RECURRENT GLIOBLASTOMA: STUDY PROTOCOL FOR NCT04205357

Abstract Glioblastoma (GBM) is one of the most aggressive, radioresistant types of cancer with a dismal prognosis. Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties in preclinical studies. The antioxidant glutathione (GSH) produced at high levels in glioma cells normally protects against radiation injury by scavenging reactive oxygen species produced during radiation therapy (RT). SAS blocks cysteine uptake through the xCT-channel, a rate-limiting step for GSH production. We have previously shown slowing of tumor growth and prolonged survival when SAS was combined with stereotactic radiosurgery (SRS) in vivo compared to either treatment alone. Our hypothesis is that SAS potentiates the efficacy of SRS for recurrent GBM with a low risk of adverse events (AE). The primary end-point is to establish the recommended dose for efficacy testing in phase II/III trials. This phase 1 dose-escalation trial utilizes a standard 3 + 3 design with 3-6 patients per cohort. Patients will be treated with oral SAS (1.5, 3.0, 4.5 or 6.0 g/day) 3 days prior to single session SRS. The SAS-dose will be escalated depending on the absence/presence of toxicity in the previous cohort of treated patients. If more than 1 of 3-6 patients ( ≥ 33 %) is experiencing grade 3 or higher toxicity levels, the study will be terminated. The dose below will be the recommended dose. Toxicity is graded using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 recorded the first 30 days. Secondary end-points are assessments of 1) intratumoral GSH production (GSH-spectroscopy), 2) late AE utilizing 11C-MET-MRI-PET 3) changes in KPS/quality of life (FACT-Br), 4) need for steroidal treatment, 5) progression free and overall survival. Novel treatment modalities are urgently needed. This trial will establish the recommended dose for SAS repurposed as a radiosensitizer for a future phase 2/3 trial and may ultimately lead to improvement of current GBM treatment.

Stereotactic radiosurgery for intracranial chordomas: an international multiinstitutional study.

The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas. This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology. A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively. SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

P18.09.A Single-session stereotactic radiosurgery for large parasellar meningiomas

Abstract Background The purpose of this study is to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) perioptic intracranial benign meningiomas. Material and Methods In this retrospective study we included 175 patients with large perioptic benign meningiomas (≥ 10 cc) who were treated by single-session SRS. Perioptic meningiomas were defined as meningiomas touching, compressing or within 3 mm of the optic pathway. The median tumor volume was 15 (10-57.3 cc (IQR 8.4 cc)). The median prescription dose was 12 Gy (9-14 Gy (IQR 1 Gy)). Results The median follow up period was 72 months (13-217 months (IQR 65 months)). The tumor control rate was 92%. The PFS at 5- and 10- years was 97% and 80%. Favorable (better/stable) visual outcome was reported in 169 patients (97%) and unfavorable (worse) outcome in 6 patients (3%). Temporary adverse radiation effects were observed in 21 patients (12%) but only 7 (4%) were symptomatic. Sixty-three patients had a blind/non-useful eye according the pre-treatment visual field examination. Visual improvement was observed in blind/non-useful eye in 17 patients (27%) while vision remained unchanged in 46 patients (73%). Ocular nerve palsy improved in 36 patients (61%). Tumor shrinkage was not a prerequisite for cranial nerve improvement. Conclusion Stereotactic radiosurgery provides an effective and safe treatment option for large perioptic meningiomas.

Repeat stereotactic radiosurgery for cerebral arteriovenous malformations.

