Using Plasma TGFB1 as a Marker to Select Patients for Radiotherapy Dose Escalation

摘要

Transforming growth factor β (TGFB) is a multifunctional cytokine which plays an important role in a number of pathological conditions characterised by excessive fibrosis. TGFB has been shown to both increase the production of extracellular matrix and inhibit its degradation, which may lead to an excess of fibrous tissue formation. Successful treatment of fibrosing conditions results in the reduction in tissue TGFB expression. Many cancer patients have been found to have elevated circulating levels of TGFB at the time of diagnosis. In addition, TGFB has been implicated in the pathogenesis of normal tissue injury after cancer therapy. Furthermore, changes in plasma TGFB levels during cancer treatment may correlate with risk of normal tissue injury from radiation therapy. The ability to select patients for different treatments based on relative risks for normal tissue injury has important implications for radiation oncologists. For certain malignancies, including non-small cell lung cancer, the delivery of higher doses of radiation may result in both improved local control and survival. Based on our preliminary data, we hypothesised that one could use serial plasma TGFB measurements to identify patients at low risk for normal tissue injury from conventional doses of radiation therapy and safely escalate the radiation dose in this subset of patients. Herein, we report the results of a clinical trial designed to test this hypothesis in patients with non-small cell lung cancer.