Treatment outcomes of single-fraction stereotactic radiosurgery for adenoid cystic carcinoma: a case series of 55 patients.

PURPOSE: This study aimed to analyze the treatment outcomes of single-fraction stereotactic radiosurgery (SRS) for adenoid cystic carcinoma patients. METHODS: Retrospective analysis was conducted for 55 patients with 66 lesions. SRS intentions were categorized as definitive, adjuvant, salvage, and palliative. Tumor control was defined as local (within 50% isodose line), marginal (outside 50% isodose line), and distant (metastasis outside head/neck). RESULTS: The median age was 60 years (range 21-85), with 53% males. Tumor origin was head/neck for 88% and trachea/lung for 12%. 61% were recurrent lesions. Median interval from diagnosis to SRS was 14 months. Preceding surgery was performed in 30%. SRS was administered as definitive (30 lesions), adjuvant (13), salvage (19), and palliative (4). SRS was used as a boost to external beam radiation therapy (EBRT) in 39%. Concurrent chemotherapy was administered in 26%. 5-, 10-, and 15-year local control rates were 60%, 33%, and 27%, respectively; local/marginal control rates were 29%, 13%, and 10%. For recurrent lesions treated with SRS without EBRT, 5-year local control rate was 14%, and local/marginal control rate was 5%. For recurrent lesions treated with SRS and EBRT, 5-year local control rate was 100%, and local/marginal control rate was 40%. The rate of distant failure after SRS was 40%. Older age and distant metastasis before SRS were negative factors for overall survival. CONCLUSION: SRS provided a high rate of local tumor control, but marginal failure was frequent. Integrating SRS with added EBRT exhibits potential for enhancing local and local/marginal tumor control, particularly in recurrent cases.

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).

The role of single-fraction stereotactic radiosurgery for atypical meningiomas (WHO grade II): treatment results based on a 25-year experience.

PURPOSE: To clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM). METHODS: A retrospective analysis of 68 patients with AM having SRS from 1995 until 2019. RESULTS: Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54 Gy). The median follow-up period was 52 months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6 months), early salvage (7-18 months), or late salvage treatment (> 18 months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01). CONCLUSION: PFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.

Long-term outcomes of grade I/II skull base chondrosarcoma: an insight into the role of surgery and upfront radiotherapy.

PURPOSE: To clarify the need for post-operative radiation treatment in skull base chondrosarcomas (SBCs). METHODS: A retrospective analysis of patients with grade I or II SBC. Patients were divided according to post-surgical treatment strategies: (A) planned upfront radiotherapy and (B) watchful waiting. Tumor control and survival were compared between the treatment groups. The median follow-up after resection was 105 months (range, 9-376). RESULTS: Thirty-two patients (Grade 1, n = 16; Grade 2, n = 16) were included. The most frequent location was petroclival (21, 64%). A gross total resection (GTR) was achieved in 11 patients (34%). Fourteen (44%) underwent upfront radiotherapy (group A) whereas 18 (56%) were followed with serial MRI alone (group B). The tumor control rate for the entire group was 77% and 69% at 10- and 15-year, respectively. Upfront radiotherapy (P = 0.25), extent of resection (P = 0.11) or tumor grade (P = 0.83) did not affect tumor control. The majority of Group B patients with recurrent tumors (5/7) obtained tumor control with repeat resection (n = 2), salvage radiotherapy (n = 2), or a combination of both (n = 1). The 10-year disease-specific survival was 95% with no difference between the group A and B (P = 0.50). CONCLUSION: For patients with grade I/II SBC, a reasonable strategy is deferral of radiotherapy after maximum safe resection until tumor progression or recurrence. At that time, most patients can be successfully managed with salvage radiotherapy or surgery. Late recurrences may occur, and life-long follow-up is advisable.

Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature.

INTRODUCTION: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. METHODS: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. RESULTS: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. DISCUSSION/CONCLUSION: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.

