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对于早期乳腺癌保乳术后复发风险较高患者，全乳放疗之后再对肿瘤切除部位（瘤床）进行加强放疗，可以显著提高局部癌症控制率、降低同侧乳腺肿瘤复发率，但是患者就诊次数增加，并且可能增加乳房硬结风险。全乳放疗同时加强放疗，与全乳放疗之后加强放疗相比，虽然可以缩短疗程，但是能否同时保持出色的局部控制率和相似或较低的毒性发生率？ 2023年6月8日，国际四大医学期刊之一、创刊200周年、影响因子高达202.731的英国《柳叶刀》正刊在线发表剑桥大学、伦敦大学癌症研究院、皇家马斯登医院、剑桥大学阿登布鲁克医院、基尔大学医学院、基尔大学皇家斯托克医院、切尔滕纳姆医院、萨里大学、伦敦大学国王学院盖伊和圣托马斯医院、克拉特布里奇癌症中心、弗农山癌症中心的IMPORT HIGH研究报告，对全乳放疗之后加强放疗与全乳放疗同时两种剂量递增方案加强放疗的有效性和安全性进行了比较。 IMPORT HIGH (ISRCTN47437448): Randomised trial testing dose escalated intensity modulated radiotherapy in women with higher than average local tumour recurrence risk after breast conservation therapy for early breast cancer 该全国多中心三期非劣效非盲随机对照研究于2009年3月4日至2015年9月16日从英国39个放疗中心和37个转诊中心入组乳腺浸润癌病理肿瘤1～3期、病理淋巴结0～3a期、未远处转移、保乳手术后女性2617例，通过计算机生成的随机排列区组根据不同中心对患者进行分层，按1∶1∶1的比例分为三组： 对照组871例：40戈瑞分15次全乳放疗，随后16戈瑞分8次瘤床光子放疗 测试1组874例：36戈瑞分15次全乳放疗、40戈瑞分15次部分放疗、同时48戈瑞分15次瘤床光子放疗 测试2组872例：36戈瑞分15次全乳放疗、40戈瑞分15次部分放疗、同时53戈瑞分15次瘤床光子放疗
根据术中钛夹标记的瘤床进行光子放疗，瘤床体积中位13（四分位7～22）立方厘米。未对患者和临床医师进行治疗分配设盲。主要终点为全部入组患者的同侧乳腺肿瘤复发，假设对照组的5年复发率为5%，预设非劣效为测试组的5年复发率增加绝对值≤3%（双侧95%置信区间上限）。不良事件根据临床医师、患者和照片进行评定。 结果，中位随访74个月时，对照组、测试1组、测试2组相比： 与对照组相比，5年同侧乳腺肿瘤复发率增加绝对值： 测试1组与对照组相比，95%置信区间上限未超过3%，表明48戈瑞非劣效。 
临床医师报告的中度或显著乳房硬结5年累积发生率： 因此，该大样本随机对照研究结果证实，无论全乳放疗之后加强放疗，还是全乳放疗同时加强放疗，5年同侧乳腺肿瘤复发率都低于最初预计的5%。全乳放疗同时加强放疗由48戈瑞增加至53戈瑞反而显著增加5年同侧乳腺肿瘤复发率。全乳放疗同时加强放疗48戈瑞的5年中度或显著不良事件发生率最低，而且患者就诊次数减少。经过十几年，始于2009年的IMPORT HIGH与始于2007年的IMPORT LOW两大研究终于珠联璧合、高低兼顾，将共同减少早期乳腺癌保乳术后高风险与低风险患者的复发风险、放疗负担以及不良反应。 相关链接 Lancet. 2023 Jun 8. IF: 202.731Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial.Charlotte E Coles, Joanne S Haviland, Anna M Kirby, Clare L Griffin, Mark A Sydenham, Jenny C Titley, Indrani Bhattacharya, A Murray Brunt, H Y Charlie Chan, Ellen M Donovan, David J Eaton, Marie Emson, Penny Hopwood, Monica L Jefford, Sara V Lightowlers, Elinor J Sawyer, Isabel Syndikus, Yat M Tsang, Nicola I Twyman, John R Yarnold, Judith M Bliss; IMPORT Trial Management Group.University of Cambridge, Cambridge, UK; Institute of Cancer Research, Sutton, UK; Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Addenbrooke's Hospital, Cambridge, UK; School of Medicine, University of Keele, Keele, UK; University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK; Nuffield Health Cheltenham Hospital, Cheltenham, UK; University of Surrey, Guildford, UK; Guy's and St Thomas' Hospitals, London, UK; Independent Cancer Patients Voice, London, UK; Guy's and St Thomas' Foundation Trust, Kings College London, London, UK; Clatterbridge Cancer Centre, Bebington, UK; Mount Vernon Cancer Centre, Northwood, UK.BACKGROUND: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity.METHODS: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants.FINDINGS: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1.9% (95% CI 1.2 to 3.1) for the control group, 2.0% (1.2 to 3.2) for test group 1, and 3.2% (2.2 to 4.7) for test group 2. The estimated absolute differences versus the control group were 0.1% (-0.8 to 1.7) for test group 1 and 1.4% (0.03 to 3.8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11.5% for the control group, 10.6% for test group 1 (p=0.40 vs control group), and 15.5% for test group 2 (p=0.015 vs control group).INTERPRETATION: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits.FUNDING: Cancer Research UK.DOI: 10.1016/S0140-6736(23)00619-0
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