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Stephen T. Magill, David S. Lee, Adam J. Yen, Calixto-Hope G. Lucas, David R. Raleigh, Manish K. Aghi, Philip V. Theodosopoulos, and Michael W. McDermott

OBJECTIVE

Skull base meningiomas are surgically challenging tumors due to the intricate skull base anatomy and the proximity of cranial nerves and critical cerebral vasculature. Many studies have reported outcomes after primary resection of skull base meningiomas; however, little is known about outcomes after reoperation for recurrent skull base meningiomas. Since reoperation is one treatment option for patients with recurrent meningioma, the authors sought to define the risk profile for reoperation of skull base meningiomas.

METHODS

A retrospective review of 2120 patients who underwent resection of meningiomas between 1985 and 2016 was conducted. Clinical information was extracted from the medical records, radiology data, and pathology data. All records of patients with recurrent skull base meningiomas were reviewed. Demographic data, presenting symptoms, surgical management, outcomes, and complications data were collected. Kaplan-Meier analysis was used to evaluate survival after reoperation. Logistic regression was used to evaluate for risk factors associated with complications.

RESULTS

Seventy-eight patients underwent 100 reoperations for recurrent skull base meningiomas. Seventeen patients had 2 reoperations, 3 had 3 reoperations, and 2 had 4 or more reoperations. The median age at diagnosis was 52 years, and 64% of patients were female. The median follow-up was 8.5 years. Presenting symptoms included cranial neuropathy, headache, seizure, proptosis, and weakness. The median time from initial resection to first reoperation was 4.4 years and 4.1 years from first to second reoperation. Seventy-two percent of tumors were WHO grade I, 22% were WHO grade II, and 6% were WHO grade III. The sphenoid wing was the most common location (31%), followed by cerebellopontine angle (14%), cavernous sinus (13%), olfactory groove (12%), tuberculum sellae (12%), and middle fossa floor (5%). Forty-four (54%) tumors were ≥ 3 cm in maximum diameter at the time of the first reoperation. In 100 reoperations, 60 complications occurred in 30 cases. Twenty of the 60 complications required surgical intervention (33%). Complications included hydrocephalus (12), CSF leak/pseudomeningocele (11), wound infection (9), postoperative hematoma (4), venous infarction (1), and pneumocephalus (1). Postoperative neurological deficits included new or worsened cranial nerve deficits (10) and hemiparesis (3). There were no perioperative deaths in this series. On multivariate analysis, posterior fossa location was significantly associated with complications (OR 3.45, p = 0.0472). The 1-, 2-, 5-, and 10-year overall survival rates according to Kaplan-Meier analysis after the first reoperation were 94%, 92%, 88%, and 76%, respectively. The median survival after the first reoperation was 17 years.

CONCLUSIONS

Recurrent skull base meningiomas are surgically challenging tumors, and reoperation is associated with high morbidity and complication rates. Despite these cautionary data, repeat resection of recurrent skull base meningiomas in appropriately selected patients provides excellent long-term survival.

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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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William C. Chen, Stephen T. Magill, Ashley Wu, Harish N. Vasudevan, Olivier Morin, Manish K. Aghi, Philip V. Theodosopoulos, Arie Perry, Michael W. McDermott, Penny K. Sneed, Steve E. Braunstein, and David R. Raleigh

OBJECTIVE

The goal of this study was to investigate the impact of adjuvant radiotherapy (RT) on local recurrence and overall survival in patients undergoing primary resection of atypical meningioma, and to identify predictive factors to inform patient selection for adjuvant RT.

METHODS

One hundred eighty-two patients who underwent primary resection of atypical meningioma at a single institution between 1993 and 2014 were retrospectively identified. Patient, meningioma, and treatment data were extracted from the medical record and compared using the Kaplan-Meier method, log-rank tests, multivariate analysis (MVA) Cox proportional hazards models with relative risk (RR), and recursive partitioning analysis.

