Medical Bulletin 28/October/2022

Researchers have identified a range of genetic alterations in glioma brain cancers that will help them to understand how different mutations in one particular gene interact with other gene alterations and which ones are more susceptible to targeted treatments in adults.

BRAF alterations are important to identify in brain tumours because they can determine treatment. However, it is unclear what types of BRAF alterations occur in adults with glioma, and whether specific BRAF alterations are associated with other gene alterations or with a different clinical course.

The term 'glioma' covers several types of tumours that originate in the glial cells in the brain. Glioblastoma is the most common type in adults and children, occurring in 3.23 per 100,000 of the population, and only 7% of glioblastoma patients survive for five years after diagnosis.New and better treatments are urgently needed, and drugs have been developed that target specific BRAF mutations, such as dabrafenib and trametinib, which inhibit the BRAFv600E mutation. Knowing which mutation or combination of genetic alterations are driving a patient's cancer is crucial to choosing the best therapy that is most likely to prolong survival.

Reference:

Dr Karisa Schreck et al,Integrated molecular and clinical analysis of BRAF-mutant glioma in adults,MEETING 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

Crossword puzzles slow memory loss better than computer video games

A new study by researchers from Columbia University and Duke University published in the journal NEJM Evidence shows that doing crossword puzzles has an advantage over computer video games for memory functioning in older adults with mild cognitive impairment.

In a randomized, controlled trial, led by D.P. Devanand, researchers determined that participants (average age 71) trained in doing web-based crossword puzzles demonstrated greater cognitive improvement than those who were trained on cognitive video games.

To conduct their study, researchers at Columbia and Duke randomly assigned 107 participants with mild cognitive impairment (MCI) at the two different sites to either crossword puzzles training or cognitive games training with intensive training for 12 weeks followed by booster sessions up to 78 weeks. Both interventions were delivered via a computerized platform with weekly compliance monitoring.

Reference:

"Computerized Games Versus Crosswords Training in Mild Cognitive Impairment" 27 October 2022, NEJM Evidence,DOI: 10.1056/EVIDoa2200121

Olaparib and adavosertib, work best when given sequentially in patients with advanced tumours: results from Phase Ib STAR clinical trial

Presenting results from the phase Ib STAR clinical trial to the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain Timothy A. Yap, said that sequential dosing with the two drugs was a strategy that was safe and well-tolerated, with promising signs of anti-tumour activity in patients with a range of different cancers.

"Based on these compelling pre-clinical data, we started the STAR study investigating sequential olparib and adavosertib to patients with BRCA1, BRCA2, PALB2, ATM, ARID1A and CCNE1 alterations," said Dr Yap.

Two men and eleven women, with an average age of 50 years, enrolled in the study between April 2020 and November 2021. Five had breast cancer, five had ovarian cancer, one patient had prostate cancer, one had gastric cancer and one had bowel cancer. Ten of the patients had received three or more previous lines of chemotherapy, and cancer had continued growing in seven patients who had been treated previously with a PARP inhibitor.

Reference:

Timothy A. Yap, et al, NCI10329: Phase Ib Sequential Trial of Agents against DNA Repair (STAR) Study to investigate the sequential combination of the Poly(ADP-Ribose) Polymerase inhibitor (PARPi) olaparib (ola) and WEE1 inhibitor (WEE1i) adavosertib (ada) in patients (pts) with DNA Damage Response (DDR)-aberrant advanced tumors, enriched for BRCA1/2 mutated and CCNE1 amplified cancers