Brain cancer metabolite: NMR homes in on prognosis

IDing IDH1 via biomarker

NMR has the potential to predict the prognosis and response to treatment of patients with low-grade infiltrating brain cancer, gliomas, that have mutations in the isocitrate dehydrogenase 1 (IDH1) gene, according to ex vivo and in vivo imaging studies.

Adam Elkhaled, Llewellyn Jalbert, Joanna Phillips, Hikari Yoshihara, Rupa Parvataneni, Radhika Srinivasan, Gabriela Bourne, Mitchel Berger, Susan Chang, Soonmee Cha and Sarah Nelson of the University of California, San Francisco, explain in the current issue of the journal Science Translational Medicine how following neurosurgery, patients with low-grade glioma, a type of brain cancer, have a good or bad prognosis that is dependent on how quickly new tumours re-grow after excision of the original cancer. Oncologists can monitor tumour growth closely using imaging technology, However, until now there was no method for determining with any great certainty whether or not the new tissue growth is in a more malignant state than the original cancer and so requires more aggressive treatment.

Nelson and her colleagues have turned to NMR spectroscopy, or as it is more commonly known medically just magnetic resonance (MR) spectroscopy to develop just such a method for distinguishing between highly malignant tissue and growths of less concern. NMR, they suggest, can be used to identify a biomarker in tissue samples from brain tumours that has been linked to improved survival rates. They say that testing for this biomarker in the patient's brain non-invasively could give their oncologists a much simpler way to determine an accurate prognosis after neurosurgery.

Optimizing

The researchers concede that they are yet to optimize the technique for routine clinical use in hospital oncology departments. Nevertheless, that will happen and the approach look sets to become a useful tool to help oncologists better assess cancer recurrence, improve their follow-up treatment decisions and to determine how well a patient is responding to a given treatment as their therapy is undertaken.

"If a tumour transforms to a higher grade, then it is important to use more aggressive treatments," explains Nelson, who is a professor of advanced imaging and of radiology and biomedical imaging at UCSF.

The UCSF research team used spectroscopy to collect data from image-guided tissue samples from more than fifty glioma patients where the biomarker 2-HG (2-hydroxyglutarate) was present. The presence of this biomarker is closely linked to mutations in the IDH1 gene, which have been shown to be associated more commonly with low-grade tumours and thus have longer survival rates. More than two-thirds of glioma patients with the low-grade form of this tumour display mutations in the IDH1 gene of their cancer cells. An associated paper from researchers in Massachussetts by Ovidiu Andronesi, Grace Kim, Elizabeth Gerstner, Tracy Batchelor, Aria Tzika, Valeria Fantin, Matthew Vander Heiden, and Gregory Sorensen, was published back to back in the same issue of Science Translational Medicine that gave the preliminary results to suggest that 2-HG could be detected non-invasively from relatively large regions of tumour tissue in two patients with the IDH1 mutations using spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy; this approach avoids the false positives of one-dimensional proton NMR. 

Clinical engineering challenges ahead

"Developing methods to obtain images in a clinical setting is an engineering challenge now," Nelson adds. Refinements are needed so that standard hospital MRI scanners can be used to carry out the requisite spectroscopic imaging for the presence of 2-HG.

Nelson and her colleagues were funded in their efforts through a US$1.5 million annual National Cancer Institute grant from its Specialized Program for Research Excellence. The grant has been awarded for a decade and was instigated to translate basic laboratory and clinical discoveries into the best and most appropriate clinical practice for delivering treatment and monitoring cancer patient progress.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.