{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:24:17Z","timestamp":1790396657557,"version":"4.1.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor\u2013positive (HR\n +<\/jats:sup>\n ) breast cancer with delayed time to surgery and high pathologic complete response rates.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To examine the maximum tolerated dose (MTD) of sPBI and to evaluate clinical outcomes, including pathological complete response (pCR), time to surgery, and toxic effects, associated with dose escalation.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This phase 1 nonrandomized clinical trial of dose escalation enrolled patients with HR\n +<\/jats:sup>\n ,\n ERBB2<\/jats:italic>\n -negative, cN0 invasive breast cancer not requiring chemotherapy from a single academic center between December 2019 and April 2024.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were treated with 30, 34, or 38 Gy using MR-guided linear accelerator (MR-LINAC), robotic radiosurgery, or cobalt stereotactic unit. Patients received endocrine therapy and delayed surgery (\u226412 months).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The MTD was evaluated using dose-limiting toxicity (DLT), defined as grade 3 or higher toxic effects within 90 days. Additionally, pCR, near pCR (npCR), the association of dose escalation with time to surgery, local control, surgical morbidity, and cosmesis were evaluated.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 44 patients (median [range] age, 64.5 [44.0-77.0] years) were treated, with 14 (31.8%) receiving 30 Gy (median [IQR] follow-up, 52.0 [28.2-54.5] months), 15 (34.1%) receiving 34 Gy (median [IQR] follow-up, 40.0 [36.5-41.0] months), and 15 (31.4%) receiving 38 Gy (median [IQR] follow-up, 20.0 [17.0-22.0] months). MTD was not reached. pCR rates were 35.7% (5 patients), 46.7% (7 patients), and 66.7% (10 patients), while pCR with npCR rates were 64.3% (9 patients), 93.3% (14 patients), and 93.3% (14 patients), respectively. Local control was 100%, and surgical morbidity was 2.2% (1 of 44 patients). The mean (SD) Ki-67 was 11.3% (6.4%) at diagnosis, and on evaluable residual disease, it was 1.9% (2.0%) (\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). A time-to-surgery threshold of 277 days was the optimal cutoff for pCR (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.62-0.91). In patients with surgery more than 9 months after sPBI, pCR rates were 100% (5 of 5 patients), 66.7% (4 of 6 patients), and 64.3% (9 of 14 patients) (\n P<\/jats:italic>\n \u2009=\u2009.40), and combined pCR and npCR rates were 100%, 83.3% (5 patients), and 92.9% (13 patients) (\n P<\/jats:italic>\n \u2009=\u2009.69) for the 30, 34, and 38 Gy groups, respectively. For all patients who received surgery more than 9 months after sPBI, the pCR rate was 72.0% (18 of 25 patients). Longer time to surgery was associated with pCR (odds ratio, 1.02; 95% CI, 1.01-1.03;\n P<\/jats:italic>\n \u2009=\u2009.005), while higher radiation dose was not. Acute toxic effects included 32 grade 1, 3 grade 2 (breast pain and dermatitis), and 1 late grade 3 (wound dehiscence in patient with uncontrolled diabetes) events. Cosmesis remained stable at 36 months.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this nonrandomized clinical trial, the rate of toxic effects was low, and treatments were tolerable up to 38 Gy. Delaying surgery more than 9 months after sPBI with endocrine therapy was associated with increased pCR and npCR (&amp;gt;90%), while higher doses were not. These findings support further investigation of sPBI as a potential nonsurgical approach for selected patients with early-stage HR\n +<\/jats:sup>\n breast cancers.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04040569<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.43689","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T16:30:35Z","timestamp":1763137835000},"page":"e2543689","source":"Crossref","is-referenced-by-count":2,"title":["Ablative Preoperative Single-Fraction Radiation Dose Escalation Among Patients With Breast Cancer"],"prefix":"10.1001","volume":"8","author":[{"given":"Asal","family":"Rahimi","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Leitch","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basak","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanna","family":"Alluri","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Arbab","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D. 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