Laura B. Ngwenya and E. Antonio Chiocca
Maximilian I. Ruge, Daniel Rueß, Alexandra Hellerbach, and Harald Treuer
Alexander M. Stessin, Allie Schwartz, Grigorij Judanin, Susan C. Pannullo, John A. Boockvar, Theodore H. Schwartz, Philip E. Stieg, and A. Gabriella Wernicke
The aim of this study was to examine the effect of postoperative external-beam radiation therapy (EBRT) on disease-specific survival in patients with nonbenign meningiomas.
The Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2007 was queried for cases of resected Grades II (atypical) and III (malignant) meningioma. Disease-specific survival outcomes were determined using Kaplan-Meier survival analysis and Cox proportional hazards models. Logistic regression analysis was used to determine the likelihood of receiving EBRT for Grade II versus Grade III. Because atypical and malignant meningiomas underwent WHO reclassification in 2000, the authors carried out an additional analysis of outcomes of these tumors from 2000 to 2008.
There were 657 patients included in the analysis; of these, 244 received adjuvant radiation. Compared with patients with Grade II meningioma, patients with Grade III disease were 41.9% more likely to receive EBRT after gross-total resection and 36.7% more likely to receive it after subtotal resection (95% CI 0.58–3.26). Controlling for grade, extent of resection, size and anatomical location of the tumor, year of diagnosis, race, age, and sex, adjuvant EBRT did not impart a survival benefit (HR 1.492; 95% CI 0.827–2.692). There was also no survival advantage to EBRT in an analysis of cases diagnosed after the WHO 2000 reclassification of meningiomas (HR 0.828; 95% CI 0.350–1.961).
The results of this population-based retrospective analysis demonstrate that the role of radiation remains unclear. They underscore the need for randomized prospective clinical trials to assess the usefulness of adjuvant EBRT in Grades II and III meningioma so as to define more precisely the subset of patients who may benefit from the addition of adjuvant radiation.
Diana A. Julie, Stefanie P. Lazow, Daniel B. Vanderbilt, Shoshana Taube, Menachem Z. Yondorf, Albert Sabbas, Susan Pannullo, Theodore H. Schwartz, and A. Gabriella Wernicke
Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM.
Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared.
With a median follow-up of 17.5 months for Cs-131–treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082–0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417).
Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.
A. Gabriella Wernicke, Andrew W. Smith, Shoshana Taube, Menachem Z. Yondorf, Bhupesh Parashar, Samuel Trichter, Lucy Nedialkova, Albert Sabbas, Paul Christos, Rohan Ramakrishna, Susan C. Pannullo, Philip E. Stieg, and Theodore H. Schwartz
Managing patients whose intraparenchymal brain metastases recur after radiotherapy remains a challenge. Intraoperative cesium-131 (Cs-131) brachytherapy performed at the time of neurosurgical resection may represent an excellent salvage treatment option. The authors evaluated the outcomes of this novel treatment with permanent intraoperative Cs-131 brachytherapy.
Thirteen patients with 15 metastases to the brain that recurred after stereotactic radiosurgery and/or whole brain radiotherapy were treated between 2010 and 2015. Stranded Cs-131 seeds were placed as a permanent volume implant. Prescription dose was 80 Gy at 5-mm depth from the resection cavity surface. The primary end point was resection cavity freedom from progression (FFP). Resection cavity freedom from progression (FFP), regional FFP, distant FFP, median survival, overall survival (OS), and toxicity were assessed.
The median duration of follow-up after salvage treatment was 5 months (range 0.5–18 months). The patients' median age was 64 years (range 51–74 years). The median resected tumor diameter was 2.9 cm (range 1.0–5.6 cm). The median number of seeds implanted was 19 (range 10–40), with a median activity per seed of 2.25 U (range 1.98–3.01 U) and median total activity of 39.6 U (range 20.0–95.2 U). The 1-year actuarial local FFP was 83.3%. The median OS was 7 months, and 1-year OS was 24.7%. Complications included infection (3), pseudomeningocele (1), seizure (1), and asymptomatic radionecrosis (RN) (1).
After failure of prior irradiation of brain metastases, re-irradiation with intraoperative Cs-131 brachytherapy implants provides durable local control and limits the risk of RN. The authors' initial experience demonstrates that this treatment approach is well tolerated and safe for patients with previously irradiated tumors after failure of more than 1 radiotherapy regimen and that it results in excellent response rates and minimal toxicity.
Asif Raza Shafiq, A. Gabriella Wernicke, Charles Alex Riley, Peter F. Morgenstern, Lucy Nedialkova, Susan C. Pannullo, Bhupesh Parashar, Rajiv Magge, and Theodore H. Schwartz
There are few therapeutic options available for the treatment of recurrent meningiomas that have failed treatment with surgery and external-beam radiation therapy (EBRT). As additional EBRT is clinically risky, brachytherapy offers an important alternative for optimizing local control. In skull base meningiomas, the endoscopic endonasal approach (EEA) has demonstrated an excellent extent of resection. However, in the case of recurrent, atypical, or residual meningiomas, the EEA alone may not be adequate to address microscopic, residual, highly proliferative disease. In this situation, local radioactive seed brachytherapy has been shown to improve control, but few reports of this technique exist. A 48-year-old right-handed man presented on multiple occasions with recurrence of an anaplastic skull base meningioma, after multiple prior gross-total resections and multiple rounds of radiotherapy had failed. The authors performed a maximally safe neurosurgical tumor resection via EEA supplemented by the intraoperative implantation of 131Cs low-dose permanent brachytherapy seeds. They describe a technique for permanent implantation of brachytherapy seeds and provide operative video of this technique. The authors submit that utilizing this technique in combination with EEA tumor resection renders a minimally invasive approach to improving local control in a patient with a recurrent anaplastic or atypical meningioma of the skull base.
A. Gabriella Wernicke, Menachem Z. Yondorf, Luke Peng, Samuel Trichter, Lucy Nedialkova, Albert Sabbas, Fridon Kulidzhanov, Bhupesh Parashar, Dattatreyudu Nori, K. S. Clifford Chao, Paul Christos, Ilhami Kovanlikaya, Susan Pannullo, John A. Boockvar, Philip E. Stieg, and Theodore H. Schwartz
Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10–15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 (131Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent 131Cs brachytherapy at the resection for brain metastases.
After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded 131Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity.
The median follow-up was 19.3 months (range 12.89–29.57 months). The median age was 65 years (range 45–84 years). The median size of resected tumor was 2.7 cm (range 1.5–5.5 cm), and the median volume of resected tumor was 10.31 cm3 (range 1.77–87.11 cm3). The median number of seeds used was 12 (range 4–35), with a median activity of 3.82 mCi per seed (range 3.31–4.83 mCi) and total activity of 46.91 mCi (range 15.31–130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%–99.1%). One-year distant FFP was 48.4% (95% CI 26.3%–67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%–67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis.
The use of postresection permanent 131Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.