New research helps advance how individuals with rare form of brain cancer are treated based on age group

Research led by The Hospital for Sick Children (SickKids) may have significant implications for the best treatment approach for a highly malignant brain tumour called pineoblastoma. The study, published on December 9, 2019 in Acta Neuropathologica, represents a critical advancement in how individuals with this rare form of cancer are treated based on their age group.

Brain tumours are the leading cause of paediatric cancer-related disability and death, and rare types make up approximately three to five per cent. Embryonal brain tumours (EBTs) make up 20 per cent of all paediatric brain tumours, and include rare tumours called pineoblastoma.  To date, clinical studies of pineoblastoma have been limited by the disease’s rarity, and a lack of large, disease-specific cohorts to inform new therapeutic approaches. Together with two other studies published at the same time by the German Cancer Research Center (DKFZ) and St Jude Children’s Research Hospital, this work led by SickKids Drs. Annie Huang and Eric Bouffet, presents the first molecular picture of pineoblastoma.

“Up to now, there’s been limited progress in our biological and therapeutic understanding of pineoblastoma,” says Dr. Annie Huang, Staff Oncologist, Paediatric Brain Tumour Program and Senior Scientist, Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre at SickKids; and Professor of Paediatrics, Medical Biophysics, Lab Medicine and Pathobiology at the University of Toronto.

Traditionally, clinicians have considered pineoblastoma arising at any age to be a high-risk disease. The new research led by the Huang Lab studied one of the largest cohorts of patients and showed pineoblastoma arising in young children is molecularly and clinically very different from the disease found in adolescents and adults.

The researchers looked at tumour tissue, blood and clinical data from 93 patients diagnosed with pineoblastoma, collected from 29 centres as part of the global Rare Brain Tumor Consortium and Registry (RBTCR). Using an integrated molecular and clinic-pathologic analyses, they found that pineoblastoma is comprised of five molecular sub-groups with distinct clinical and survival features. The researchers also found that although pineoblastoma is most common in children, it can occur in a wide range of age ranges, from six months to 60 years.

Pineoblastoma in older children and adults had 70 to 100 per cent survival rates, indicating highly aggressive therapy, including intensive chemotherapy and high dose radiation, may not be needed for all individuals.

“In contrast, we see that children under the age of three have high incidence of metastases and very poor survival. Our studies provide a molecular framework critical for reducing toxic treatment for some patients and for discovering new, more effective therapies for the very high-risk disease in young children. This finding may help to accurately diagnose this disease and ensure that appropriate treatment is applied based on the individual’s risk factors,” says Dr. Bryan Li, a PhD candidate and Garron Family Cancer Center Research Fellow, who shares the first authorship with Dr. Alexandre Vasiljevic, a neuropathologist from Lyon, France.

“In addition, the SickKids study showed pineoblastoma in some patients arises due to defects in microRNA-related genes. These findings are of utmost significance for how we evaluate, treat, and think of ways of preventing development of this rare form of brain tumour in the future.”

This work, representing the largest advancement in understanding of pineoblastoma, was made possible by the RBTCR, which was started at SickKids by Huang to advance research in rare childhood brain cancers for which there remains very little information to guide diagnosis and treatment.

This work was supported by the Canadian Institutes of Health Research, b.r.a.i.n.child and SickKids Foundation.

Li holds a Garron Family Cancer Centre fellowship and SickKids Clinician-Scientist Training award, while Huang holds a Canada Research Chair in Rare Childhood Brain Tumours (Tier 1).