Randomized Trial on Intraoperative Radiotherapy Full Dose Vs External Radiotherapy
Condition: Carcinoma Breast
MeSH terms: Carcinoma; Breast Neoplasms
Study type: Interventional

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 .
    

Intervention name(s): external fractionated radiotherapy; intraoperative radiotherapy
Intervention type(s): Radiation; Radiation
Intervention description(s): conventional external beam radiotherapy; Intraoperative radiotherapy (IORT). Total delivered dose 21Gy (Gray), 90% isodose
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Breast cancer; conservative surgery; intraoperative radiation therapy; mobile linear accelerator