This is the current release of the guideline.

Early-stage breast cancer

Women who have undergone breast-conserving surgery for early-stage breast cancer

For the purposes of this literature review, the task force defined hypofractionated (HF) as a daily dose exceeding 2 Gy and conventionally fractionated (CF) as a daily dose of 2 Gy or less. Whole breast irradiation (WBI) was defined as radiation intended to treat all clinically detectable breast tissue ipsilateral to the index cancer. Studies pertinent to the guideline topic were identified by searching the National Library of Medicine's PubMed database for articles published from January 1, 1990, through February 28, 2009. For the initial screen, the task force selected English-language studies categorized under the Medical Subject Heading (MeSH) "Breast neoplasms/radiotherapy" with any of the following key words: hypofractionation, hypofractionated, fractionation, fraction, accelerated, short, or shorter. Of 558 candidate abstracts screened, the task force sought to identify randomized trials that compared HF-WBI with other treatments and also nonrandomized clinical studies with the primary purpose of evaluating any aspect of HF-WBI. The task force identified six randomized clinical trials that compared HF-WBI with CF-WBI: Hôpital Necker, Queen Elizabeth, Canadian, Royal Marsden Hospital/Gloucester Oncology Center (RMH/GOC), and Standardization of Breast Radiotherapy (START) A and B. The task force also identified two randomized clinical trials that compared HF-WBI with partial breast irradiation (PBI), two randomized clinical trials that compared HF-WBI with no irradiation, and one randomized trial that compared HF-WBI alone with HF-WBI followed by a boost to the tumor bed. Additionally, 34 nonrandomized clinical studies met inclusion criteria (see www.redjournal.org , Table e1 [see appendices in the "Availability of Companion Documents" field). Articles in which the sole focus was postmastectomy radiation or concurrent chemoradiation were excluded. Bibliographies of candidate articles were also reviewed to ensure that all relevant articles were included. Studies published in abstract form only were not included, with the exception of the updated results of the Canadian trial presented at the 2008 American Society for Radiation Oncology Annual Meeting (the manuscript corresponding to this abstract was published on February 11, 2010, and was also included in final deliberations of this guideline).

The task force identified six randomized clinical trials that compared hypofractionated whole breast radiation (HF-WBI) with conventionally-fractionated whole breast radiation (CF-WBI), two randomized clinical trials that compared HF-WBI with partial breast irradiation (PBI), two randomized clinical trials that compared HF-WBI with no irradiation, and one randomized trial that compared HF-WBI alone with HF-WBI followed by a boost to the tumor bed. Additionally, 34 nonrandomized clinical studies met inclusion criteria.

Not stated

On the basis of results of the systematic literature review, evidence tables were constructed to summarize tumor control (local control, local-regional control, disease-free survival, overall survival) and toxicity (cosmesis, skin, soft tissue, pulmonary, cardiac, brachial plexus, rib) endpoints.

The quality of randomized clinical trials was evaluated using criteria adapted from the United States Preventive Services Task Force Procedure Manual. The Queen Elizabeth trial reported psychological outcomes only and thus was not included in the evidence tables or formally scored for quality.

The American Society for Radiation Oncology (ASTRO) Health Services Research Committee (HSRC) convened a task force to formulate clinically useful evidence-based guidelines on whole breast irradiation (WBI) fractionation. The task force conducted a systematic review of the literature, which, supplemented by the expertise and clinical experience of the task force members, provided the rationale for the recommendations.

The task force included eight recognized experts in breast cancer radiation oncology, one in radiobiology, one in radiation physics, two representatives from the HSRC, one radiation oncologist in private practice, one radiation oncology resident, and one patient advocate. The task force was charged with using currently available evidence to develop a clinically practical, evidence-based guideline to help radiation oncologists and breast cancer patients determine the appropriate use of HF-WBI as adjuvant treatment for breast cancer following breast-conserving surgery.

Through a series of conference calls, the task force completed the systematic literature review, reviewed evidence tables, and formulated the guidelines contained herein.

