Single-Fraction Very Accelerated Partial Breast Irradiation (sfVAPBI)

Official title

Single-Fraction Very Accelerated Partial Breast Irradiation (sfVAPBI) in Low-Risk Invasive or Ductal In Situ Breast Carcinoma - Phase II Multicenter Trial

Overview

To investigate clinical outcomes, late side effects, and cosmetic results of a single-fraction very accelerated partial breast irradiation as postoperative local treatment for the treatment of early stage breast cancer.

Detailed description

Accelerated Partial Breast Irradiation (APBI) has demonstrated the non-inferiority compared to external beam radiotherapy (EBRT) in the conserving-treatment of early breast carcinoma by using high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIBT). The standard treatment regimen is 7-8 sessions with two treatments per day, for a total treatment time of 4-5 days. Based on 5-year results of the Groupe Européen de Curiethérapie European SocieTy for Radiotherapy \& Oncology (GEC-ESTRO) Very Accelerated Partial Breast Irradiation (VAPBI) phase I-II trial, in low-risk cases, 3-4 fractions delivered in 2 days reduced the overall treatment time with low rate of side effects and excellent oncological outcome.

Retrospective and prospective studies with a single fraction HDR MIBT-based VAPBI suggest that by further increasing the dose delivered in one fraction, the total treatment time can be reduced to a single session safely.

A phase II multicenter trial is proposed to confirm this hypothesis.

Interventions

• Radiation single-fraction very accelerated partial breast irradiation
  Adjuvant accelerated partial breast brachytherapy, with interstitial multicatheter technique, in one fraction.

Primary outcome measures

• Five-year incidence of late grade ≥ 2 side effects [Time frame: From the third month of treatment to the end of the fifth year of follow-up.]

Secondary outcome measures (10)

• Incidence (5-year actuarial rate) of ipsilateral breast recurrence (IBR) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of regional relapse (RR) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of contralateral breast cancer (CBC) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of distant metastasis (DM) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of any relapse (local, regional or distant, whichever came first) for disease free survival (DFS) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of breast cancer death for cause specific survival (CSS) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence (5-year actuarial rate) of death by any cause for overall survival (OS) [Time frame: From treatment to the end of the fifth year of follow-up.]
• Incidence of acute side effects [Time frame: From treatment to the end of the first 3 months of follow-up.]
• Cosmetic results at 5 years [Time frame: From treatment to the end of the fifth year of follow-up.]
• Quality of Life (QoL) [Time frame: From treatment to the end of the fifth year of follow-up.]

Eligibility criteria

Inclusion criteria

• Stage 0 \& I \& II (< 3 cm) breast carcinoma
• Lesions of < 3 cm diameter
• Invasive carcinoma of any subtype and grade or ductal carcinoma in situ (DCIS)
• Nodal status: node-negative (pN0) or micro-metastatic (pN1mi) (patients with pN1mi status can be treated, but due to the limited clinical evidence, individual decision is needed)
• M0: Absence of distant metastasis
• Clear resection margins by National Surgical Adjuvant Breast and Bowel Project (NSABP) definition (no tumor on ink)
• Unifocal (multifocality limited within 2 cm) and unicentric breast cancer
• Age> 40 years
• Luminal A or B tumors
• Time interval from surgery preferably less than 12 weeks and no longer than 20 weeks, and from adjuvant chemotherapy less than 4 weeks
• Human Epidermal growth factor Receptor 2 positive (HER2+) patients receiving postoperative anti-HER2 systemic therapy
• Specific signed consent form prior to randomization

Exclusion criteria

• Stage III-IV breast cancer
• Surgical margins that cannot be microscopically assessed
• Extensive intraductal component (EIC+)
• Extensive lymphovascular invasion (LVI+) (focal is allowed)
• Triple negative breast cancer
• BReast CAncer gene (BRCA) 1-2 mutation
• Human Epidermal growth factor Receptor 2 positive (HER2+) patients not receiving postoperative anti-HER2 systemic therapy
• Neoadjuvant systemic therapy
• Paget's disease or pathological skin involvement
• Synchronous or previous breast cancer.
• Pregnant or lactating women

