Chemoradiotherapy interactions and lung toxicity

Background: The combination of high-dose radiotherapy with intensive chemot herapy may improve the prognosis of patients with inoperable, locally advan ced non-small-cell lung cancer. In the design of suitable clinical protocol s, potential interactions of drugs and radiation in the tumour, the lung an d other critical normal tissues have to be considered. Methods: From experimental data on chemotherapy radiotherapy interactions a nd based on knowledge about the biology of non-small cell lung cancer and t he pathogenesis of radiation pneumopathy, the principles which should be co nsidered in the design of treatment schedules are developed. Results: For the increase in local tumour control, further escalation of ra diation dose should be considered first. The most critical issue for lung t oxicity may be the volume of the 30 Gy isodose. Yet, the most critical norm al tissue which may limit the further increase in dose and dose intensity a ppears to be the oesophagus. Conclusions: Since the main cause of treatment failure remains local recurr ence, further increase in locoregional cytotoxicity is the first priority i n locally advanced non-small-cell lung cancer. This can best be achieved by increasing radiation dose and dose intensity further. Yet, there may also be a role for simultaneous radiochemotherapy, even if this would increase t he lung volume which develops radiation pneumopathy and thus the severity o f symptoms. This problem should be dealt with by reducing the irradiated lu ng volume by use of conformal treatment planning. The most critical side ef fects will then be due to increased severity of acute oesophagitis.