Intraoperative Radiotherapy After Local Recurrence in Breast Cancer

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02386371

Acronym

RE-IORT01

Enrollment

Registered

2015-03-11

Start date

2014-03-31

Completion date

2023-09-18

Last updated

2025-02-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Carcinoma

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.

Interventions

PROCEDUREtumorectomy

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.

RADIATIONIntra 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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

50 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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
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
Disease-free Survival.	from the baseline to 5 years after treatment	Number of patient with and without a relapse

Countries

France

Participant flow

Participants by arm

Arm	Count
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. 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. 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	53
Total	53

Arm

Count

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. 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. 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

Total

Baseline characteristics

Characteristic	Surgery and Intra Operative Radiotherapy	—
Age, Continuous	68 years	—
Race and Ethnicity Not Collected	—	— Participants
Sex: Female, Male Female	53 Participants	—
Sex: Female, Male Male	0 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	6 / 59
other Total, other adverse events	59 / 59
serious Total, serious adverse events	3 / 59

Outcome results

Primary

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

Time frame: Up to 12 months post radiation

Arm	Measure	Group	Value (NUMBER)
Surgery and Intra Operative Radiotherapy	The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer	number of patients without fibrosis	34 participants
Surgery and Intra Operative Radiotherapy	The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer	number of patients with fibrosis	19 participants

Secondary