Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx. Part 2. Normal tissue responses: acute and late effects.

The early responses of normal tissues of the oral cavity and oropharynx in 498 patients, and the slowly-developing responses in 268 patients who survived a minimum of 18 months after radiotherapy for squamous cell carcinoma were analyzed. The severity of acute responses correlated with dose intensity. The incidence of severe late responses increased with increase in dose per fraction and was characterized by a low alpha/beta ratio. Severe late responses were significantly associated with severe acute responses independently of dose per fraction and total dose, and were also ameliorated slightly by protraction of treatment time suggesting that some late effects were, at least partly, a consequence of acute injury. Probability of local tumor control correlated with severity of acute response, suggesting that excessive protraction of overall treatment time to minimize acute toxicity may compromise local control of the tumor. There was no demonstrable correlation between the volume of tissue irradiated and the severity of acute or late response.