Reply to Letter Neuro-oncology 611

The debate over how much to push the limits of surgical resection for malignant gliomas is not a recent controversy. The cost-benefit analysis about increasing survival with more resection at the expense of function has existed for decades. In 1928, Walter Dandy at the Johns Hopkins Hospital performed hemispherectomies for patients with glioblastoma (GB) and found that these tumors still recurred despite this aggressive resection. Over the next decades, the debate continued and led to discussion whether surgical resection was any more effective than needle biopsy. Despite a Cochrane Review demonstrating that there were no well-designed studies to assess the benefit of surgical resection over biopsy, Laws and Buckner in 2003 each independently showed that surgical resection was associated with prolonged survival for patients with high-grade gliomas. This then led to the controversy if more aggressive resection provided better patient outcomes. While we appreciate and respect the comments by Dr. Solheim and colleagues, we recognize that we did not do a good job explaining the reason for conducting our study. It goes beyond establishing volumetric thresholds for surgical resection of these difficult lesions to also giving hope to patients and health care providers caring for these patients and their families. It is about knowing that we, as health care providers, can do something to influence the course of this devastating disease. It dispels the notion that we need to accomplish 98% resection and, if this is not to be achieved, then we should just do a biopsy. This dichotomy of treatment has unfortunately been a misconception over the last decade in the United States and throughout the world. We recognize that GB is characterized by its ability to invade and infiltrate surrounding parenchyma, making curative resection difficult. Elucidating the role that surgery can play in prolonging the lives of patients who suffer from this devastating disease has been a gradual progress. In 2009, we showed that patients who underwent gross-total resection (GTR) had better outcomes than near-total resection (NTR) and that patients who underwent NTR had better outcomes than subtotal resection (STR). Moreover, we also showed that surgical resection is of benefit to the older patient population, where most of these individuals are only offered biopsies based on their age. Similarly, Solheim and colleagues have shown that early resection of low-grade gliomas is associated with better outcomes than a watchful waiting approach. The beneficial effect of surgery, however, is always tempered by the fact that causing an iatrogenic deficit is associated with worse outcomes independent of extent of resection. Despite these findings, the ability to truly evaluate the role of extent of resection requires volumetric analyses. Studies using volumetric analyses, however, are few and limited. Lacroix et al. in 2001 examined 416 patients with primary and recurrent GB who were operated on from 1993 to 1999 and found that a threshold of 98% was needed to confer a significant survival advantage. More recently, Sanai et al. in 2011 evaluated 500 patients with newly diagnosed GB who were operated on from 1997 to 2009 and identified a survival threshold of 78%. We conducted our study to add to the literature and the ongoing discussion about this important issue since there are several aspects that remain unclear. First, there is a large discrepancy between the 78% and 98% resection thresholds established in these previous studies, making it unclear which threshold is more accurate. Second, since residual volume (RV) and percent resection (EOR) can be different, it is unclear if RV is associated with outcome. Third, the patients from previous studies predate current standard of adjuvant care (temozolomide and radiation therapy), so the role of surgery in this more modern context remains unclear. As a result, we studied 259 patients who underwent nonbiopsy surgery of a newly diagnosed intracranial GBM from 2007 to 2011 and found that EOR Reply to letter