Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery.

BACKGROUND AND OBJECTIVES: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs. METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17). CONCLUSION: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

Classification of subdural hematomas: proposal for a new system improving the ICD Coding Tools.

Background: The International Statistical Classification of Diseases (ICD) classifies subdural hematoma (SDH) as traumatic or non-traumatic. In clinical settings, however, SDH is typically described as either acute or chronic. Objective: The goal of this study was to assess how the ICD Coding Tools captures the clinical terminology and propose an improved classification that would increase the system's usefulness in administrative, statistical and research applications. Methods: We performed a retrospective analysis of patients who presented to our center with an ICD diagnostic code for either traumatic or non-traumatic SDH. A qualitative analysis of patients' charts was performed to identify elements relevant to management and prognosis, following which a meeting between expert investigators was held to elaborate a new classification of SDH. Imaging from all patients was then reviewed and cases were reclassified according to our proposed system. Results: A total of 277 SDH cases were included. Themes documented in the charts included chronicity, etiology, side, and symptoms. We created a new classification which distinguishes acute SDH (aSDH) from membrane-associated SDH (mSDH). aSDH were further divided into traumatic aSDH (taSDH) and non-traumatic aSDH (ntaSDH), while mSDH were divided into acute on chronic (a/cSDH), subacute (sSDH) and chronic (cSDH) categories. Conclusion: The ICD coding system correctly identifies taSDH and ntaSDH. However, it remains non-specific for mSDH. We propose this new SDH classification system to better capture chronicity and etiology - factors felt to impact management and prognosis.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old: a multi-institutional retrospective study.

BACKGROUND: Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old. METHOD: This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up. RESULTS: One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients. CONCLUSION: SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study.

OBJECTIVE: Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS. METHODS: This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non-life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis. RESULTS: Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively. CONCLUSIONS: SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non-life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis.

OBJECTIVE: Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs. METHODS: This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed. RESULTS: Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01). CONCLUSIONS: SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

Stereotactic radiosurgery and local control of brain metastases from triple-negative breast cancer.

OBJECTIVE: Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS. METHODS: Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy. RESULTS: Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70-90) and age of 57 years (IQR 48-67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03-0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18-20 Gy) to the median 71% isodose line (IQR 50%-84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis. CONCLUSIONS: SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study.

PURPOSE: Surgery is the treatment of choice for large vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has been suggested as an alternative to resection in selected patients. However, the safety and efficacy of SRS in Koos grade IV patients ≤ 45 years old has not been evaluated. The aim of this study is to describe the clinical and radiological outcomes of Koos grade IV in young patient managed with a single-session SRS. METHODS: This retrospective, multicenter analysis included SRS-treated patients, ≤ 45 years old presenting with non-life threatening or incapacitating symptoms due to a Koos Grade IV VS and with follow-up ≥ 12 months. Tumor control and neurological outcomes were evaluated. RESULTS: 176 patients [median age of 36.0 (IQR 9) and median tumor volume of 9.3 cm3 (IQR 4.7)] were included. The median prescription dose was 12 Gy (IQR 0.5). Median follow-up period was 37.5 (IQR 53.5) months. The 5- and 10-year progression-free survival was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases and was associated with tumor progression at the last follow-up. The probability of serviceable hearing preservation at 5- and 10-years was 56.8% and 45.2%, respectively. The probability of improvement or preservation of facial nerve function was 95.7% at 5 and 10-years. Adverse radiation effects were noted in 19.9%. New-onset hydrocephalus occurred in 4.0%. CONCLUSION: Single-session SRS is a safe and effective alternative to surgical resection in selected patients ≤ 45 years old particularly those with medical co-morbidities and those who decline resection. Longer term follow up is warranted.

Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE: To investigate the safety and efficacy of SRS for OGMs. METHODS: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001). CONCLUSION: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

OBJECTIVE: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs. METHODS: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS. RESULTS: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS. CONCLUSIONS: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.

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

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

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

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

Gliosarcoma in a Young Filipino Woman: A Case Report and Review of the Literature.

BACKGROUND Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), which is typically seen in patients age 40-60 years and located in the supratentorial region. We present an unusual case of GS in a young patient with an unusual presentation, which eventually led to the finding of this neoplasm. CASE REPORT Our patient was a 38-year-old woman originally from the Philippines who was transferred to our institution with an isolated left foot drop that developed over the course of several months. Subsequent neuroimaging revealed an extensive mixed cystic and solid mass in the posterior mesial right frontal lobe. Subtotal surgical resection revealed a multi-lobed tumor with a malignant glioma-like surface component overlying a smooth, well-encapsulated, avascular, sarcoma-like component. Neuropathologic examination of the resected tumor revealed a biphasic histologic pattern of predominantly sarcomatous components with fewer adjacent-area glial components. Post-operatively, the patient was left with a mild worsening of left leg segmental strength. She was referred to our neurooncologist colleagues for adjuvant treatment options. CONCLUSIONS Our case is unique in that it represents a rare neoplasm in a patient whose demographics are atypical for this type of tumor, as well as the unusual presentation of isolated foot drop.

Gamma Knife Stereotactic Radiosurgery for Nonvestibular Cranial Nerve Schwannomas.

BACKGROUND: Nonvestibular cranial schwannomas represent a rare type of benign intracranial tumor. Few studies have evaluated the use of stereotactic radiosurgery (SRS) as a primary management option for these lesions. We performed a retrospective review of our institution's experience focusing on efficacy with regard to tumor control and clinical symptom stabilization as well as treatment safety. METHODS: Patients were included if they underwent at least 1 SRS procedure for a nonvestibular schwannoma and had at least 6 months of available imaging follow-up. Demographic, SRS dose planning, clinical, and imaging data were collected from chart reviews of treated patients. χ2 and Kaplan-Meier analyses were performed. RESULTS: Between 2004 and 2016, 35 schwannomas were treated in 34 patients. Median follow-up was 48 months. Median age at time of treatment was 51 years. Three patients had neurofibromatosis 2. Schwannoma location was trigeminal (57%), facial (20%), jugular foramen (14%), abducens (6%), and trochlear (3%). Median margin dose delivered was 13 Gy. The 5-year and 10-year tumor control rates were 94.4% and 88.5%, respectively. Presenting clinical symptoms stabilized or improved in 79% of cases after radiosurgery, and new or worsening symptoms were seen in 21%. CONCLUSIONS: SRS is a safe and effective modality for treatment of nonvestibular cranial nerve schwannomas.