Brain metastases resection cavity radio-surgery based on T2-weighted MRI: technique assessment.

PURPOSE: Stereotactic radiosurgery (SRS) is commonly performed after surgical resection of brain metastases to reduce the chance of local tumor recurrence while maintaining cognitive function. Target delineation in these cases is typically based off T1-weighted post-gadolinium MRI (T1Gd). In this study, we report outcomes for patients having postoperative SRS in which the planning target volume (PTV) was based on T2-weighted MRI (T2W). METHODS: Sixty-two consecutive patients having single-fraction SRS after brain metastases resection were retrospectively reviewed. Excluded were patients with prior whole brain radiation therapy, multiple resection cavities, and small cell pathologies. RESULTS: The median time from surgery to SRS was 11 days; 26 patients (42%) had SRS ≤ 7 days. The median PTV was 8.0 cm3; the median margin dose was 18 Gy. The crude rates of local tumor control (LC), leptomeningeal disease (LMD), distant brain recurrence (DBR), and radiation necrosis (RN) were 85%, 19%, 37%, and 2%, respectively. The 1-year LC, LMD, DBR, and RN rates were 88%, 25%, 36%, and 0%, respectively. No tumor or dosimetric factor was associated with LC. Sub-total tumor resection was a risk factor for LMD (HR 5.11, P = 0.003), whereas patients with multiple brain metastases had a greater risk of DBR (HR 2.88, P = 0.01). The median PTV was smaller compared to the median PTV based off the consensus guidelines utilizing T1Gd MRI (8.0 cm3 vs. 9.1 cm3, P = 0.004). CONCLUSION: T2W MRI provided accurate resection cavity delineation even in the early postoperative period and was associated with decreased PTV compared to T1Gd MRI in the majority of cases.

Single-fraction stereotactic radiosurgery for spindle cell oncocytoma: preliminary experience and systematic review of the literature.

PURPOSE: Spindle cell oncocytoma (SCO) is a rare benign pituitary tumor. No patient series regarding stereotactic radiosurgery (SRS) for SCO has been published. We report the clinical outcomes of SCO treated with single-fraction SRS, as well as a systematic review of the literature. METHODS: Retrospective cohort series and systematic literature review. RESULTS: Five patients (four male, one female) having single-fraction SRS for persistent or recurrent SCO between 2002 and 2018. Median age was 56 (range 54-79) years. Pre-SRS treatments included transsphenoidal resection (TSR) (n = 3), multiple TSR (n = 1), and TSR, radiotherapy, and craniotomy (n = 1). Median target volume was 4.7 (range 1.8-8.4) cm3, with a median tumor margin dose of 17 (range 14-20) Gy. Median follow-up was 24 (range 10-69) months. All radiation-naïve patients achieved tumor control after SRS; tumor progression was noted 24 months after SRS in one patient who failed prior radiotherapy. No radiation-induced complications were observed after SRS. Systematic literature review of 43 cases in addition to the five cases presented here showed that tumor progression/recurrence was more frequent after STR compared to GTR (P < 0.001). Ten previous cases of radiotherapy for SCO have been reported, but most did not detail radiation volumes, doses, or outcomes. CONCLUSIONS: SCO are uncommon sellar lesions with a propensity for progression or recurrence. Based on the clinically aggressive course of these tumors, adjuvant SRS after STR or at the time of tumor recurrence should be considered. Further case accumulation and follow-up is required to better understand the long-term treatment outcomes after single-fraction SRS for these rare tumors.

Gamma Knife radiosurgery for neurofibromatosis type 2-associated meningiomas: a 22-year patient series.

