Single-dose preoperative partial breast irradiation in low-risk breast cancer patients

Patients with early stage breast cancer, and a low risk of recurrence of
disease after treatment, are currently being treated with breast-conserving
surgery followed by whole or partial breast irradiation according to
(inter)national guidelines. If patients receive preoperative partial breast
radiotherapy preoperative instead of postoperative irradiation, smaller volumes
of the breast can be irradiated. Consequently, the radiotherapy can be
administered in less fractions, even in a single dose. In preoperative partial
breast irradiation, tumor response can be monitored, and pathologic complete
response after radiotherapy can be observed.
In a previous trial (ABLATIVE trial, NL 46017.041.13) only mild toxicity was
found after single dose preoperative radiotherapy. In this study a pathologic
complete response was observed in 42% of the treated patients.
In the ABLATIVE-2 trial, we will investigate whether predictors for pathologic
complete response can be identified. We will use MRI, tumor tissue and liquid
biopsy for response monitoring after preoperative radiotherapy. If a large
proportion of patients achieve a pathologic compete response, and (bio)markers
for response monitoring can be found, a sequential study will be performed to
develop a prediction model for pathologic complete response. The blue sky is
that in patients with a predicted pathologic complete response, surgery could
be omitted. In patients with no predicted pathologic complete response, need to
undergo surgery, and have the benefit of only one single dose radiotherapy
instead of radiotherapy during 1 to 4 weeks.

The goal of this study is to assess the efficacy of single dose preoperative
radiotherapy in patients with low-risk breast cancer. In this context, efficacy
is the proportion of patients achieving a pathologic complete response after
single dose radiotherapy. In addition, we will investigate possible predictors
of response in blood and tumor tissue, and evaluate treatment-induced toxicity,
patient-reported outcomes and oncologic outcomes.

This is a single arm interventional cohort trial. Patients who initially
fulfill inclusion criteria will undergo a diagnostic MRI scan. If MRI shows a
unifocal tumor, the patient can be treated with single dose partial breast
irradiation. After 2 weeks, and after 3, 6, 9 and 12 months an MRI will be
performed and blood samples will be taken to evaluate the tumor response after
the single dose radiotherapy. This will be combined with a consultation by the
radiation oncologist.
After 12 months breast conserving surgery and sentinel node procedure will be
performed. If progression of the tumor is observed on MRI, breast conserving
surgery will be performed as soon as possible.
Patients will be followed for a total of 10 years through mammography and
physical examination. During the entire study the patients will be asked to
fill out questionnaires, to evaluate patient-reported outcomes including
toxicity and cosmetic outcome. In addition, digital photographs of the breasts
will be taken to evaluate cosmetic outcome.

MR-guided single dose preoperative radiotherapy 20 Gy to the tumor.

Patients have to undergo multiple MR images, and additional blood sampling
(that will be combined as much as possible with the venipuncture for
intravenous contrast administration during MRI).
Patients can give extra consent for additional tumor biopsy that can be
combined with insertion of a clip (in case the clip has not been inserted
already). If the clip has already been inserted, than this additional biopsy
will be an additional procedure (after extra informed consent).

For patients the period between radiotherapy and surgery can be a mental
burden.
The burden of radiotherapy treatment will be reduced in the ABLATIVE-2 to one
single session instead of 5 to 20 radiotherapy sessions in the standard
treatment.
The risks for patients participating in the study are similar to those of
patients receiving standard of care. To keep the risk of recurrent disease to a
minimum we will perform surgery ahead of time if tumor progression is observed
on MRI.