Results Of A Prospective Cohort Trial: Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy (Signal) For Early-Stage Breast Cancer

For certain low-risk patients, recurrences after lumpectomy tend to be localized to the resection cavity, suggesting a role for partial-breast irradiation. Neoadjuvant single-fraction radiation therapy (SFRT) is a novel approach in which unresected disease is irradiated prior to surgery. SFRT has been associated with favorable local control, survival and toxicity. However, because most large-scale studies of SFRT employed specialized treatment delivery platforms that were not widely available, its implementation has been limited. For such reasons, we developed SIGNAL, a single-arm, single-institution phase 2 study examining neoadjuvant SFRT followed by surgery. We report the dosimetry and outcomes of a cohort of 27 patients treated according to this novel regimen. SIGNAL was open to postmenopausal women, with biopsy-proven ductal carcinoma, any grade, unifocal, ≤3 cm, ER-positive, without axillary involvement. All patients received contrast-enhanced prone breast MR and prone 4DCT simulation. The GTV was delineated on T2 diffusion MR. CTV and PTV were delineated by successive 5mm expansions of the GTV. A prescription dose of 21 Gy was delivered in a single fraction to the PTV via an opposed, 2-beam volumetric modulated arc therapy (VMAT) technique. Relevant dosimetric constraints were defined via review of the published literature and from basic radiobiological principles. Patients went for lumpectomy and sentinel node dissection (SND) 1 week after surgery and were seen at regular intervals after that for clinical follow-up and toxicity assessment using both visual toxicity scales and validated QOL questionnaires. We enrolled 52 patients. Of these, 13 were excluded at the time of MR, leaving 39 patients who were scanned and eligible for planning. Over the course of the study, we applied two different sets of dosimetric constraints. Using our original constraints, acceptable treatment plans were attainable for only 16 of 28 (57%) patients. After implementation of revised dosimetric constraints, acceptable treatment plans were attainable for 11 of 11 (100%) patients. In total, 27 patients were treated with SFRT. All 27 pts went on to lumpectomy: 25 pts had T1 disease; 1 pt had T2 disease; 1 pt had Tis. Only 23 pts received SND: 20 pts had N0 disease; 3 pts had axillary nodal spread (1 macroscopic; 1 microscopic; 1 seen on IHC); 4 pts did not receive SND. All 27 pts were ER-positive; 15 pts received hormonal therapy; 4 pts received chemotherapy. At a median follow-up of 487 days from radiotherapy, all 27 patients were alive and free of recurrence. At 6-months post-surgery, toxicity, patient-rated cosmesis and QOL were not significantly different from baseline. SIGNAL represents a feasible method of implementing single-dose radiotherapy for neoadjuvant treatment of low-risk breast cancer. It appears to be clinically effective, practicable and without significant toxicity. Randomized studies to corroborate these findings are ongoing.