Accelerated Partial Breast Irradiation Versus Standard or Hypofractionated Whole-Breast Irradiation, in Early Breast Cancer, After Breast-conserving Surgery

Official title

Clinical Trial, Randomized, Open Label, With an Active Comparator to Assess the Efficacy and Safety of Using Accelerated Partial Irradiation Versus Standard or Hypofractionated Irradiation of the Entire Breast in Patients With Initial Breast Cancer After Conservative Surgery

Overview

Radiotherapy has been confirmed as an important treatment breast-conserving surgery reducing the risk of any recurrence of breast cancer and breast cancer-related mortality in patients with early breast cancer. There are no comparative data on the ideal radiotherapy treatment regimen for patients with early stage breast cancer who underwent conservative surgery in the Brazilian population.

Detailed description

The investigators propose a prospective, randomized, pilot study, with active control, to evaluate the viability and safety of accelerated partial breast irradiation, in 5 fractions, comparing with the radiotherapy regimens of the whole breast in 15 and 5 fractions, in patients with breast cancer, in initial stage, who underwent conservative surgery.

Interventions

• Radiation Active Comparator: Standard
  Radiation: Whole Breast Irradiation + Boost Whole breast, either 40Gy, in 15 fractions, in 3 weeks
• Radiation Experimental 1: Hypofractionated radiotherapy
  Radiation: Hypofractionated irradiation Whole Breast Irradiation 26Gy in 5 fractions in one week
• Radiation Experimental 2: Accelerated Partial Breast Irradiation
  Radiation: Accelerated partial breast irradiation Tumor bed 26Gy in 5 fractions, in 5 days.

Primary outcome measures

• Rate of local recurrence [Time frame: 5 years]

Secondary outcome measures (12)

• Time to occurrence of distant metastases [Time frame: 5 years]
• Disease-free survival [Time frame: 5 years]
• Overall survival [Time frame: 5 years]
• Medico-economic study [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Health-related Quality of Life [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Evaluation of quality of life change by European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Fatigue Questionnaire (Functional Assessment of Cancer Therapy-Fatigue - FACT-F) [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Measurement Satisfaction of Body Image of the participants [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Changes in anxiety and depression [Time frame: Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end]
• Early and late adverse effects in normal tissues [Time frame: 5 years]
• Late adverse effects [Time frame: 5 years]
• Acute toxicity rate [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Information to the patient and signed informed consent;
• Women aged ≥50 years
• Breast conserving surgery
• Pathologic tumor size < 3 cm (maximum microscopic diameter of the invasive component)
• Invasive adenocarcinoma (except classic invasive lobular carcinoma)
• Unifocal disease
• Histopathologic grades I or II
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Lymphovascular invasion absent
• Negative axillary lymph nodes
• Minimum microscopic margins of non-cancerous tissue of 2mm (excluding deep margin when in deep fascia)
• No prior breast or mediastinal radiotherapy
• No hematogenous metastases

Exclusion criteria

• Previous malignancy (except non-melanomatous skin cancer)
• Mastectomy
• Classical-Type Invasive Lobular Carcinoma
• Neoadjuvant chemotherapy
• Human Epidermal growth factor Receptor-type 2 positive (HER2+)
• Triple-negative breast cancers
• Intravascular lymphoma present
• Contraindications to radiotherapy.
• No geographical, social or psychologic reasons that would prevent study follow

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 1 center

• IBCC Oncologia — São Paulo

Publications

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. PMID 22019144
• Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez Miguelez C, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Malzer M, Uter W, Polgar C; Groupe Europeen de Curietherapie of European Society for Radiotherap PMID 26494415
• Polgar C, Fodor J, Major T, Sulyok Z, Kasler M. Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial. Radiother Oncol. 2013 Aug;108(2):197-202. doi: 10.1016/j.radonc.2013.05.008. Epub 2013 Jun 3. PMID 23742961
• Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Leonardi MC, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(1 PMID 24225155
• Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013 Nov 10;31(32 PMID 23835717
• Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, White J, Harris JR. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Pract Radiat Oncol. 2017 Mar-Apr;7(2):73-79. doi: 10.1016/j.prro.2016.09.007. Epub 2016 Sep 17. PMID 27866865
• Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca Cardillo C, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015 Mar;51(4):451-463. PMID 25605582
• Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. PMID 24055415

Identifiers

NCT: NCT04669873 · 38341220.8.0000.0072

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