MRI-guided single dose preoperative radiotherapy in low-risk breast cancer

Patients with early stage breast cancer, with 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 guidelines.
If patients receive partial breast radiotherapy preoperative instead of
postoperative, smaller volumes of the breast can be irradiated. Consequently
the radiotherapy can be administered in less fractions, even in a single dose.
Furthermore, in preoperative partial breast irradiation, tumor response can be
monitored and pathologic complete response to radiotherapy can be observed.
In an earlier similar trial (ABLATIVE NL46017.041.13) no or only mild toxicity
was found after single dose preoperative radiotherapy. In this study a
pathologic complete response was observed in 1 out of every 3 treated patients.
In the current study we want to investigate whether a predictors for pathologic
complete response are present. We will make use of 3T MRI, 7T MRI, a biopsy of
the irradiated tumor and liquid biopsies for this cause. If a large proportion
of patients achieve a pathologic compete response and a strong correlation is
found with one or several of the preoperative imaging techniques, this can lead
to the further research in which patients expected to have a pathologic
complete response will not undergo surgery.

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. Furthermore we will investigate possible predictors
of response, such as MRI and liquid biopsies, and treatment-induced toxicity.

This is a single arm interventional cohort trial.
Patients who initially fulfill inclusion criteria will undergo a diagnostic MRI
scan a sentinel node biopsy. If MRI shows a unifocal tumor and sentinel node is
without malignancy, the patient can be treated with single dose radiotherapy.
After 1 week, and after 3, 6, 9 and 12 months a MRI will be made to assess the
response, this will be combined with a consult with the radiation oncologist.
After 12 months breast conserving surgery will take place. If no radiologic
complete response is observed on MRI after 6 months, the breast conserving
surgery will be performed earlier. 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 exam.
During the entire study the patients will be asked to fill out questionnaires
and cosmetic photographs of the breasts will be taken.

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

The burden consists of two surgeries patients have to undergo instead of one,
in standard of care sentinel node biopsy and breast conserving surgery will be
performed in one session. Furthermore patients have to undergo multiple MRI
scans and an additional biopsy of the irradiated tumor. For patients the period
between radiotherapy and surgery can be be a mental burden. 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 decided
to perform surgery ahead of time in case no radiologic complete response is
observed at 6 months following radiotherapy.