乳腺导管原位癌或者淋巴结阴性乳腺癌
保乳术后外照射快速局部放疗长期结局
早期乳腺癌保乳术后，3～5周内每天进行一次全乳放疗可以减少局部复发并且美观效果良好。快速局部乳房放疗在1周内对肿瘤局部进行放疗，可以提供更为方便的治疗选择，不过效果尚不明确。
2019年12月5日，国际四大医学期刊之一英国《柳叶刀》正刊在线发表加拿大麦克马斯特大学、朱拉文斯基癌症中心、不列颠哥伦比亚癌症中心、不列颠哥伦比亚大学、拉瓦尔大学魁北克医院、曼尼托巴大学、蒙特利尔大学中心医院、多伦多大学、玛格丽特公主癌症中心、卡尔加里大学、西安大略大学、艾伯塔大学癌症研究所、克雷迪特河谷医院、麦吉尔大学、犹太综合医院、西格尔癌症中心、维多利亚大学、澳大利亚新南威尔士大学威尔士亲王医院的RAPID研究报告，探讨了乳腺导管原位癌或者淋巴结阴性乳腺癌保乳术后，外照射快速局部乳房放疗与全乳放疗相比，效果是否相似。该研究由加拿大卫生研究院、加拿大乳腺癌研究联盟提供资助。
RAPID: Randomized Trial of Accelerated Partial Breast Irradiation: An RCT to Determine if APBI, Utilizing 3D CRT, is as Effective as Whole Breast Irradiation Following Breast Conserving Surgery in Women With Ductal Carcinoma in Situ or Invasive Breast Cancer With Negative Axillary Lymph Nodes (NCT00282035)
该多中心随机对照非劣效研究于2006年2月7日～2011年7月15日从加拿大、澳大利亚和新西兰33个癌症中心入组年龄≥40岁的乳腺原位导管癌或淋巴结阴性乳腺癌女性2135例，按1∶1随机分为两组，外照射快速局部乳房放疗组于5～8天内将38.5戈瑞分割为10次每天2次，全乳放疗组于21天内将42.5戈瑞分割为16次每天1次或35天内将50戈瑞分割为25次每天1次。患者和临床医师对治疗分组非盲。主要结局为意向治疗患者的同侧乳腺肿瘤复发。该研究预设非劣效标准为全乳放疗组与快速局部乳房放疗组相比，5年预计同侧乳腺肿瘤复发风险比的双向90%置信区间上限小于2.02。
结果，1070例患者被随机分入快速局部乳房放疗组，1065例患者被随机分入全乳放疗组。快速局部乳房放疗组6例患者治疗前退出，另外4例未接受放疗、16例改为接受全乳放疗；随访期间14例失访、9例退出随访。全乳放疗组16例患者退出治疗，另外2例未接受放疗，随访期间20例失访、35例退出随访。
中位随访8.6年（四分位：7.3～9.9）期间，快速局部乳房放疗组、全乳放疗组的8年累计同侧乳腺肿瘤复发比例为3.0%、2.8%（95%置信区间：1.9～4.0、1.8～3.9；风险比：1.27，90%置信区间：0.84～1.91，符合预设非劣效标准）。
快速局部乳房放疗组、全乳放疗组相比：
不良事件数据可供分析的患者：1070例、1065例：
≥2级急性（放疗开始3个月内）放射毒性反应：300例、484例（28%比45%，P<0.0001）
≥2级迟发（放疗开始3个月后）放射毒性反应：346例、142例（32%比13%，P<0.0001）
3年美观结局不良比例：绝对值高11.3%（95%置信区间：7.5～15.0）
5年美观结局不良比例：绝对值高16.5%（95%置信区间：12.5～20.4）
7年美观结局不良比例：绝对值高17.7%（95%置信区间：12.9～22.3）
因此，该研究结果表明，乳腺导管原位癌或者淋巴结阴性乳腺癌保乳术后，外照射快速局部乳房放疗与全乳放疗，预防同侧乳腺肿瘤复发效果相似。虽然外照射快速局部乳房放疗的急性毒性反应比例较低，但是中度迟发放射毒性反应比例较高、美观结局不良比例较高，可能与每天治疗2次相关。其他方案，例如每天治疗1次，可能对美观结局的不利影响较小，故有必要开展进一步研究。
对此，英国剑桥大学、伦敦癌症研究院、法国巴黎文理研究大学居里研究院发表同期评论：快速局部乳房放疗——问题多于答案？
很多患者喜欢问：某种治疗究竟好不好？其实，答案可以有很多，需要具体情况具体分析，无法一概而论。治疗没有好坏之分，只有合不合适。
Lancet. 2019 Dec 5. [Epub ahead of print]
External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.
Timothy J Whelan, Jim A Julian, Tanya S Berrang, Do-Hoon Kim, Isabelle Germain, Alan M Nichol, Mohamed Akra, Sophie Lavertu, Francois Germain, Anthony Fyles, Theresa Trotter, Francisco E Perera, Susan Balkwill, Susan Chafe, Thomas McGowan, Thierry Muanza, Wayne A Beckham, Boon H Chua, Chu Shu Gu, Mark N Levine, Ivo A Olivotto; RAPID Trial Investigators.
McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada; BC Cancer - Victoria, University of British Columbia, Vancouver, BC, Canada; CHU de Québec - Université Laval, Québec, QC, Canada; University of British Columbia and BC Cancer - Vancouver, BC, Canada; University of Manitoba, Winnipeg, MB, Canada; Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada; University of British Columbia and BC Cancer - Kelowna, BC, Canada; University of Toronto and Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Calgary, Calgary, AB, Canada; Western University and London Regional Cancer Program, London, ON, Canada; BC Cancer - Surrey, BC, Canada; University of Alberta and Cross Cancer Institute, Edmonton, AB, Canada; Trillium Health Partners Credit Valley Hospital, Mississauga, ON, Canada; McGill University and Jewish General Hospital Segal Cancer Centre, Montreal, QC, Canada; University of Victoria and BC Cancer - Victoria, BC, Canada; University of New South Wales and Prince of Wales Hospital, Sydney, NSW, Australia.
BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation.
METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38.5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42.5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1.5% in the whole breast irradiation group with 85% power to exclude a 1.5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2.02. This trial is registered with ClinicalTrials.gov, NCT00282035.
FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8.6 years (IQR 7.3-9.9). The 8-year cumulative rates of IBTR were 3.0% (95% CI 1.9-4.0) in the APBI group and 2.8% (1.8-3.9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1.27 (90% CI 0.84-1.91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0.0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0.0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11.3%, 95% CI 7.5-15.0), 5 years (16.5%, 12.5-20.4), and 7 years (17.7%, 12.9-22.3).
INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied.
FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.
DOI: 10.1016/S0140-6736(19)32515-2
Lancet. 2019 Dec 5. [Epub ahead of print]
Accelerated partial breast irradiation: more questions than answers?
Charlotte E Coles, Judith M Bliss, Philip M Poortmans.
University of Cambridge, Cambridge, UK; The Institute of Cancer Research, London, UK; Institut Curie, Paris, France; Université Paris Sciences et Lettres, Paris, France.
DOI: 10.1016/S0140-6736(19)32959-9
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