The purpose of this retrospective, single-institution study was to evaluate radiological and clinical outcomes of patients managed with repeat stereotactic radiosurgery (SRS) for residual cerebral arteriovenous malformation (AVM) after prior SRS. The authors evaluated the clinical and radiological outcomes of consecutive patients treated with repeat single-session SRS for a residual brain AVM from 1989 to 2021. In total, 170 patients underwent repeat SRS for AVM (90 [52.9%] females; median [interquartile range] age at the first SRS procedure 28 [21.5] years; median [interquartile range] age at the second SRS procedure 32 [22.5] years). After repeat SRS, the actuarial 3-, 5-, and 10-year AVM obliteration rates were 37.6%, 57.3%, and 80.9%, respectively. Higher obliteration rates were associated with margin dose ≥ 19 Gy (p = 0.001). After the second SRS procedure, hemorrhage occurred in 8.2% of patients and was lethal in 1 patient. The risk factors of intracranial hemorrhage were age < 18 years (p = 0.03) and residual AVM diameter > 20 mm (p = 0.004). Lower obliteration rates were noted in patients with residual AVM diameter > 20 mm (p = 0.04) and those < 18 years of age (p = 0.04). Asymptomatic, symptomatic, and permanent radiation-induced changes (RICs) after the second SRS procedure occurred in 25.9%, 8.8%, and 5.3% of patients, respectively, and were associated with RIC after the first SRS procedure (p = 0.006). There was 1 case of a radiation-induced meningioma 12 years after SRS. Repeat SRS is a reasonable therapeutic option, in particular for patients with residual AVM. Repeat SRS was associated with more favorable outcomes in adult patients and those with residual AVM smaller than 20 mm in maximum diameter. To increase the rate of residual AVM obliteration, a prescription dose ≥ 19 Gy should ideally be used for repeat SRS.

Effect of distance from target on hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. The aim of this study was to investigate the relationship between the distance from the hypothalamic-pituitary axis to the treatment target and anterior pituitary function preservation after SRS. Between 2007 and 2020, consecutive adult patients who underwent single-session SRS for non-functioning or hormone-secreting pituitary adenomas with ≥ 6months of follow-up were included. Distance measurements between hypothalamic-pituitary axis structures and the SRS target volume were quantified on MRI. The primary outcome was anterior pituitary function preservation. Outcomes were compared using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. The study cohort comprised 224 patients, who were categorized by preservation (n = 168) and no preservation (n = 56) of anterior pituitary function after SRS. The mean and median clinical follow-up durations were 53.7 (38.0) and 46.0 (17.0-75.0) months, respectively. Independent predictors of anterior pituitary function preservation were a greater distance between the center of the pituitary gland and center of the SRS target [OR 1.101 (1.000-1.213), p = 0.050], and a shorter clinical follow-up duration [OR 0.985 (0.977-0.993), p < 0.0001]. The adjusted AUROC for the distance from the center of the pituitary gland and center of the SRS target in predicting anterior pituitary function preservation was 0.595. The sensitivity, specificity, positive predictive value and negative predictive value in predicting anterior pituitary function preservation at the optimal cut-off distance of 15mm were 30.0, 88.0, 89.9 and 26.2%, respectively. Greater distance between the normal pituitary gland and the SRS target is associated with anterior pituitary function preservation and increasing this distance should be a goal of adenoma resection. Larger prospective, multi-center studies are necessary to corroborate this finding and establish the effects of distance on hypopituitarism after SRS for pituitary adenomas.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature

Simple SummaryMeningiomas represent the most common central nervous system (CNS) tumor. Despite their often benign nature, a tumor location in direct proximity to vital brain structures may lead to significant morbidity. This is the case for foramen magnum meningiomas (FMMs) as they grow at the skull base, next to the brain stem and foramen magnum. Surgical resection represents the mainstay of FMM treatments. In patients unsuitable for surgery, with tumor recurrences or tumor remnants after surgery, non-invasive treatment modalities may play a crucial role in patient management. Reports and studies on stereotactic radiosurgery (SRS) for the treatment of FMMs are scarce. This multicenter analysis reported the outcome data of 62 patients with FMMs. SRS achieved a high local tumor control and demonstrated a favorable safety profile. These results are in agreement with previous findings. SRS should be considered for selected FMM patients.Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Clinical Outcomes of Non-Small Cell Lung Cancer Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors, EGFR Tyrosine Kinase Inhibitors, Chemotherapy and Immune Checkpoint Inhibitors, or Chemotherapy Alone

Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have shown responses in the management of non-small cell lung cancer (NSCLC) brain metastases (BM). However, optimizing control with stereotactic radiosurgery (SRS) and various systemic therapies in the management of NSCLC BM remains an area of investigation. We evaluated clinical outcomes in NSCLC BM treated with SRS and ICI, EGFR-TKI, ICI and chemotherapy, compared to conventional chemotherapy.A total of 174 NSCLC BM patients, treated between 2015 and 2019, to a total of 660 intact (non-operative) BM over 239 single-fraction SRS sessions within 3 months of receiving ICI (n = 58; 33%), EGFR-TKI (n = 30; 17%), chemotherapy and ICI (n = 22; 13%) or standard chemotherapy (n = 64; 37%) were identified. Time-to-event analysis was conducted with the Kaplan-Meier method, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival (OS) from SRS. Cox proportional hazards model was utilized for multivariate analysis (MVA) to identify correlations of clinical variables with outcomes.Median follow-up from BM diagnosis was 8.9 months (0.26-126.5 months) and 7.3 months from SRS (2.5-17.6 months). No significant differences in age (P = 0.55), gender (P = 0.49), treated gross tumor volume (P = 0.31), presence of systemic metastasis (P = 0.1), SRS dose (P = 0.61), or KPS (0.35) were noted between treatment groups. The 12-month DIC was 35%, 53%, 41%, and 20% (P = 0.02) for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively. No differences were noted in LC (P = 0.1) and OS (P = 0.5) between treatment groups. Upon MVA, factors found to be significant for improved DIC included treatment with EGFR-TKI therapy compared to conventional chemotherapy (HR 0.4; 95% CI 0.25-0.76; P = 0.04) and treatment with SRS before systemic therapy (HR 0.6; 95% CI 0.3-0.9; P = 0.03). Factors found to be significant for improved LC on MVA included treatment with SRS before (HR 0.4; 95% CI 0.2-0.9; P = 0.03) or concurrent (HR 0.3; 95% CI 0.1-0.6; P = 0.003) compared to following receipt of systemic therapy. Rates of radiation necrosis (RN) did not differ between treatment groups and were 6% (n = 12), 5% (n = 12), 3% (n = 3), 3% (n = 3), for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively, P = 0.43. In addition, no differences were noted in RN between timing of SRS and receipt of systemic therapy, (P = 0.81).In our analysis of NSCLC BM patients treated with single session SRS alongside systemic therapy, we found significant differences in DIC based on receipt of systemic therapy. In addition, treatment with SRS before or concurrent with systemic therapy improved control rates. No differences in RN were noted between treatment groups or by timing of SRS and systemic therapy. Prospective evaluation of the potential synergistic effect between systemic therapy and SRS in NSCLC BM management is warranted.A.E. Dohm: None. J. Tang: None. M.N. Mills: None. B.A. Perez: Research Grant; BMS.T.J. Robinson: None. B. Creelan: Research Grant; NGenomics Laboratories, Adaptive Biotechnologies Corp. Consultant; Xilio Inc, E.R. Squibb LLC, F. Hoffmann-La Roche AG, AstraZeneca plc, AbbVie, KSQ Therapeutics Inc, GlaxoSmithKline plc, Gilead Sciences Inc, Celgene corp. Speaker's Bureau; AstraZeneca plc, ARIAD Pharmaceuticals, Hoffmann-La Roche AG.J. Gray: None. A.B. Etame: None. M. Vogelbaum: Honoraria; Celgene, Tocagen. Stock Options; Infuseon Therapeutics. Royalty; Infuseon Therapeutics. P. Forsyth: Research Grant; Pfizer, Celgene. Advisory Board; Novocure, BTG, Inovio, AbbVie, Ziopharm, Tocagen, Pfizer. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech.

Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas.

While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial. Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy. At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients. Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.

Optimizing stereotactic radiosurgery in patients with recurrent or residual craniopharyngiomas

Stereotactic radiosurgery (SRS) is an important management strategy for residual and recurrent craniopharyngiomas. The current study evaluated the factors which affected tumor control and complications in craniopharyngioma SRS. This study includes 53 consecutive patients who underwent single-session SRS for recurrent or residual craniopharyngiomas. The median age was 41years with 28 male and 25 females. The median tumor volume was 0.63cm3 and median margin dose was 12Gy (range 9-25Gy). The overall 3-, 5-, and 10-year survival rates were 97.8%, 92.7% and 88.5%. The overall 3-, 5-, and 10-year tumor control rates were 81.0%, 72.1%, and 53.4%. In univariate analysis, ≥ 3mm distance from optic structures (p = 0.002), only solid or cystic tumor type (p = 0.037), and ≥ 12Gy to ≥ 85% of the tumor (p < 0.001) were significantly associated with improved tumor control. In multivariate analysis, only solid or cystic tumor type, (p = 0.034), and ≥ 85% of the tumor receiving ≥ 12Gy (p = 0.004) were significantly associated with better tumor control. When ≥ 85% of the tumor received ≥ 12Gy the tumor control rates at 3-, 5-, and 10-year were 100%, 93.3%, and 93.3%. Higher conformity index was not associated with better tumor control. The tumor control rates after recurrent or residual craniopharyngiomas SRS were improved by ensuring that at least 85% of the tumor received ≥ 12Gy even when the distance between the tumor and the optic system is < 3mm. This concept refutes the conformity theory that a high conformity index is a critical feature of effective SRS.

