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.

Long-Term Patient-Reported Outcomes of Stereotactic Radiosurgery for Trigeminal Neuralgia.

BACKGROUND: We aimed to evaluate patient-reported outcomes (PROs) of stereotactic radiosurgery (SRS) for TN in terms of treatment efficacy and toxicity. METHODS: We retrospectively analyzed patients who underwent Gamma Knife SRS for idiopathic or classic TN between January 2013 and February 2022. Questionnaires regarding pain relief, treatment toxicity, and post-SRS treatment were sent between late 2022 and early 2023, and the responses received were analyzed. The Faces Pain Scale (FPS, 0: best, 5: worst) was used for quantitative evaluation. RESULTS: Responses were received from 51 patients (76%). The mean pre-SRS FPS score was 4.1 (standard deviation (SD) 1.1). Forty-three patients (83%) reported initial pain relief and the best post-SRS FPS score was 1.1 (SD 1.5) (P < 0.001). At a median follow-up of 50 months, the FPS score was still 1.1 (SD 1.6) (P < 0.001). Analysis of factors contributing to durable pain relief showed neurovascular compression to be associated with FPS score improvement (Odds ratio 5.7, 95% CI 1.1-29.7, P = 0.038). Facial dysesthesia had a mean pre-SRS FPS score of 1.7 (SD 2.0) and a mean score of 1.4 (SD 1.7) at the last follow-up (P = 0.32). Eight patients (15%) received post-SRS interventions and 21 (40%) no longer required pharmacotherapy without post-SRS intervention. Forty-four patients (85%) reported being satisfied with SRS. CONCLUSIONS: We analyzed PROs of SRS for TN using the FPS and showed SRS to be a safe and effective treatment modality achieving long lasting pain relief.

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.

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).

Synergistic effects of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with lung cancer and brain metastases: a propensity score-matched analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) is the mainstay treatment for brain metastases (BMs) from lung cancer. In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic lung cancer and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for lung cancer BMs prolongs overall survival (OS), improves intracranial disease control, and raises safety concerns. METHODS: Patients who underwent SRS for lung cancer BMs at Aizawa Hospital between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by propensity score matching (PSM; match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI + SRS vs SRS) by time-dependent analyses, taking into account competing events. RESULTS: Five hundred eighty-five patients with lung cancer BM (494 with non-small cell lung cancer and 91 with small cell lung cancer) were eligible. Of those patients, 93 (16%) received concurrent ICIs. Two groups, each with 89 patients (ICI + SRS group and SRS group), were generated by PSM. The 1-year survival rates of the ICI + SRS and SRS groups after the initial SRS were 65% and 50% and the median survival times were 16.9 and 12.0 months, respectively (HR 0.62, 95% CI 0.44-0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR 0.55, 95% CI 0.28-1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR 0.73, 95% CI 0.53-0.99, p = 0.047). The 2-year local failure rates were 12% and 18% (HR 0.72, 95% CI 0.32-1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR 0.82, 95% CI 0.55-1.23, p = 0.34). Severe adverse radiation events (Common Terminology Criteria for Adverse Events [CTCAE] grade 4) occurred in 1 patient in each group, and CTCAE grade 3 toxicities were observed in 3 patients in the ICI + SRS group and in 5 in the SRS group (OR 1.53, 95% CI 0.35-7.7, p = 0.75). CONCLUSIONS: The present study found that SRS with concurrent ICIs for patients with lung cancer BMs was associated with longer survival and durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Uterine Cervical and Endometrial Carcinomas: Histopathological Analysis of Survival and Local Control. A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study.

