Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia.
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.
Lancet. 2022 Aug 6;400(10350):431-440. doi: 10.1016/S0140-6736(22)01246-6.
Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS.
The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236).
Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001).
In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results.
National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.
保乳手术后行全乳放疗（WBI）可降低导管原位癌（DCIS）的局部复发率。我们研究了 WBI 后肿瘤床加量放疗是否能改善预后，并检查了非低危 DCIS 对不同放疗剂量分割的敏感性。
本研究为国际性、随机、非盲、III 期临床试验，涉及 6 个临床试验组织的 136 个参与中心，分布于 11 个国家（澳大利亚、新西兰、新加坡、加拿大、荷兰、比利时、法国、瑞士、意大利、爱尔兰和英国）。入组患者为年龄 18 岁及以上、经组织学证实的单侧非低危 DCIS 患者，接受保乳手术治疗，且至少有 1mm 的切缘无肿瘤累及。患者被随机分配至无肿瘤床加量放疗组（n=805）、常规 WBI 后加量放疗组（n=803）、常规 WBI 组（n=831）或 hypofractionated WBI 后加量放疗组（n=777），比例为 1:1:1:1。常规 WBI 组放疗剂量为 50Gy/25 次，hypofractionated WBI 组为 42.5Gy/16 次。如果加量放疗，则在 WBI 后给予 16Gy/8 次的 boost 剂量。患者和临床医生对治疗分配均不知情。主要终点为局部复发时间。本研究在 ClinicalTrials.gov 注册（NCT00470236）。
2007 年 6 月 25 日至 2014 年 6 月 30 日期间，共纳入 1608 例患者，随机分为无加量放疗组（n=805）或加量放疗组（n=803）。831 例患者接受常规 WBI，777 例患者接受 hypofractionated WBI。中位随访时间为 6.6 年。无加量放疗组的 5 年无局部复发生存率为 92.7%（95%CI 90.6-94.4%），加量放疗组为 97.1%（95.6-98.1%）（风险比 0.47；0.31-0.72；p<0.001）。加量放疗组中 2 级及以上乳房疼痛（10%[8-12%] vs 14%[12-17%]）和硬结（6%[5-8%] vs 14%[11-16%]）的发生率更高（均 p<0.001）。
在接受保乳手术治疗的非低危 DCIS 患者中，WBI 后肿瘤床加量放疗可降低局部复发率，同时增加 2 级及以上毒性反应的发生率。该研究结果首次提供了随机临床试验数据，支持在这些患者中应用术后 WBI 后的加量放疗来改善局部控制。该研究具有国际规模，支持结果的推广性。
澳大利亚国家卫生和医学研究委员会、Susan G Komen for the Cure、乳腺癌防治基金会、瑞士肿瘤研究协会、荷兰癌症协会、加拿大癌症临床试验组。
