SINGLE DOSE ABLATIVE PREOPERATIVE RADIATION TREATMENT FOR EARLY-STAGE BREAST CANCER IN ELDERLY PATIENTS

The current treatment for early stage breast cancer consists of
breast-conserving surgery followed by 16-23 radiation fractions on the entire
breast. Despite the good prognosis, the current treatment is perceived as
challenging due to the long duration of the radiation treatment. This is
particular the case in the elderly patients with co-morbidity. In some cases a
mastectomy is performed as a radical alternative for breast-conserving therapy
in order to avoid the multiple radiotherapy sessions. Other patients receive
inadequate breast cancer treatment when solely endocrine treatment is
administered following the diagnosis. Therefore, in elderly patients with early
stage breast cancer, optimization of disease management by means of innovative
alternatives are required.
An alternative to whole breast irradiation is accelerated partial breast
irradiation (APBI) on the previous tumor bed. Given that the great majority of
tumor recurrences occur at or near the region of the prior surgery, the latter
technique has been investigated to be safe in low-risk breast cancer patients.
A great advantage of APBI is the reduction in the number of radiotherapy
fractions thereby reducing the treatment duration. In addition, the irradiation
of a smaller breast volume could possibly result in decreased toxicity rates
and improved breast cosmesis. Intraoperative radiotherapy (IORT) is an APBI
method that has the major advantage of administering one fraction immediately
after BCS in the operation room. However, external beam APBI trial has the
advantage of being non-invasive when compared to single fraction IORT.
The ABLATIVE study evaluates the feasibility of a single dose ablative external
beam radiotherapy as an optimal alternative to BCT in elderly patients with
early stage and low-risk breast cancer. This approach could result in minimal
treatment burden for all patients with low-risk breast cancer, but is of
particular interest in selected elderly whom are currently not treated
according to guidelines due to comorbidity.

The purpose of the study is to investigate the feasibility of a preoperative,
single dose, ablative partial breast radiation treatment in patients with early
stage breast cancer. This study aims to present a concept that could resolve to
some extent the disadvantages of current breast conserving treatment in elderly
low-risk breast cancer patients who are currently not treated according to
guidelines due to co-morbidity.

Feasibility study.

Preoperative, single dose, ablative partial breast radiotherapy.

BURDEN ASSESSMENT
The radiotherapy treatment will take be minimized to a single fraction for the
study patient from the conventional 16-23 fractions (3-5 weeks). Despite a
reduction in the number of radiotherapy sessions, the burden for the study
patient will consist of vigilant clinical and radiological monitoring:
- The sentinel node procedure will be performed in another session than breast
conserving surgery in order to assure that no patients with nodal involvement
are included.
- 6-7 preoperative MRI scans will be performed for diagnosis, radiotherapy
planning and radiological response evaluation. In addition, one MRI will be
performed in the first follow-up year following radiotherapy.
- 2 additional FDG-PET-CTs will be performed for radiological response
evaluation (optional).
- 3 mammograms will be performed for the monitoring of possible local
recurrences.
- the patients will be required to fill in additional questionnaires on quality
of life, toxicity, breast cosmesis, frailty and functionality aspects.
- digital photographs of the patient's both breasts will be taken for objective
cosmetic response evaluation.

RISK ASSESSMENT
Partial breast irradiation appears to be as effective as whole breast
irradiation with regard to local recurrence rates in patients with low-risk
breast cancer. Given that strictly this category patients are eligible for the
single fraction ablative treatment, we anticipate low local recurrence rates in
our study population.
Another risk that is associated with participation is the possibility of
increased toxicity in the irradiated area and impaired cosmesis due to a higher
radiotherapy fraction dose. Since the ablative radiotherapy dose is strictly
intended for (peri)tumoral tissue, thus confined to a limited volume of the
breast, we anticipate that the risk on toxicity is low.

BENEFIT AND GROUP RELATEDNESS
By delivering a single fraction ablative radiotherapy dose, we hope to minimize
the treatment burden associated with the protracted WBI sessions. Our treatment
approach will probably result in less heart, lung or contralateral breast
radiotherapy induced toxicity given the reduction in treatment volume.
The concept of a single fraction ablative radiotherapy can be favorable in all
early-stage breast cancer patients with low-risk characteristics due to the
anticipated reduction in treatment burden. However, elderly patients with
low-risk breast cancer that are currently not treated according to guidelines
will benefit the most.