Early Reactions as Dose-Limiting Factors in Radiotherapy

Early side effects of radiation therapy are generally the result of mitotic-linked cell death in rapidly renewing tissues and secondary impaired tissue function. Various types of acute normal tissue reactions are briefly summarized in this article. In general, with conventionally fractionated radiation treatment, the acute normal tissue reactions are within acceptable limits. However, new radiotherapy strategies, such as hyperfractionation and accelerated fractionation, induce more severe acute toxicity. Particularly, with most altered fractionation schedules, the mucosal reaction of the upper aerodigestive tract is elevated to the upper limit of tolerance. Early mucosal reactions may also become dose limiting when radiation is combined with chemotherapy as, for instance, for the treatment of head and neck cancer or pelvic neoplasms. Bone marrow is the critical organ for combination of chemotherapy and wide field irradiation. There is an increasing body of evidence that iatrogenic acute normal tissue toxicity has become a major obstacle for treatment intensification for a variety of cancers. Therefore, effective measures to ameliorate these side effects are essential for further development of cancer therapy. Methods to reduce the severity of acute toxicity are being investigated.