Neurofibromatosis type 2 (NF2) is a debilitating genetic condition with potential development of multiple meningiomas. We report our experience treating a series of NF2-associated intracranial meningiomas with Gamma Knife radiosurgery (GKRS). Between 1992 and 2013, 15 consecutive patients (age 20-54 years) with 62 intracranial meningiomas were treated with single-fraction GKRS. Fifty-five percent of tumors involved the convexity or parasagittal/falx. The median prescription dose was 16 Gy (range 13-20 Gy). The median tumor diameter was 2.1 cm (range 0.7-4.5 cm). The median radiographic and clinical follow-up periods were 103 and 111 months, respectively. The 5-year and 10-year local controls were both 96 %. The disease specific survival was 93 % at 5 years and 68 % at 10 years. Fifty-three percent of patients had multiple meningiomas and received multiple GKRS treatments (range 1-7) for new or enlarging intracranial meningiomas. 11 (73 %) patients were alive at last follow-up, with 60 (97 %) tumors controlled (smaller or unchanged in size). There were 2 in-field failures, one at 1 year and the other at 3.5 years. There were no marginal failures. Major Complications after GKRS included: 1 case of radiation necrosis, 1 case of post treatment edema, and 1 case of a presumed radiation induced cavernous malformation 5 years after GKRS. GK is an effective treatment for enlarging NF2-associated meningiomas. No cases of malignant transformation or secondary malignancies were seen during the follow-up period.

Magnetic resonance imaging-guided laser interstitial thermal therapy for previously treated hypothalamic hamartomas.

OBJECTIVE Hypothalamic hamartomas (HHs) are associated with gelastic seizures and the development of medically refractory epilepsy. Magnetic resonance imaging-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive ablative treatment that may have applicability for these deep-seated lesions. Here, the authors describe 3 patients with refractory HHs who they treated with MRg-LITT. METHODS An institutional review board-approved prospective database of patients undergoing Visualase MRg-LITT was retrospectively reviewed. Demographic and historical medical data, including seizure and medication histories, previous surgeries, procedural details, and surgical complications, along with radiological interpretation of the HHs, were recorded. The primary outcome was seizure freedom, and secondary outcomes included medication reduction, seizure frequency, operative morbidity, and clinical outcome at the latest follow-up. RESULTS All 3 patients in the multi-institutional database had developed gelastic seizures related to HH at the ages of 7, 7, and 9 years. They presented for further treatment at 25, 28, and 48 years of age, after previous treatments with stereotactic radiosurgery in all cases and partial hamartoma resection in one case. One ablation was complicated by a small tract hemorrhage, which was stable on postoperative imaging. One patient developed hyponatremia and experienced weight gain, which were respectively managed with fluid restriction and counseling. At the most recent follow-up at a mean of 21 months (range 1-32 months), one patient was seizure free while another had meaningful seizure reduction. Medication was reduced in one case. CONCLUSIONS Adults with gelastic seizures despite previous treatments can undergo MRg-LITT with reasonable safety and efficacy. This novel therapy may provide a minimally invasive alternative for primary and recurrent HH as the technique is refined.

Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.

IMPORTANCE: Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE: To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS: At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS: The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES: The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS: There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04). CONCLUSIONS AND RELEVANCE: Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00377156.

Single-fraction stereotactic radiosurgery of meningeal hemangiopericytomas.

Meningeal hemangiopericytomas (M-HPC) are challenging tumors with a high rate of recurrence despite surgical resection and external beam radiotherapy (EBRT). To better understand the role of single-fraction stereotactic radiosurgery (SRS) for patients with M-HPC, we reviewed our experience with 22 patients (12 men, 10 women) from 1990 until 2010. Twelve patients (55%) underwent a single SRS procedure, whereas 10 patients (45%) had more than one SRS procedure (range 2-6). In total, 47 SRS procedures were performed to treat 64 tumors. Fourteen patients (64%) had undergone prior EBRT (median dose, 56.0 Gy). Follow-up after the initial SRS (median, 66 months) was censored at the time of death (n = 15) or last clinical evaluation (n = 7). Eleven patients (50 %) died of intracranial tumor progression (n = 10) or treatment-related complications (n = 1). One patient (5%) died of systemic disease progression. Disease-specific survival (DSS) at 1-, 3- and 5-years after SRS was 96, 82, and 61%, respectively. Prior EBRT (HR 9.0, 95% CI 1.1-78.1, p < 0.05) and larger initial tumor volume (HR 1.09, 95% CI 1.02-1.2, p = 0.02) were associated with worse DSS. Local tumor control (LTC) after SRS at 1-, 3-, and 5-years was 89, 68, and 59%, respectively. Improved LTC was noted in patients who had not undergone prior EBRT (HR 6.3, 95% CI 2.1-19.5, p = 0.001). One patient (5%) had symptomatic radiation-relation complications after SRS. Overall, single-fraction SRS was effective in providing LTC for more than half of recurrent or residual M-HPC at 5-years after the procedure. Repeat SRS is often required secondary to either distant or local tumor progression.