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations

ObjectiveTo determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). Patients and MethodsWe studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity–[1–specificity]). ResultsThis study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001). ConclusionBiological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.

Single-Session Stereotactic Radiosurgery for Large Benign Meningiomas: Medium-to Long-Term Results

The use of stereotactic radiosurgery for the treatment of intracranial meningiomas has been established as an effective and safe treatment modality. Larger meningiomas typically are managed by surgery followed by radiosurgery. Treatment of large meningiomas (usually defined as >10 cc) by stereotactic radiosurgery has been investigated in some recent reports, either by single-session, volume-staged, or the hypofractionation technique. We sought to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) intracranial benign meningiomas. In this retrospective study, we included 273 patients with large benign meningiomas (≥10 cc) who were treated by single-session SRS and followed up for more than 2 years. Tumors were in a basal location in 228 patients (84%). There were 161 tumors (59%) in the perioptic location. The median tumor volume was 15.5 (10-57.3 cc [interquartile range {IQR} 12.3 cc]). The median prescription dose was 12 Gy (9-15 Gy [IQR 1 Gy]). The median follow-up period was 6.1 years (2-18 years [IQR 5.5 years]). The tumor control rate was 90%. The progression-free survival at 5 and 10 years was 96% and 81%, respectively, for the whole cohort. Among 161 patients with perioptic meningiomas, favorable (better/stable) visual outcome was reported in 155 patients (96%) and unfavorable (worse) outcome in 6 patients (4%). Temporary adverse radiation effects were observed in 41 patients (15%) but only 16 (6%) were symptomatic. Stereotactic radiosurgery provides an effective and safe treatment option for large meningiomas.

Dose homogeneity analysis of adjuvant radiation treatment in surgically resected brain metastases: Comparison of IORT, SRS, and IMRT indices

PurposeAlthough surgery remains a treatment option for symptomatic brain metastases, the need for adjuvant radiation after surgery is widely accepted as standard. Despite a multitude of randomized trials aimed at identifying the ideal radiation treatment plan for surgically resected metastases, the development of new delivery regiments necessitates a periodic re-evaluation of dosimetric performance/outcome. Here, we compare the homogeneity index (HI) across three platforms: single-session stereotactic radiosurgery (SRS), multisession stereotactic radiotherapy, and intraoperative radiotherapy (IORT). Methods and MaterialsPatients treated with IORT after surgical resection of brain metastases were identified and dosimetric parameters collected from the dose-volume histograms based on the development of conformal plans for adjuvant radiation using Gamma Knife-SRS (GK-SRS), linear accelerator based intensity-modulated radiation therapy, and IORT. HIs were calculated using four established methods and compared across platforms within the patient cohort. Statistical analyses were performed using analysis of variance. ResultsThe mean maximal doses for the GK-SRS and IMRT plans were 30 Gy and 29 Gy with margin prescription doses of 16 Gy and 24 Gy, respectively. The IORT dose was 30 Gy to the applicator surface. HIs varied based on calculation methods, but maintained consistency when comparing across platforms with IORT having the lower mean HI value (0.56; 95% confidence interval (CI) 0.55–0.60) in single-fraction treatment, compared with GK-SRS (0.77; 95% CI 0.76–0.80). The mean multisession IMRT HI was lower than both single-fraction treatment modalities at 0.41 (95% CI 0.40–0.42). ConclusionsWhen using the HI as the primary dosimetric parameter for adjuvant radiation plans after surgical resection of brain metastases IORT offers improved dose homogeneity compared with GK-SRS in single-fraction treatment, whereas fractionated LINAC-based IMRT was superior with respect to the HI in comparison among all three methods.

Commentary: Effect of Anatomic Segment Involvement on Stereotactic Radiosurgery for Facial Nerve Schwannomas: An International Multicenter Cohort Study.

Background Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined. Objective To analyze the effect of facial nerve segment involvement on functional outcome for these tumors. Methods Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function. Results A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients). Conclusion SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.

