brain tumour

The Launch of the Brain Tumour Registry of Canada

admin — Wed, 03 Jul 2019 20:36:27 +0000

The Launch of the Brain Tumour Registry of Canada admin Wed, 07/03/2019 - 16:36

The Brain Tumour Registry of Canada (BTRC) which was launched this May is a national, multi-center initiative to create an epidemiological surveillance tool of brain tumours across the country. It will facilitate the development of a pan-Canadian surveillance report similar to the Central Brain Tumour Registry of the United States (CBTRUS). The similar registries in the US allow researchers to identify evolving patterns

in the incidence rates related to geographical, regional and socioeconomic differences. A Canadian-centric brain tumour registry will improve evidence-based medicine and provide critical data for improving patient care.

One of the major limitations of existing national pan-cancer registries is that benign tumours in the brain, such as acoustic neuromas and meningiomas, are not tracked. The omission of benign brain tumours provides an incomplete census on brain tumour statistics in the country. Unlike in most other organs, benign tumours that develop in the brain may lead to significant morbidity and mortality, even when successfully surgically removed. Therefore, it is imperative we track these important tumours within the country to provide accurate epidemiological data and provide government and institutions with information to help allocate health care and research funds appropriately.

Efforts to develop a Canadian brain tumour registry began in earnest in 2007, with the government passing a private member’s motion mandating the collection of all primary brain tumours. Dr. Faith Davis, a professor at the University of Alberta supported by generous funds from the Canadian Brain Tumour Foundation, has spearheaded the development of this comprehensive registry. Currently, four provincial cancer registries (British Columbia, Alberta, Manitoba and Ontario) have provided data representing 70% of the Canadian population.

The first report released in May 2019 provides a summary of the incidence of brain tumours between 2010-2015. The registry reported an average of 23.5 new brain tumours diagnosed per 100,000 population, of which 64% were benign tumours. Early data from the registry emphasizes how previously available pan-cancer tumour registries would under-represent the incidence of brain tumour registries, if only malignant tumours were recorded.

In the context of the Acoustic Neuroma Association of Canada (ANAC), the development of the Brain Tumour Registry of Canada will help better understand the epidemiological profile of acoustic neuromas in Canada and identify potential gaps in care. The first report identified over 1000 cases of new acoustic neuromas being diagnosed in a span of five years. Representative epidemiological data is important to help raise awareness in the general public and lobby the government for additional resources to help specific under-recognized disease processes.

Dr. Gelareh Zadeh, who is a neurosurgeon-scientist and Co-Director of the Krembil Research Institute at the Toronto Western Hospital, University Health Network, and Chair of ANAC’s Scientific Medical Affairs Committee states that “the Brain Tumour Registry of Canada will be a powerful tool for us to understand the impact of acoustic neuromas in Canada. Data gleaned from this initiative will elucidate areas within Canada that are underserviced with regard to the management of acoustic neuromas and further develop Centers of Excellence with expertise in multi-modal management”.

Notably, Jennifer Gouchie-Terris of Moncton, N.B., clearly demonstrates the true power of patient-led advocacy and how loud their voices can resonate. After her son, Brandon Dempsey, was diagnosed with a non-malignant brain tumour in 1998, she started advocating for a national brain tumour registry. Her persistence and strength led to the initial government’s private member’s motion in 2007. The Brain Tumour Registry of Canada will be a great tool to amplify the voice of the Acoustic Neuroma Association of Canada and bring awareness across the country.

Dr Suppiah

Dr Suganth Suppiah is a neurosurgery resident and graduate student pursuing his Ph.D. under the supervision of Dr Gelareh Zadeh at the University Health Network.

He has a strong interest in understanding the molecular drivers of oncogenesis in peripheral nerve sheath tumours, such as acoustic neuromas. He completed his medical training at the University of Western Ontario and is in the process of completing his neurosurgery training at the University of Toronto. Ultimately, Dr Suppiah aspires to be a surgeon-scientist who aims to uncover novel therapeutics for peripheral nerve tumours.

brain tumour

neurosurgery

Current and Future Treatment Modalities For Acoustic Schwannomas

admin — Tue, 31 Jul 2018 21:28:12 +0000

Current and Future Treatment Modalities For Acoustic Schwannomas admin Tue, 07/31/2018 - 17:28

Acoustic schwannomas (also known as acoustic neuromas or vestibular schwannomas) are a relatively rare non-cancerous tumour that arises from the vestibulocochlear nerve. These tumours grow slowly due to the over proliferation of Schwann cells, which normally wrap around nerves to provide support and insulation. Most commonly, patients present with hearing loss, sensation of fullness in the ear or ringing in the ears. In addition, the vestibulocochlear nerve runs through the cerebellopontine angle alongside important cranial nerves, blood vessels and the brainstem. Large tumours can compress these nearby structures and cause additional symptoms, such as facial paralysis and balance problems or unsteadiness. Once the preliminary diagnostic procedures including hearing tests (audiometry) and computed tomography (CT) scans are completed, the gold standard for diagnosis of acoustic schwannomas is magnetic resonance imaging (MRI) scans, which help determine the location and the size of the tumours.

