R01.2: History of the Therapeutic Ratio

Recognition of Acute Injury

Henri Coutard, in 1934, published a paper on the Principles of X Ray Therapy of Malignant Diseases. He describes 'accidents' occuring with radiotherapy although the exact nature of these events is not described. He describes in detail the three types of epithelial radioreaction - on the squamous cells of the epidermis, the mucosal squamous cells, and the columnar cells. In 1913 Regaud and Nogier described "radio-epidermitis" of the skin; in 1922 mucousitis was described by Coutard himself. It was understood that the reactions would only occur after a certain time period, and that the daily dose delivered was important in their development (at low enough doses the reaction would not appear at all).

It was also understood that as long as these reactions were not too severe, they would eventually heal at some point after the treatment was completed - usually within two weeks.

Coutard also reported that when treatments were given over shorter sessions but over a longer period of time, the outcomes for many cancers appeared to be superior.

Understanding of Early and Late Effects

Treating to Tolerance

Radiotherapy damages both cancer cells and normal cells. To obtain the best chance of cure, a dose sufficient to eradicate all cancer cells is required; however in many cases this dose exceeds that which can be tolerated by the normal tissues without serious morbidity. Therefore in the early years of radiotherapy, "treatment to tolerance" - i.e. as high as the normal tissues can tolerate - was used as it gave the best chance of eradicating the cancer while preserving normal tissue function.