Radiation therapy and wound healing delay. Animals and man.

Abstract

One of the adverse effects of radiation therapy is its interference with surgical wound healing. Although some of the earliest observations suggest that irradiation of a wounded area increased its healing rate, generally it has been accepted that radiation delivered either before or immediately after wounding the skin or other tissues would interfere with reconstitution of the structures and re-epithelialization. Many studies have investigated the particular characteristics of postoperative irradiation, and some have been concerned with the effects of preoperative radiotherapy. In considering any preoperative radiotherapy, it must first be noted that a surgical wound must heal without adverse reaction to the patient. A skin wound which does not completely reconstitute itself may not be life-threatening, but a non-reconstituted gastrointestinal anastomosis may result in intraperitoneal leakage of intestinal contents with disastrous results. It has seemed reasonable to review the characteristics of wound healing as applied to the problem of preoperative radiation therapy, and to this end studies have been undertaken in both animals and man. Two significant problems are immediately apparent. One concerns the effects of increasing doses of radiation and the second the effects of increasing the delay between administration of the radiation and the surgery. No animal study is directly applicable to man, as it is reasonable to presume a different response because of variations in tissue-healing characteristics and cell turnover time. In addition, single doses are the rule in most animal studies, while in man experience has proved the benefits of fractionation. Human Investigations The clinical material in this study consists of 225 patients with moderately advanced carcinoma of the head and neck given preoperative irradiation. In 214 of these, a radical surgical removal of the primary tumor was carried out, with an en bloc radical neck dissection when appropriate. The tumor origins of the resected specimens are indicated in Table I. The radiation doses varied in accordance with individual clinical problems, and the intervals between irradiation and operation were dependent on technical problems of acquiring rooms for the patients. In 11 patients the lesion was too far-advanced for surgery, and these received the highest radiation doses—5,500 to 6,500 rads. To assess wound healing, the patients were arbitrarily divided into two groups: (a) those with normal healing, i.e., complete healing within the first two weeks, and (b) those with delayed healing, i.e., with an open wound for more than two weeks. Table I shows, as would be expected, an association between wound-healing delay and extent of surgical involvement of both mucosa and cutaneous structures.