Patterns of Care and Clinical Decision Making for Recurrent Glioblastoma Multiforme (2016)

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. For newly diagnosed GBM, a widely adopted standard of care, including maximal surgical resection, concurrent radiation and temozolomide, and subsequent adjuvant temozolomide, was established in 2005.1 However, essentially all patients with GBM suffer disease progression, and there is no established standard of care for the treatment of recurrent GBM.2 Once a patient treated with the Stupp regimen is diagnosed with recurrent disease, a number of treatment options may be available. These options include repeat surgical resection, repeat fractionated radiation, radiosurgery, salvage chemotherapy such as repeat temozolomide challenge, nitrosoureas, other alkylating agents, bevacizumab, tumor-treating fields, and experimental agents used in clinical trials. Given the lack of consensus on optimal management of recurrent GBM, knowledge of care patterns used for these patients and the criteria used to determine therapeutic strategy is germane to clinicians who care for these patients. In a recent study, Hundsberger et al3 investigated which treatments are currently being used for recurrent GBM within a single nation (Switzerland) and how clinicians are deciding to use them. The authors surveyed Swiss hospitals with comprehensive multidisciplinary neuro-oncology practices (neurosurgery, radiation therapy, medical neuro-oncology, and a dedicated neuro-oncology tumor board) about treatment recommendations for recurrent GBM. They identified relevant clinical decision-making criteria, called diagnostic nodes or “dodes,” and compared treatment recommendations using a decision-tree format (Figure).Figure: A through F, clinical decision-making tree for recurrent glioblastoma multiforme (GBM) based on clinical scenarios that achieved a majority recommendation (ie, at least 5 of 8 Swiss hospitals). BEV, bevacizumab; BSC, best supportive care; rGBM, recurrent glioblastoma multiforme; TMZ, temozolomide. Modified with kind permission from Springer Science+Business Media: Journal of Neuro-Oncology, Patterns of care in recurrent glioblastoma in Switzerland: a multicenter national approach based on diagnostic nodes (published online ahead of print October 12. 2015), Hundsberger T, Hottinger AF, Roelcke U, et al [doi: 10.1007/s11060-015-1957-0. Available at: http://link.springer.com/article/10.1007%2Fs11060-015-1957-0].3Eight hospitals participated. The most common treatment options for recurrent GBM were combination repeat surgical resection with temozolomide or bevacizumab, monotherapy temozolomide or bevacizumab, and best supportive care. Alternative therapies, including radiotherapy, were less common. Despite widespread disagreement between centers in clinical decision making, the decision-tree analysis found agreement (>63%) between most centers for only 4 specific clinical scenarios. Patients without an appropriate performance status were usually managed with best supportive care. Patients with rapid recurrence, nonresectable tumors, unmethylated O(6)-methylguanine DNA methyltransferase (MGMT) promoter, and high performance status were usually managed with bevacizumab. Patients with late recurrence, nonresectable tumors, overt clinical symptoms, methylated MGMT promoter, multifocal disease, and high performance status were usually managed with repeat temozolomide therapy. Patients with late recurrence, nonresectable tumors, no clinical symptoms, methylated MGMT promoter, tumor multifocality, and high performance status were usually managed with temozolomide. The findings of this study underscore the lack of effective first- and second-line treatments for GBM, and the interhospital variability in practice patterns is not surprising. It seems likely that similar heterogeneity would also be noted in a study of American neuro-oncology centers. It is interesting to note that despite the availability of an increasing number of molecular markers for GBM stratification, MGMT promoter methylation appears to be the only biological marker widely used across multiple centers in this study. It remains to be seen when and how broadly other markers such as the epidermal growth factor receptor variant III or isocitrate dehydrogenase mutations will be adopted for clinical decision making. The authors are to be congratulated for identifying core clinical decision-making criteria that may be useful in future studies of recurrent GBM. This decision tree is an excellent reference for clinical trial development, and several active clinical trials already target the dodes identified in this study. Subsequent studies may help to determine whether similar decision trees exist in American neuro-oncologic centers now or will exist in the future.