Intraoperative Radiotherapy After Local Recurrence in Breast Cancer

Not Applicable

Completed

Conditions: Breast Carcinoma

Interventions: Procedure: tumorectomy
Radiation: Intra Operative Radiotherapy

Registration Number: NCT02386371

Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 66

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
surgery and Intra Operative Radiotherapy	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.
surgery and Intra Operative Radiotherapy	tumorectomy	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.

Primary Outcome Measures

Name	Time	Method
The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer	Up to 12 months post radiation	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

Secondary Outcome Measures

Name	Time	Method
Rate of Early and Late Toxicities	from the baseline to 5 years after treatment	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
Local Relapse-free Survival	from the baseline to 5 years after treatment	Number of patient with or without the apparition of local relapse
Metastasis Relapse-free Survival	from the baseline to 5 years after treatment	number of patient with and without the apparition of metastatic relapse.
Disease-free Survival.	from the baseline to 5 years after treatment	Number of patient with and without a relapse
Overall Survival	from the baseline to 5 years after treatment	number de patient dead
Free Interval Without Mastectomy.	from the baseline to 5 years after treatment	Number of patient with a mastectomy during the study and follow up

Trial Locations

Locations (8): Institut Paoli Calmette
🇫🇷
Marseille, France
Institut de Cancérologie de l'Ouest
🇫🇷
Nantes, France
Chu Brest
🇫🇷
Brest, France
Centre George Francois Leclerc
🇫🇷
Dijon, France
Centre Léon Bérard
🇫🇷
Lyon, France
Institut Bergonié
🇫🇷
Bordeaux, France
CHU La TIMONE
🇫🇷
Marseille, France
ICM
🇫🇷
Montpellier, France