الفهرس 
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Abstract
Summary
Brain metastases are the most common brain tumors in adult. They most commonly arise from cancers of the lung, breast and skin (melanoma), but also occur at a reduced frequency in patients with diverse cancer types. Most patients with BM suffers from brain edema, seizures, cognitive impairment and other neurologic deficit depending on the tumor location. The management of BM encompasses definitive therapy and supportive care, often used in combination. Definitive therapy is directed against the tumor itself and is designed to eradicate or at least diminish the malignancy. It encompasses surgery, SRS and WBRT. In most cases, WBRT is indicated because either patients have multiple BM or other comorbidities making surgery and SRS not applicable. There has been an increasing effort to develop strategies to enhance the effect of WBRT on tumor control without increasing its lethal effect on normal tissue.
Several agents have been tested for radiosensitizing effect but still none has proven to be effective yet. Statins, a class of drugs that has been used for hypercholesterolemia management, have been shown to have radiosensitizing effect in preclinical studies. The statins as a group are generally very well tolerated, with gastrointestinal complaints such as diarrhea, pain, constipation, and flatulence being the most commonly reported adverse effects. However, there are two uncommon but potentially serious adverse effects; asymptomatic elevation in liver enzymes, and statin induced myopathy. Simvastatin, a lipophilic member of statins, was selected for this study as it has shown to have potential to cross the BBB in animal studies compared to other members.
This study was designed to evaluate the effect of simvastatin addition to WBRT on the clinical outcomes of patients with BM. The study was conducted, at Clinical Oncology Department, Ain Shams University Hospitals, on 50 Egyptian patients with BM who were randomly assigned to either:
Control group: who received WBRT [30 Gy divided on 10 fractions (5 fractions /week) using 2 dimensional technique], or
Simvastatin Group: who received WBRT [30 Gy divided on 10 fractions (5 fractions /week) using 2 dimensional technique] in addition to Simvastatin 80 mg once daily.
Summary
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All patients have received dexamethasone, furosemide and omeprazole in addition to their regimens.
All patients were subjected to history taking, baseline evaluation, and the following parameters were assessed during the study:
1- Radiological response at 4 weeks after WBRT.
2- One-year PFS and 1-year OS.
3- Neurocognitive function assessment using MoCA test at baseline, after WBRT and 4 weeks after WBRT.
4- Patients’ QOL evaluation using katz index and EORTC QLQ-C30/BN20 questionnaires at baseline, after WBRT and 4 weeks after WBRT.
5- Safety and tolerability through evaluation of liver function tests, myopathy occurrence and WBRT acute side effects.
6- Serum S100B protein evaluation at baseline, after WBRT and 4 weeks after WBRT.
The current study has shown that:
There has been a non-significant difference between the two groups regarding radiological response.
Non-significant differences have been found with respect to 1-year PFS and 1-year OS.
A non-significant difference between the two group has been found regarding neurocognitive function.
There has been a non-significant difference between the two groups regarding patients’ QOL.
No myopathy occurred during the study and all elevations in serum transaminases were clinically non-significant.
The side effects of WBRT were expected with no added toxicity.
At baseline, there has been a non-significant difference in serum levels of S100B protein in patients with BM compared to healthy control. There was a non-significant change in serum S100B protein after WBRT and the effect of simvastatin addition was non-significant