Genomic Health reveals results from Oncotype DX studies . . . Genomic Health (Redwood City, California) reported results from three studies of the Oncotype DX Colon Cancer test at the 2013 Gastrointestinal (GI) Cancers Symposium, including new data demonstrating that Recurrence Score (RS) results changed treatment recommendations in 45 percent of the enrolled stage II colon cancer patients. Presentations also include positive findings from a second health economics analysis suggesting that use of the test may result in a significant reduction in direct medical costs and improve patient well-being. Additionally, the company announced that the Journal of Clinical Oncology (JCO) has accepted for publication results from its second large clinical validation study of stage II colon cancer patients enrolled in CALGB 9581 confirming that the Oncotype DX test improves the ability to differentiate higher from lower recurrence risk beyond conventional factors. “These new data reinforce the value of an individualized recurrence risk assessment score that enables physicians to identify those at high risk of recurrence who can experience a greater potential benefit from chemotherapy, as well as patients with a low risk of recurrence who can be spared unnecessary treatment,“ said Steven Shak, M.D., chief medical officer and executive vice president for research and development at Genomic Health. “Oncotype DX represents an important advance in bringing personalized medicine into the modern paradigm for cancer care. With a growing body of evidence, and a second publication in JCO, we now have expanded support for broader reimbursement and increased patient access to our colon cancer test.“ Conducted in collaboration with the Mayo Clinic Cancer Research Consortium, a prospectively designed study analyzed treatment decisions for 141 stage II, T3 MMR-proficient colon cancer patients across 17 sites demonstrating that the use of the Oncotype DX Colon Cancer test changed treatment decisions 45% of the time and led to an overall reduction in chemotherapy use.

New test predicted presence of harmful BRCA mutations . . . A new multiple gene expression profile test was able to predict the presence of harmful BRCA1 or BRCA2 mutations in otherwise healthy women carrying the mutations, according to data published in Cancer Prevention Research, a journal of the American Association for Cancer Research (Philadelphia). “This novel technology aims to provide a layer of information regarding the cell functionality aspect of BRCA mutations that could greatly enhance the doctor's ability to identify high-risk carriers,“ said Asher Salmon, MD, a breast cancer specialist at the Hadassah Hebrew University Medical Center (Jerusalem, Israel). Women with a mutation in their BRCA1 or BRCA2 gene have a significantly increased risk for developing breast cancer or ovarian cancer, and for many of those at risk disease may develop at an early age. Researchers are investigating ways to detect these genetic mutations so women carrying the genes can consider taking measures to reduce their cancer risk or increase the chance for detecting cancer in its early stages. “The current tool for mutation detection is gene sequencing, which is expensive, time-consuming and, in many cases, lacking clear and decisive clinical decision making information,“ said Salmon. “In many cases, the current sequencing tool identifies a mutation, but we do not know if the mutation is neutral or harmful.“ According to Salmon, emerging evidence has revealed that cells with a mutation in one of the two copies of the BRCA1 or BRCA2 genes have a distinct gene expression profile when exposed to causes of DNA damage, such as radiation.

Researchers find that simple blood test can help identify trauma patients at greatest risk of death . . . A simple, inexpensive blood test performed on trauma patients upon admission can help doctors easily identify patients at greatest risk of death, according to a new study by researchers at Intermountain Medical Center (Salt Lake City). The Intermountain Medical Center research study of more than 9,500 patients discovered that some trauma patients are up to 58 times more likely to die than others, regardless of the severity of their original injuries. Researchers say the study findings provide important insight into the long-term prognosis of trauma patients, something not previously well understood. “The results were very surprising,“ said Sarah Majercik, MD, an Intermountain Medical Center surgeon and trauma researcher, whose team discovered that a tool developed at Intermountain Medical Center, called the Intermountain Risk Score, can predict mortality among trauma patients. Majercik will present the findings from the study Friday at the 27th annual Scientific Session of the Eastern Association for the Surgery of Trauma in Phoenix. The Intermountain Risk Score is a computerized tool available to physicians that combines factors like age, gender, and common blood tests known as the complete blood count (CBC) and the basic metabolic profile (BMP) to determine an individual's mortality risk. All of the components of the tool have been helpful in evaluating individuals with medical problems like heart failure or chronic pulmonary disease. But until now, the benefit of the tool had not been tested for trauma patients hospitalized due to an accident or traumatic injury, rather than an underlying condition. “As surgeons, we don't often use all of the CBC results in evaluating a patient who needs surgery for a bleeding spleen or after a motor vehicle accident, said Majercik. “There are certain values, such as hemoglobin, hematocrit, and platelets that we scrutinize closely as part of good clinical care, but then other parts, such as the red blood cell distribution width (RDW) that we pay no attention to at all in the acute setting. These factors are generally overlooked, even though they are part of the CBC that every trauma patient gets when he or she arrives in the emergency room.“ Date from the Intermountain Risk Score tool will allow physicians to take additional precautions with patients who are at greatest risk, and also give doctors important information to consider when talking about prognosis with patients and families. Majercik and her colleague Benjamin Horne, PhD, director of cardiovascular and genetic epidemiology at the Intermountain Medical Center Heart Institute, reviewed the cases of 9,538 patients who had been admitted to the hospital with trauma during a six-year period.

DNA Chip to Diagnose Attention Deficit Hyperactivity Disorder . . . Attention Deficit Hyperactivity Disorder (ADHD) is the most common childhood neuropsychiatric disorder. Yet there is currently no tool that will confirm the diagnosis of ADHD. In her thesis entitled “Development of a genotyping system to be applied in Attention Deficit Hyperactivity Disorder and its Pharmacogenetics,“ the researcher Alaitz Molano, a graduate in biochemistry and PhD holder in Pharmacology from the UPV/EHU-University (San Sebastian, Spain) of the Basque Country, presents a tool that could improve not only the diagnosis of but also the therapeutics for this disorder. The prevalence of ADHD is between 8% and 12% among the infant-adolescent population worldwide, and 50% continue with the symptoms into adult life. Children with ADHD have difficulty paying attention, do not complete the tasks they have been assigned and are frequently distracted. They may also display impulsive behaviour and excessive, inappropriate activity in the context they find themselves in, and experience great difficulty restraining their impulses. “All these symptoms seriously affect the social, academic and working life of the individuals, and impact greatly upon their families and milieu close to them,“ says Molano. In view of the problems existing in diagnosing ADHD patients and deciding about their treatment, this PhD thesis set out to develop and clinically validate a genotyping tool that could help to confirm the diagnosis, to predict how it will evolve, and to select the most suitable pharmacological treatment in each case. Molano studied how genetic polymorphisms (variations in the DNA sequence between different individuals) are associated with ADHD. “We looked for all the associations that had been described previously in the literature worldwide, and did a clinical study to see whether these polymorphisms also occurred in the Spanish population; the reason is that genetic associations vary a lot between some populations and others.“ About 400 saliva samples of patients with ADHD and a further 400 samples from healthy controls without a history of psychiatric diseases were analysed. And the use of over 250 polymorphisms led to the discovery of 32 polymorphisms associated not only with the diagnosis of ADHD but also with the evolution of the disorder, with the ADHD subtype, the symptomatological severity and the presence of comorbidities. On the basis of these results, Molano is proposing a DNA chip with these 32 polymorphisms, which could be updated with new polymorphisms, as a tool not only for diagnosing but also for calculating genetic susceptibility to different variables (responding well to drugs, normalisation of symptoms, etc.). The study has also confirmed the existence of the 3 ADHD subtypes: lack of attention, hyperactivity, and a combination.

— Compiled by Omar Ford, MDD