Surgical Management of Meningiomas Involving the Torcula, Transverse Sinus, and Jugular Bulb: A Technical Note and Review of the Literature.

Meningiomas that invade the confluens sinuum are rare and require extensive preoperative planning. Here, we describe the surgical and radio-oncological management of an aggressive large occipital meningioma invading the superior sagittal sinus, torcula, right and left transverse sinus down to the level of the jugular bulb in a 21-year-old female patient. Details of the surgical approach are presented to highlight the planned staged resection of this tumor at the level of the torcula to initially debulk the lesion while preserving venous outflow through the patent's sinus. Once the tumor fully occluded the confluens, a second-stage en bloc resection ensued. Postsurgical adjuvant radiation therapy was delivered via fractionated external beam therapy which has provided local control of the tumor since. This case is being discussed in the context of the pertinent literature to demonstrate the highly complex interdisciplinary and staged management of partially intravascular meningiomas involving the major venous sinuses.

Low-risk meningioma: Initial outcomes from NRG Oncology/RTOG 0539.

BACKGROUND: Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539. METHODS: This phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3. RESULTS: Among 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs. CONCLUSIONS: These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

Association of circulating markers with cognitive decline after radiation therapy for brain metastasis.

BACKGROUND: A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline. METHODS: In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment. RESULTS: The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P < .01) and higher amyloid beta (Aß 1-42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014). CONCLUSIONS: Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline.

Association of Long-term Outcomes With Stereotactic Radiosurgery vs Whole-Brain Radiotherapy for Resected Brain Metastasis: A Secondary Analysis of The N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) Randomized Clinical Trial.

Importance: Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases. Objective: To determine how the use of postoperative whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) is associated with quality of life (QOL), cognitive function, and intracranial tumor control in long-term survivors with 1 to 4 brain metastases. Design, Setting, and Participants: This secondary analysis of a randomized phase 3 clinical trial included 48 institutions in the US and Canada. Adult patients with 1 resected brain metastases but limited to those with 1 to 4 brain metastasis were eligible. Unresected metastases were treated with SRS. Long-term survivors were defined as evaluable patients who lived longer than 1 year from randomization. Patients were recruited between July 2011 and December 2015, and data were first analyzed in February 2017. For the present study, intracranial tumor control, cognitive deterioration, QOL, and cognitive outcomes were measured in evaluable patients who were alive at 12 months from randomization and reanalyzed in June 2017. Interventions: Stereotactic radiosurgery or WBRT. Main Outcomes and Measures: Intracranial tumor control, toxic effects, cognitive deterioration, and QOL. Results: Fifty-four patients (27 SRS arm, 27 WBRT arm; female to male ratio, 65% vs 35%) were included for analysis with a median follow-up of 23.8 months. Cognitive deterioration was less frequent with SRS (37%-60%) compared with WBRT (75%-91%) at all time points. More patients declined by 2 or more standard deviations (SDs) in 1 or more cognitive tests for WBRT compared with SRS at 3, 6, and 9 months (70% vs 22%, 46% vs 19%, and 50% vs 20%, respectively). A 2 SD decline in at least 2 cognitive tests was associated with worse 12-month QOL in emotional well-being, functional well-being, general, additional concerns, and total scores. Overall QOL and functional independence favored SRS alone for categorical change at all time points. Total intracranial control for SRS alone vs WBRT at 12 months was 40.7% vs 81.5% (difference, -40.7; 95% CI, -68.1% to -13.4%), respectively. Data were first analyzed in February 2017. Conclusions and Relevance: The use of SRS alone compared with WBRT resulted in less cognitive deterioration among long-term survivors. The association of late cognitive deterioration with WBRT was clinically meaningful. A significant decline in cognition (2 SD) was associated with overall QOL. However, intracranial tumor control was improved with WBRT. This study provides detailed insight into cognitive function over time in this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT01372774; ALLIANCE/CCTG: N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group).

Hypofractionated Stereotactic Radiotherapy for the Treatment of Benign Intracranial Meningiomas: Long-Term Safety and Efficacy.

