Partial Breast Radiotherapy in Low-risk Breast cancer group using a stereotactic MR-guided adaptive approach; a phase II study

Breast conserving therapy (BCT) consists of local excision of the primary tumor
followed by postoperative radiotherapy (RT) of the remaining glandular tissue
of the ipsilateral breast, with or without surdosage to the surgical cavity.
Several recently conducted randomized trials have demonstrated equipoise with
respect to local control between this approach and accelerated partial breast
irradiation (APBI) [Strnad 2016, Livi 2015]. Livi et al has proven an
hypofractionated scheme to be equally efficient and tolerated as well als
conventionally fractionated treatments, with the advantage that treatment can
be deliverd within two weeks.

The clinical introduction of stereotactic MRI-guided adaptive radiation therapy
(SMART) using the MRIdian treatment machine will enable visualisatoin of target
volume and adjacent normal organs such as the heart and lungs prior to and
during treatment delivery. Online imaging allows to deliverd "gated" treatment,
enabling the use of small uncertainty margins, which can potentially limit
clinical toxicity. One further advantage of the SMART approach is the ability
to perform adaptive treatment planning for each delivered fraciton. This means
that de original treatment plan can be optimized immediately prior to treatment
delivery, especially optimized with respect to the position and volume of the
adjacent normal organs such as heart and lungs.

Despite the results of Livi et al, partial breast is not yet a standard
treatment in the Netherlands for low-risk breast cancer. Because of the
relatively short follow-up of published randomised studies, Dutch guidelines
recommended partial breast radiotherapy to be investigated within study context
[www.oncoline.nl]. The MRIdian allows more accurate partial breast radiation
delivery en the results will be evaluated in this phase 2 study.

The main goal of this prospective phase II observational study of APBI for *low
risk* breast cancer (cT1-T2N0M0) is to evaluate early and early-delayed
toxicity with this approach, after daily adaptive radiotherapy treatment.

A prospective phase II observational study.

The use of APBI has a number of potential benefits for patients. Most
importantly, irradiation of a smaller breast volume obviously results in lower
radiation doses to surrounding normal tissues such as the chest wall, lung, and
for left-sided breast cancer the heart, and allows for hypofractionated
treatment with a higher dose per fraction. This approach could decrease early,
early-delayed and late toxicity, potentially resulting in optimal breast
cosmetics. Finally, the use of APBI decreases both the number of radiation
fractions as well as the overall treatment duration for patients in comparison
to the standard treatment of 3 to 4 weeks.

This novel SMART approach could set a new standard of care for patients with
low-risk breast cancer by limiting radiation doses to surrounding normal organs
and thereby potentially decreasing radiation-induced toxicity. Disadvantages
for patients include the need to be positioned within the MRI bore during
radiation delivery, and a prolonged time per treatment fraction (estimated at
60 minutes per fraction compared to 20 minutes per fraction for standard
treatment on the linac), which has to be weighed against the use of a total of
only five fractions. As the radiation fractionation scheme that is used in this
study has been evaluated in prior trials, no further patient-related risks are
anticipated.

Patient will be followed-up with the frequency according to regional guidelines
for breast cancer. The extra time for filling in the questionnaires will be
around 5-10 minutes