The butterfly effect on glioblastoma: is volumetric extent of resection more effective than biopsy for these tumors?

Abstract

A subset of patients with glioblastoma (GBM) have butterfly GBM (bGBM) that involve both cerebral hemispheres by crossing the corpus callosum. The prognoses, as well as the effectiveness of surgery and adjuvant therapy, are unclear because studies are few and limited. The goals of this study were to: (1) determine if bGBM have worse outcomes than patients with non-bGBM, (2) determine if surgery is more effective than biopsy, and (3) identify factors independently associated with improved outcomes for these patients. Adult patients who underwent surgery for a newly diagnosed primary GBM at an academic tertiary-care institution between 2007 and 2012 were retrospectively reviewed and tumors were volumetrically measured. Of the 336 patients with newly diagnosed GBM who were operated on, 48 (14 %) presented with bGBM, where 29 (60 %) and 19 (40 %) underwent surgical resection and biopsy, respectively. In multivariate analysis, a bGBM was independently associated with poorer survival [HR (95 % CI) 1.848 (1.250-2.685), p < 0.003]. In matched-pair analysis, patients who underwent surgical resection had improved median survival than biopsy patients (7.0 vs. 3.5 months, p = 0.03). In multivariate analysis, increasing percent resection [HR (95 % CI) 0.987 (0.977-0.997), p = 0.01], radiation [HR (95 % CI) 0.431 (0.225-0.812), p = 0.009], and temozolomide [HR (95 % CI) 0.413 (0.212-0. 784), p = 0.007] were each independently associated with prolonged survival among patients with bGBM. This present study shows that while patients with bGBM have poorer prognoses compared to non-bGBM, these patients can also benefit from aggressive treatments including debulking surgery, maximal safe surgical resection, temozolomide chemotherapy, and radiation therapy.

Fig. 1

Examples of patients with bGBMs that cross the corpus callosum. a, b A 46-year old patient presented with headaches as well as confusion and memory loss, and had evidence of a bGBM that crosses the body of the corpus callosum and underwent surgical debulking. c, d A patient who is 58 years old and presented with headaches and seizures and had evidence of a bGBM that crossed the genus of the corpus callosum and underwent surgical debulking

Fig. 2

Overall survival curves for patients with glioblastoma (GBM). a, b Overall survival for patients who underwent surgery of a newly diagnosed butterfly (bGBM) and non-butterfly glioblastoma (nonbGBM). a Overall survival of all GBM patients. The median survival for patients who underwent surgery of a bGBM was significantly shorter than patients who underwent surgery of a non-bGBM (5.1 vs. 12.5 months, p < 0.0001). The 6-and 12-month survival rates for patients with bGBM were 47 and 22 % as compared to 75 and 55 % for patients with non-bGBM, respectively. b Overall survival of bGBM patients matched with non-bGBM. In order to control for potential pre and perioperative differences, groups were matched for age (±5 years), KPS (±10 points), preoperative tumor size (±5 cm³), eloquent cortex involvement (yes/no), extent of resection (±5 %), temozolomide (yes/no), and radiation (yes/no). The median survival for patients with bGBM (n = 17) was significantly shorter than matched patients with non-bGBM (n = 17) (7.0 vs. 11.6 months, p = 0.009). c, d Overall survival for bGBM patients by increasing surgical resection. c Overall survival of bGBM patients who underwent debulking surgery matched to patients who underwent biopsy. Groups were matched for age (±5 years), KPS (±10 points), preoperative tumor size (±5 cm³), percent tumor on contralateral side (±5 %), motor cortex involvement (yes/no), temozolomide chemotherapy (yes/no), and radiation therapy (yes/no). The median survival for patients who underwent surgical resection (n = 11) was significantly longer than for patients who underwent biopsy of a bGBM (n = 11) (7.0 vs. 3.5 months, p = 0.03). The 6- and 12-month survival rates for patients who underwent surgical resection of a bGBM were 60 and 12 % as compared to 12 and 0 % for matched patients who underwent needle biopsy, respectively. d Survival of bGBM patients who underwent >65 % resection as compared to patients who underwent ≤65 % resection. The median survival for patients who underwent >65 % percent resection (n = 15) was significantly longer than patients who underwent ≤65 % percent resection (n = 33) (7.1 vs. 4.5 months, p = 0.047). The 6- and 12-month survival rates for patients who underwent >65 % resection were 64.6 and 24.6 % as compared to 28.1 and 7.0 % who underwent ≤65 % resection, respectively