OBJECTIVE: A retrospective comparative analysis of the outcomes of gamma knife radiosurgery (GKRS) for brain metastases from uterine cervical carcinoma (CC) and endometrial carcinoma (EC), investigated the efficacy and prognostic factors for survival and local tumor control. Histopathological analysis was also performed. METHODS: The authors retrospectively reviewed 61 patients with 260 tumors of CC and 73 patients with 302 tumors of EC who had undergone GKRS. RESULTS: The survival times after GKRS had no difference between CC and EC. Uncontrolled primary cancer was significant unfavorable factor. CC resulted in significantly higher neurological death and post-GKRS neurological deterioration. New lesions appeared intracranially after GKRS, with no significant difference between CC and EC. Local tumor control rates at 6, 12, and 24 months after GKRS were 90.0%, 86.6%, and 78.0% for CC and 92.2%, 87.9%, and 86.4% for EC. Primary cancer of CC, more than 7 cm3 volume, and prescription dose less than 20 Gy were significantly correlated in control failure. Local tumor control rates were significantly lower for squamous cell carcinoma in CC. No significant differences were found between histopathological subtypes of EC. CONCLUSIONS: This study established a relationship between the efficacy of GKRS for CC and EC brain metastases and the histopathological. Though, survival time after GKRS has no difference between CC and EC, CC was significantly higher neurogenic death and neurological deterioration after GKRS. Squamous cell carcinoma had a significantly lower rate of local tumor control among all CC, thereby resulting in CC having lower local tumor control than EC.

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.

Effectiveness of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with brain metastases from renal cell carcinoma: inverse probability of treatment weighting using propensity scores.

OBJECTIVE: Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from renal cell carcinoma (RCC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic RCC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for RCC BM prolongs overall survival (OS) and improves intracranial disease control and whether there are any safety concerns. METHODS: Patients who underwent SRS for RCC BMs at the authors' institution between January 2010 and January 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The time-to-event analysis of OS and intracranial progression-free survival (IC-PFS) between the groups with and without ICIs (ICI+SRS and SRS, respectively) was performed using inverse probability of treatment weighting (IPTW) based on propensity scores (PSs) to control for selection bias. Four baseline covariates (Karnofsky Performance Scale score, extracranial metastases, hemoglobin, and number of BMs) were selected to calculate PSs. RESULTS: In total, 57 patients with 147 RCC BMs were eligible. The median OS for all patients was 9.1 months (95% CI 6.0-18.9 months), and the median IC-PFS was 4.4 months (95% CI 3.1-6.8 months). Twelve patients (21%) received concurrent ICIs. The IPTW-adjusted 1-year OS rates in the ICI+SRS and SRS groups were 66% and 38%, respectively (HR 0.30, 95% C 0.13-0.69; p = 0.005), and the IPTW-adjusted 1-year IC-PFS rates were 52% and 16%, respectively (HR 0.30, 95% CI 0.14-0.62; p = 0.001). Severe tumor hemorrhage (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or 5) occurred immediately after SRS in 2 patients in the SRS group. CTCAE grade 2 or 3 toxicity was observed in 2 patients in the ICI+SRS group and 5 patients in the SRS group. CONCLUSIONS: Although the patient number was small and the analysis preliminary, the present study found that SRS with concurrent ICIs for RCC BM patients prolonged survival and provided durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Stereotactic Radiosurgery for Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) are often treated with stereotactic radiosurgery (SRS) to achieve complete obliteration (CO), prevent future hemorrhages, and ameliorate neurological symptoms. OBJECTIVE: To summarize outcomes after SRS for dAVFs and propose relevant practice recommendations. METHODS: Using a PICOS/PRISMA/MOOSE protocol, we included patients with dAVFs treated with SRS and data for at least one of the outcomes of the study. Relevant outcomes were CO, symptom improvement and cure, and post-SRS hemorrhage or permanent neurological deficits (PNDs). Estimated outcome effect sizes were determined using weighted random-effects meta-analyses using DerSimonian and Laird methods. To assess potential relationships between patient and lesion characteristics and clinical outcomes, mixed-effects weighted regression models were used. RESULTS: Across 21 published studies, we identified 705 patients with 721 dAVFs treated with SRS. The CO rate was 68.6% (95% CI 60.7%-76.5%) with symptom improvement and cure rates of 97.2% (95% CI 93.2%-100%) and 78.8% (95% CI 69.3%-88.2%), respectively. Estimated incidences of post-SRS hemorrhage and PNDs were 1.1% (95% CI 0.6%-1.6%) and 1.3% (95% CI 0.8%-1.8%), respectively. Noncavernous sinus (NCS) dAVFs were associated with lower CO (P = .03) and symptom cure rates (P = .001). Higher grade was also associated with lower symptom cure rates (P = .04), whereas previous embolization was associated with higher symptom cure rates (P = .01). CONCLUSION: SRS for dAVFs results in CO in the majority of patients with excellent symptom improvement rates with minimal toxicity. Patients with NCS and/or higher-grade dAVFs have poorer symptom cure rates. Combined therapy with embolization and SRS is recommended when feasible for clinically aggressive dAVFs or those refractory to embolization to maximize the likelihood of symptom cure.

