br Key words br Chemotherapy br Metastasis br Neoplasm recur

Key words
- Chemotherapy
- Metastasis
- Neoplasm recurrence
- Stereotactic radiosurgery
- Survival
Abbreviations and Acronyms
BBB: Bloodebrain barrier
CSF: Cerebrospinal fluid
HR: Hazard ratio
KPS: Karnofsky Performance Status
MRI: Magnetic resonance imaging
NSCLC: Nonesmall-cell lung cancer 
SRS: Stereotactic radiosurgery
WBRT: Whole-brain radiation therapy
From the Departments of 1Neurosurgery and 2Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; and 3Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
To whom correspondence should be addressed: Chetan Bettegowda, M.D., Ph.D.
[E-mail: [email protected]]
Journal homepage: www.journals.elsevier.com/world-neurosurgery
Available online: www.sciencedirect.com
WORLD NEUROSURGERY -: e1-e10, - 2019 www.journals.elsevier.com/world-neurosurgery e1
ORIGINAL ARTICLE
TIMOUR AL-KHINDI ET AL. EFFECT OF POST-SRS SYSTEMIC THERAPY ON PATIENT OUTCOMES
(WBRT) seems to improve overall survival in patients with mela-noma1,2 and other cancer types,3 but most patients in these studies (between 79% and 85%) had active systemic disease at the time of SRS or WBRT. Recently, Niwinska4 showed that post-WBRT systemic therapy improved overall survival in patients with iso-lated 1360614-48-7 metastases from breast cancer; however, this study did not examine other cancer types or the effect of systemic therapy on brain and systemic relapse.
The aim of the present study was to measure the effect of post-SRS systemic therapy on brain relapse, systemic relapse, and all-cause mortality in patients with isolated brain metastases and controlled or absent extracranial disease. We hypothesized that post-SRS systemic therapy would reduce the risk of subsequent brain relapse, systemic relapse, and death by eliminating sites of micrometastatic disease.
METHODS
Study Population
We retrospectively reviewed the medical records of 387 patients who received SRS for brain metastases without previous WBRT at a single institution between February 2008 and January 2017. Pa-tients were included if they met the following criteria: must have received SRS for 1 brain metastasis; >18 years of age; must have had 1 brain magnetic resonance imaging scan and 1 body computed tomography or positron emission tomography scan after SRS to assess for intracranial or systemic recurrence; must have a controlled primary tumor and absent or controlled extra-cranial metastatic disease at the time of SRS. Informed consent was exempted from retrospective review. All protocols were approved by the institutional review board.
Data Collection
We recorded the following variables from patients’ medical re-cords: age at time of SRS, gender, Karnofsky Performance Status (KPS) at time of SRS, number of brain metastases at time of SRS, volume of each brain metastasis, cancer histology, whether neurosurgical resection for the brain metastases was performed, whether controlled extracranial metastases were present or absent, time between primary cancer diagnosis and brain metastasis diagnosis, systemic therapy type and duration before and after SRS, date and extent of intracranial and systemic relapse, and date of death or last follow-up. KPS was recorded in real time during clinical encounters and was not abstracted from details in the medical record. Relapse was defined as the appearance of new metastases or the expansion of previous metastases on magnetic resonance imaging (for brain metastases) or computed tomogra-phy (for systemic metastases).
Statistical Analysis
Survival was defined as the time between SRS and the event (intracranial relapse, extracranial relapse, death, or last follow-up). Differences in Kaplan-Meier survival curves were assessed using the log-rank test. To assess factors that affect the risk of intracranial relapse, systemic relapse, and death, we performed Cox proportional hazards regression with the following pre-dictor variables: age, gender, KPS, cancer type, number of brain metastases, average brain metastasis volume, pre-SRS
systemic therapy, post-SRS systemic therapy, whether surgical resection of a brain metastasis was performed, presence of controlled extracranial metastases (vs. absent extracranial me-tastases), and time between primary tumor diagnosis and brain metastasis diagnosis. Predictor variables were selected a priori. Breast cancer was arbitrarily designated as the reference cancer type in comparisons of primary histologies. Any cancer types with a sample size 3 were binned into a category called “Other.”