"The Effect of Simvastatin on The Clinical Outcome of Patients with Brain Metastases Treated with Radiation Therapy: a Pilot Study"

Abstract

Introduction: Brain metastases (BM) are the most common intracranial tumors in adult and are considered one of the most feared complication of cancer. The management of BM encompasses combination of definitive and supportive treatment.Definitive treatment options are surgery, stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT).Whole brain radiation therapy is indicated for most patients due to the presence of multiple brain lesions, extracranial metastases or other comorbidities that make surgery and SRS not suitable. Whole brain radiation therapy only extends patients survival from 1-2 months to 6-8 months compared to the use of supportive treatment only. Hence, there have been increasing efforts to develop strategies to enhance the efficacy of WBRT without adding additional toxicity to normal tissue. Preclinical studies have shown that statins might have a radiosensitizing radioprotective effect that may enhance BM treatment. Aim of the work: The current study was designed to evaluate the effect of simvastatin addition to WBRT on the clinical outcome of patients with BM. Patients and methods: The study was carried out, at the Clinical Oncology Department-Ain Shams University Hospitals, on 50 Egyptian cancer patients with BM who were randomized to one of the two groups: Control group received WBRT 30 Gy (divided on 10 fractions, 5 fractions/week), andSimvastatin group received the same regimen of WBRT in addition to simvastatin 80 mg once dailyfor the radiation therapy period. The study objectives were evaluation of radiological responseat 4-weeks after WBRT, 1-year progression free survival (PFS) and1-year overall survival (OS), in addition to evaluation of the following parameters at baseline, after WBRT and 4-weeks after WBRT; neurocognitive function assessment using Montreal cognition assessment (MoCA) test and quality of life (QOL) assessment using Katz index of independence in activities of daily livingand health related quality of life (HRQL)questionnaire EORTC QLQ-C30and its brain module BN20. Safety evaluation included myopathy assessment, liver function tests evaluation at baseline and after WBRT and assessment of WBRT toxicity profile. Baseline and after WBRT levels of serum S100B protein, a potential prognostic marker of brain injury, were also evaluated. Results: The current study has shown that there were non-significant differences between the two arms with respect to radiological response, 1-year PFS and 1-year OS. At baseline, all patients had cognition impairment (MoCA score < 26). Non-significant differences were found between groups and within group with respect to baseline, after WBRT and 4-weeks after WBRT scores of MoCA. Regarding patients' QOL,non-significant changes were found between the two groups and within group regarding Katz index scores at baseline, after WBRT and 4-weeks after WBRT. The HRQL questionnaires' results have shown thatthere were non-significant differencesbetween groups and within groupexcept with the hair loss scale that showed significant deterioration at 4-weeks after WBRT in both arms. The addition of simvastatin was tolerated with no added or unexpected toxicity.There was no significant difference at baseline among the two groups and the healthy control regarding serum S100B protein and the comparisons of baseline and after WBRT between groups showed non-significant changes. Conclusion: The addition of simvastatin 80 mg once daily to WBRT was tolerated but it has not improved the clinical outcomes of patients with BM. Key words: Simvastatin–Brain metastases–Whole brain radiation therapy –Quality of life – S100B protein.