Diagnosis and treatment of recurrent high-grade astrocytoma

High-grade gliomas represent a significant source of cancer-related death, and usually recur despite treatment. In this analysis of current brain tumor medicine, we review diagnosis, standard treatment, and emerging therapies for recurrent astrocytomas. Difficulties in interpreting radiographic evidence, especially with regard to differentiating between tumor and necrosis, present a formidable challenge. The most accurate diagnoses come from tissue confirmation of recurrent tumor, but a combination of imaging techniques, such as magnetic resonance spectroscopy imaging, may also be relevant for diagnosis. Repeat resection can prolong life, but repeat irradiation of the brain poses serious risks and results in necrosis of healthy brain tissue; therefore, reirradiation is usually not offered to patients with recurrent tumors. We describe the use of conventional radiotherapy, intensity-modulated radiotherapy, brachytherapy, radiosurgery, and photodynamic therapy for recurrent high-grade glioma. The use of chemotherapy is limited by drug distribution and toxicity, but the development of new drug-delivery techniques such as convection-enhanced delivery, which delivers therapeutic molecules at an effective concentration directly to the brain, may provide a way to reduce systemic exposure to cytotoxic agents. We also discuss targeted therapies designed to inhibit aberrant cell-signaling pathways, as well as new experimental therapies such as immunotherapy. The treatment of this devastating disease has so far been met with limited success, but emerging knowledge of neuroscience and the development of novel therapeutic agents will likely give patients new options and require the neuro-oncology community to redefine clinical trial design and strategy continually.