INTRODUCTION: Hypofractionated stereotactic radiotherapy (hSRT) has emerged as an alternative to single-fraction stereotactic radiosurgery (SRS) and conventionally fractionated radiotherapy for the treatment of intracranial meningiomas (ICMs). However, there is a need for data showing long-term efficacy and complication rates, particularly for larger tumors in sensitive locations. METHODS: A retrospective review was conducted on adult patients with ICMs seen at a tertiary care center. Eligible patients were treated with the CyberKnife platform and had a planned treatment course of 3-5 fractions from 2011-2020. The local control was assessed based on radiographic stability and the late toxicity/radionecrosis rates were recorded. Radiographic progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: In total, 62 patients (age 26-87) with 67 treated tumors were included in this study with a median follow-up of 64.7 months. RT was delivered as the primary treatment in 62.7% of cases and for recurrence in 37.3%. The most common tumor locations were the convexity of the brain and the base of the skull. The tumor sizes ranged from 0.1-51.8 cc and the median planning target volume was 4.9 cc. The most common treatment schedule was 18 Gy in 3 fractions. The five-year PFS and OS were 85.2% and 91.0%, respectively. The late grade III/IV toxicity rate was 3.2% and the radionecrosis rate was 4.8%. CONCLUSIONS: Based on our data, hSRT remains an effective modality to treat low-grade ICMs with acceptable long-term toxicity and radionecrosis rates. hSRT should be offered to patients who are not ideal candidates for SRS while preserving the benefits of hypofractionation.

Optimizing Whole Brain Radiation Therapy Dose and Fractionation: Results From a Prospective Phase 3 Trial (NCCTG N107C [Alliance]/CEC.3).

PURPOSE: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. METHODS AND MATERIALS: NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher's exact tests. RESULTS: Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03). CONCLUSIONS: This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.

Amelanotic melanocytoma of the sella mimicking pituitary adenoma.

We describe a 50-year-old man with a well-demarcated intra- and extrasellar lesion and clinical signs of a non-functioning pituitary adenoma. Neuropathological examination revealed tumor composed of non-pigmented spindle cells arranged in tightly packed nests separated by delicate vascular septae. There was no significant cellular atypia or mitotic activity, and Ki67-positive nuclei were present in less than 1% of cells. The neoplastic cells were positive for S-100 and vimentin, and negative for numerous cellular markers including HMB45, anti-melanoma cocktail antibodies, and Masson melanin stain. Electron microscopy revealed scattered cells with small numbers of premelanosomes, aiding in the correct diagnosis of an amelanotic melanocytoma. This is the first case report of entirely amelanotic melanocytoma of meninges, and in a very unique location. BRAF was negative supporting the diagnosis of intracranial origin of the tumor. Approximately 2 years after subtotal resection and stereotactic radiosurgery the patient is alive and well with a non-progressive residual tumor.
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Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. METHODS: In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. FINDINGS: Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. INTERPRETATION: Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. FUNDING: National Cancer Institute.

Health status measurements at diagnosis as predictors of survival among adults with brain tumors.

PURPOSE: The intent of this study was to determine whether baseline measures of functional capacity and performance could be used to predict survival in adults following the diagnosis of brain tumors. PATIENTS AND METHODS: Comprehensive health status and health-related quality of life (HRQL) were measured using the Health Utilities Index (HUI; McMaster University, Hamilton, Canada) system by a self-assessment questionnaire in a survey of 100 consecutive patients. The Karnofsky Performance Score (KPS) and Folstein's Mini-Mental State Examination (MMSE) scores were measured by a physician blinded to the HUI results. The patients were observed for up to 5 years to recorded dates of death. RESULTS: An HUI questionnaire was completed for 93% of the patients and 69% died within 5 years of assessment. The HUI revealed a burden of morbidity and complexity of disability that far exceeded that reported for the general population. KPS and MMSE correlated strongly with each other (r = 0.52; P < .001). A decrease of 0.1 units in HUI Mark 2 (HUI2) self-care single-attribute utility score was associated with an increased hazard of death of 30% (P = .023) for patients with low-grade tumors (n=25). For patients with high-grade tumors (n=56), a 10 unit decrease in the KPS, a 5 unit decrease in MMSE, and a 0.1 decrease in HUI Mark 3 (HUI3) speech and dexterity single-attribute scores were associated with an increased hazard of death of 20% (P = .022), 26% (P = .015), 36% (P = .021), and 18% (P = .035), respectively. CONCLUSION: Scores derived from the measurement of HRQL following diagnosis can predict survival in adults with brain tumors.