Gamma Knife radiosurgery for metastatic brain tumors from ovarian cancer: histopathological analysis of survival and local control. A Japanese multi-institutional cooperative and retrospective cohort study.

OBJECTIVE: Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. METHODS: The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. RESULTS: After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). CONCLUSIONS: This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

Outcomes of Gamma Knife radiosurgery for skull base chondrosarcomas: a multi-institutional retrospective study.

OBJECTIVE: Radiotherapy has an essential role in the management of skull base chondrosarcomas (SBCs) after resection. This multi-institutional study evaluated the outcomes of Gamma Knife radiosurgery (GKRS) for histopathologically proven SBCs. METHODS: Data of patients who underwent GKRS for SBCs at Gamma Knife centers in Japan were retrospectively collected. Patients without a histopathological diagnosis and those who had intracranial metastases from extracranial chondrosarcomas were excluded. Histologically, grade III and some nonconventional variants were identified as aggressive types. The cumulative local control rates (LCRs) and disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method. Factors potentially affecting the LCR were evaluated using the Cox proportional hazards model for bivariate and multivariate analyses. The incidence of radiation-induced adverse effects (RAEs) was calculated as crude rates, and factors associated with RAEs were examined using Fisher's exact test. RESULTS: Fifty-one patients were enrolled, with a median age of 38 years. Thirty patients (59%) were treated with upfront GKRS for residual SBCs after resection (n = 27) or biopsy (n = 3), and 21 (41%) underwent GKRS as a salvage treatment for recurrence. The median tumor volume was 8 cm3. The overall LCRs were 87% at 3 years, 78% at 5 years, and 67% at 10 years after GKRS. A better LCR was associated with a higher prescription dose (p = 0.039) and no history of repeated recurrence before GKRS (p = 0.024). The LCRs among patients with the nonaggressive histological type and treatment with ≥ 16 Gy were 88% at 3 years, 83% at 5 years, and 83% at 10 years. The overall survival rates after GKRS were 96% at 5 years and 83% at 10 years. Although RAEs were observed in 3 patients (6%), no severe RAEs with Common Terminology Criteria for Adverse Events grade 3 or higher were identified. No significant factor was associated with RAEs. CONCLUSIONS: GKRS for SBCs has a favorably low risk of RAEs and could be a reasonable therapeutic option for SBC in multimodality management. A sufficient GKRS prescription dose is necessary for higher LCRs. Histological grading and subtype evaluations are important for excluding exceptional SBCs. Patients with conventional SBCs have a long life expectancy and should be observed for life after treatment.

Stereotactic radiosurgery results for brain metastasis patients with renal cancer: A validity study of Renal Graded Prognostic Assessment and proposal of a new grading index (JLGK2101 Study).

