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  • br Table also shows prognostic factors for

    2020-08-12


    Table 3 also shows prognostic factors for systemic relapse after SRS. Systemic therapy after SRS did not affect the risk of systemic relapse, although there was a trend to significance (HR, 0.38; P ¼ 0.09). Women had a 92% reduced risk of systemic relapse compared with men (HR, 0.08; P < 0.001) and patients with squamous cell NSCLC had a 95% reduced risk of systemic relapse compared with those with breast cancer (HR, 0.05; P ¼ 0.02). In addition, for every 1 year increase in patient age, risk of post-SRS systemic relapse decreased by 4% (HR, 0.96; P ¼ 0.04).
    The effect of post-SRS systemic therapy on death was assessed in 2 ways (Table 3). In model 1, systemic therapy after SRS was defined as systemic therapy given at any time before death, including after 52-39-1 relapse or systemic relapse. Model 1 was, overall, not statistically significant (likelihood ratio test, 24.4; P ¼ 0.06), indicating that none of the factors affected the risk of death. In model 2, systemic therapy after SRS was defined as systemic therapy given before brain and systemic relapse, if either occurred. Model 2 was, overall, statistically significant (likelihood ratio test, 26.4; P ¼ 0.03). Giving systemic therapy after SRS did not affect the risk of all-cause mortality (HR, 2.16; P ¼ 0.09). Women had a 62% reduced risk of death compared with men (HR, 0.38; P ¼ 0.01) and for every 1-point increase in KPS, risk of death decreased by 3% (HR, 0.97; P ¼ 0.02).
    A secondary Cox proportional hazards regression analysis was performed to assess whether the ability of a drug to cross the BBB and the type of systemic therapy affected the risk of brain relapse, systemic relapse, and death. Compared with those not receiving any systemic therapy, patients receiving BBB-permeable (HR, 0.28; P ¼ 0.02) or BBB-impermeable (HR, 0.15; P ¼ 0.01) thera-pies had a 72% and 85% reduced risk of brain relapse, respectively (Table 4). Patients receiving BBB-permeable therapies also had an 84% reduced risk of systemic relapse compared with those not receiving any therapy (HR, 0.16; P ¼ 0.01). Patients receiving BBB-impermeable therapies had a higher risk of death compared with those not receiving any therapy (HR, 3.19; P ¼ 0.03). Brain and systemic relapse risks were similar among patients receiving different therapy types (Table 5), with the exception of patients receiving kinase inhibitors, red blood cell had a 95% reduced risk of systemic relapse compared with those not receiving post-SRS
    WORLD NEUROSURGERY -: e1-e10, - 2019 www.journals.elsevier.com/world-neurosurgery e3
    ORIGINAL ARTICLE
    TIMOUR AL-KHINDI ET AL. EFFECT OF POST-SRS SYSTEMIC THERAPY ON PATIENT OUTCOMES
    Table 2. Systemic Therapy Agents Received After Stereotactic Radiosurgery
    Systemic Number of
    BloodeBrain
    Therapy Patients
    Barrier
    Agent Receiving Agent Drug Class Permeable?
    5-fluorouracil 1 DNA disruption Yes5
    Anastrozole 4 Hormone No6
    antagonist
    Bevacizumab 2 Angiogenesis No7
    inhibitor
    Capecitabine 6 DNA disruption Yes8
    Carboplatin 4 DNA disruption No9
    Crizotinib 1 Kinase inhibitor No10
    Cyclophosphamide 2 DNA disruption Yes11
    Dabrafenib 2 Kinase inhibitor No12
    Docetaxel 2 Microtubule No13
    antagonist
    Doxorubicin 2 DNA disruption No14
    Eribulin 1 Microtubule No15
    antagonist
    Erlotinib 4 Kinase inhibitor Yes16
    Everolimus 2 Kinase inhibitor Yes17
    Exemestane 2 Hormone Unknown
    antagonist
    Fulvestrant 2 Hormone No18
    antagonist
    Gemcitabine 6 DNA disruption No19
    Ifosfamide 1 DNA disruption Yes11
    Ipilimumab 2 Immunotherapy No20
    Irinotecan 2 DNA disruption Yes21
    Lapatinib 3 Kinase inhibitor Yes8
    Letrozole 1 Hormone Yes6
    antagonist
    Nivolumab 5 Immunotherapy No20
    Olaparib 1 DNA disruption No22
    Osimertinib 1 Kinase inhibitor Yes23
    Paclitaxel 6 Microtubule No24
    antagonist
    Pazopanib 1 Kinase inhibitor Yes25
    Pembrolizumab 1 Immunotherapy No20
    Pemetrexed 3 DNA disruption No26
    Pertuzumab 1 Kinase inhibitor No20
    Tamoxifen 2 Hormone Yes27
    antagonist
    Temozolomide 1 DNA disruption Yes28
    Continues
    Table 2. Continued
    Systemic Number of
    BloodeBrain
    Therapy Patients
    Barrier
    Agent Receiving Agent Drug Class Permeable?
    Topotecan 2 DNA disruption Yes29
    Trametinib 2 Kinase inhibitor No30
    Trastuzumab 6 Kinase inhibitor No20
    Trastuzumab emtansine 1 Kinase inhibitor No20
    Vincristine