Stereotactic Image-Guided Neoadjuvant Ablative Single-Dose Radiation, then Lumpectomy, for Early Breast Cancer: The Signal Prospective Single-Arm Trial of Single-Dose Radiation Therapy

Abstract

Background and Purpose Adjuvant whole-breast irradiation after breast-conserving surgery, typically delivered over several weeks, is the traditional standard of care for low-risk breast cancer. More recently, hypofractionated, partial-breast irradiation has increasingly become established. Neoadjuvant single-fraction radiotherapy (rt) is an uncommon approach wherein the unresected lesion is irradiated preoperatively in a single fraction. We developed the signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) trial, a prospective single-arm trial to test our hypothesis that, for low-risk carcinoma of the breast, the preoperative single-fraction approach would be feasible and safe.Methods Patients presenting with early-stage (T < 3 cm), estrogen-positive, clinically node-negative invasive carcinoma of the breast with tumours at least 2 cm away from skin and chest wall were enrolled. All patients received prone breast magnetic resonance imaging (mri) and prone computed tomography simulation. Treatable patients received a single 21 Gy fraction of external-beam rt (as volumetric-modulated arc therapy) to the primary lesion in the breast, followed by definitive surgery 1 week later. The primary endpoints at 3 weeks, 6 months, and 1 year were toxicity and cosmesis (that is, safety) and feasibility (defined as the proportion of mri-appropriate patients receiving rt).Results Of 52 patients accrued, 27 were successfully treated. The initial dosimetric constraints resulted in a feasibility failure, because only 57% of eligible patients were successfully treated. Revised dosimetric constraints were developed, after which 100% of patients meeting mri criteria were treated according to protocol. At 3 weeks, 6 months, and 1 year after the operation, toxicity, patient- and physician-rated cosmesis, and quality of life were not significantly different from baseline.Conclusions The signal trial presents a feasible method of implementing single-dose preoperative rt in earlystage breast cancer. This pilot study did not identify any significant toxicity and demonstrated excellent cosmetic and quality-of-life outcomes. Future randomized multi-arm studies are required to corroborate these findings.

Intrafraction motion during partial breast irradiation depends on treatment time

“…Accelerated partial breast irradiation (APBI) is an alternative to whole breast irradiation after lumpectomy for low risk breast cancer patients selected according to several international guidelines [1][2][3][4][5][6]. There is a tendency to reduce the number of treatment fractions for APBI from ten to five, or even down to single fraction treatments [7][8][9][10][11][12][13][14]. Hypofractionation has the advantage of convenience both for the patient and the radiotherapy facility, but could create challenges for the treatment delivery.…”

Optimizing MR-Guided Radiotherapy for Breast Cancer Patients

“…In the neoadjuvant setting, the use of T1-weighted fatsuppressed contrast-enhanced MRI is recommended for optimal tumour and tumour spiculae visualization, because differences in contrast uptake provide a clear distinction between tumour and glandular breast tissue (Figure 3) (35)(36)(37)(38). Additionally, T2weighted images might aid in the differentiation between tumour and postbiopsy changes (35).…”

“…Several publications have reported on neoadjuvant MR-guided PBI on a conventional linac including favourable toxicity profiles (35,37,85). However, no patients have yet been treated with neoadjuvant PBI on a hybrid machine.…”

“…These recommend the use of contrast-enhanced MRI, which, because of increased contrast uptake in tumours compared to the surrounding glandular breast tissue, allows for better visualization of breast tumours than using CT ( Figure 3 ) ( 9 , 38 ). Contrast-enhanced MRI has been used for the delineation of target volumes in several recent studies of neoadjuvant PBI ( 37 , 52 ). In these studies, insertion of an additional fiducial marker by a radiologist was necessary both to help localize the tumour for subsequent surgical resection in case of tumour downstaging and for tumour position verification because the tumour cannot be visualized on CBCT in most patients.…”

Improved Ipsilateral Breast and Chest Wall Sparing With MR-Guided 3-fraction Accelerated Partial Breast Irradiation: A Dosimetric Study Comparing MR-Linac and CT-Linac Plans

“…This treatment paradigm also provides an opportunity to test biomarkers for radiation response. Two single-institution studies that used 15Gy-21Gy SFRT have reported favorable early cosmetic outcomes (31,32). MRI-guided RT could potentially contribute to this evolving paradigm by reducing PTV margins and thereby treatment volumes (clinical trials.gov: NCT03863301).…”