Harry Bartelink1, Philippe Maingon2, Philip Poortmans3, Caroline Weltens4, Alain Fourquet5, Jos Jager6, Dominic Schinagl7, Bing Oei8, Carla Rodenhuis9, Jean-Claude Horiot10, Henk Struikmans9, Erik Van Limbergen4, Youlia Kirova5, Paula Elkhuizen11, Rudolf Bongartz12, Raymond Miralbell13, David Morgan14, Jean-Bernard Dubois15, Vincent Remouchamps16, René-Olivier Mirimanoff17, Sandra Collette18, Laurence Collette18. 1. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands. Electronic address: h.bartelink@nki.nl. 2. Department of Radiation Oncology, Centre Georges-Francois Leclerc, Dijon, France. 3. Department of Radiation Oncology, Institute Verbeeten, Tilburg, Netherlands; Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands. 4. Department of Radiation Oncology, KU Leuven, University Hospitals Leuven, Belgium. 5. Department of Radiation Oncology, Institut Curie, Paris, France. 6. Department of Radiation Oncology, Maastro Clinic, Maastricht, Netherlands. 7. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands. 8. Department of Radiation Oncology, Institute Verbeeten, Tilburg, Netherlands. 9. Department of Radiation Oncology, Medical Center Utrecht, Utrecht, Netherlands. 10. Clinique de Genolier, Genolier, Switzerland. 11. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands. 12. Department of Radiation Oncology, Universitaetsklinikum Köln, Köln, Germany. 13. Division of Radiation Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 14. Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK. 15. Institut Régional du Cancer Montpellier, Montpellier, France. 16. Department of Radiotherapy, Clinique et Maternité Sainte Elisabeth, Namur, Belgium. 17. Clinique La Source, Lausanne, Switzerland. 18. EORTC Headquarters, Brussels, Belgium.
Abstract
BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS:Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS:Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001). INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. FUNDING: Fonds Cancer, Belgium.
RCT Entities:
BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS:Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001). INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. FUNDING: Fonds Cancer, Belgium.
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