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