BACKGROUND AND PURPOSE: The Renal Graded Prognostic Assessment (GPA) is relatively new and has not been sufficiently validated using a different dataset. We thus developed a new grading index, the Renal Brain Metastasis Score (Renal-BMS). MATERIALS AND METHODS: Using our dataset including 262 renal cancer patients with brain metastases (BMs) undergoing stereotactic radiosurgery (SRS) (test series), we validity tested the Renal-GPA. Next, we applied clinical factor-survival analysis to the test series and thereby developed the Renal-BMS. This system was then validated using another series of 352 patients independently undergoing SRS at nine gamma knife facilities in Japan (verification series). RESULTS: Using the test series, with the Renal-GPA, 95% confidence intervals (CIs) of the post-SRS median survival times (MSTs) overlapped between pairs of neighboring subgroups. Among various pre-SRS clinical factors of the test series, six were highly associated with overall survival. Therefore, we assigned scores for six factors, i.e., "KPS ≥ 80%/<80% (0/3)", "tumor numbers 1-4/≥5 (score; 0/2)", "controlled primary cancer/not (0/2)", "existing extra-cerebral metastases/not (0/3)", "blood hemoglobin ≥ 11.0/<11.0 g/dl (0/1)" and "interval from primary cancer to SRS ≥ 5/<5 years (0/1)". Patients were categorized into three subgroups according to the sum of scores, i.e., 0-4, 5-8 and 9-12. In the test and verification series, post-SRS MSTs differed significantly (p < 0.0001) with no overlaps of 95% CIs among the three subgroups. CONCLUSIONS: The Renal BMS has the potential to be very useful to physicians selecting among aggressive treatment modalities for renal cancer patients with BMs.

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

PURPOSE: To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society. METHODS AND MATERIALS: A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS), and vertebral compression fracture probability was conducted. RESULTS: The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase 1 and 2 clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. Ten studies used a magnetic resonance imaging (MRI) scan fused to computed tomography (CT) simulation for treatment planning, and 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported vertebral compression fracture rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. CONCLUSIONS: Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients who may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses, or those with a history of prior irradiation to the affected spinal segment. The International Stereotactic Radiosurgery Society recommends a minimum interval of 8 to 14 days after invasive surgery before simulation for SBRT, with initiation of radiation therapy within 4 weeks of surgery. An MRI fused to the planning CT, or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2 mm for the spinal cord is advised.

Role of Microelectrode Recording in Deep Brain Stimulation of the Pedunculopontine Nucleus: A Physiological Study of Two Cases.

BACKGROUND: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been reported to improve gait disturbances in Parkinson's disease (PD); however, there are controversies on the radiological and electrophysiological techniques for intraoperative and postoperative confirmation of the target and determination of optimal stimulation parameters. OBJECTIVES: We investigated the correlation between the location of the estimated PPN (ePPN) and neuronal activity collected during intraoperative electrophysiological mapping to evaluate the role of microelectrode recording (MER) in identifying the effective stimulation site in two PD patients. MATERIALS AND METHODS: Bilateral PPN DBS was performed in two patients who had suffered from levodopa refractory gait disturbance. They had been implanted previously with DBS in the internal globus pallidus and the subthalamic nucleus, respectively. The PPN was determined on MRI and identified by intraoperative MER. Neuronal activity recorded was analyzed for mean discharge rate, bursting, and oscillatory activity. The effects were assessed by clinical ratings for motor signs before and after surgery. RESULTS: The PPN location was detected by MER. Groups of neurons characterized by tonic discharges were found 9-10 mm below the thalamus. The mean discharge rate in the ePPN was 19.1 ± 15.1 Hz, and 33% of the neurons of the ePPN responded with increased discharge rate during passive manipulation of the limbs and orofacial structures. PPN DBS with bipolar stimulation at a frequency range 10-30 Hz improved gait disturbances in both patients. Although PPN DBS provided therapeutic effects post-surgery in both cases, the effects waned after a year in case 1 and three years in case 2. CONCLUSIONS: Estimation of stimulation site within the PPN is possible by combining physiological guidance using MER and MRI findings. The PPN is a potential target for gait disturbances, although the efficacy of PPN DBS may depend on the location of the electrode and the stimulation parameters.

Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations.

OBJECTIVE: A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS: The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis. RESULTS: For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS: SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

[Anterior Cervical Discectomy and Fusion:Safe Surgical Operation Based on Detailed Anatomical Knowledge].

Anterior cervical discectomy and fusion(ACDF)was developed by R.B. Cloward in the 1950s and it has spread over the world for the treatment of the spinal degenerative disorders. It is considered to be the most effective treatment for patients with anterior compression of the spinal cord. Because most of the surgical complications reportedly occur while approaching the vertebral column through the subcutaneous tissues, precise knowledge of the topographic anatomy of the neck is crucial for effective and safe surgery. In this paper, we describe the appropriate surgical maneuvers in each surgical step, based on anatomical knowledge, for avoiding surgery-related complications. We would like to emphasize that anatomical features differ with individual patients; therefore, careful preoperative evaluation is very important. Surgical strategy, based on adequate preoperative evaluation, will lead to good postoperative results.

Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis.

OBJECTIVE: The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs). METHODS: Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events. RESULTS: In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007). CONCLUSIONS: The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Stereotactic Radiosurgery for Postoperative Metastatic Surgical Cavities: A Critical Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines.

PURPOSE: The purpose of this critical review is to summarize the literature specific to single-fraction stereotactic radiosurgery (SRS) and multiple-fraction stereotactic radiation therapy (SRT) for postoperative brain metastases resection cavities and to present practice recommendations on behalf of the ISRS. METHODS AND MATERIALS: The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach to search for manuscripts reporting SRS/SRT outcomes for postoperative brain metastases tumor bed resection cavities with a search end date of July 20, 2018. Prospective studies, consensus guidelines, and retrospective series that included exclusively postoperative brain metastases and had at minimum 100 patients were considered eligible. RESULTS: The Embase search revealed 157 manuscripts, of which 77 were selected for full-text screening. PubMed yielded 55 manuscripts, of which 23 were selected for full text screening. We deemed 8 retrospective series, 1 phase 2 prospective study, 3 randomized controlled trials, and 1 consensus contouring paper appropriate for inclusion. The data suggest that SRS/SRT to surgical cavities with prescription doses of 30 to 50 Gy equivalent effective dose (EQD) 210, 50 to 70 Gy EQD25, and 70 to 90 EQD22 are associated with rates of local control ranging from 60.5% to 91% (median, 80.5%). Randomized data suggest improved local control with single-fraction SRS compared with observation and improved cognitive outcomes compared with whole-brain radiation therapy (WBRT). The toxicity of SRS/SRT in the postoperative setting was limited and is reviewed herein. CONCLUSIONS: Although randomized data raise concern for poorer local control after resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses used in the SRS arm. Retrospective studies suggest high rates of local control after single-fraction SRS and hypofractionated SRT for postoperative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible postoperative patients. Emerging data suggest that fractionated SRT may provide superior local control compared with single-fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a preoperative diameter greater than 2.5 cm.

Safety and efficacy of upfront stereotactic radiosurgery for brain metastases with high cumulative intracranial tumor volume (> 7 ml): analysis of 233 consecutive patients.

BACKGROUND: The cumulative intracranial tumor volume (CITV) has recently been suggested to be a more relevant predictive factor for patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS). We aimed to investigate the feasibility of upfront SRS for patients with BM having a high CITV, i.e., exceeding 7 ml. METHODS: Two hundred thirty-three consecutive patients with BM having a CITV > 7 ml who underwent SRS as first-line treatment from 2011 to 2019 were retrospectively identified. The overall survival (OS) and intracranial disease control rates were analyzed. Multivariate proportional hazards models were used to identify prognostic factors associated with treatment outcome. Toxicity and salvage therapy were also investigated. RESULTS: The median OS was 8.7 months (95% confidence interval: 7.1-10.4), and 6-month and 1-year OS rates were 60 and 40%, respectively. Systemic anticancer therapy (hazard ratio (HR): 0.45, p < 0.001), female sex (HR: 0.61, p = 0.001), synchronous SRS (HR: 0.57, p = 0.003), number of BM (HR: 1.04, p = 0.008), controlled extracranial disease (HR: 0.56, p = 0.009), Karnofsky performance status (HR: 0.87, p = 0.015), and staged SRS (HR: 0.71, p = 0.037) were found to be factors independently associated with OS. Post-SRS toxicities of CTCAE grades 3, 4, and 5 were observed in 14, 5, and 1 patient, respectively. As salvage management, repeat SRS, whole brain radiotherapy, and surgical resection were required for 84, 16, and 10 patients, respectively, CONCLUSIONS: With vigilant surveillance and appropriate salvage management, upfront SRS alone can be considered as a relatively safe and effective treatment strategy even for BM with CITV > 7 ml.