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Best treatment option written in cancer's genetic script

January 16, 2017

An international collaboration led by clinical researchers at the Wellcome Trust Sanger Institute has shown proof-of-concept that truly personalised therapy will be possible in the future for people with cancer. Details of how a knowledge bank could be used to find the best treatment option for people with acute myeloid leukaemia (AML) are published today in Nature Genetics.

AML is an aggressive blood cancer that develops in bone marrow cells. Earlier this year, the team reported there are 11 types of AML, each with distinct genetic features. Now they report how a patient's individual genetic details can be incorporated into predicting the outcome and treatment choice for that patient.

They built a knowledge bank using data from 1,540 patients with AML who participated in clinical trials in Germany and Austria, combining information on genetic features, treatment schedule and outcome for each person. From this, the team developed a tool that shows how the experience captured in the knowledge bank could be used to provide personalised information about the best treatment options for a new patient.

There are two major treatment options for young patients with AML - a stem cell transplant or chemotherapy. Stem cell transplants cure more patients overall but up to one in four people die from complications of the transplant and a further one in four experience long-term side effects. Weighing up the benefits of better cure rates with transplant against the risks of worse early mortality is a harrowing decision for patients and their clinicians. The team showed that these benefits and risks could be accurately calculated for an individual patient, enabling therapeutic choices to become personalised.

The team estimates that up to one in three patients would be prescribed a different treatment regimen using the tool compared with current practice. In the long term they hope the tool could spare one in ten young AML patients from a transplant while maintaining overall survival rates.

Senior author Dr Peter Campbell of the Wellcome Trust Sanger Institute said: "The knowledge bank approach makes far more detailed and accurate predictions about the likely future course of a patient with AML than what we can make in the clinic at the moment. Current guides use a simple set of rules based on only a few genetic findings. For any given patient, using the new tool we can compare the likely future outcomes under a transplant route versus a standard chemotherapy route - this means that we can make a treatment choice that is personally tailored to the unique features of that particular patient."

The tool is currently available for scientists to use in research but needs further testing before it can be used to prescribe treatments in AML clinics.

Lead author Dr Moritz Gerstung of the European Bioinformatics Institute said: "It has long been recognised that cancer is a complex genetic disease. Our study provides an example of how detailed genetic and clinical information can be rationally incorporated into clinical decisions for individual patients. We tested this philosophy in one type of leukaemia, but the concept could theoretically be applied in other cancers with difficult clinical decisions as well. Our analysis reveals that knowledge banks of up to 10,000 patients would be needed to obtain the precision needed for routine clinical application."

Using large scale genetic studies as a source to predict the best treatment option for future patients is an idea that Genomics England is trying to build alongside similar programmes around the world, such as the National Institutes of Health Precision Medicine Initiative in the US.

The authors believe this paper is a step towards validation of genetic techniques as a route to personalised medicine.

Co-senior author Dr Hartmut Döhner of University of Ulm said: "Building knowledge banks is not easy. To get accurate treatment predictions you need data from thousands of patients and all tumour types. Furthermore, such knowledge banks will need continuous updating as new therapies become approved and available. As genetic testing enters routine clinical practice, there is an opportunity to learn from patients undergoing care in our health systems. Our paper gives the first real evidence that the approach is worthwhile, how it could be used and what the scale needs to be."
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Notes to editors:

About acute myeloid leukaemia:
  • Acute myeloid leukaemia (AML) is a type of blood cancer that develops when the cells in the bone marrow that produce myeloid cells become cancerous. As blood cells are made in the bone marrow, the cancer will be present in the bone marrow and in the blood.
  • Every day we make around 10 billion new blood cells, and the information which controls how these blood cells reproduce is held within our DNA. Every time a cell divides, the entire DNA code has to be copied exactly, and mistakes are made by chance. AML develops when there are a series of errors in the DNA. It usually takes mistakes in several key genes that control blood production to cause AML.
  • There were around 2,900 new cases of acute myeloid leukaemia (AML) in the UK in 2013, that's around 8 cases diagnosed every day (CRUK figures).
  • Worldwide, 351,965 people were estimated to have AML in 2012 (GLOBOCAN figures).
For more information on AML please see: https://bloodwise.org.uk/understanding-blood-cancers/what-acute-myeloid-leukaemia-aml

Selected websites:

Ulm University

Ulm University, the youngest university in Baden-Württemberg, was founded in 1967 as university for medicine and natural sciences. The subject spectrum has been expanded considerably since then. There are currently about 10,000 students enrolled across four Faculties ('Medicine', 'Natural Sciences', 'Mathematics and Economics', and 'Engineering, Computer Sciences and Psychology').Ulm University is the centre of and driving force behind the Science City of Ulm, a dynamically growing research environment including hospitals, technology companies and other institutions. The University's research foci comprise life sciences and medicine, bio-, nano- and energy materials, financial services and their mathematical methods, as well as information, communication and quantum technologies. http://www.uni-ulm.de/en/homepage.html

Department of Internal Medicine III at Ulm University

The Focus of the Department of Internal Medicine III in patient care, research and teaching lies in hematological, oncological, infectious and rheumatologic diseases as well as palliative care for cancer patients. http://www.uniklinik-ulm.de/index.php?id=1453&L=1

EMBL-EBI (European Bioinformatics Institute)

The European Bioinformatics Institute is part of EMBL, and is a global leader in the storage, analysis and dissemination of large biological datasets. EMBL-EBI helps scientists realise the potential of 'big data' by enhancing their ability to exploit complex information to make discoveries that benefit mankind. We are a non-profit, intergovernmental organisation funded by EMBL's 21 member states and two associate member states. Our 570 staff hail from 57 countries, and we welcome a regular stream of visiting scientists throughout the year. We are located on the Wellcome Genome Campus in Hinxton, Cambridge in the United Kingdom. http://www.ebi.ac.uk

Memorial Sloan Kettering

We are the world's oldest and largest private cancer center, home to more than 14,000 physicians, scientists, nurses, and staff united by a relentless dedication to conquering cancer. As an independent institution, we combine 130 years of research and clinical leadership with the freedom to provide highly individualized, exceptional care to each patient. And our always-evolving educational programs continue to train new leaders in the field, here and around the world. For more information, go to http://www.mskcc.org.

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk

Wellcome

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Wellcome Trust Sanger Institute

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