Intraoperative Radiotherapy After Local Recurrence in Breast Cancer (RE-IORT01)

Feasibility Clinical Trial of Intraoperative Radiotherapy (IORT) and Second Breast-conserving-surgery After Local Recurrence of Breast Carcinoma

The investigators propose a prospective, multicenter, single arm Phase II design to evaluate the feasibility of repeated breast-conserving surgery combined with re- irradiation using IORT after local recurrence of breast carcinoma.

Study Overview

• Status: Completed
• Conditions: Breast Carcinoma
• Intervention / Treatment: Procedure: tumorectomy; Radiation: Intra Operative Radiotherapy

Detailed Description

Currently, the rate of ipsilateral breast tumor recurrence (IBTR) after breast- conserving surgery and radiotherapy remains at 10% at 10 years to 15% at 20 years, respectively. IBTR is an independent predictor of poor survival with a 3 to 4.6 increased risk of cancer-related death.

In a heterogeneous population, local control remains a major therapeutic challenge for these relapses, especially those considered of better prognosis, namely occurring late and of low histological grade. Therapeutic de-escalation is possible for these relapses to avoid a mutilating and often traumatic mastectomy.

However, this second conservative surgery has a high rate of second local relapse (19 to 50% at 5 years) due to the absence of a re-irradiation, rendered impossible by the problem of tolerance of previously irradiated tissues.

Retrospective or prospective studies on partial breast irradiation (PBI) in adjuvant setting report promising results, both in terms of tolerance (saving healthy tissue) and local control (74% to 100% at 5 years). Used techniques include brachytherapy, external beam radiotherapy and intraoperative radiotherapy (IORT).

IORT is now the subject of renewed interest in breast cancer. It has the advantages of high-precision ballistics on the operated area and of preservation of healthy tissue. To date, no prospective data, however, have been published in the indication of ipsilateral breast recurrence.

A prospective, multicenter, single arm Phase II design will evaluate the feasibility of repeated breast-conserving surgery combined with re- irradiation using IORT after local recurrence of breast carcinoma.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Institut Bergonie
  • Brest, France
    • CHU Brest
  • Dijon, France
    • Centre George François Leclerc
  • Lyon, France, 69
    • Centre Leon Berard
  • Marseille, France, 13
    • CHU La Timone
  • Marseille, France, 13
    • Institut Paoli Calmette
  • Montpellier, France, 34298
    • ICM
  • Nantes, France
    • Institut de Cancérologie de l'Ouest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven non-lobular invasive breast recurrence
• Time from whole breast radiation following the initial lumpectomy >5 years
• Unifocal tumor
• Recurrent tumor size ≤ 2 cm
• Adequate breast size for a second breast-conserving surgery with acceptable cosmetic result
• Bilateral breast mammogram within 90 days prior to study entry
• Breast MRI within 90 days prior to study entry
• Histological grade I-II
• Estrogen-receptor-positive tumor (ER+)
• Cerb2-negative tumor
• N0
• M0
• Prior radiotherapy delivered within a standard fractionation schedule
• Performance status (ECOG) 0-1
• Women ≥ 50 years -Absence of any psychological, familial, sociological, or geographical conditions with a potential to hamper compliance with the study and follow- up schedule
• Affiliated to the French Health Insurance regimen
• Written and signed informed consent form.

Exclusion Criteria:

• Multifocal and/or multicenter recurrence
• Lobular carcinoma
• Estrogen-receptor-negative tumor (ER-)
• Cerb2 (her2) overexpressed - breast cancer
• Extensive intraductal component (EIC) on biopsy
• Lymph vessel invasion on biopsy
• N1-3 status: Regional cytological or histologically proven node recurrence
• M1 status: Metastatic disease
• cT4 (Skin or muscle involvement) or Paget's disease of the nipple
• Prior radiotherapy delivered within an accelerated or hypo-fraction schedule
• Prior malignancy other than non-melanoma skin cancer unless the patient has been disease free for at least 5 years
• Patients with a small breast volume, technically unsatisfactory for a second conservative surgery or intraoperative breast irradiation.
• Preoperative chemotherapy or hormone therapy for local relapse
• Connective tissue disease or scleroderma, contraindicating radiotherapy
• Known BRCA1/2 gene mutation (genetic testing is not required)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: surgery and Intra Operative Radiotherapy; Surgery : Tumorectomy will be performed according to the current standards, obtaining "clear" margins. The axillary lymph node control will depend on the initial management (clinical and ultrasound) of these N0 patients, chosen by the teams. Intra Operative Radiotherapy (IORT): After the excision of the tumor, IORT will be delivered. A single dose of 20 Gy by 50 kV photons (Intrabeam™) will be administered in tumor bed. The addition of IORT does not modify the surgical procedure.

Procedure: tumorectomy; Tumorectomy will be performed according to the current standards, obtaining "clear" margins. The axillary lymph node control will depend on the initial management (clinical and ultrasound) of these N0 patients, chosen by the teams.; Radiation: Intra Operative Radiotherapy; After the excision of the tumor, IORT will be delivered. A single dose of 20 Gy by 50 kV photons (Intrabeam™) will be administered in tumor bed. The addition of IORT does not modify the surgical procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer	Fibrosis rate of RIOP grade 2 at 12 months of IORT (Intra Operative Radiotherapy) according to NCI CTCAE v4.0 classification grade 0 is the better outcomes Grade >= 2 is the worse outcomes	Up to 12 months post radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Early and Late Toxicities	Rate of Early toxicities (Hematoma, Lymphorrhea, Breast infection) Late toxicities (telangiectasia, breast pain, skin hyperpigmentation, skin ulceration, skin atrophy) grade 0 is the better outcomes	from the baseline to 5 years after treatment
Local Relapse-free Survival	Number of patient with or without the apparition of local relapse	from the baseline to 5 years after treatment
Metastasis Relapse-free Survival	number of patient with and without the apparition of metastatic relapse.	from the baseline to 5 years after treatment
Disease-free Survival.	Number of patient with and without a relapse	from the baseline to 5 years after treatment
Overall Survival	number de patient dead	from the baseline to 5 years after treatment
Free Interval Without Mastectomy.	Number of patient with a mastectomy during the study and follow up	from the baseline to 5 years after treatment

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Study Chair: LEMANSKI Claire, Institut régional du Cancer - Val d'Aurelle

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): June 12, 2020
• Study Completion (Actual): September 18, 2023

Study Registration Dates

• First Submitted: March 2, 2015
• First Submitted That Met QC Criteria: March 10, 2015
• First Posted (Estimated): March 11, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Recurrence; Carcinoma; Breast Neoplasms
• Other Study ID Numbers: ICM-URC2014/07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No