Table 1 Summary of breast cancer practice-defining RT clinical trials

From: Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie?

Trial name (first author) Trial methodology Practice-defining trial results and methods Publications of trial results Publications related to trial conduct Evidence of practice change
Hypofractionation trials
 Canadian hypofractionation trial (Whelan) Standard whole-breast RT 50 Gy in 25 fractions vs. hypofractionated 42.5 Gy in 16 fractions. Randomised 1234 patients. Hypofractionated group non-inferior to control. 15, 131 NA International: ASTRO.21
 START-B (Agrawal) 50 Gy in 25 fractions over 5 weeks vs. 40 Gy in 15 fractions over 3 weeks. Randomised 2215 patients. 40 Gy in 15 fractions non-inferior to 50 Gy in 25 fractions in terms of locoregional relapse. Significantly less late normal tissue effects for 40 Gy in 15 fractions. Standardisation of: - patient position - target volumes - dose and fractionation - prescription points - quality assurance. 16, 132 133,134,135,136,137,138,139,140,141,142,143,– 144 International: ASTRO.21 UK: NICE.22 RCR Breast consensus meeting.145
Effect of boost dose
 EORTC 22881-10882 boost vs. no boost (Bartelink) Boost dose of 16 Gy to the primary tumour bed after tumourectomy and 50 Gy whole-breast irradiation vs. no additional boost. Randomised 2661 patients. Improved local control with boost dose, but no significant effect on survival. Increased late normal tissue toxicity with boost. Improved RT QA for boost techniques. Validation of methodology for cosmetic assessment of breast. 25, 26, 146 147,148,149,150,– 151 International: ESMO.152 UK: RCR consensus statement.145
Partial breast irradiation
 GEC-ESTRO APBI (Strnad) Compared several different regimens of accelerated partial breast irradiation (APBI) using brachytherapy vs. whole-breast RT 50 Gy in 15 fractions ± boost. Randomised 1184 patients. APBI using brachytherapy was non-inferior to whole-breast RT. 32 NA NA
 IMPORT LOW (Coles) Whole-breast radiotherapy (WBRT) 40 Gy in 15 fractions vs. 40 Gy to the tumour bed and 36 Gy to the rest of the breast OR 40 Gy to the tumour bed only. Randomised 2018 patients. PBI non-inferior to WBRT at 5 years in terms of locoregional recurrence, with a reduction in some late normal tissue toxicity endpoints. Introduction of forward planned intensity modulated RT. BASO guidelines now recommend placement of surgical clips to facilitate accurate post-operative radiotherapy planning. 33 153,154,155,156,– 157 International: Danish Breast Cancer Group national guidelines. UK: RCR consensus statement.145
Nodal irradiation
 EORTC 10981-22023 – AMAROS trial (Donker) Surgical vs. radiation treatment of axilla after positive sentinel lymph node biopsy. Randomised 4823 patients. Comparable local control results for both treatments (under-powered), decreased lymphoedema with RT. Improved RT QA for axillary RT. Improved surgical QA for SLNB. 34 158, 159 UK: RCR consensus statement.145 Association of Breast Surgeons consensus statement.160
 EORTC 22922/10925 IMC trial (Poortmans) Whole-breast/thoracic-wall RT + regional nodal irradiation vs. whole-breast/thoracic-wall RT alone. Randomised 4004 patients. Addition of regional nodal irradiation improved disease-free survival. Improved RT QA for IMC & medial supraclavicular nodal RT. 35 161,162,163,164,– 165 International: ASCO.38
 MA20 (Whelan) Women with node-positive or high-risk node-negative breast cancer: whole-breast irradiation plus regional nodal irradiation vs. whole-breast irradiation alone. Randomised 1832 patients Addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. 36 NA International: ASCO.38
 DBCG -IMN (Thorsen) Prospective population-based cohort study. Patients with right-sided disease were allocated to IMC RT, whereas patients with left-sided disease were allocated to no IMC RT (risk of radiation-induced heart disease). Included 3089 patients. IMC RT increased overall survival in patients with early-stage node-positive breast cancer. 37 166 NA
  1. ASCO American Society of Clinical Oncology, ASTRO American Society for Radiation Oncology, BASO British Association of Surgical Oncology, ESMO European Society for Medical Oncology, NICE National Institute for Health and Care Excellence, RCR Royal College of Radiologists