Saito, Nobuhito

Abstract Purpose This study investigated whether Ki-67 labeling index (LI) correlated with clinical outcomes after SRS for atypical meningiomas. Methods This retrospective study examined 39 patients with atypical meningiomas who underwent SRS over a 10-year study period. Ki-67 LI was categorized into 3 groups: low (< 5%), intermediate (5–10%), and high (> 10%). Local tumor control rates (LCRs), progression-free rates (PFRs), disease-specific survival (DSS) rates, and adverse radiation-induced events (AREs) were evaluated. Results The median follow-up periods were 26 months. SRS was performed at a median prescription dose of 18 Gy for tumors with a median Ki-67 LI of 9.6%. The 3-year LCRs were 100%, 74%, and 25% in the low, intermediate, and high LI groups, respectively (p = 0.011). The 3-year PFRs were 100%, 40%, and 0% in the low, intermediate, and high LI groups (p = 0.003). The 5-year DSS rates were 100%, 89%, and 50% in the low, intermediate, and high LI groups (p = 0.019). Multivariable Cox proportional hazard analysis showed a significant correlation of high LI with lower LCR (hazard ratio [HR], 3.92; 95% confidence interval [CI], 1.18–13.04, p = 0.026), lower PFR (HR, 3.80; 95% CI, 1.46–9.88, p = 0.006), and shorter DSS (HR, 6.55; 95% CI 1.19–35.95, p = 0.031) compared with intermediate LI. The ARE rates were minimal (8%) in the entire group. Conclusion Patients with high Ki-67 LI showed significantly more tumor progression and tumor-related death. Ki-67 LI might offer valuable predictive insights for the post-SRS management of atypical meningiomas.

BAKGROUND Polymorphous adenocarcinomas (PACs) are rare tumors arising from the salivary glands. Radical resection and postoperative radiotherapy are the mainstays of treatment. However, complete tumor resection is not always achievable when the tumor invades the skull base. Stereotactic radiosurgery (SRS) could be a less invasive alternative for treating skull base PACs. OBSERVATIONS A 70-year-old male with a history of surgery for a right palatine PAC presented with right visual impairment, diplopia, and ptosis. Imaging studies revealed tumor recurrence invading the right cavernous sinus (CS). SRS using a gamma knife was performed for this recurrence, prescribing a marginal dose of 18 Gy at a 50% isodose line. Five months after SRS, his symptoms were relieved, and the tumor was well-controlled for 55 months without any adverse events. LESSONS To the best of the authors’ knowledge, this is the world’s first case of recurrent skull base PAC invading the CS that was successfully treated with salvage SRS. Thus, SRS may be an applicable treatment option for skull base PACs.

The central nervous system germ cell tumor (CNS GCT) is a rare and incompletely understood disease. A major outstanding question in the 2015 consensus document for CNS GCT management was the utility and interpretation of the tumor markers human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) in the diagnosis of malignant non-germinomatous GCTs (hereafter NGGCTs) prior to treatment. In the current study, we assembled two geographically and ethnically different clinical cohorts from the Mayo Clinic (1988–2017) and the intracranial GCT Genome Analysis Consortium (iGCT Consortium) in Japan to address this question. Patients with both histopathological diagnosis and tumor markers available were eligible for inclusion (n = 162). Biopsy and surgical resection were performed in 85 and 77 cases, respectively. Among 77 resections, 35 demonstrated positivity for HCG, AFP, or both (45%). Seventeen of the marker-positive cases had no malignant non-germinomatous component identified on histopathology, but they were composed strictly of germinoma, teratoma, or both (49%). One embryonal carcinoma was the only marker-negative NGGCT in the study sample. Among 85 biopsies, 18 were marker positive (21%). Seven of these patients had no malignant non-germinomatous component on histopathology, suggesting the potential limitations of limited tissue sample volumes. Neither histopathological diagnosis nor tumor markers alone reliably diagnose NGGCTs due to the secretion of HCG and AFP by germinomas and teratomas. Treatment planning should incorporate integrated histopathological and laboratory-based diagnosis to optimize diagnostic and treatment strategies for this unusual and histologically heterogeneous tumor.

Stereotactic radiosurgery (SRS) is known to provide excellent tumor control with functional preservation for vestibular schwannomas (VS), but its efficacy in the other major intracranial schwannomas including trigeminal (TS), facial (FS), and jugular foramen schwannomas (JFS) has not been established yet due to their rarity. We retrospectively analyzed data of 514 consecutive patients who had intracranial schwannomas (460 VS, 22 TS, 7 FS, and 25 JFS) and underwent SRS. The 5- and 10-year tumor control rates were 97% and 94% for VS, 100% and 100% for TS, 80% and 80% for FS, and 100% and 80% for JFS. Radiation-induced complications included one hydrocephalus for TS (4.5%), no cases for FS (0%), and one hydrocephalus and one lower palsy for JFS (8.0%). Through matched cohort analysis between patients with VS and each of the non-VS, we found no statistical difference in tumor control and radiation-induced adverse events. SRS seems to provide long-term tumor control with functional preservation for TS, FS and JFS and the efficacies are similar to VS.

