Does the dose fractionation schedule influence local control of adjuvant radiotherapy for early stage breast cancer?

Purpose: To explore the correlation between dose fractionation and local co ntrol for the adjuvant radiotherapy of early stage breast cancer. Methods and Materials: A matched-pair analysis of early stage invasive brea st cancer treated adjuvantly with two different dose fractionation schedule s, 4000 cGy in 16 fractions (Cohort A) vs. 5000 cGy in 25 fractions (Cohort B) was undertaken to compare local control rates. A systematic review of t he published experience in similar patient populations was conducted and th e reported dose fractionation schedule was converted to a biologic effect d ose (BED) based upon the linear quadratic equation. The BED was then used a s a basis for comparing reported local control rates with different dose fr actionation schemes. Results: The 118 patient pairs were matched from Cohort A and Cohort B usin g known significant prognostic factors including age, histology, surgical m argins, receptor status, lymphvascular space invasion, extensive intraducta l disease, lymph node status, and systemic therapy. The local recurrence ra te at 5 years for those treated with 4000 cGy (BED = 65 cGy(4)) and 5000 cG y (BED = 75 cGy(4)) was 12.7% and 6.8%, respectively, and this difference w as not statistically significant (p = 0.09). Overall survival was 84% at 5 years for both groups. Comparison of the different dose fractionation schem es reported in the literature revealed a highly statistically significant d ifference between those treated with less than a BED of 75 Cy, and those tr eated with a BED of 75 Gy(4) or greater. Conclusion: Although not statistically significant, there was a trend in th e matched pair analysis which suggests that 4000 cGy in 16 fractions (BED = 65 cGy(4)) provides inferior local control compared to 5000 cGy in 25 frac tions (BED = 75 cGy(4)). Moreover, the literature review demonstrates that a dose control relationship may exist for local control in the adjuvant set ting. A dose fractionation schedule equivalent to 5000 cGy in 25 fractions to the whole breast may represent the optimal dose fractionation schedule f or local control. (C) 1999 Elsevier Science Inc.