Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study

被引：72

作者：

Chua, Boon H. ^{[1
,2
]}

Link, Emma K. ^{[3
,4
]}

Kunkler, Ian H. ^{[5
]}

Whelan, Timothy J. ^{[6
,7
]}

Westenberg, A. Helen ^{[8
]}

Gruber, Guenther ^{[9
]}

Bryant, Guy ^{[10
]}

Ahern, Verity ^{[11
,12
]}

Purohit, Kash ^{[13
,14
]}

Graham, Peter H. ^{[1
,15
]}

Akra, Mohamed ^{[16
,17
]}

McArdle, Orla ^{[18
,19
]}

O'Brien, Peter ^{[20
,21
]}

Harvey, Jennifer A. ^{[10
,22
]}

Kirkove, Carine ^{[23
,24
]}

Maduro, John H. ^{[25
]}

Campbell, Ian D. ^{[26
,27
]}

Delaney, Geoff P. ^{[1
,28
]}

Martin, Joseph D. ^{[29
,30
]}

Vu, T. Trinh T. ^{[31
,32
]}

Muanza, Thierry M. ^{[33
]}

Neal, Anthony ^{[34
]}

Olivotto, Ivo A. ^{[35
]}

机构：

[1] Univ New South Wales, Fac Med & Hlth, Sydney, NSW, Australia

[2] Prince Wales Hosp, Nelune Comprehens Canc Ctr, Randwick, NSW 2031, Australia

[3] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[4] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia

[5] Univ Edinburgh, Western Gen Hosp, Edinburgh Canc Res Ctr, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[6] McMaster Univ, Dept Oncol, Hamilton, ON, Canada

[7] Juravinski Canc Ctr, Hamilton, ON, Canada

[8] Radiotherapiegrp Arnhem, Arnhem, Netherlands

[9] Klin Hirslanden, Inst Radiotherapy, Zurich, Switzerland

[10] Univ Queensland, Brisbane, Qld, Australia

[11] Univ Sydney, Westmead, NSW, Australia

[12] Westmead Hosp, Westmead, NSW, Australia

[13] Univ Sheffield, Sheffield, S Yorkshire, England

[14] Weston Pk Hosp, Sheffield, S Yorkshire, England

[15] St George Hosp, Kogarah, NSW, Australia

[16] Univ Manitoba, Winnipeg, MB, Canada

[17] Canc Care Manitoba, Winnipeg, MB, Canada

[18] Canc Trials Ireland, Dublin, Ireland

[19] Beaumont Hosp, St Lukes Radiat Oncol Network, Dublin, Ireland

[20] Univ Newcastle, Newcastle, NSW, Australia

[21] GenesisCare, Gateshead, NSW, Australia

[22] Princess Alexandra Hosp, Woolloongabba, Qld, Australia

[23] Catholic Univ Louvain, Brussels, Belgium

[24] Clin Univ St Luc, Brussels, Belgium

[25] Univ Groningen, Univ Med Ctr Groningen, Dept Radiat Oncol, Groningen, Netherlands

[26] Univ Auckland, Auckland, New Zealand

[27] Waikato Hosp, Hamilton, New Zealand

[28] Liverpool Hosp, Liverpool, NSW, Australia

[29] Natl Univ Ireland, Galway, Ireland

[30] Univ Hosp Galway, Galway, Ireland

[31] Univ Montreal, Montreal, PQ, Canada

[32] Ctr Hosp Univ Montreal, Montreal, PQ, Canada

[33] McGill Univ, Dept Oncol, Montreal, PQ, Canada

[34] Royal Surrey Cty Hosp, Guildford, Surrey, England

[35] Univ Calgary, Calgary, AB, Canada

来源：

LANCET | 2022年 / 400卷 / 10350期

基金：

英国医学研究理事会;

关键词：

QUALITY-OF-LIFE; CONSERVING THERAPY; FOLLOW-UP; CONSERVATIVE TREATMENT; ADJUVANT RADIOTHERAPY; RECURRENCE RISK; EORTC BOOST; CANCER; SURGERY; HYPOFRACTIONATION;

D O I：

10.1016/S0140-6736(22)01246-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background 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. Methods 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). Findings 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). Interpretation 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. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

引用

页码：431 / 440

页数：10

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