Partial breast irradiation with interstitial 60CO brachytherapy results in frequent grade 3 or 4 toxicity. evidence based on a 12-year follow-up of 70 patients

Abstract

Purpose To investigate the radiation-induced toxicity and cosmesis of brachytherapy (BT) alone in early stage breast cancer. Methods and materials A total of 70 women diagnosed with Stage I or II breast carcinoma participated in a BT study at the Municipal Oncoradiological Center, Uzsoki Hospital, Budapest, Hungary, between November 1987 and June 1992. They had undergone breast-conserving surgery with an unknown surgical margin. The postoperative tumor bed irradiation was performed with interstitial 60Co sources with an active length of 4 cm, with 10-mm center-to-center spacing arranged in a single plane. The median number of inserted sources was 5 (range, 2–8), with a linear activity of 133–137 MBq/cm at the beginning of the study. The 50 Gy delivered dose at 5 mm from the surface of the 60Co sources was administered during 10–22 h to the virtual postoperative lumpectomy cavity (i.e., plane). For radiobiologic considerations, the clinical target volume (CTV) was calculated retrospectively with a 10-mm safety margin, resulting in a 72-cm 3 median CTV (range, 36–108 cm 3) irradiated with a reference dose of 28 Gy. In the assessment of the skin and subcutaneous toxicity, the RTOG late radiation morbidity scoring system was applied. The radiosensitivity of the cultured fibroblasts was determined by clonogenic assay to check whether individual radiosensitivity played a role in the development and course of radiation-induced side-effects. Results The median follow-up was 12 years (range, 10–15 years). The population of the final study (34 cases) comprised all survivors with tumor-free breasts (27 cases) and patients with breasts erroneously ablated/excised for misinterpreted radiation-induced sequelae (7 patients). A total of 97% of the cohort (33/34) had grade ≥2, and 59% (20/34) had grade ≥3 radiation-induced toxicity. By the end of the follow-up, 85% of the patients experienced Grade ≥2 telangiectasis and 41% had Grade 3 telangiectasis. Eighty-eight percent had fibrosis of some form, and 35% had grade ≥3 fibrosis. Forty-one percent of the cohort displayed fat necrosis, which was always accompanied by Grade ≥3 fibrosis or telangiectasis. The cosmetic results were poor in 50% (17/34) of the patients. The radiosensitivity of the fibroblasts was increased in only 2/24 patients (8% of the investigated cases, in agreement with data published for the general population). Comparisons of our fibrosis prevalence data with those of others allowed an estimate of 0.47 h −1 for the rate of recovery of DNA damage in the fibroblasts. Conclusions Interstitial 60Co BT of the breast tumor bed alone with a limited CTV (median, 72 cm 3) and a total dose of 28 Gy is associated with a high rate (59%) of grade ≥3 radiation-induced toxicity and a high rate (50%) of poor cosmetic outcome at the end of a median follow-up of 12 years. A relatively high BT dose rate (1.3–2.8 Gy/h) applied during a short overall treatment time (10–22 h) and a possible geographic miss (close to skin implantation) might have contributed to the development of these sequelae.