Uncovering the mysteries of relapsed brain tumours
Findings from a large international study on the genomic profile of medulloblastoma at the time of relapse may lay foundation for future clinical trials to develop new therapeutic strategies.
Research led by The Hospital for Sick Children (SickKids), St. Jude Children’s Research Hospital and the German Cancer Research Centre has provided a comprehensive view of the genomics of medulloblastoma tumours at diagnosis and relapse in the largest international study of its kind.
Medulloblastoma is the most common type of malignant brain cancer in children and a major cause of cancer-related death. The cancer is often fatal if it re-occurs after radiotherapy, so the team of researchers sought to understand how the tumour changes at the time of relapse by studying tissues before and after treatment.
Published on January 27 in the Journal of Clinical Oncology, the researchers found that recurrent tumours were different from the primary tumours, yet they shared the same “driver mutations” that originally caused the cancer to develop. In addition, the team also found that five per cent of the tumours investigated were not relapsed medulloblastoma, but, in fact, separate radiation-induced tumours.
“Unfortunately, we don’t have effective options for treating medulloblastoma when the tumours have relapsed which occurs in up to one-third of patients. With these findings, we have an even deeper clinical and biological understanding of relapsed medulloblastoma that will help us design better approaches at the time of initial diagnosis to improve outcomes,” says Dr. Vijay Ramaswamy, Staff Physician in the Division of Haematology/Oncology and Scientist-Track Investigator in the Developmental & Stem Biology program at SickKids and co-senior author of the publication.
Medulloblastoma tumour specimens from over 400 patients were collected and analyzed – both before and after treatment – using detailed molecular characterization. Through DNA methylation arrays and next-generation whole-exome sequencing, the researchers were able to find out how the tumours changed at relapse. They also determined that the subgroup and subtype of the tumour did not change at the time of relapse, confirming the strength and accuracy of initial classifications of medulloblastoma at diagnosis.
With a new detailed molecular understanding of the tumours, the next step for the team will be planning clinical trials for novel therapies to treat relapsed medulloblastoma. These future trials will study the use of options such as individualized therapies based on the tumour profile at the time of diagnosis, rather than the widespread approach of trying to predict who will relapse.
This work was supported by the American Lebanese Syrian Associated Charities, Alexander and Margaret Stewart Trust, American Association for Cancer Research, Alex's Lemonade Stand Foundation for Childhood Cancer, C.R. Younger Foundation, Canadian Institutes of Health, St. Jude Children's Research Hospital, St. Baldrick's Foundation and SickKids Foundation.