Brain tumor study: Using Gleolan fluorescent marker to reveal diffusely infiltrative glioma tumor

Resecting visible high-grade glioma may not get it all; highlighting tumor cells helps get enough tissue without removing too much.

The patient

A 57-year-old man presented to the Norton Brownsboro Hospital emergency department with complaints of headaches that started two weeks earlier and worsened over the preceding few days. In addition, his family reported subtle changes in behavior, including increased sleepiness and issues with memory. A magnetic resonance imaging (MRI) scan demonstrated a brain mass in the right temporal lobe, with significant mass-effect and associated cerebral edema concerning for high-grade glioma.

The challenge

Unlike some tumor types that displace normal brain tissue as they grow, high-grade gliomas are diffusely infiltrative and spread into normal brain tissue. For this reason, high-grade gliomas cannot be removed with clean margins and are best treated with a goal of gross total resection: the complete removal of whatever tumor is visible on MRI without injury to functioning brain tissue. While some regions of tumor look clearly different from normal brain, other areas cannot be distinguished easily. The surgical challenge is to maximize tumor removal while sparing healthy brain — that is, to remove enough without removing too much.

The physicians

David A. Sun, M.D., Ph.D., neurosurgeon with the Norton Healthcare Brain Tumor Center and medical director, Norton Neuroscience Institute

Hilary Highfield, M.D., neuropathologist with the Norton Healthcare Brain Tumor Center.

The solution

The patient underwent craniotomy with an intended goal of gross total resection at the Norton Healthcare Brain Tumor Center at Norton Brownsboro Hospital. Multiple surgical adjuncts are used in the Norton Healthcare Brain Tumor Center. A stereotactic navigation system provides localization of surgical instruments on preoperative MRI scans and is useful for planning trajectories to protect healthy tissue and identifying initial tumor boundaries. As tumor is removed, the shifting brain’s appearance eventually differs from the preoperative MRI, making the navigation system less valid. Intraoperative ultrasound provides real-time information regarding the extent of residual tumor during surgery and accounts for brain shift. Rapid neuropathologist intraoperative review of tissue samples further enhances our ability to safely remove as much tumor as possible.

Recently, the addition of a tumor fluorescence marker, call Gleolan, further has enhanced our ability to safely increase the extent of tumor resection. Several hours after a patient takes this fluorescent marker by mouth it will preferentially concentrate within tumor cells. When the surgeon uses specific blue-light filters in the operating room microscope, the tumor cells will fluoresce with a red-violet color in comparison with the normal brain tissue.

The result

The patient had an unremarkable recovery from surgery with gross total resection. Final pathology confirmed astrocytoma, World Health Organization (WHO) grade 4 (Glioblastoma). The patient then underwent standard of care adjuvant therapy with fractionated radiation, temozolomide oral chemotherapy and Optune tumor treatment fields.

Treatment and results may not be representative of all similar cases.

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