Abstract ES4-2: What have we learned from the randomized trials of partial breast RT?

Abstract

Abstract Accelerated Partial Breast Irradiation (APBI) was developed to improve convenience and reduce toxicity of RT after breast conserving surgery (BCS). Results from the APBI randomized trials (RCTs) will be reviewed. Two RCTs of 3D-CRT have been conducted.(1,2) APBI was 38.5Gy in 10 fractions, twice daily over 1 week. Neither has reported efficacy. In the RAPID trial, 3-year cosmesis and grade 1-2 toxicities were significantly worse with 3D-CRT compared to whole breast irradiation (WBI).(1) Interim toxicities from the NSABP/RTOG study were similar.(2) Explanations for the excess toxicity have been proposed but ultimately, 3D-CRT using the dose and technique of the RCTs should not be used. Different dose/fractionations may result in lower toxicity but need to be validated. Various brachytherapy techniques have been used for APBI. In Hungary, 258 patients were randomized to WBI or APBI using HDR-brachytherapy.(3) Only 88 (69%) APBI patients received HDR; others had electron-PBI. Median follow up was 10.2 years. Ipsilateral Breast Tumor Recurrence (IBTR) rates were similar for APBI (5.9%) and WBI (5.1%; p=0.77). Rates of excellent-good cosmesis were higher for HDR-APBI patients compared to WBI or electron-PBI. These promising results support further investigation of brachytherapy APBI. Two RCTs of single-fraction, intra-operative APBI are published. The ELIOT trial delivered 21Gy using electrons.(3) At 5.8 years median follow-up, IBTR rates were 0.4% with WBI and 4.4% (p<0.0001) with intra-operative RT. Subsets of patients with higher risk features had IBTR rates exceeding 10% following intra-operative RT. In TARGIT, 50kV x-rays delivered 5-7Gy at 1cm from a spherical device inserted into the surgical cavity.(4) The TARGIT intervention was delivered at the time of initial surgery (n=2298; pre-pathology stratum), or after BCS pathology had shown no high-risk factors for IBTR (n=1153; post-pathology stratum). 22% of higher-risk APBI patients received WBI in the pre-pathology stratum. The post-pathology stratum therefore provides insight about the efficacy of intra-operative kV RT alone. With 2.4 years median follow up, IBTR rates were 1.7% (WBI) and 5.4% with intra-operative RT alone (p=0.069). IBTR rates in the pre-pathology stratum, where WBI was used if patients had high risk pathology features, were 1.1% (WBI) and 2.1% with intra-operative RT+/-WBI (p=-.31). Whole breast RT consistently reduces IBTR risk by two-thirds.(5) One conclusion from the greater than 3-fold higher IBTR rates following intra-operative RT alone, is that this intervention is consistent with not using any RT following BCS. The low IBTR rates with or without intra-operative RT or WBI reinforce that selecting patients with a very low IBRT risk after BCS without RT, should be possible. But, since 1 breast cancer death is caused by each 4 unnecessary local recurrences(5), 10-year IBTR rates should be 5% or less or women will be subjected to a greater than 1% excess risk of death over 10-15 years. Age alone is insufficient to identify patients at very low IBTR risk.