Table showing the radiobiological calculations for the Biologically Equivalent Doses (BED) of dose schedules to be used for the trial assuming different scenarios for the α/β ratio for breast tumour. Note that for normal tissue reactions, the α/β ratio is more well defined at 3 - 3.5. Gy3, Gy3.5 and Gy 4 represent the BED calculations assuming the α/β ratio of 3, 3.5 and 4 respectively. The dose calculations for breast conservation are for the volume receiving SIB. If sequential boost of 12 Gy in 4 fractions is given then the BED values are 99.6 Gy3, 92.8 Gy3.5 and 87.7 Gy4.
Dosimetrically, use of an IMRT SIB is desirable as it reduces the volume of breast exposed to higher doses per fraction. This is a particular concern when hypofractionated radiotherapy regimens are used due to the so-called “triple-trouble”, where the higher dose, higher dose per fraction and larger volume exposed to the said dose combine to increase the risk of late toxicity. However IMRT SIB not only increases the delivery time if fixed fields are used but also increases the exposure of the normal tissues to low doses of radiotherapy. Hence the study will be using a VMAT based SIB approach where reduction of normal tissue doses to organs at risk is prioritised. A class solution for the VMAT SIB technique has been developed in our institute and has been reported separately. As shown in the report, our SIB technique results in better conformity while maintaining the low dose sparing for the normal organs and also reduces the MU requirements.
Use of a one-week radiotherapy course is likely to be substantially resource sparing if efficacy is equivalent. If radiotherapy is completed in one week, instead of three weeks, an indirect cost saving of approximately 66% is expected. Additionally, machine time will be significantly spared allowing three patients to be treated in the same treatment slot improving the accessibility of radiotherapy significantly. A separate substudy will look at the cost-effectiveness of the technique.
A large multi-centric randomized controlled trial poses unique challenges in our setting. While the number of eligible patients is large, a significant number of patients face issues in maintaining follow up for a long duration of time as they often present from far-flung areas. Institutional practices are variable and availability of planning techniques and equipment is not equitable. As most of the health care expenditure is out of pocket, patients are often unable to afford the latest systemic therapy regimens. Hence results obtained in Western trials cannot be generalized for our nation. As a part of this study, we also hope to standardize breast cancer radiotherapy delivery in India, as well as, integrate image-guided radiotherapy in major cancer centres across the nation.
In summary the study aims to investigate a shorter treatment schedule offering a more accessible essential treatment option in patients with breast cancer. Although five fraction regimes have been tested in the FAST and FAST FORWARD study(18,35), our study tests a few novel elements to complement this research. This include a) Testing the efficacy and toxicities of a five fraction adjuvant radiation therapy regime in a population with higher percentage of node positive disease b) Simultaneous Integrated Boost to the tumour bed and internal mammary chain nodes in 5 fractions c) Validating five fraction RT in a non Caucasian population