RESULTS

The median patient age and imaging follow-up were 57 years (interquartile range [IQR] 45–67 years) and 4.4 years (IQR 1.8–7.5 years), respectively. Gross-total resection (GTR) was achieved in 114 cases (63%), and 42 patients (23%) received adjuvant RT. On MVA, prognostic factors for death from any cause included GTR (RR 0.4, 95% CI 0.1–0.9, p = 0.02) and MIB1 labeling index (LI) ≤ 7% (RR 0.4, 95% CI 0.1–0.9, p = 0.04). Prognostic factors on MVA for local progression included GTR (RR 0.2, 95% CI 0.1–0.5, p = 0.002), adjuvant RT (RR 0.2, 95% CI 0.1–0.4, p < 0.001), MIB1 LI ≤ 7% (RR 0.2, 95% CI 0.1–0.5, p < 0.001), and a remote history of prior cranial RT (RR 5.7, 95% CI 1.3–18.8, p = 0.03). After GTR, adjuvant RT (0 of 10 meningiomas recurred, p = 0.01) and MIB1 LI ≤ 7% (RR 0.1, 95% CI 0.003–0.3, p < 0.001) were predictive for local progression on MVA. After GTR, 2.2% of meningiomas with MIB1 LI ≤ 7% recurred (1 of 45), compared with 38% with MIB1 LI > 7% (13 of 34; p < 0.001). Recursive partitioning analysis confirmed the existence of a cohort of patients at high risk of local progression after GTR without adjuvant RT, with MIB1 LI > 7%, and evidence of brain or bone invasion. After subtotal resection, adjuvant RT (RR 0.2, 95% CI 0.04–0.7, p = 0.009) and ≤ 5 mitoses per 10 hpf (RR 0.1, 95% CI 0.03–0.4, p = 0.002) were predictive on MVA for local progression.

CONCLUSIONS

Adjuvant RT improves local control of atypical meningioma irrespective of extent of resection. Although independent validation is required, the authors’ results suggest that MIB1 LI, the number of mitoses per 10 hpf, and brain or bone invasion may be useful guides to the selection of patients who are most likely to benefit from adjuvant RT after resection of atypical meningioma.

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William C. Chen, Stephen T. Magill, Ashley Wu, Harish N. Vasudevan, Olivier Morin, Manish K. Aghi, Philip V. Theodosopoulos, Arie Perry, Michael W. McDermott, Penny K. Sneed, Steve E. Braunstein, and David R. Raleigh

OBJECTIVE

The goal of this study was to investigate the impact of adjuvant radiotherapy (RT) on local recurrence and overall survival in patients undergoing primary resection of atypical meningioma, and to identify predictive factors to inform patient selection for adjuvant RT.

METHODS

One hundred eighty-two patients who underwent primary resection of atypical meningioma at a single institution between 1993 and 2014 were retrospectively identified. Patient, meningioma, and treatment data were extracted from the medical record and compared using the Kaplan-Meier method, log-rank tests, multivariate analysis (MVA) Cox proportional hazards models with relative risk (RR), and recursive partitioning analysis.

RESULTS

The median patient age and imaging follow-up were 57 years (interquartile range [IQR] 45–67 years) and 4.4 years (IQR 1.8–7.5 years), respectively. Gross-total resection (GTR) was achieved in 114 cases (63%), and 42 patients (23%) received adjuvant RT. On MVA, prognostic factors for death from any cause included GTR (RR 0.4, 95% CI 0.1–0.9, p = 0.02) and MIB1 labeling index (LI) ≤ 7% (RR 0.4, 95% CI 0.1–0.9, p = 0.04). Prognostic factors on MVA for local progression included GTR (RR 0.2, 95% CI 0.1–0.5, p = 0.002), adjuvant RT (RR 0.2, 95% CI 0.1–0.4, p < 0.001), MIB1 LI ≤ 7% (RR 0.2, 95% CI 0.1–0.5, p < 0.001), and a remote history of prior cranial RT (RR 5.7, 95% CI 1.3–18.8, p = 0.03). After GTR, adjuvant RT (0 of 10 meningiomas recurred, p = 0.01) and MIB1 LI ≤ 7% (RR 0.1, 95% CI 0.003–0.3, p < 0.001) were predictive for local progression on MVA. After GTR, 2.2% of meningiomas with MIB1 LI ≤ 7% recurred (1 of 45), compared with 38% with MIB1 LI > 7% (13 of 34; p < 0.001). Recursive partitioning analysis confirmed the existence of a cohort of patients at high risk of local progression after GTR without adjuvant RT, with MIB1 LI > 7%, and evidence of brain or bone invasion. After subtotal resection, adjuvant RT (RR 0.2, 95% CI 0.04–0.7, p = 0.009) and ≤ 5 mitoses per 10 hpf (RR 0.1, 95% CI 0.03–0.4, p = 0.002) were predictive on MVA for local progression.