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 5 centers

• Klinikum Bremerhaven — Bremerhaven
• University Hospital Erlangen — Erlangen
• Universitätsklinikum Schleswig-Holstein — Lübeck
• Sana Klinikum Offenbach — Offenbach
• Universitätsklinikum Würzburg — Würzburg

Poland · 5 centers

• Maria Skłodowska-Curie Bialystok Oncology Center — Bialystok
• Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny — Brzozów
• National Institute of Oncology — Gliwice
• Greater Poland Cancer Centre — Poznan
• Lower Silesian Oncology, Pulmonology and Hematology Center — Wroclaw

Spain · 4 centers

• Fundacion IMOR's Oncology Clinic — Barcelona
• Institut Catala d'Oncologia — Barcelona
• Hospital Universitario de Navarra — Pamplona
• Instituto Valenciano de Oncologia — Valencia

France · 3 centers

• Centre Léon Bérard — Lyon
• Institut de Cancérologie de Lorraine — Nancy
• Antoine Lacassagne Cancer Centre — Nice

Hungary · 1 center

• National Institute of Oncology — Budapest

Lithuania · 1 center

• National Cancer Institute — Vilnius

Portugal · 1 center

• Instituto Português de Oncologia do Porto — Porto

Serbia · 1 center

• Oncology Institute Vojvodina — Kamenica

Switzerland · 1 center

• Inselspital, Universitätsspital Bern — Bern

Publications

• Hannoun-Levi JM, Montagne L, Sumodhee S, Schiappa R, Boulahssass R, Gautier M, Gal J, Chand ME. APBI Versus Ultra-APBI in the Elderly With Low-Risk Breast Cancer: A Comparative Analysis of Oncological Outcome and Late Toxicity. Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):56-67. doi: 10.1016/j.ijrobp.2021.03.052. Epub 2021 Apr 6. PMID 33831490
• Hannoun-Levi JM, Gimeno Morales M, Gal J, Anchuelo J, Guinot JL, Gaztanaga M, Meszaros N, Polgar C, Strnad V, Schiappa R, Gutierrez C. Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort. Radiother Oncol. 2024 May;194:110217. doi: 10.1016/j.radonc.2024.110217. Epub 2024 Mar 8. PMID 38460552
• Hannoun-Levi JM, Lam Cham Kee D, Gal J, Schiappa R, Hannoun A, Fouche Y, Gautier M, Boulahssass R, Chand ME. Accelerated partial breast irradiation in the elderly: 5-Year results of the single fraction elderly breast irradiation (SiFEBI) phase I/II trial. Brachytherapy. 2020 Jan-Feb;19(1):90-96. doi: 10.1016/j.brachy.2019.10.007. Epub 2019 Nov 23. PMID 31767533
• Guinot JL, Gutierrez-Miguelez C, Meszaros N, Gonzalez-Perez V, Santos MA, Najjari D, Slocker A, Major T, Polgar C. Five-year results of the very accelerated partial breast irradiation VAPBI phase I-II GEC-ESTRO trial. Radiother Oncol. 2024 Dec;201:110543. doi: 10.1016/j.radonc.2024.110543. Epub 2024 Sep 24. PMID 39321957
• Strnad V, Polgar C, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Gutierrez Miguelez C, Slampa P, Allgauer M, Lossl K, Polat B, Fietkau R, Schlamann A, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Dunst J, Gall C, Uter W; Groupe Europeen de Curietherapie and European Society for Radiotherapy and Oncology. Accelerated partial breast irradiation using sole i PMID 36738756

Identifiers

NCT: NCT07067437 · GEC-ESTRO sfVAPBI · 1012

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