Prevention of endometrial cancer through lifestyle Interventions: A systematic review and synthesis.

Endometrial cancer is the most common gynaecological malignancy in Australia. Epidemiological studies have widely documented the association of endometrial cancer with modifiable lifestyle risk factors, most notably obesity. However, preventative strategies for endometrial cancer have not been well reported. The objective of this systematic review was to identify interventions targeted towards modifiable lifestyle risk factors that may reduce the risk of endometrial cancer. Literature published in the past ten years (January 2010 - January 2021) was retrieved from PubMed, Embase and Web of Science literature databases. Of 593 studies potentially eligible, 41 were assessed in full-text, and nine studies were included in the systematic review and synthesis without meta-analysis following the SWiM guidelines. The included studies were highly heterogenous with respect to the type of interventions implemented and the outcomes measured. We identified that diet and physical activity interventions, surgical weight loss interventions, and hormonal interventions were associated with changes in endometrial cancer biomarkers including circulating hormones and tissue markers. We identified a reduction in endometrial proliferation following lifestyle intervention as measured by the ki-67 proliferation index. Furthermore we identified an increase in adiponectin (a circulating biomarker of adiposity) following lifestyle intervention and a reduction in circulating insulin levels following lifestyle intervention. This review highlighted that the area of endometrial cancer prevention research is in its infancy and that further investigation of diet and physical activity interventions, surgical weight loss interventions, and hormonal interventions should be undertaken due to promising preliminary evidence.

Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma.

Glioblastoma is a brain neoplasm with limited 5-year survival rates. Developments of new treatment regimens that improve patient survival in patients with glioblastoma are needed. It is likely that a number of existing drugs used in other conditions have potential anticancer effects that offer significant survival benefit to glioblastoma patients. Identification of such drugs could provide a novel treatment paradigm.

Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method.

INTRODUCTION: Accurate knowledge of O(6)-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. METHODS: We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. RESULTS: A strong trend between a measure of 'minimum ADC' and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the 'low ADC' component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). CONCLUSION: This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.