Brain tumor clinical trials imaging: a (well-standardized) picture is worth a thousand words.

FDA approval of oncology therapies requires demonstration of direct clinical benefit measured by improvement in how patients “function, feel or survive.”1 Prolonged overall survival has long been the preferred benchmark for establishing patient benefit; however, outcomes such as progression-free survival and tumor response have been recognized as acceptable surrogates for clinical benefit in the appropriate settings. Historically, FDA has supported the use of imaging as a tool to expedite the drug and device development processes2; in fact, most accelerated approvals of cancer drugs have been granted on the basis of durable objective responses in a refractory setting, including approval of therapies for patients with high-grade gliomas. Assessment of response and progression in neuro-oncology has been particularly challenging given the unique biological, physiological, and anatomic characteristics of the brain. Moreover, determining disease status requires appraisal of not only the tumor, but its vasculature and neighboring reactive cells. The advent of MRI provided exceptional visualization of neuroanatomy and pathological processes such as ischemia; paradoxically, it also increased uncertainty in the ability to interpret radiographic changes.