CONCLUSIONS

Adjuvant RT improves local control of atypical meningioma irrespective of extent of resection. Although independent validation is required, the authors’ results suggest that MIB1 LI, the number of mitoses per 10 hpf, and brain or bone invasion may be useful guides to the selection of patients who are most likely to benefit from adjuvant RT after resection of atypical meningioma.

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David R. Raleigh, Zachary A. Seymour, Bryan Tomlin, Philip V. Theodosopoulos, Mitchel S. Berger, Manish K. Aghi, Sarah E. Geneser, Devan Krishnamurthy, Shannon E. Fogh, Penny K. Sneed, and Michael W. McDermott

OBJECTIVE

Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases.

METHODS

A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models.

RESULTS

The median age at surgery was 59 years (range 29.9–81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21–76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4–93), and the median activity was 0.73 mCi (range 0.34–1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0–22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02–13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05).

CONCLUSIONS

Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients.

▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

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Stephen T. Magill, Cecilia L. Dalle Ore, Michael A. Diaz, Daara D. Jalili, David R. Raleigh, Manish K. Aghi, Philip V. Theodosopoulos, and Michael W. McDermott

OBJECTIVE

Recurrent meningiomas are primarily managed with radiation therapy or repeat resection. Surgical morbidity after reoperation for recurrent meningiomas is poorly understood. Thus, the objective of this study was to report surgical outcomes after reoperation for recurrent non–skull base meningiomas.

METHODS

A retrospective review of patients was performed. Inclusion criteria were patients with recurrent meningioma who had prior resection and supratentorial non–skull base location. Univariate and multivariate logistic regression and recursive partitioning analysis were used to identify risk factors for surgical complications.

RESULTS

The authors identified 67 patients who underwent 111 reoperations for recurrent supratentorial non–skull base meningiomas. The median age was 53 years, 49% were female, and the median follow-up was 9.8 years. The most common presenting symptoms were headache, weakness, and seizure. The WHO grade after the last reoperation was grade I in 22% of cases, grade II in 51%, and grade III in 27%. The tumor grade increased at reoperation in 22% of cases. Tumors were located on the convexity (52%), parasagittal (33%), falx (31%), and multifocal (19%) locations. Tumors involved the middle third of the sagittal plane in 52% of cases. In the 111 reoperations, 48 complications occurred in 32 patients (48%). There were 26 (54%) complications requiring surgical intervention. There was no perioperative mortality. Complications included neurological deficits (14% total, 8% permanent), wound dehiscence/infection (14%), and CSF leak/pseudomeningocele/hydrocephalus (9%). Tumors that involved the middle third of the sagittal plane (OR 6.97, 95% CI 1.5–32.0, p = 0.006) and presentation with cognitive changes (OR 20.7, 95% CI 2.3–182.7, p = 0.001) were significantly associated with complication occurrence on multivariate analysis. The median survival after the first reoperation was 11.5 years, and the 2-, 5-, and 10-year Kaplan-Meier survival rates were 91.0%, 68.8%, and 50.0%, respectively.

CONCLUSIONS

Reoperation for recurrent supratentorial non–skull base meningioma is associated with a high rate of complications. Patients with cognitive changes and tumors that overlap the middle third of the sagittal plane are at increased risk of complications. Nevertheless, excellent long-term survival can be achieved without perioperative mortality.

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Cecilia L. Dalle Ore, Stephen T. Magill, Adam J. Yen, Maryam N. Shahin, David S. Lee, Calixto-Hope G. Lucas, William C. Chen, Jennifer A. Viner, Manish K. Aghi, Philip V. Theodosopoulos, David R. Raleigh, Javier E. Villanueva-Meyer, and Michael W. McDermott

OBJECTIVE

Extracranial meningioma metastases are uncommon, occurring in less than 1% of patients diagnosed with meningioma. Due to the rarity of meningioma metastases, patients are not routinely screened for distant disease. In this series, we report their experience with meningioma metastases and results of screening for metastases in select patients with recurrent meningiomas.

METHODS

All patients undergoing resection or stereotactic radiosurgery for primary or recurrent meningioma from 2009 to 2017 at a single center were retrospectively reviewed to identify patients who were diagnosed with or underwent imaging to evaluate for systemic metastases. Imaging to evaluate for metastases was performed with CT scanning of the chest, abdomen, and pelvis or whole-body PET/CT using either FDG or 68Ga-DOTA-octreotate (DOTATATE) tracers in 28 patients. Indications for imaging were symptomatic lesions concerning for metastasis or asymptomatic screening in patients with greater than 2 recurrences being evaluated for additional treatment.