Treatment options for acoustic schwannomas can range from clinical observation to surgery or radiotherapy. The treatment for acoustic schwannomas depends on the size of the tumour, patient’s general health and preferences. For some small acoustic schwannomas with minimal symptoms clinical observation is acceptable, especially in elderly patients or patients with medical comorbidities where the risks of therapy may be greater. Surgery can often remove the tumour completely, through a suboccipital, translabyrinthine or middle fossa approaches. The goal of surgery is the removal of the tumour and the preservation of the facial nerve, and to preserve hearing when possible.

Another option is radiosurgery, where focused radiation is applied to the tumour to reduce the size or limit the growth of the tumour. It often takes months before the effects of radiosurgery are evident on the tumour. For tumours that are less than 3 cm in size, both surgery and radiosurgery are an option, with similar efficacy. For larger tumours, surgery is the only option. The risks of treatment include hearing loss, ringing in the ears, facial weakness/numbness, balance problems and treatment failure (continued growth in the case of radiosurgery).

To date, there are no effective medical treatment options established for the treatment of acoustic schwannomas. The limited understanding of the molecular drivers of tumour development, in part, is a reason for the dearth of drug development. Our laboratory is focused on uncovering the genetic alterations that lead to the growth of acoustic schwannomas.

We published a study in Nature Genetics (2016) characterizing the genomic landscape of sporadic schwannomas, which identified mutations in NF2, ARID1A, ARID1B and DDR11. Most notably, we identified a novel genomic rearrangement resulting in a fusion gene SH3PX2DA-HTRA1 in a subset of schwannomas that was demonstrated to increase the growth of these tumours. Experiments in our lab showed that MEK inhibitors, a class of targeted therapies, is a potential therapeutic option for the subset of schwannomas with the gene fusion. This study highlights the possibility of developing targeted therapies for acoustic schwannomas based on preclinical studies focused on understanding the tumour biology.

Clinical trials studying the efficacy of a subset of targeted medical therapies are in their infancy. Bevacizumab has been demonstrated to prolong tumour stability and prolong time to hearing loss in two clinical trials2. Based on these trials, the Congress of Neurological Surgeons (CNS) have recommended the use of bevacizumab in patients without surgical options. In another study, a receptor tyrosine kinase inhibitor, acting on epidermal growth factor receptor, demonstrated significant reduction in tumour volume in 23.5% of patients, with a median response time of 4.5 months3. However, not all clinical trials have demonstrated positive results4. There are currently four clinical trials studying targeted medical therapies in acoustic schwannomas.

In an era of precision medicine, the most difficult step is translating bench-side laboratory research into clinical practice. The ongoing basic scientific research has identified potential molecular pathways and targeted therapies that could prove to be beneficial in treating acoustic schwannomas. However, current data from clinical trials has demonstrated mixed results with these targeted therapies. More work is needed to characterize the biological subgroups of acoustic schwannomas that are driven by different genomic alterations. One possible explanation for the mixed results in the clinical trials is that only a subset of tumours with specific genomic alterations respond to the specific targeted therapies. Further concerted effort is required from both biologists and clinicians to develop targeted therapies for treatment of acoustic schwannomas.

References:

Agnihotri, S. et al. The genomic landscape of schwannoma. Nat. Genet. 48, 1339–1348 (2016).
Blakeley, J. O. et al. Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From

Neurofibromatosis Type 2–Associated Vestibular Schwannomas. J. Clin. Oncol. 34, 1669–1675 (2016).
Karajannis, M. A. et al. Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis

type 2 and progressive vestibular schwannomas. Neuro-Oncol. 14, 1163–1170 (2012).
Plotkin, S. R. et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients.

Otol. Neurotol. Off. Publ. Am. Otol. Soc. Am. Neurotol. Soc. Eur. Acad. Otol. Neurotol. 31, 1135–1143 (2010).

Dr Zadeh

Gelareh Zadeh, MD, PhD, FRCS(C), FAANS; Wilkins Family Chair in Brain Tumour Research, Co-Director Krembil Brain Institute, Associate Professor, University of Toronto & Scientific Medical Chair, ANAC.

Dr Radovanovic

Ivan Radovanovic, MD, PhD, FMH;Scientist, Toronto Western Research Institute, UHN & Assistant Professor of Surgery, University of Toronto.

Dr Suppiah

Suganth Suppiah, MD, PhD Candidate; Resident Physician, Department of Neurosurgery, University of Toronto

treatment

brain tumour