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Brain metastases represent a devastating complication of melanoma. Our understanding of the mechanisms driving metastasis to the brain is limited. PLEKHA5 functions as a regulator of brain metastasis in melanoma, and further investigation is warranted to explore the use of PLEKHA5 as a potential therapeutic target. Clin Cancer Res; 21(9); 1978–80. ©2015 AACR. See related article by Jilaveanu et al., p. 2138

Treatment options for most nervous system tumors remain limited and patients are often confronted with significant morbidity and reduced life expectancy. However, significant efforts are underway to find more effective therapies for patients with primary and secondary brain tumors. As more and more clinical trials for nervous system tumors are being conducted, it is increasingly important to optimize the conduct of clinical trials in neuro-oncology. One of the key aspects in this regard is the development of objective and standardized criteria that allow for accurate response assessment in clinical trials and prevent the misclassification of responders and non-responders. Such misclassification may lead to premature discontinuation of an actually effective agent, thereby withholding a potentially active treatment from the patient. Conversely, patients may be inappropriately continued on an inactive treatment. Moreover, such misclassification may confound the data obtained in such studies and may lead to false conclusions with regards to the efficacy of the investigated drug. Therefore, reliable response assessment criteria are necessary that not only accurately capture radiographic changes but also account for treatment-related changes and incorporate the assessment of clinical status and quality of life (QoL). The Response Assessment in Neuro-Oncology (RANO) working group is an international collaboration of neuro-oncologists, medical oncologists, radiation oncologists, neurosurgeons, neuroradiologists, and regulatory groups (among others) commissioned to develop objective and tumor-specific response criteria for various tumor subtypes. This article reviews the currently available response criteria for high-grade glioma, low-grade glioma, and brain metastases and discusses some of the barriers to accurate assessment of treatment response in neuro-oncology.

Central nervous system vascular disease is a common complication of cancer. It may result from the direct or indirect effects of cancer and cancer treatment on blood vessels, from cancer and cancer treatment-related coagulopathies, or from infection. Tumor-related infarction occurs in the setting of cerebral tumor embolization from systemic cancer, intravascular lymphomatosis, or venous sinus compression from adjacent skull or dural tumor. Parenchymal intratumoral hemorrhage occurs in a wide variety of primary and metastatic tumor histologies. Subdural hemorrhage is a well-recognized sequela to dural metastasis of solid or hematological tumors. Treatment-related vascular toxicity includes the posterior reversible encephalopathy syndrome described in a large number of chemotherapy, immunotherapy, and targeted agents. The delayed effects of radiation on cervical carotid arteries are increasingly recognized as a cause of cerebral ischemia in patients radiated for head and neck tumors. Thrombotic coagulopathies may result in arterial thrombosis, notably in patients with solid tumors who develop nonbacterial thrombotic endocarditis. Thrombotic coagulopathy also underlies most cases of venous sinus thrombosis, most commonly in pediatric patients treated with l-asparaginase for acute leukemia. Hemorrhagic coagulopathies, including acute disseminated intravascular coagulation, may result in parenchymal, subdural, or subarachnoid hemorrhage. Cerebral infarction or hemorrhage due to infection is uncommon and is typically related to fungal infections associated with host immunosuppression.