Low-grade brain tumor diagnosis redefined

A tumor's DNA, and not just the tumor stage and what the affected cells look like under a microscope, is key to determining if a lower-grade malignant brain tumor (glioma) may rapidly progress to glioblastoma, the most common and deadliest form of malignant brain cancer. This multicenter, national study, and its proposed changes in how some brain tumors are classified and ultimately treated, were published in the New England Journal of Medicine (2015; doi:10.1056/NEJMoa1402121).

The findings, according to researchers from the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, MI, could result in earlier and more aggressive treatment for those tumors projected to be on the fast path. Looking at DNA changes may also open treatment options in a move toward precision medicine.

Glioma is the most common type of malignant brain tumor with 6,500 expected cases of grade 2 and grade 3, and 12,500 expected cases of grade 4 (glioblastoma) each year.

Though glioblastoma has notably poor prognosis, the lower grades have survival that is harder to predict. Some patients may progress and succumb by 6 months, while others may survive 15 years. In this study, diagnosis criteria using changes in tumor DNA was found to improve the prediction.

Glioma is very difficult to treat successfully because, rather than being a clearly defined mass, the tumor blends with healthy brain tissue and sends out tentacles of microscopic cancer cells. This makes complete neurosurgical resection impossible and leaves the chance for tumor recurrence and progression.

"This new study holds a great deal of promise for our patients because we will no longer have to wait the months or years after surgery to determine if a particular glioma will progress to a glioblastoma," said Steven N. Kalkanis, MD, co-director of the Hermelin Brain Tumor Center.

"Now genes in the tumor can be quickly analyzed to look for any changes, deletions or other mutations, allowing us the opportunity to treat gliomas that may become glioblastomas more aggressively at the start, potentially leading to longer survival."

For more than 100 years, clinicians have been diagnosing and determining treatment for gliomas based on histologic classes developed in the early 1900s. Using this method, gliomas were classified microscopically on the basis of their similarity to a specific cell of origin (astrocyte, oligodendrocyte or a mixture of these cells), often making diagnosis subjective.

But diagnosis based on the molecular make up of a tumor takes away a great deal of uncertainty and offers a more concrete diagnosis. The study analyzed 293 lower-grade gliomas (grade 2 and grade 3) from adults. The samples were integrated with patient clinical data to test for associations.

For the study, gliomas were clustered into classes based on their genetic similarity. These clusters were then compared against tumor grade, histologic class, and molecular subtype.

When the researchers grouped gliomas according to IDH gene mutation and chromosome deletion status, they found three distinct molecular classes emerge that were more consistent with IDH gene mutation and 1p/19q chromosome deletion than with histologic class.

These findings suggest that lower-grade gliomas with wild-type IDH gene mutations are likely to behave like tumors diagnosed as glioblastoma with wild-type IDH.

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