Early and late normal tissue injury after postmastectomy radiotherapy.

Abstract

Postmastectomy radiotherapy has played — and continues to play — a leading role in the clinical radiobiology of normal tissues. There are several reasons for this: 1. The loco-regional control rate is relatively high in these patients: in the Danish Breast Cancer Cooperative Group (DBCG) high-risk pre- and postmenopausal patients had an actuarial 10-year loco-regional control rate ranging between 83% and 94% (Overgaard et al. 1988). (High-risk patients according to the DBCG 1977 criteria are those in whom histologically positive lymph nodes were found, or the diameter of the primary tumor exceeded 5 cm, or there was microscopic evidence of invasion of the skin or the deep fascia.) Thus observation of normal tissue reactions in the treated region is possible without the confounding effect of progressive loco-regional disease. 2. The life expectancy of these patients is sufficient to allow long-term follow-up in a large proportion of them, which is necessary for studying the radiobiology of late-responding normal tissues in humans where the typical latent periods are several years. Even in high-risk patients the crude survival rate at 5 years is about 50% or better. Patients with incomplete follow-up, either because they are alive without having reached a specific endpoint at the time of the analysis, or have died from any cause, give rise to time-censored observations. Statistical methods are available to analyze such data in a multivariate setting, for example by means of the mixture model (Farewell 1977; Bentzen et al. 1989d,e) or the Cox proportional hazards model (Cox 1972; Taylor et al. 1987). 3. A number of tissues are included in the irradiated area which means that several endpoints are evaluable in each patient. Late endpoints that have been analyzed include subcutaneous fibrosis, telangiectasia, pulmonary fibrosis, spontaneous rib fractures, impaired shoulder movement, brachial plexopathy, and persistent arm edema. Acute endpoints include erythema, moist desquamation, and radiation-induced pneumonitis. Among these, the most extensive quantitative studies have been on endpoints in the skin and the subcutis; however, impaired shoulder movement, a functional endpoint, has also been thoroughly analyzed. 4. Postmastectomy radiotherapy often involves different doses to a specific reference point and/or different radiation qualities. Examples are the application of a wax bolus to increase the surface dose around the surgical scar, or the use of an abutted electron field to treat the chest wall while minimizing the dose to the lung. 5. Finally, breast cancer is unfortunately the most common cancer in women in western countries, which means that relatively large series of patients treated with a consistent policy may be collected in a short time period even within a single institution.