During the formulation of this evidence-based guideline, the task force sought to adhere to the American Medical Association's Physician Consortium for Performance Improvement guidance for measure development and recent calls for reform of the guideline process. It was noted that although this guideline strives to be firmly evidence-based, the opinions of the individual task force members inevitably inform their interpretation and application of the available evidence. As a result, it has been recommended that guidelines include "alternate interpretations and viewpoints" along with the majority opinion to ensure that the final guideline is representative of all task force members' input. In this guideline, unanimous recommendations based firmly on evidence are specified with a "(U-evidence)" and unanimous recommendations based on expert opinion are specified with a "(U-opinion)." When unanimity could not be reached, majority and minority opinions are presented and specified.

Unanimous recommendations based firmly on evidence are specified with a "(U-evidence)" and unanimous recommendations based on expert opinion are specified with a "(U-opinion)."

Widespread adoption of hypofractionated whole breast irradiation (HF-WBI) for appropriately selected patients has the potential to enhance the convenience of treatment and lower the costs of whole breast irradiation (WBI).

The initial draft of the manuscript was reviewed by five expert reviewers and American Society for Radiation Oncology (ASTRO) legal counsel and was subsequently placed on the ASTRO Web site in January 2010 for a 3-week period of public comment. Following integration of all feedback, the document was submitted to the International Journal of Radiation Oncology, Biology, and Physics for additional peer review and, finally, to the ASTRO Board of Directors for their review and approval in May 2010.

The bases of recommendations (U-evidence or U opinion) are defined at the end of the "Major Recommendations" field.

1. Which patients obtain equivalent results from hypofractionated whole breast irradiation (HF-WBI) and conventionally fractionated whole breast irradiation (CF-WBI)?

   Guideline

   Evidence from randomized clinical trials has demonstrated that HF-WBI and CF-WBI are equally effective for in-breast tumor control and comparable in long-term side effects for patients meeting all the criteria listed in the Table 1 (below) (U-evidence). The task force was unable to reach agreement as to the equivalence of HF-WBI to CF-WBI for patients who do not satisfy all these criteria, and thus, they could not make a recommendation either for or against the use of HF-WBI in such patients.

   Table 1. Evidence Supports the Equivalence of Hypofractionated Whole Breast Irradiation with Conventionally Fractionated Whole Breast Irradiation for Patients who Satisfy all of These Criteria*

   Patient is 50 years or older at diagnosis Pathologic stage is T1–2 N0 and patient has been treated with breast-conserving surgery Patient has not been treated with systemic chemotherapy Within the breast along the central axis, the minimum dose is no less than 93% and maximum dose is no greater than 107% of the prescription dose (±7%;) (as calculated with 2-dimensional treatment planning without heterogeneity corrections)

   *For patients who do not satisfy all of these criteria, the task force could not reach consensus and therefore chose not to render a recommendation either for or against hypofractionated whole breast irradiation in this setting. Please see the text for a thorough discussion of tumor grade. Patients receiving any type of whole breast irradiation should generally be suitable for breast-conserving therapy with regards to standard selection rules (e.g., not pregnant, no evidence of multicentric disease, no prior radiotherapy to the breast, no history of certain collagen-vascular diseases).

2. What is the role of a tumor-bed radiation boost in patients treated with HF-WBI?

   Guideline

   There were few data to define the indications for and toxicity of a tumor bed boost in patients treated with HF-WBI (U-evidence). The task force agreed that the use of HF-WBI alone (without a boost) is not appropriate when a tumor bed boost is thought to be indicated (U-opinion). When a boost is indicated, there was lack of consensus regarding the appropriateness of HF-WBI. Although the majority of the task force members thought that there were sufficient data showing the safety of HF-WBI followed by a tumor bed boost to recommend its use in otherwise suitable patients, a minority believed that CF-WBI should be used instead when a tumor bed boost is indicated.

3. What are appropriate regimens for HF-WBI and a tumor-bed boost?

   Guideline

   For patients not receiving a tumor-bed boost, the task force favored a dose of 42.5 Gy in 16 fractions over approximately 22 days when HF-WBI is planned (U-evidence). The optimal HF-WBI regimen to use when a boost is given and the optimal tumor-bed boost dose-fractionation to use in conjunction with HF-WBI have not been determined (U-evidence).