Effect of Anatomic Segment Involvement on Stereotactic Radiosurgery for Facial Nerve Schwannomas: An International Multicenter Cohort Study.

Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined. To analyze the effect of facial nerve segment involvement on functional outcome for these tumors. Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function. A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0± 2.4cm3 and 12.2±0.54Gy, respectively. Mean radiological follow-up was 45.5±38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P=.04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P=.03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2patients). SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.

Image-Guided Multisession Radiosurgery of Skull Base Meningiomas.

Simple SummaryStereotactic radiosurgery has changed the landscape of treatment for skull base meningiomas. Lesions encasing or compressing radiosensitive structures are considered not suitable for single session stereotactic radiosurgery because of the high risk of side effects. Multisession stereotactic radiosurgery can reduce these risks, allowing for normal tissue repair between fractions, while delivering a high dose per fraction. The aim of this study is to validate the role of multi-session stereotactic radiosurgery in the treatment of skull base meningiomas, through a retrospective analysis of 156 patients affected by skull base meningioma, treated at the University of Messina between 2008 and 2018. Our study suggests that multisession stereotactic radiosurgery represents a safe and effective profile in the treatment of skull base meningioma, providing a satisfactory local control and a low toxicity rate, together with patient comfort from a frameless procedure.Background: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. Methods: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. Results: 156 patients met the inclusion criteria. The median follow-up period was 36.2 ± 29.3 months. Progression-free survival at 2-, 5-, and 10- years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. Conclusion: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited.

Treatment of intracranial meningioma with single-session and fractionated radiosurgery: a propensity score matching study

Single-session stereotactic radiosurgery (SSRS) is recognized as a safe and efficient treatment for meningioma. We aim to compare the long-term efficacy and safety of fractionated stereotactic radiotherapy (FSRT) with SSRS in the treatment of grade I meningioma. A total of 228 patients with 245 tumors treated with radiosurgery between March 2006 and June 2017were retrospectively evaluated. Of these, 147 (64.5%) patients were treated with SSRS. The remaining 81 patients (35.5%) were treated with a fractionated technique. Protocols to treat meningioma were classified as 12–16 Gy per fraction for SSRS and 7 Gy/fraction/day for three consecutive days to reach a total dose of 21 Gy for FSRT. In univariate and multivariate analyses, tumor volume was found to be associated with local control rate (hazard ratio = 4.98, p = 0.025). The difference in actuarial local control rate (LCR) between the SSRS and FSRT groups after propensity score matching (PSM) was not statistically significant during the 2-year (96.86% versus 100.00%, respectively; p = 0.175), 5-year (94.76% versus 97.56%, respectively; p = 0.373), and 10-year (74.40% versus 91.46%, respectively; p = 0.204) follow-up period. FSRT and SSRS were equally well-tolerated and effective for the treatment of intracranial benign meningioma during the10-year follow-up period.

Clinico-Radiologic Outcomes After Stereotactic Radiosurgery for Patients with Complex High-Risk Multiple Arteriovenous Malformations

The present study aims to define the outcome and risks of patients with multiple arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS). We retrospectively analyzed the records of 1232 patients with AVMs who underwent SRS at our center between 1987 and 2017. We identified 10 patients who had SRS for multiple AVMs (total of 25). Eight patients presented with intracranial hemorrhage before SRS. Four patients had hereditary hemorrhagic telangiectasia. A Spetzler-Martin grade I AVM was diagnosed in 11 AVMs, grade II in 7, grade III in 6, and grade IV in 1 AVM. The median maximum diameter was 12 mm, the median target volume was 1.1 cm3, and the median margin dose was 20 Gy. Twenty-four AVMs were treated with single-session SRS, and 1 AVM was treated with volume-staged SRS. The angiographic complete obliteration rate of each AVM was 18.2%, 58.0%, and 66.4% at 3, 5, and 7 years, respectively. The angiographic complete obliteration rate of all treated AVMs in each patient was 11.1%, 51.4%, and 51.4% at 3, 5, and 7 years, respectively. In multivariate analysis, higher marginal dose (≥18 Gy, P= 0.031) was significantly associated with complete obliteration of AVMs. After obliteration of all their AVMs was confirmed no patient bled. Patients with complex multiple AVMs often presented with a brain hemorrhage. Reduction in bleeding risk after SRS requires complete obliteration that is more likely if the initial AVM margin dose is ≥18 Gy for each AVM.