Predicting long-term outcomes after microvascular decompression for hemifacial spasm according to lateral spread response and immediate postoperative outcomes: a cohort study.

OBJECTIVE: Microvascular decompression (MVD) is a well-established and highly effective treatment option for hemifacial spasm (HFS). Lateral spread response (LSR) has been used as an intraoperative indicator of HFS resolution, with controversial reliability. The purpose of this study was to determine long-term outcomes of MVD for HFS and the role of LSR and other preoperative predictors. METHODS: The authors conducted a cohort study of all patients treated with MVD for HFS at a single institution from January 1, 1998, to December 31, 2019. In addition to a retrospective chart review, all patients were contacted at the time of the study to provide informed consent and responded to a telephone survey to ascertain their current disease and medication status. Patients with at least 12 months of postoperative follow-up were included. Statistical testing included a Student t-test, Fisher's exact test, logistic regression, and Cox proportional hazards analysis. RESULTS: One hundred nineteen patients met study criteria; 41 (34%) had at least 10 years of clinical follow-up. HFS fully resolved in 93 (78%), symptoms subjectively improved in 11 (9%) and were unchanged in 15 (13%). Immediate postoperative HFS status did not correlate with long-term outcome (p = 0.13). Changes in LSR were not associated with outcome. Patients receiving neuromodulating agents had significantly longer preoperative duration of symptoms and were more likely to show persistent LSR intraoperatively. HFS recurrence was associated with younger age at the time of surgery but not with intraoperative LSR resolution. CONCLUSIONS: This study demonstrated that MVD for HFS is highly effective for most patients. Neither intraoperative LSR change nor immediate postoperative status was predictive of long-term outcomes.

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.

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.

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

The risk of stroke or clinical impairment after stereotactic radiosurgery for ARUBA-eligible patients.

BACKGROUND AND PURPOSE: The best management of patients with unruptured brain arteriovenous malformations (BAVM) is controversial. In this study, we analyzed the stroke rate and functional outcomes of patients having stereotactic radiosurgery (SRS) for unruptured BAVM using the same eligibility criteria and primary end points as the ARUBA trial. METHODS: Retrospective observational study of 174 ARUBA-eligible patients having SRS from 1990 to 2005. RESULTS: The median follow-up after SRS was 64 months. Fifteen patients (8.7%) had a hemorrhagic stroke at a median of 21 months after SRS. Six patients (3.5%) had a focal neurological deficit and 4 patients died (2.3%). The risk of stroke or death was 10.3% at 5 years and 11.5% at 10 years. Twelve additional patients (6.9%) had a focal neurological deficit from either radiation-related complications (n=7) or subsequent resection (n=5). The risk of patients' having clinical impairment (modified Rankin Score ≥ 2) was 8.4% at 5 years and 12.0% at 10 years. Increasing BAVM volume was associated with both stroke or death (hazard ratio=1.06; 95% confidence interval, 1.0-1.11; P=0.04) and clinical impairment (hazard ratio=1.06; 95% confidence interval, 1.01-1.09; P=0.01). The 10-year risk of stroke or death and clinical impairment for patients with BAVM ≤ 5.6 cm(3) was 5% and 4%, respectively. CONCLUSIONS: The observed risk of stroke or death after SRS was approximately 2% per year for the first 5 years after SRS, declining to 0.2% annually for years 6 to 10. Patients with small volume BAVM may benefit from SRS compared with the natural history of unruptured BAVM over the planned follow-up interval of the ARUBA trial (5-10 years).

