Paediatric Low Grade Gliomas (PLGG)

In collaboration with the Hawkins Laboratory, we currently have the largest PLGG clinical-pathological database in the world which includes more than 1000 patients and tumours. Furthermore, this clinical and biological repository is linked to >30 years of follow-up on these patients. We have utilised this Canadian effort in a series of >20 papers to demonstrate the following:

  1. Clinical observations:
    • Defined the clinical and epidemiological role of PLGG located in the optic pathway, brain-stem and spinal cord; each with it’s unique clinical outcome;
    • Defined the role of surgery, chemotherapy and radiation therapy in these tumours; specifically we have shown that radiation is not superior to other modalities and should be avoided if possible to these children;
    • Demonstrated that second line chemotherapy is as efficacious as first line in this unique group of tumours; a fact that relates to oncogene induced senescence.
    • Radiation therapy results in risk of late deaths in adult survivors of PLGG (Cancer 2016).
  2. With funding from OICR, we were able to construct 2 prospective trans-Canadian and international clinical trials for PLGG. These are the ONLY prospective clinical trials which collect biological tissues (J Clin Oncol 2013, J Clin Oncol 2016).
  3. Together with Dr Nada Jabado from Montreal, we were one of the first to demonstrate that PLGGs possess the unique BRAF duplication (Brit Journal Cancer, 2008). We then extended our findings to demonstrate that this results in oncogene induced senescence and favourable outcome for these patients (Clin Cancer Res, 2011, Jacob et al Clin Cancer Res, 2011). We also uncovered the genetic events leading to transformation of PLGG (J clin Oncol 2015).
  4. With funding from the Pediatric Brain Tumor Foundation USA, we are currently finalising results from a long term outcome study looking at host and tumour determinants of neurocognitive and functional status of PLGG survivors.
  5. As a result of our work, we currently serve as a Canadian and international reference centre for biology and clinical testing of PLGG and are leading a clinical trial with targeted BRAF V600E inhibitor.

Over the next few years our aims are to transform observations in our 3 areas of research to clinical implications for children with cancer.