Chemoradiation schedules--what radiotherapy?

Synchronous chemoradiation (SCRT) is playing an increasing role in the primary and multimodality management of cancer in many disease sites. Current schedules have been in the main empirically derived, and the addition of chemotherapy has in some cases led to a compromise in the total dose or scheduling of radiotherapy. Non-randomised phase II studies abound, but there are few well designed phase III randomised studies with comprehensive acute toxicity data and mature follow-up. In many sites long-term survival is unusual. So severe morbidity and long term functional outcome is poorly documented. It is therefore difficult to assess the real benefit of SCRT. This review uses the endpoints of local control and overall survival from randomised trials in small and non-small cell lung cancer, head and neck cancer, oesophageal cancer, rectal and anal cancer. We explore the evidence for total dose; fractionation; fraction size; the effects of a gap in treatment; and scheduling of radiation in SCRT.

An optimal schedule of SCRT has not yet been derived. The enhanced acute toxicity and persistent high risk of local failure in many disease settings with current SCRT schedules demand that more effective and less toxic treatment strategies must be identified in the future. These schedules should be tested in randomised trials with the emphasis on meticulous reporting of acute toxicity endpoint and documenting the field sizes or proportions of critical organs within the high dose area if we are to derive the optimal therapeutic ratio.