br Table also shows prognostic factors for

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