Interventions

Explanation for the choice of comparators {6b}

One week hypofractionated radiotherapy is likely to become the standard for delivery of breast adjuvant radiotherapy if the results of the FAST Forward trial support the primary objective. Hence the current trial will also test a one-week regimen. The three-week course of radiotherapy used in the control arm has already demonstrated non-inferiority in terms of oncological outcomes in the START trials. Currently, this is the standard radiotherapy schedule used for most breast cancer patients in the participating centers.

Intervention Description {11a}

Overview

Patients will be randomized into two arms equally:
  1. Control Arm: 40 Gy in 15 fractions over 3 weeks to the whole breast or chest wall. Patients undergoing breast conservation therapy will receive additional boost radiotherapy to the tumour bed. The supraclavicular fossa will be treated in patients with node-positive disease or those receiving neoadjuvant chemotherapy. IMC and Axillary radiotherapy will be given as per the institutional policy. Boost radiotherapy will be delivered using SIB of 8 Gy in 15 fractions (or alternatively using a sequential boost of 12 Gy in 4 fractions)
  2. Test Arm: 26 Gy in 5 fractions over 1 week to the whole breast or chest wall. Treatment volumes will be the same as the control arm. Additional boost will be delivered to patients who have undergone breast conservation. Boost radiotherapy will be delivered using SIB of 6 Gy in 5 fractions (or alternatively using a sequential boost of 12 Gy in 4 fractions)

Radiotherapy

Radiotherapy should be started within 12 weeks of the last date of surgery or last cycle of planned adjuvant chemotherapy. All patients would be treated on linear accelerators (6 - 15 MV energies). Radiotherapy planning would be performed on volumetric planning CT scans with a pre-defined simulation protocol. Patients with left sided breast cancers should preferably receive cardiac sparing radiotherapy. Field based planning for the breast and chest wall is allowed in the protocol where anatomical landmarks are identified and coverage ensured. This is the current practice in most of the centers in this trial.
The organs at risk to be delineated include the ipsilateral and contralateral lung, heart, and the contralateral breast. In patients undergoing radiotherapy for left sided breast, the left anterior descending artery may also be delineated (31). The brachial plexus may be delineated in patients undergoing regional nodal radiation (32). Tangential beams would be utilized for irradiating the breast or chest wall, while regional nodal radiation should be delivered using a technique that ensures no overlap of the field - in most patients, this would imply a enface field to cover the supraclavicular fossa (SCF) with a half beam block or a collimator-couch rotation based technique. Dose will be prescribed at a point in the midplane for the breast and chest wall for tangents. For patients receiving SCF radiation, the dose will be prescribed at the depth of maximum dose (Dmax). In patients who have undergone breast conservation, boost will be delivered using the technique used in the institute. Use of a volumetric modulated arc therapy (VMAT) based Simultaneous Integrated Boost (SIB) for tumor bed irradiation is allowed. Inverse planned radiation is allowed for patients receiving radiation to the internal mammary nodal chain.
Dose in the target volume should be homogenous and use of a forward planned field in field IMRT technique is allowed. Alternatively centers can specify the technique to be used for ensuring dose homogeneity. Individualized treatment planning will be done with a target to ensure that the breast/chest wall is covered with 95% of the prescribed dose and that the maximum dose does not exceed 107% of the prescribed dose. In patients undergoing VMAT simultaneous tumour bed boost (SIB), the dose to the boost target volume will be restricted to < 107% of the total dose.
Table 2 shows the dose constraints to be used for plan evaluation.