4. What are the characteristics of an acceptable radiotherapy plan for patients treated with HF-WBI?

   Guideline

   Two-dimensional treatment planning with optimization of dose homogeneity in the central axis is the minimum acceptable standard for HF-WBI treatment planning (U-evidence). However, CT-guided treatment planning using three-dimensional dose compensation is strongly recommended to optimize dose homogeneity throughout the entire breast (U-opinion). As a conservative measure, the task force recommended exclusion of the heart from the primary treatment fields provided that coverage of the primary tumor site is not compromised (U-opinion).

5. What insights relevant to the radiobiology of breast cancer can be gained from recently published clinical trials comparing CF-WBI with HF-WBI?

   Guideline

   The randomized trials comparing CF-WBI with HF-WBI have suggested that the extent of both local control of subclinical breast cancer and late change in breast appearance exhibit similar sensitivity to fraction size as modeled by the α/β ratio in the linear-quadratic (LQ) formulation (U-evidence). Additional clinical data are needed to quantify the effects of overall treatment time, dose homogeneity, and systemic agents on tumor control and normal tissue toxicity (U-evidence) (see Table 7 in the original guideline document).

Definitions:

Bases of Recommendations

Unanimous recommendations based firmly on evidence are specified with a "(U-evidence)" and unanimous recommendations based on expert opinion are specified with a "(U-opinion)."

None provided

The type of evidence supporting the recommendations is not specifically stated.

Appropriate treatment with hypofractionated whole breast irradiation (HF-WBI) or conventionally fractionated whole breast irradiation (CF-WBI) in patients with early stage breast cancer

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

American Society for Radiation Oncology

American Society for Radiation Oncology (ASTRO) Task Force

Task Force Members: Benjamin D. Smith, M.D., Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston; Soren M. Bentzen, Ph.D., D.Sc., Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI; Candace R. Correa, M.D., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI; Carol A. Hahn, M.D., Department of Radiation Oncology, Duke University Medical Center, Durham, NC; Patricia H. Hardenbergh, M.D., Shaw Regional Cancer Center, Vail, CO; Geoffrey S. Ibbott, Ph.D., Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX; Beryl McCormick, M.D., FACR., Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; Julie R. McQueen, CHES., RHEd., Oncology Patient Navigator, Duke Raleigh Cancer Center, Durham, NC; Lori J. Pierce, M.D., Department of Radiation Oncology, University of Michigan, Ann Arbor; Simon N. Powell, M.D., PH.D., Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; Abram Recht, M.D., Department of Radiation Oncology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA; Alphonse G. Taghian, M.D., Ph.D., Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Frank A. Vicini, M.D., FACR., Department of Radiation Oncology, Beaumont Cancer Institute, Royal Oak, MI; Julia R. White, M.D., Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI; and Bruce G. Haffty, M.D., Department of Radiation Oncology, Cancer Institute of New Jersey, New Brunswick, NJ

Prior to initiation of this guideline, all members of the Task Force writing the Guideline were required to complete Conflict of Interest statements. These statements are maintained at American Society for Radiation Oncology (ASTRO) Headquarters in Fairfax, VA and pertinent conflict information is published with the report. Individuals with disqualifying conflicts have been recused from participation in this Consensus Statement (please see www.redjournal.org , Appendix eI [see the "Availability of Companion Documents" field], for comprehensive disclaimers and notifications).

Conflicts of interest: none

This is the current release of the guideline.

Electronic copies: Available from the International Journal of Radiation Oncology, Biology, Physics Web site .

The following is available:

• Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Appendices. Electronic copies: Available from the International Journal of Radiation Oncology, Biology, Physics Web site .

The following is available:

• Radiation therapy for breast cancer. Brochure. Fairfax (VA): American Society for Radiation Oncology; 2011. 2 p. Electronic copies: Available from the RT Answers Web site . Also available in Spanish from the RT Answers Web site .

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This NGC summary was completed by ECRI Institute on July 24, 2012. The information was verified by the guideline developer on August 22, 2012.

This summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.