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Minh P. Nguyen, Ramin A. Morshed, Cecilia L. Dalle Ore, Daniel D. Cummins, Satvir Saggi, William C. Chen, Abrar Choudhury, Akshay Ravi, David R. Raleigh, Stephen T. Magill, Michael W. McDermott, and Philip V. Theodosopoulos

OBJECTIVE

Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas.

METHODS

The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence.

RESULTS

The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%–99.9%), 91.0% (95% CI 87.7%–93.6%), 83.6% (95% CI 78.6%–87.6%), and 77.3% (95% CI 69.7%–83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13–1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03–1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery.

CONCLUSIONS

Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

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Penny K. Sneed, Jason W. Chan, Lijun Ma, Steve E. Braunstein, Philip V. Theodosopoulos, Shannon E. Fogh, Jean L. Nakamura, Lauren Boreta, David R. Raleigh, Benjamin P. Ziemer, Olivier Morin, Shawn L. Hervey-Jumper, and Michael W. McDermott

OBJECTIVE

The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs.

METHODS

Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI.

RESULTS

A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7–9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6–13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01–3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS.

CONCLUSIONS

RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.

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Joseph H. Garcia, Ramin A. Morshed, Jason Chung, Miguel A. Millares Chavez, Vivek Sudhakar, Satvir Saggi, Lauro N. Avalos, Aaron Gallagher, Jacob S. Young, Mariza Daras, Michael W. McDermott, Paul A. Garcia, Edward F. Chang, and Manish K. Aghi

OBJECTIVE

Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors.

METHODS

Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non–small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures.

RESULTS

Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively.

CONCLUSIONS

Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion–targeting therapeutic interventions on seizure control in these patients.

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Tiit Mathiesen, Jeppe Haslund-Vinding, Jane Skjøth-Rasmussen, Lars Poulsgaard, Kåre Fugleholm, Christian Mirian, Andrea Daniela Maier, Thomas Santarius, Frantz Rom Poulsen, Vibeke Andrée Larsen, Bjarne Winther Kristensen, David Scheie, Ian Law, and Morten Ziebell

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William C. Chen, Matthieu Lafreniere, Christina Phuong, S. John Liu, Joe D. Baal, Michael Lometti, Olivier Morin, Benjamin Ziemer, Harish N. Vasudevan, Calixto-Hope G. Lucas, Shawn L. Hervey-Jumper, Philip V. Theodosopoulos, Stephen T. Magill, Shannon Fogh, Jean L. Nakamura, Lauren Boreta, Penny K. Sneed, Michael W. McDermott, David R. Raleigh, and Steve E. Braunstein

OBJECTIVE

The authors’ objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors.

METHODS

The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0.

RESULTS

Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7–25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3–3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6–36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively.

CONCLUSIONS

Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

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Maria R. H. Castro, Stephen T. Magill, Ramin A. Morshed, Jacob S. Young, Steve E. Braunstein, Michael W. McDermott, and Edward F. Chang

OBJECTIVE

Tumors compressing the trigeminal nerve can cause facial pain, numbness, or paresthesias. Limited data exist describing how these symptoms change after resection and what factors predict symptom improvement. The objective of this study was to report trigeminal pain and sensory outcomes after tumor resection and identify factors predicting postoperative symptom improvement.

METHODS

This retrospective study included patients with tumors causing facial pain, numbness, or paresthesias who underwent resection. Trigeminal schwannomas were excluded. Logistic regression, recursive partitioning, and time-to-event analyses were used to report outcomes and identify variables associated with facial sensory outcomes.