RESULTS

Of 1193 patients treated for meningioma, 922 (77.3%) patients had confirmed or presumed WHO grade I tumors, 236 (19.8%) had grade II tumors, and 35 (2.9%) had grade III tumors. Mean follow-up was 4.3 years. A total of 207 patients experienced recurrences (17.4%), with a mean of 1.8 recurrences. Imaging for metastases was performed in 28 patients; 1 metastasis was grade I (3.6%), 16 were grade II (57.1%), and 11 were grade III (39.3%). Five patients (17.9%) underwent imaging because of symptomatic lesions. Of the 28 patients screened, 27 patients had prior recurrent meningioma (96.4%), with a median of 3 recurrences. On imaging, 10 patients had extracranial lesions suspicious for metastasis (35.7%). At biopsy, 8 were meningioma metastases, 1 was a nonmeningioma malignancy, and 1 patient was lost to follow-up prior to biopsy. Biopsy-confirmed metastases occurred in the liver (5), lung (3), mediastinum (1), and bone (1). The observed incidence of metastases was 0.67% (n = 8). Incidence increased to 2% of WHO grade II and 8.6% of grade III meningiomas. Using the proposed indications for screening, the number needed to screen to identify one patient with biopsy-confirmed malignancy was 3.83.

CONCLUSIONS

Systemic imaging of patients with multiply recurrent meningioma or symptoms concerning for metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision making for additional treatments.

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Michael A. Garcia, Ann Lazar, Sai Duriseti, David R. Raleigh, Christopher P. Hess, Shannon E. Fogh, Igor J. Barani, Jean L. Nakamura, David A. Larson, Philip Theodosopoulos, Michael McDermott, Penny K. Sneed, and Steve Braunstein

OBJECTIVE

High-resolution double-dose gadolinium-enhanced Gamma Knife (GK) radiosurgery-planning MRI (GK MRI) on the day of GK treatment can detect additional brain metastases undiagnosed on the prior diagnostic MRI scan (dMRI), revealing increased intracranial disease burden on the day of radiosurgery, and potentially necessitating a reevaluation of appropriate management. The authors identified factors associated with detecting additional metastases on GK MRI and investigated the relationship between detection of additional metastases and postradiosurgery patient outcomes.

METHODS

The authors identified 326 patients who received GK radiosurgery at their institution from 2010 through 2013 and had a prior dMRI available for comparison of numbers of brain metastases. Factors predictive of additional brain metastases on GK MRI were investigated using logistic regression analysis. Overall survival was estimated by Kaplan-Meier method, and postradiosurgery distant intracranial failure was estimated by cumulative incidence measures. Multivariable Cox proportional hazards model and Fine-Gray regression modeling assessed potential risk factors of overall survival and distant intracranial failure, respectively.

RESULTS

The mean numbers of brain metastases (SD) on dMRI and GK MRI were 3.4 (4.2) and 5.8 (7.7), respectively, and additional brain metastases were found on GK MRI in 48.9% of patients. Frequencies of detecting additional metastases for patients with 1, 2, 3–4, and more than 4 brain metastases on dMRI were 29.5%, 47.9%, 55.9%, and 79.4%, respectively (p < 0.001). An index brain metastasis with a diameter greater than 1 cm on dMRI was inversely associated with detecting additional brain metastases, with an adjusted odds ratio of 0.57 (95% CI 0.4–0.9, p = 0.02). The median time between dMRI and GK MRI was 22 days (range 1–88 days), and time between scans was not associated with detecting additional metastases. Patients with additional brain metastases did not have larger total radiosurgery target volumes, and they rarely had an immediate change in management (abortion of radiosurgery or addition of whole-brain radiation therapy) due to detection of additional metastases. Patients with additional metastases had a higher incidence of distant intracranial failure than those without additional metastases (p = 0.004), with an adjusted subdistribution hazard ratio of 1.4 (95% CI 1.0–2.0, p = 0.04). Significantly worse overall survival was not detected for patients with additional brain metastases on GK MRI (log-rank p = 0.07), with the relative adjusted hazard ratio of 1.07, (95% CI 0.81–1.41, p = 0.65).

CONCLUSIONS

Detecting additional brain metastases on GK MRI is strongly associated with the number of brain metastases on dMRI and inversely associated with the size of the index brain metastasis. The discovery of additional brain metastases at time of GK radiosurgery is very unlikely to lead to aborting radiosurgery but is associated with a higher incidence of distant intracranial failure. However, there is not a significant difference in survival.

▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class IV.

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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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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.