Upfront boost Gamma Knife "leading-edge" radiosurgery to FLAIR MRI-defined tumor migration pathways in 174 patients with glioblastoma multiforme: a 15-year assessment of a novel therapy.

OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22-87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5-220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6-14 Gy) at the 50% isodose line. RESULTS The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1-3 grades in 10% due to symptomatic treatment-related imaging changes. CONCLUSIONS LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.

Timing of surgery and bevacizumab therapy in neurosurgical patients with recurrent high grade glioma.

Malignant gliomas continue to have a dismal prognosis despite all available treatments and advances made in understanding molecular mechanisms and signaling pathways. Conventional treatments, such as surgery, chemotherapy and radiation, have been used with limited success. Bevacizumab is a recently described molecule, which inhibits endothelial proliferation and prevents formation of new blood vessels in tumor. However, this treatment confers increased hemorrhage risk and impairs wound healing. Therefore, the timing of surgery for patients receiving bevacizumab, who are in need of surgery, is critical. We performed a literature review to establish the appropriate timing between the cessation of bevacizumab therapy and surgical intervention. Our literature review indicated that the optimum time between cessation of bevacizumab therapy and surgery was 4 weeks. The timing for re-initiation of bevacizumab post-surgery was at least 2 weeks. The duration of preoperative cessation of bevacizumab treatment is critical in preventing life threatening surgical complications. The interval between the surgery and re-initiation of bevacizumab can be shortened. However, more studies are needed to ascertain the exact timing of preoperative and postoperative therapy.