An MRI-based method that can track the state and progression of a common type of genetically mutated brain cancer (lat. Carcinoma) has been developed by the researchers at UT Southwestern Medical Center. The study showed that 2HG is an excellent biomarker for tracking certain gliomas with IDH mutations and also can provide a diagnosis when neurological risk from surgery is too high. Researchers used MR spectroscopy, a method for distinguishing the chemical makeup of normal vs. mutated brain tissue, to track 2HG concentrations. The team can measure 2HG concentration and follow it during the disease course - it's stable over long periods of time when the tumor is stable, increases when the disease progresses and is an excellent marker of tumor response because it falls in response to treatment that is working.
Using MR spectroscopy, the team announced in 2012 that they could detect 2HG in the tumor with high sensitivity and specificity. This next-step study showed that 2HG can be useful in tracking the disease. This is the first non-invasive biomarker for brain cancer and represents a major advance for the field. The current imaging is not nearly as precise and takes a longer time to see results. This new method will be a much more rapid way of assessing the therapy - allowing the physician to know to stop treatments that aren't working or continue treatments that are.
Most biomarkers are in the blood, so identifying biomarkers that can be tracked without drawing blood or obtaining a tissue biopsy is particularly valuable. The technique also may serve as a model to develop other imaging biomarkers for the brain, and already is being used to learn more about the biology of glioma, the most common type of brain cancer. In terms of research, the biomarker is a 'window' into IDH-mutant glioma biology and the researchers are using it to learn more about how the tumor grows, responds to therapy, and ultimately becomes resistant to treatment.
2HG tracking also could prove useful in diagnosing some brain tumors in which typical surgical procedures to obtain tissue samples can't be done. That may be because the tumor isn't accessible, such as near the brainstem, or when trying to get a sample could cause neurological damage. These patients are excluded from clinical trials because of the lack of available tumor tissue for diagnostic analyses.
2HG levels in these tumors can be used to make a 'presumptive' molecular diagnosis of an IDH mutation, based solely on imaging. The impact of this finding is that the patient's physician will have a clear direction for treatment, including recommending a patient for treatment in a clinical trial. This contribution may help change clinical practice in this field and demonstrates the importance of tracking an imaging biomarker.