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Title: Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence ofmore » dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.« less
Authors:
 [1] ; ;  [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ; ;  [1] ;  [6] ;  [2] ; ;  [1] ;  [7] ;  [8] ;  [1] ;
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)
  2. Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States)
  3. Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States)
  4. Department of Surgery, Duke University Medical Center, Durham, North Carolina (United States)
  5. Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States)
  6. Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States)
  7. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States)
  8. (United States)
Publication Date:
OSTI Identifier:
22462380
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 92; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; BIOLOGICAL MARKERS; BIOMEDICAL RADIOGRAPHY; CARCINOMAS; CLINICAL TRIALS; DISEASE INCIDENCE; ELDERLY PEOPLE; ESTROGENS; MAMMARY GLANDS; PATIENTS; PROGESTERONE; RADIATION DOSES; RADIOTHERAPY; RECEPTORS; WOMEN