One for all and all for one: a unified approach to defeat brain cancer
Brain cancer has a poor prognosis but a unified approach to defeating the disease is gaining momentum.
by Dr Kerrie L McDonald
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Sanaz Maleki (a Research Assistant working in the Cerebral Tumour Research Group) operating an autostainer. This autostainer screens hundreds of tumours every day looking for markers of therapeutic response.
Brain cancer has a poor outlook with unacceptable survival. The five-year relative survival is less than 20 per cent. 1 Even with the most sophisticated technologies and treatments available, the median survival of a patient diagnosed with a malignant tumour is still just 15 months.
Brain cancer affects patients of all ages, both male and female and there are no preventative measures available. In a recent report from the Cancer Council NSW, the most costly cancer per person in NSW is brain cancer. 2 The financial burden includes a reduction in income due to lost productivity and carers costs and the increase in out of pocket expenses such as health care.
Brain cancer is a complex disease and very difficult to treat. High grade brain tumours, such as glioblastoma multiforme (GBM), are invariably fatal because:
- the remarkable ability of individual brain tumour cells to infiltrate the normal brain and migrate long distances away from the original tumour mass. Surgical removal of the visible mass has limited effectiveness and the tumour typically recurs;
- high levels of proteins that specifically repair the toxicity induced by chemotherapy drugs (effectively neutralizing the effect of chemotherapy agent); and
- the genetic variability associated with each and every patient.
The research challenges for brain tumours lie in the discovery and translation of new therapies that target the tumour invasion and chemotherapy resistance into mainstream medical practice and the optimisation of existing therapies.
Even with the most sophisticated technologies and treatments available, the median survival of a patient diagnosed with a malignant tumour is still just 15 months.
A unified approach
The momentum in neuro-oncology is accelerating. This is predominantly due to the formation of major networks in NSW and Australia. The NSW Oncology Group (NSWOG): neuro-oncology, an initiative of the Cancer Institute NSW, brought clinicians, allied health workers, support group members and researchers together to work as one team. Significant outcomes have already come to fruition.
Professor Michael Barton (Guideline Chair) and Dr Elizabeth Hovey (Guideline Project Officer) promoted the development of Consensus Guidelines for the Management of Adult Gliomas, a national collaborative project under the auspices of the Australian Cancer Network, an affiliate of COSA. The guidelines will be launched at COSA in November 2009.
Another significant outcome of the NSWOG: neuro-oncology group was the production of a series of fact sheets for brain tumour patients and their families to access. This project began as a pilot project funded by the Cancer Institute NSW awarded to social worker Ms Teresa Simpson and neurosurgical nurse Kylie Wright. The project addressed the cognitive and behavioural sequelae of brain tumour. The major objective was to improve the information resources for patients and their families. The fact sheets have received excellent feedback, both from the national and international brain tumour community.
The NSWOG: neuro-oncology group continues to improve patient outcome through the betterment of data registry, synoptic reporting, promoting multidisciplinary care and advocating improvements in patient care. It is critical that clinical indicators are identified so that we can benchmark improvements in patient treatment and care.
Further research
A growing area of neuro-oncology is the incorporation of translation studies into new clinical trials for brain tumours. Translational research is critical for the success of clinical trials for several reasons. Due to the high genetic variability associated with brain tumour patients, it is acknowledged that there is no ‘magic pill’ that is going to benefit all patients. Translational research seeks to unravel the biological basis of disease and factors underlying response to disease and identify patients who will benefit most from treatment (and avoid unnecessary adverse affects).
It is acknowledged that there is no ‘magic pill’ that is going to benefit all patients.
Many clinical trials have failed because only 10 per cent of patients responded. We need to start examining why the 10 per cent showed benefit. To achieve this, fresh frozen brain tissue needs to be routinely collected at the time of surgery and deposited into a -80°C facility. Additionally, clinical trial enrolment needs to be promoted. Two newly established networks are working closely with NSWOG: neuro-oncology to make this a reality: AGOG (Australian Genomics and Clinical Outcomes of Glioma) and COGNO (Co-operative trials for Neuro-Oncology).
In 2008, a research alliance coined AGOG was formed through the Cancer Council NSW Strategic Partnership Grant Scheme. AGOG comprises clinical specialists in neurosurgery, radio-oncology, medical oncology, together with scientists working in cancer genetics and biomarker discovery to address key research issues in brain tumours. This multidisciplinary approach promotes the sharing of clinical information and the exchange of biological samples between centres with established expertise. Sub-standard tissue and data collection is well recognised as a significant road block to cancer research and AGOG is determined to overcome this.
Patients frequently ask the question: Why me?
