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Knowledge Bank Tapped for Precision Cancer Treatments

Personal data illustration

(Gerd Altmann, Pixabay)

17 January 2017. An international research team devised techniques for analyzing accumulated clinical trial data to help determine precise treatment strategies for people with cancer. The team headed by researchers from Wellcome Trust Sanger Institute in Cambridge, U.K. published its findings in the 16 January issue of the journal Nature Genetics (paid subscription required).

The Wellcome Trust Sanger Institute researchers led by cancer geneticist Peter Campbell — with colleagues from Europe, the U.S., and New Zealand — are seeking new and better tools to determine precise courses of treatment for cancer patients. Genomic sequencing of cancer cells can identify cancer-causing mutations, but decisions on safe and effective treatments need to take in more information relevant to the patient’s individual conditions. In short, evidence-based treatment decisions need more evidence than just the cancer’s genetic defects.

Campbell’s team looked specifically at patients with acute myeloid leukemia, a cancer of the blood and bone marrow that worsens quickly if left untreated. As the disease develops, bone marrow produces abnormal white blood stem cells called myeloblasts that do not mature into normal functioning white blood cells. The excessive growth of abnormal myeloblasts crowds out healthy white, red, and platelet blood cells, and can spread to other parts of the body. The Globocan project in World Health Organization estimates in 2012 some 352,000 people worldwide had acute myeloid leukemia.

One of the difficulties in determining precise therapies for acute myeloid leukemia is the disease’s multiple sub-types, as well as heterogeneous nature of patient populations. With acute myeloid leukemia in younger patients, the two main treatment strategies are stem cell transplants from bone marrow or chemotherapy. Stem cell transplants generally have a better chance at curing the disease, say the authors, but they also run a higher rate of long-term adverse side effects, with deaths occurring in as many as 1 in 4 cases. More real-world evidence, say the researchers, would help physicians and patients make better informed decisions on these critical questions.

To find that evidence, the team created a knowledge bank of data from clinical trials with patients having acute myeloid leukemia. The trials were held in Germany and Austria, which contributed 1,540 cases. The researchers included analysts from European Bioinformatics Institute who wrote multi-stage statistical models that factored in and matched genomic sequencing results with treatments and clinical outcomes. The models were then validated independently with patient data in the Cancer Genome Atlas, a National Institutes of Health initiative in the U.S.

The results indicate risks and benefits for acute myeloid leukemia patients can be accurately calculated from these clinical trial cases, with different treatments than normally recommended in a large segment of these individuals. The researchers estimate that with this analysis, as many as 1 in 3 patients would receive a different type of treatment compared to current practices. In addition, the number of stem cell transplants could be reduced by 20 to 25 percent, while maintaining current survival rates.

“Current guides use a simple set of rules based on only a few genetic findings,” says Campbell in an institute statement. “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 authors point out that this study may have proven the concept, but more testing and validation are still needed before it’s ready for clinical practice. In addition, knowledge banks like the kind created for this study need continuous updating, large numbers of participants, and diverse populations to be effective decision-making tools.

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