Designing Clinical Trials for Combination Immunotherapy: A Framework for GlioblastomaCombining Immunotherapy for Glioblastoma

Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents

Operative and peri‐operative considerations in the management of brain metastasis

Abstract The number of patients who develop metastatic brain lesions is increasing as the diagnosis and treatment of systemic cancers continues to improve, resulting in longer patient survival. The role of surgery in the management of brain metastasis (BM), particularly multiple and recurrent metastases, remains controversial and continues to evolve. However, with appropriate patient selection, outcomes after surgery are typically favorable. In addition, surgery is the only means to obtain a tissue diagnosis and is the only effective treatment modality to quickly relieve neurological complications or life‐threatening symptoms related to significant mass effect, CSF obstruction, and peritumoral edema. As such, a thorough understanding of the role of surgery in patients with metastatic brain lesions, as well as the factors associated with surgical outcomes, is essential for the effective management of this unique and growing patient population