Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

Abstract

Current standard of care for glioblastoma is surgical resection followed by temozolomide chemotherapy and radiation. Recent studies have demonstrated that >95% extent of resection is associated with better outcomes, including prolonged progression-free and overall survival. The diffusely infiltrative pattern of growth in gliomas results in microscopic extension of tumor cells into surrounding brain parenchyma that makes complete resection unattainable. The historical goal of surgical management has therefore been maximal safe resection, traditionally guided by MRI and defined as removal of all contrast-enhancing tumor. Optimization of surgical resection has led to the concept of supramarginal resection, or removal beyond the contrast-enhancing region on MRI. This strategy of extending the cytoreductive goal targets a tumor region thought to be important in the recurrence or progression of disease as well as resistance to systemic and local treatment. This approach must be balanced against the risk of impacting eloquent regions of brain and causing permanent neurologic deficit, an important factor affecting overall survival. Over the years, fluorescent agents such as fluorescein sodium have been explored as a means of more reliably delineating the boundary between tumor core, tumor-infiltrated brain, and surrounding cortex. Here we examine the rationale behind extending resection into the infiltrative tumor margins, review the current literature surrounding the use of fluorescein in supramarginal resection of gliomas, discuss the experience of our own institution in utilizing fluorescein to maximize glioma extent of resection, and assess the clinical implications of this treatment strategy.