TIME FACTORS IN BREAST-CARCINOMA - INFLUENCE OF DELAY BETWEEN EXTERNAL IRRADIATION AND BRACHYTHERAPY

From 1971 to 1983, 398 (33 T1, 309 T2, 56 T3) biopsy-proven breast adenocarcinomas were treated conservatively at Hopital Henri Mondor by an initial course of external irradiation (45 Gy, 25 fractions, 5 weeks) followed by interstitial iridium-192 implant for a further 37 Gy to the tumor. The mean interval between external irradiation and brachytherapy was 5.9 weeks (S.D. 1.7, range 1-18). Seventy-seven local failures were observed at 10-148 months (median 34.5). The actuarial probabilities (S.E.) of local control at 5 and 10 years were 0.86 (0.02) and 0.74 (0.03), respectively. The follow-up for patients free of local recurrence was 4-205 months (median 95). Multivariate analysis showed an increasing probability of local failure with longer interval between external irradiation and brachytherapy (Relative Risk [R.R.] 1.23 [95% confidence limits: 1.07, 1.411 per week, p = 0.005), and a lower risk of failure in case of complete tumor regression after external irradiation (R.R. 0.47 [0.25, 0.90 ], p = 0.022), and higher brachytherapy dose rate (R.R. 0. 13 [0.02, 1.021 per Gy/h, p = 0.053). No influence of tumor size and total dose (possibly because only limited variations in total dose were observed), or histological grading (not performed in 140 [ 35 % ] patients) was found. Because of the lack of dose-control relationship, quantification of the effects of delay between external irradiation and brachytherapy (in terms of compensatory dose) and of dose rate (Incomplete Repair Model) was not possible. The present analysis suggests that the implant dose rate should be high (but no extrapolation can be made above 1 Gy/h) or that total dose should be increased to compensate lower dose rate. However, our data do not indicate how much extra dose is necessary, since no dose-control relationship was elicited. In addition, the treatment duration should remain as short as possible in order to maximize local control.