Children with a rare brain tumour may not need to undergo radiation therapy, a group of scientists has found. In the past, for a child diagnosed with atypical teratoid rhabdoid tumours (ATRT) it was uncertain what the best post-surgery treatment would be after removing the tumor. Typically, one of two options, and sometimes a combination of both, is followed: radiation or chemotherapy, both of which are known to have negative affects on cancerous, and healthy cells alike. These treatments take a serious toll on the emotional and physical wellbeing of the patient.However, what if a doctor could confidently avoid radiation? Imagine that doctors could predetermine whether or not radiation is going to be effective for a child with ATRT? These are the questions that motivated professor Annie Huang and, PhD candidate, Jonathon Torchia from U of T’s department of laboratory medicine and pathobiology. To find answers, they have collected 259 tumour samples of ATRT the samples were gathered from 37 international institutions.Because of the many ways that genes drive cancers, Torchia performed a complete profile of the kinds of genes expressed using the entire pool of genes from all the tumour samples. After identifying what was expressed in each sample, he then cross-referenced it with that of all the samples, highlighting specific trends, or patterns, in gene expression, resulting in something similar to a fingerprint.It turns out, that at least two such distinct fingerprints for ATRT exist. Additionally, the researchers were able to recognize a protein that can serve as a “protein marker” to distinguish between the two fingerprints.The scientist then combined gene expression fingerprints with an array of clinical features, such as the location of the tumour in the brain, whether the patient received radiation or chemotherapy, how the tumour spread, whether the entire tumour was removed, as well as the age and sex of the patient. This analysis allowed scientists to distill risk, into three distinct groups of ATRT: average, high, and very high risk.In their results, published in The Lancet Oncology, the researcher showed that the average risk group does just as well with surgery and chemotherapy, and that for this group, the use of radiation is not needed.“[N]ow when a patient comes in, a doctor can look at the features of the tumour, and the protein marker we identified, and identify which risk group the patient likely falls under, allowing him to make better post-surgery treatment decisions,” Torchia explained.While the high-risk group benefitted from radiation, unfortunately, the very high-risk group did not respond well to the current treatment options. Nevertheless, Torchia was able to identify a particular pathway of cellular signals that were prevalent within this group. He believes this signalling pathway has provided a clue that will help in designing future research to investigate the biological implications of the very high-risk group.“[B]eyond the clinical decision to use radiation or not, our study opens the doors for future clinical trials on subgroups specific treatment.” Torchia said, expressing his hope for more development in the future.Figuring out more details of these groups and the subgroups within them, will be the next step, followed by more research into enabling subgroup-driven treatment options for ATRT that are more focused.
Published: 6:06 pm, 1 July 2015