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  • Microtubule No br antagonist br Vinorelbine Microtubule No b

    2020-08-04

    1 Microtubule No31
    antagonist
    Vinorelbine 2 Microtubule No32
    antagonist
    DISCUSSION
    The purpose of this study was to determine if giving post-SRS systemic therapy to patients with Mocetinostat (MGCD0103, MG0103) metastases and controlled extracranial disease acts prophylactically to reduce the risk of subsequent brain relapse, systemic relapse, and death. Although 63% of patients received systemic therapy after SRS, only a minority (31%) received it prophylactically before brain or sys-temic relapse. Kaplan-Meier analyses showed no effect of post-SRS systemic therapy on the risk of brain relapse, systemic relapse, or death. However, after adjusting for potential con-founding variables using Cox proportional hazards regression, post-SRS systemic therapy was found to reduce the risk of brain relapse but not systemic relapse or all-cause mortality.
    Our findings suggest that post-SRS systemic therapy may be an effective prophylaxis against subsequent brain relapse. The pres-ence of isolated brain metastases indicates active cancer dissem-ination; giving systemic therapy may eliminate microscopic metastases that are not yet visible by imaging or may eliminate circulating tumor cells before they reach the brain. Given that post-SRS systemic therapy did not affect all-cause mortality or systemic relapse, the benefits of post-SRS systemic therapy in reducing brain relapse must be weighed against the risks of toxicity and the financial burden to both the patient and the health care system.
    Our results highlight the lack of clinical consensus regarding the use of systemic therapy in patients with isolated brain me-tastases and controlled or absent extracranial disease. Clinical guidelines reflect this uncertainty: American Society of Clinical Oncology guidelines for management of brain metastases from breast cancer33 and melanoma34 indicate that post-SRS systemic therapy for patients with controlled extracranial disease is a viable treatment option, but insufficient evidence exists to make a strong recommendation. In our sample, only 31% of patients received post-SRS systemic therapy in the setting of controlled or absent metastatic disease, and the factors predicting whether or not a
    ORIGINAL ARTICLE TIMOUR AL-KHINDI ET AL. EFFECT OF POST-SRS SYSTEMIC THERAPY ON PATIENT OUTCOMES
    A
    B
    C
    D
    Figure 1. Kaplan-Meier analyses showing the relationship between
    postestereotactic radiosurgery (SRS) systemic therapy and brain relapse, systemic relapse, and all-cause mortality. (A) Kaplan-Meier plot showing the relationship between post-SRS systemic therapy and brain progression-free survival. No difference in brain progression-free survival was observed between patients who received systemic therapy after SRS and those who did not (P ¼ 0.43). (B) Kaplan-Meier plot showing the relationship between post-SRS systemic therapy and systemic progression-free survival. No difference in systemic progression-free survival was observed between patients who received systemic therapy after SRS and those who did not (P ¼ 0.16). (C) Kaplan-Meier plot showing the relationship between post-SRS systemic therapy and all-cause 
    Number at risk
    Time (months)
    mortality (model 1). In this model, patients in the post-SRS systemic therapy group received systemic therapy at any time before death. No difference in all-cause mortality was observed between patients who received systemic therapy after SRS and those who did not (P ¼ 0.33). (D) Kaplan-Meier plot showing the relationship between post-SRS systemic therapy and all-cause mortality (model 2). In this model, patients in the post-SRS systemic therapy group received systemic therapy before systemic relapse and brain relapse, if either occurred. No difference in all-cause mortality was observed between patients who received systemic therapy after SRS and those who did not (P ¼ 0.73). Crosses represent censored patients. The shaded regions above and below the curves represent 95% confidence intervals.
    patient received post-SRS systemic therapy are unclear. The probability of receiving post-SRS systemic therapy may depend on variables such as cancer type, performance status, and availability of effective chemotherapies with low toxicity; future studies should address these questions.
    Several other interesting findings emerged from our analyses. For instance, not all cancer types had the same potential for recurrence. Patients with the squamous cell subtype of NSCLC had a reduced risk of both brain and systemic relapse compared with
    patients with breast cancer. This finding complements recent work by Li et al.,35 who found that the probability of brain metastasis was smaller among patients with NSCLC compared with those with breast cancer. However, these findings must be interpreted with caution, because some cancer types may have more available or more effective therapeutic agents than others. In addition, we found that women had a dramatically reduced risk of systemic relapse and death compared with men, even after adjusting for differences in cancer type, age, and