RESULTS

Eighty-six patients met inclusion criteria, and the median follow-up was 3.1 years; 63 patients (73%) had meningiomas and 23 (27%) had vestibular schwannomas (VSs). Meningioma patients presented with pain, numbness, and paresthesias in 56%, 76%, and 25% of cases, respectively, compared with 9%, 91%, and 39%, respectively, for patients with VS. Most meningioma patients had symptoms for less than 1 year (60%), whereas the majority of VS patients had symptoms for 1–5 years (59%). The median meningioma and VS diameters were 3.0 and 3.4 cm, respectively. For patients with meningiomas, gross-total resection (GTR) was achieved in 27% of patients, near-total resection (NTR) in 29%, and subtotal resection (STR) in 44%. For patients with VS, GTR was achieved in 9%, NTR in 30%, and STR in 61%. Pain improved immediately after tumor resection in 81% of patients and in 92% of patients by 6 weeks. Paresthesias improved immediately in 80% of patients, increasing to 84% by 6 weeks. Numbness improved more slowly, with 52% of patients improving immediately, increasing to 79% by 2 years. Pain recurred in 22% of patients with meningiomas and 0% of patients with VSs. After resection, the Barrow Neurological Institute (BNI) facial pain intensity score improved in 73% of patients. The tumor diameter significantly predicted improvement in BNI score (OR 0.47/cm larger, 95% CI 0.22–0.99; p = 0.047). Complete decompression of the trigeminal nerve was associated with qualitative improvement in pain (p = 0.037) and decreased pain recurrence (OR 0.08, 95% CI 0.01–0.67; p = 0.024).

CONCLUSIONS

Most patients with facial sensory symptoms caused by meningiomas or VSs experienced improvement after resection. Surgery led to immediate and sustained improvement in pain and paresthesias, whereas numbness was slower to improve. Patients with smaller tumors and complete decompression of the trigeminal nerve were more likely to experience improvement in facial pain.

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Zachary A. Seymour, Jason W. Chan, Michael W. McDermott, Inga Grills, Hong Ye, Hideyuki Kano, Craig A. Lehocky, Rachel C. Jacobs, L. Dade Lunsford, Tomas Chytka, Roman Liščák, Cheng-Chia Lee, Huai-che Yang, Dale Ding, Jason P. Sheehan, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Veronica L. Chiang, Judith A. Hess, Samuel Sommaruga, Brendan McShane, John Y. K. Lee, Lucas T. Vasas, Anthony M. Kaufmann, and Penny K. Sneed

OBJECTIVE

The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs).

METHODS

This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3–6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic.

RESULTS

Patients received 2–4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7–94.4 cm3), with a median margin dose per stage of 17 Gy (range 12–20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE.

CONCLUSIONS

Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

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Ramin A. Morshed, Nicole T. Jiam, Elaina J. Wang, Stephen T. Magill, Renata M. Knoll, Elliott D. Kozin, Philip V. Theodosopoulos, Steven W. Cheung, Jeffrey D. Sharon, and Michael W. McDermott

OBJECTIVE

Ménière’s disease is an inner ear disorder classically characterized by fluctuating hearing loss, tinnitus, and aural fullness accompanied by episodic vertigo. While the pathogenesis of Ménière’s remains under debate, histopathological analyses implicate endolymphatic sac dysfunction with inner ear fluid homeostatic dysregulation. Little is known about whether external impingement of the endolymphatic sac by tumors may present with Ménière’s-like symptoms. The authors present a case series of 7 patients with posterior fossa meningiomas that involved the endolymphatic sac and new onset of Ménière’s-like symptoms and review the literature on this rare clinical entity.

METHODS

A retrospective review of patients undergoing resection of a posterior petrous meningioma was performed at the authors’ institution. Inclusion criteria were age older than 18 years; patients presenting with Ménière’s-like symptoms, including episodic vertigo, aural fullness, tinnitus, and/or hearing loss; and tumor location overlying the endolymphatic sac.

RESULTS

There were 7 cases of posterior petrous face meningiomas involving the vestibular aperture presenting with Ménière’s-like symptoms. Imaging and intraoperative examination confirmed no cranial nerve VIII compression or labyrinthine artery involvement accounting for audiovestibular symptoms. Of the 7 patients in the series, 6 experienced significant improvement or resolution of their vertigo, and all 7 had improvement or resolution of their tinnitus after resection. Of the 5 patients who had preoperative hearing loss, 2 experienced improvement or resolution of their ipsilateral preoperative hearing deficit, whereas the other 3 had unchanged hearing loss compared to preoperative evaluation.

CONCLUSIONS

Petrous face meningiomas overlying the endolymphatic sac can present with a Ménière’s syndrome. Early recognition and microsurgical excision of these tumors is critical for resolution of most symptoms and stabilization of hearing loss.

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Alfio Spina, Nicola Boari, and Pietro Mortini