Patients frequently ask the question: why me? The only validated risk factor for the development of a brain tumour is exposure to ionizing radiation. Very generic questions such as a family history of cancer are frequently proposed to the patient, however we need to start thinking much more broadly. For the very first time, AGOG will provide all patients with a comprehensive survey to fill out. This survey is purposely designed to be liberal and flexible to capture any information that could guide us to finding risk factors associated with brain tumours. It’s a difficult task, but it is vital for demographic information to be documented. A blood sample and, where possible, a tumour specimen will also be collected to enable future molecular-based studies to advance. The chief investigator of AGOG, Professor Lyle Palmer is a world famous geneticist and epidemiologist. Professor Palmer will screen the blood samples taken from consenting patients and look for polymorphisms in genes involved in signalling pathways for growth factors, cell cycle regulators, DNA repair and modifiers of drug metabolism, which have been associated with brain tumour diagnosis and prognosis.
To facilitate more effective enrolment and participation in clinical trials, a national neuro-oncology co-operative trials group, COGNO, having received a competitive grant from Cancer Australia, formed in 2007 and is based at the NHMRC Clinical Trials Centre at the University of Sydney. The Operations Executive of the group includes Professor Mark Rosenthal (COGNO Chair, Royal Melbourne Hospital), Professor John Simes (COGNO Deputy Chair, Royal Prince Alfred Hospital) and Dr Elizabeth Hovey (COGNO Secretary, Prince of Wales Hospital). It is critical that the number of clinical trials made available to brain tumour patients in Australia increases and it is absolutely vital that we support these trials by increasing patient numbers. COGNO specifically promotes clinical trials which evaluate current therapies and novel treatments through engaging members of the medical and scientific community through participation to assist in the conduct, evaluation, promotion and development of clinical trials in brain tumours.
Like AGOG, COGNO has brought together the very best clinicians and researchers in Australia to promote clinical trials, but will also develop new and exciting concepts too. COGNO is also encouraging protocols which address psychosocial outcomes and quality of life outcomes. COGNO is already collaborating well with international neuro-oncology groups.
Patient care
The commitment to improving patient care is paramount. Newly diagnosed patients are desperate for information, support and guidance. The Cancer Institute NSW and the Cancer Council NSW came together to host an inaugural meeting in February 2009 to unite all brain tumour stakeholders: charities, support groups, research institutes and clinicians.
The commitment to improving patient care is paramount.
The newly formed Brain Tumour Network Group will work as one body to advocate for change and improvements in cancer services. A patient centric website will be constructed and hold valuable information including basic facts about brain tumours, what the journey entails, where the support groups are, clinical advice and much more. The strong representation of consumers in the Network Group, those directly impacted by brain cancer, will ensure that the website will be a success.
The Cancer Council NSW launched a brain tumour awareness campaign earlier this month. The campaign: Grey Matters is a new national fundraising and advocacy group aimed at raising awareness and funds for brain cancer, with racing identity and newspaper columnist Kate Waterhouse acting as an ambassador. The energy and drive for brain tumour awareness is unprecedented and change will eventuate.
The way forward
From my own scientific perspective, amidst a biotechnology explosion, the scene is set for major developments in neuro-oncology. The availability of preserved tumour and blood samples acquired from consenting patients, coupled with accurate and comprehensive clinical data will accelerate the process of biomarker discovery to ultimately reduce the incidence and improve the outlook for brain tumour patients.
References
- Cancer Institute NSW. Cancer in New South Wales: Incidence and Mortality 2006. (2008).
- Cancer Council NSW. Cost of Cancer in NSW: A report by Access Economics PTY Limited for the Cancer Council NSW. (2007).
About the author: Kerrie McDonald, PhD
Research Fellow, Head Cerebral Research
Cancer Genetics Laboratory, Hormones and Cancer Unit, Kolling Institute of Medical Research
e-mail: kerriem@med.usyd.edu.au
Dr McDonald completed her PhD in 2001 at the University of Melbourne and took up a postdoctoral fellowship at the University of Oxford in 2002. Dr McDonald joined the Cancer Genetics Laboratory at the Kolling Institute of Medical Research in 2004 and has since driven the brain tumour research. Projects supervised or conducted by Dr McDonald specifically target the identification of biological markers with utility to improve diagnosis, prognosis and response to treatment.
Dr McDonald was made head of the Cerebral Tumour Research Group within the Cancer Genetics Laboratory in 2007. She has been instrumental in building the Australasian Brain Tumour Bank, obtained peer reviewed funding, published, had a provisional patent granted and is supervising four PhD students. Dr McDonald is the recipient of consecutive Cure For Life Fellowships (2006-07; 2007-08). She has active collaborations with researchers at the Children’s Medical Research Institute (CMRI), St Vincents Hospital, Westmead Hospital, University of Otago, New Zealand and Western Australia Institute for Medical Research (WAIMR, UWA).