Randomized Trial on Intraoperative Radiotherapy Full Dose Vs External Radiotherapy

NCT ID: NCT01849133

Last Updated: 2013-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1305 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-11-30
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of this study is to investigate the efficacy of exclusive intraoperative radiation therapy after conserving surgery in early-stage breast cancer compared with whole breast radiotherapy. The primary outcome was the rate of ipsilateral true recurrence ( any recurrence at or close to primary tumor bed) and new ipsilateral tumors ( any recurrence occurring in quadrants other than the previous one) and the recurrence free survival.

Detailed Description

The ELIOT trial is a prospective single center randomised phase III trial which compared intraoperative radiotherapy with electrons to the tumor bed with conventional scheme of whole breast external beam radiotherapy. Patients were randomly allocated to intraoperative radiotherapy group or external radiotherapy group in a 1:1 ratio.

The rationale for providing partial breast irradiation to the tumor bed lies on the patterns of ipsilateral breast tumor relapse reported in Literature. In fact, the majority of recurrences occur close to the tumor bed. Several randomized trials of breast conserving surgery with or without whole breast radiotherapy showed that in 75-90% of cases recurrences were at the site of original primary tumor. In this context, limiting irradiation to the tumor bed may result in a similar local control as whole breast irradiation, provided that patients are properly selected.

The intraoperative treatment was delivered with a mobile miniaturized accelerator, located in the operating room, while for external radiotherapy a 6 MV linear accelerator was used. The surgical technique to perform ELIOT has been standardized in every step. The breast gland is prepared by separating it from the subcutaneous tissue and the underlying pectoralis muscle and by restoring the continuity of the surgical breach after having protected the thoracic wall by lead and aluminium disks to optimize the delivered dose. The linear accelerator delivers electrons at variable energy, ranging from 3 to 9 MeV: the proper electron energy is chosen according to the target thickness. Collimation is achieved by hard-docking system, consisting of 5 mm thick high- quality polymethyl methacrylate round applicators of 4 to 10 -cm diameter.

For radiation protection a primary beam stopper and mobile 1.5 cm thick lead shields are provided. The prescribed dose was 21 Gy at the 90% isodose. After delivery of the radiation dose, the applicator and the disk were removed and the gland is reconstructed again.

In the conventional arm of the study, the external beam radiotherapy is given after the full recovery from the surgical excision. All patients undergo virtual simulation including a treatment-planning CT scan. The clinical target volume is defined to extend to 5 mm below the skin surface and include breast parenchyma down to the deep fascia, but not including the underlying muscle and rib cage. The irradiated volume should extend medially to the midline, laterally to the mid axillary line and inferiorly to 1-2 cm below the level of intra-mammary fold and superiorly to the suprasternal notch. Using BEV, the blocks are used to shield as much heart and lung as possible without compromising the PTV.

Treatment is delivered by a pair of tangential fields with wedges as necessary. The prescribed dose to the whole-breast was 50 Gy delivered in 2 Gy fraction over 5 weeks with a 6 -megavolt linear accelerator followed by a sequential boost of 10 Gy to the tumor bed with electrons. A PTV dose homogeneity of -5% + 7% as recommended by ICRU (International Commission on Radiation Units and Measurements) report no 50.

Patients were followed up with at least 6-month clinical examination up to 5 years and then every 8 months thereafter. Annual mammogram was performed .

Conditions

Carcinoma Breast

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ELIOT

intraoperative radiotherapy

Group Type: EXPERIMENTAL

intraoperative radiotherapy

Intervention Type: RADIATION

Intraoperative radiotherapy (IORT). Total delivered dose 21Gy (Gray), 90% isodose

EXTERNAL RT

external fractionated radiotherapy

Group Type: ACTIVE_COMPARATOR

external fractionated radiotherapy

Intervention Type: RADIATION

conventional external beam radiotherapy

Interventions

external fractionated radiotherapy

conventional external beam radiotherapy

Intervention Type: RADIATION

intraoperative radiotherapy

Intraoperative radiotherapy (IORT). Total delivered dose 21Gy (Gray), 90% isodose

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Age ≥ 48 and < 75
• Clinical mammographic/ultrasound diagnosis of unicentric carcinoma, with ultrasound diameter ≤2.5 cm. Advisable, but not mandatory, the execution of mammoscintigraphy with MDP-99mTc (Methyl diphosphonate technetium-99m) : this procedure allows the bone staging and the mapping of eventual multi-focality/multi-centricity of the breast neoplasm.
• No previous therapy (biopsy included) for breast cancer in other Institutions.
• Patients with non-palpable lesions will undergo preoperative centering and stereotactic and/or ultrasound-guided cytology (the execution of this last procedure is not mandatory).
• Adequate information to the patient and informed consent.

Exclusion Criteria

• Ductal or lobular non-infiltrating carcinoma.
• Paget disease.
• Tumor in close proximity to the skin.
• Tumor in the axillary tail.
• Documented multi-centricity/multi-focality of the tumor.
• Patients who underwent excisional biopsy in other Institutions.
• Histology different from carcinoma.
• Personal anamnesis positive for malignancy (basocellular carcinoma, in situ carcinoma of the cervix, contralateral breast cancer free of disease after 15 years of follow-up excluded).
• General contraindications to regular follow-up or radiotherapy.

• Minimum Eligible Age: 48 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UMBERTO VERONESI, PROF

Role: STUDY_CHAIR

European Institute of Oncology

Locations

European Institute of Oncology

Milan, , Italy

Countries

Italy

References

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Other Identifiers

IEO S65/500

Identifier Type: -

Identifier Source: org_study_id