The brain, cranial nerves, leptomeninges, spinal cord, and eye compose the central nervous system (CNS) and are at risk for the development of metastases from breast cancer. Such metastases are diagnosed on the basis of clinical suspicion and substantiated by neuroimaging, resection when indicated, and sampling of cerebrospinal fluid when leptomeningeal metastasis (LM) is suspected. Treatment is aimed at palliation of symptoms and preservation of neurologic function. Historically, conventional radiation therapy has been the mainstay of palliative treatment for brain, cranial nerve, spinal cord, and ocular metastases. However, additional treatment options for brain metastases have been brought about by technological advances in surgery to resect brain metastases, and stereotactic radiosurgery (SRS) to focally irradiate metastases, both of which have been substantiated by data from randomized trials. Ongoing research is aimed at refining criteria to select which patients with brain metastases should undergo surgery and SRS and how these focal therapies should be optimally integrated with whole-brain radiotherapy. Therapy for LM must carefully balance the potential risks and perceived benefits associated with CNS-directed therapies. Despite advances in neuroimaging, surgery, and radiation therapy, novel treatments are needed to improve the effectiveness of treatments for CNS metastases, especially LM, while reducing attendant neurotoxicity.

https://theoncologist.onlinelibrary.wiley.com/doi/pdf/10.1634/theoncologist.8-5-398

Diagnosis and management of central nervous system metastases from breast cancer.

Purpose: To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma. Methods and Materials: Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method. Results: Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy. Conclusion: IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT.

Intensity-modulated radiation therapy (IMRT) for meningioma

Development of hypofractionated stereotactic radiosurgery (HSRS) has expanded the size of lesion that can be safely treated by focused radiation in a limited number of treatment sessions. However, clinical data regarding the efficacy and morbidity of HSRS in the treatment of cerebral metastasis is lacking. Here, we review our experience with CyberKnife® HSRS for this indication. From 2005 to 2010, we identified 37 patients with large (>3 cm in diameter) cerebral metastases resection cavity that was treated with HSRS. This constituted approximately 8% of all treated resection cavities. We reviewed dose regimens, local control, distal control, and treatment associated morbidities. Primary sites for the metastatic lesions included: lung (n = 10), melanoma (n = 12), breast (n = 9), kidney (n = 4), and colon (n = 2). All patients underwent resection of the cerebral metastasis and received 800 cGy × 3 daily fractions to the resection cavity. Of the 37 patients treated, one-year follow-up data was available for 35 patients. The median survival was 5.5 months. Actuarial local control rate at 6 months was 80%. Local failures did not correlate with prior WBRT, or tumor histology. Distant recurrence occurred in 7 of the 35 patients. Morbidities associated with HSRS totaled 9%, including radiation necrosis (n = 1, 2.9%), prolonged steroid use (n = 1, 2.9%), and new-onset seizures (n = 1, 2.9%). This study demonstrates the safety and efficacy of an 800 cGy × 3 daily fractions CyberKnife® HSRS regimen for irradiation of large resection cavity. The efficacy compares favorably to historical data derived from patients undergoing WBRT, SRS, or brachytherapy.

Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy × 3 daily fractions regimen.

✓Surgery is the mainstay for many patients with meningiomas, and it remains the standard. In large single-institution series, gross-total resection has been reported to achieve 5-, 10-, and 15-year recurrence-free survival rates of approximately 90, 80, and 70%, respectively. There are a growing number of series of patients with prolonged follow-up in which authors have evaluated fractionated external-beam radiation therapy (EBRT) either as an adjuvant to surgery for subtotally resected, recurrent, or higher-grade meningiomas, or as an alternative to surgery. The primary focus of this review is EBRT, but to lend perspective, a comparative analysis of surgery and radiosurgery is also provided.

/pdf/role-of-radiation-therapy-in-treating-intracranial-2lmlr914rx.pdf

Role of radiation therapy in treating intracranial meningiomas

43 patients with meningiomas of the cavernous sinus form the basis of this study. Two patients were treated with microsurgery alone, 17 patients were treated by Gamma Knife radiosurgery (GKRS) as a pr

Cavernous sinus meningiomas--what is the strategy: upfront or adjuvant gamma knife surgery?

We review 48 cases of meningioma treated with Gamma Knife radiosurgery. The mean marginal dose was 15 Gy and the mean follow-up was 12 months. Follow-up computed tomography and magnetic resonance imaging showed tumor shrinkage in 19 cases, central necrosis in 1 case, loss of contrast enhancement in 1 case, and no change in 27 cases. We noted 4 cases of radiation-induced edema in supratentorial meningiomas.

Gamma Knife radiosurgery for meningiomas: four cases of radiation-induced edema.

Stereotactic radiosurgery for the treatment of brain metastases

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Gamma Knife radiosurgery for meningiomas: four cases of radiation-induced edema.

Stereotactic radiosurgery for the treatment of brain metastases