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    Assessing the Effectiveness of Systemic Therapy after Stereotactic Radiosurgery on Cancer Recurrence and All-Cause Mortality
    Timour Al-Khindi1, Colette J. Shen3, Luke Peng2, Kristin J. Redmond2, Michael Lim1, Lawrence R. Kleinberg2, Chetan Bettegowda1
    - BACKGROUND: Patients with cancer often present with brain metastases in the setting of controlled extracranial disease, for which they receive stereotactic radiosurgery (SRS) and surgical resection. The role of systemic therapy after SRS is unclear. Brain metastasis indicates active cancer dissemination, and microscopic systemic disease may be present despite absence of gross disease as assessed by conventional imaging modalities.
    - OBJECTIVE: The aim was to determine if post-SRS sys-temic therapy reduces the risk of brain relapse, systemic relapse, and death in patients with brain metastases and controlled extracranial disease.
    - METHODS: We retrospectively reviewed the medical re-cords of 67 patients with controlled extracranial disease who received SRS for brain metastases. Kaplan-Meier analysis and Cox proportional hazards regression were used to assess how post-SRS systemic therapy affected the risk of brain relapse, systemic relapse, and all-cause mortality.
    - CONCLUSIONS: Only a minority of patients with brain metastases and controlled extracranial disease receive adjuvant systemic therapy after SRS, but those that do have a reduced risk of brain relapse. Post-SRS systemic therapy may act prophylactically to reduce the risk of intracranial cancer recurrence.
    Patients with cancer often present with isolated brain me-tastases in the setting of controlled or absent extracranial disease. Surgical resection and stereotactic radiosurgery (SRS) are frequently performed to treat brain metastases, but the
    role of adjuvant systemic LDN193189 therapy is unclear. Clinicians may avoid prescribing systemic therapy because of toxicity, the lack of known extracranial disease, and the poor ability of many chemothera-peutic agents to penetrate the bloodebrain barrier (BBB). On the other hand, the presence of brain metastases indicates active cancer dissemination, and microscopic metastatic disease may be present despite the absence of gross extracranial disease by im-aging modalities such as computed tomography, magnetic reso-nance imaging, and positron emission tomography. If this hypothesis is true, then giving systemic therapy after SRS may act prophylactically to reduce the risk of subsequent brain relapse, systemic relapse, and death.
    No studies have examined the efficacy of post-SRS adjuvant systemic therapy in the setting of controlled extracranial disease. Systemic therapy after SRS and whole-brain radiation therapy