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Int J Radiat Oncol Biol Phys. 2015 Jul 15;92(4):846-55. doi: 10.1016/j.ijrobp.2015.03.007. Epub 2015 Mar 14.

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

Author information

1
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina. Electronic address: janet.horton@duke.edu.
2
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
3
Department of Pathology, Duke University Medical Center, Durham, North Carolina.
4
Department of Radiology, Duke University Medical Center, Durham, North Carolina.
5
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
6
Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
7
Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
8
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
9
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina; Center for Genomic and Computational Biology, Duke University Medical Center, Durham, North Carolina.

Abstract

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 of 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.

PMID:
26104938
PMCID:
PMC4481883
DOI:
10.1016/j.ijrobp.2015.03.007
[Indexed for MEDLINE]
Free PMC Article

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