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.
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.
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).
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