Stereotactic radiosurgery for intermediate- and high-grade arteriovenous malformations: outcomes stratified by the supplemented Spetzler-Martin grading system.

OBJECTIVE: The supplemented Spetzler-Martin (Supp-SM) grading system was developed to improve the predictive accuracy of surgical risk for patients with brain arteriovenous malformations (AVMs). The aim of this study was to apply the Supp-SM grading system to patients having stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) intermediate- (grade III) or high-grade (grade IV-V) AVMs to enable comparison with published microsurgical series. METHODS: In 219 patients who underwent SRS during the period from 1990 to 2016, the Supp-SM grade was calculated for SM grade III (n = 154) or SM grade IV-V (n = 65) AVMs. The Supp-SM grades in these patients were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). Sixty patients (27%) had deep AVMs (basal ganglia, thalamus, or brainstem). Thirty-nine patients (18%) had volume-staged SRS; 41 patients (19%) underwent repeat SRS. The median follow-up period was 69 months for SM grade III AVMs and 113 months for SM grade IV-V AVMs. RESULTS: AVM obliteration was confirmed in 163 patients (74%) at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. Thirty-one patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). Six patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurological decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of nonobliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurological decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading score did not correlate with either obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurological decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). CONCLUSIONS: The Supp-SM grading system was not predictive of outcomes after SRS of intermediate- or high-grade AVM. In a cohort that included a high percentage (47%) of "inoperable" AVMs according to Supp-SM grade (≥ 7), most patients had obliteration after SRS, although there was a high risk of neurological decline.

ISRS Technical Guidelines for Stereotactic Radiosurgery: Treatment of Small Brain Metastases (≤1 cm in Diameter).

PURPOSE: The objective of this literature review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus technical guidelines for the treatment of small, ≤1 cm in maximal diameter, intracranial metastases with stereotactic radiosurgery. Although different stereotactic radiosurgery technologies are available, most of them have similar treatment workflows and common technical challenges that are described. METHODS AND MATERIALS: A systematic review of the literature published between 2009 and 2020 was performed in Pubmed using the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) methodology. The search terms were limited to those related to radiosurgery of brain metastases and to publications in the English language. RESULTS: From 484 collected abstract 37 articles were included into the detailed review and bibliographic analysis. An additional 44 papers were identified as relevant from a search of the references. The 81 papers, including additional 7 international guidelines, were deemed relevant to at least one of five areas that were considered paramount for this report. These areas of technical focus have been employed to structure these guidelines: imaging specifications, target volume delineation and localization practices, use of margins, treatment planning techniques, and patient positioning. CONCLUSIONS: This systematic review has demonstrated that Stereotactic Radiosurgery (SRS) for small (1 cm) brain metastases can be safely performed on both Gamma Knife (GK) and CyberKnife (CK) as well as on modern LINACs, specifically tailored for radiosurgical procedures, However, considerable expertise and resources are required for a program based on the latest evidence for best practice.

Salvage radiosurgery following subtotal resection of vestibular schwannomas: does timing influence tumor control?

OBJECTIVE: The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function. METHODS: VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines. RESULTS: A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration. CONCLUSIONS: Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience.

BACKGROUND: A study was undertaken to define the variables associated with tumor control and survival after single-session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas. METHODS: Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm(3) ; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow-up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22). RESULTS: Tumor grade correlated with disease-specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression-free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm(3) were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation-related complications at a median of 6 months after radiosurgery. CONCLUSIONS: Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas.