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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.
Lancet 2019; 394(10215):2165-2172Lct

Abstract

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.

Authors+Show Affiliations

Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada. Electronic address: twhelan@hhsc.ca.Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada.Radiation Therapy Program, BC Cancer - Victoria, University of British Columbia, Vancouver, BC, Canada.Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada.Department of Radiation Oncology, CHU de Québec - Université Laval, Québec, QC, Canada.Division of Radiation Oncology, University of British Columbia and BC Cancer - Vancouver, BC, Canada.Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada.Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.Department of Radiation Oncology, CHU de Québec - Université Laval, Québec, QC, Canada; Division of Radiation Oncology, University of British Columbia and BC Cancer - Kelowna, BC, Canada.Department of Radiation Oncology, University of Toronto and Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.University of Calgary, Calgary, AB, Canada.Department of Oncology, Western University and London Regional Cancer Program, London, ON, Canada.BC Cancer - Surrey, BC, Canada.Department of Oncology, Division of Radiation Oncology, University of Alberta and Cross Cancer Institute, Edmonton, AB, Canada.Trillium Health Partners Credit Valley Hospital, Mississauga, ON, Canada.Department of Oncology, McGill University and Jewish General Hospital Segal Cancer Centre, Montreal, QC, Canada.Department of Physics and Astronomy, University of Victoria and BC Cancer - Victoria, BC, Canada.University of New South Wales and Prince of Wales Hospital, Sydney, NSW, Australia.Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada.Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada.University of Calgary, Calgary, AB, Canada.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

31813635

Citation

Whelan, Timothy J., et al. "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." Lancet (London, England), vol. 394, no. 10215, 2019, pp. 2165-2172.
Whelan TJ, Julian JA, Berrang TS, et al. 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. Lancet. 2019;394(10215):2165-2172.
Whelan, T. J., Julian, J. A., Berrang, T. S., Kim, D. H., Germain, I., Nichol, A. M., ... Olivotto, I. A. (2019). 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. Lancet (London, England), 394(10215), pp. 2165-2172. doi:10.1016/S0140-6736(19)32515-2.
Whelan TJ, et al. 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. Lancet. 2019 12 14;394(10215):2165-2172. PubMed PMID: 31813635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Whelan,Timothy J, AU - Julian,Jim A, AU - Berrang,Tanya S, AU - Kim,Do-Hoon, AU - Germain,Isabelle, AU - Nichol,Alan M, AU - Akra,Mohamed, AU - Lavertu,Sophie, AU - Germain,Francois, AU - Fyles,Anthony, AU - Trotter,Theresa, AU - Perera,Francisco E, AU - Balkwill,Susan, AU - Chafe,Susan, AU - McGowan,Thomas, AU - Muanza,Thierry, AU - Beckham,Wayne A, AU - Chua,Boon H, AU - Gu,Chu Shu, AU - Levine,Mark N, AU - Olivotto,Ivo A, AU - ,, Y1 - 2019/12/05/ PY - 2019/07/22/received PY - 2019/09/24/revised PY - 2019/10/01/accepted PY - 2019/12/10/pubmed PY - 2020/1/3/medline PY - 2019/12/10/entrez SP - 2165 EP - 2172 JF - Lancet (London, England) JO - Lancet VL - 394 IS - 10215 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/31813635/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 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)32515-2 DB - PRIME DP - Unbound Medicine ER -