Abstract BACKGROUND High-definition vascular imaging is desirable for treatment planning in Gamma Knife radiosurgery (GKRS; Elekta AB) for brain arteriovenous malformations (BAVMs). Currently, rotational angiography (RA) provides the clearest 3-dimensional visualization of niduses with high spatial resolution; however, its efficacy for GKRS has not been clarified. At our institution, RA has been integrated into GKRS (RA-GKRS) for better treatment planning and outcomes since 2015. OBJECTIVE To evaluate RA-GKRS outcomes of BAVMs and compare them with conventional GKRS (c-GKRS) outcomes. METHODS We retrospectively analyzed the radiosurgical outcomes of 50 BAVMs treated with RA-GKRS compared with the 306 BAVMs treated with c-GKRS. Considering possible differences in the baseline characteristics, we also created propensity score-matched cohorts and compared the radiosurgical outcomes between them to ensure comparability. RESULTS The obliteration time was shorter in the RA-GKRS group (cumulative rate, 88% vs 65% at 4 yr [ P = .001]). Multivariate Cox proportional hazards analysis demonstrated that the RA-GKRS group (hazard ratio 2.38, 95% CI 1.58-3.60; P = .001) had a better obliteration rate. The cumulative 4-yr post-GKRS hemorrhage rates were 4.0% and 2.6% in the RA-GKRS and c-GKRS groups, respectively ( P = .558). There was a trend toward early post-GKRS signal change in the RA-GKRS group compared with the c-GKRS group (cumulative rate, 38% vs 29% at 2 yr; P = .118). Those results were also confirmed in the matched cohort analyses. CONCLUSION The integration of RA into GKRS is promising and may provide earlier nidus obliteration.

Little is known about delayed postoperative hyponatremia (DPH) accompanied with transsphenoidal surgery for non-adenomatous skull base tumors (NASBTs). Consecutive data on 30 patients with parasellar NASBT was retrospectively reviewed with detailed analyses on perioperative serial sodium levels. Serological DPH (sodium ≤ 135 mmol/L) was observed in eight (27%), with four (13%) of them being symptomatic. DPH developed on postoperative day 7–12 where the mean sodium levels were 134 mmol/L (a mean of 7 mmol/L drop from the baseline) in asymptomatic and 125 mmol/L (a mean of 17.5 mmol/L drop from the baseline) in symptomatic DPH. Serological DPH was accompanied with “weight loss and hemoconcentration (cerebral salt wasting type)” in four (50%), “weight gain and hemodilution (syndrome of inappropriate antidiuretic hormone secretion type)” in three (38%), and no significant weight change in one. Intraoperative extradural retraction of the pituitary gland was the only significant factor for serological DPH (p = 0.035; odds ratio, 12.25 (95% confidence interval, 1.27–118.36)). DPH should be recognized as one of the significant postsurgical complications associated with TSS for NASBTs. Although the underlying mechanism is still controversial, intraoperative extradural compression of the pituitary gland and subsequent dysregulation of the hypothalamo-hypophyseal axis may be responsible.

Abstract Central nervous system hemangioblastoma (CNS HB) is a benign but highly vascular tumor, which accounts for 1.7% of all intracranial tumors. CNS HBs predominantly arise in the cerebellum, brainstem, and spinal cord. Approximately 20% of CNS HB is related to von-Hippel-Lindau (VHL) disease and repeated surgical resections are often required in VHL patients due to the presence of multiple CNS HBs. To explore the differences of surgical effect between VHL disease related and sporadic CNS HBs, outcome analyses were performed based on the tumor locations. PATIENT AND METHODS: A total 83 cases that underwent surgical resections of CNS HBs at Tokyo University in 1996-2019 were included. Clinical information including age, sex, number of past surgical resections, pre- and post-operative modified Rankin Scale(mRS) were examined. RESULTS: Regarding the etiology, 46 VHL cases(cerebellum:30, medulla oblongata:6, spinal cord:10) and 37 sporadic cases (cerebellum: 28, medulla oblongata:4, spinal cord:5) were enrolled. The average changes in the postoperative mRS minus preoperative mRS were cerebellum -0.9/medulla oblongata -0.5/spinal cord -0.8 for VHL cases, and cerebellum -0.75/medulla oblongata -1/spinal cord -1 for sporadic cases. Fisher`s exact tests were used for between-group comparison. DISCUSSION: The study showed no statistically significant difference between cerebellar and spinal cord cases regarding the perioperative change in the patient capability. Because of multiple lesions and repeated surgeries, VHL patients have a possibility to present with worse neurology after surgery. Further analysis is needed to clarify differences in surgical outcome for VHL disease related and sporadic related CNS HBs.

OBJECTIVE The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization. METHODS Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol-SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups. RESULTS The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30–2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43–2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28–3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event–free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score–matched analyses. CONCLUSIONS The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.