Workshop on Partial Breast Irradiation: State
of the Art and the Science, Bethesda, MD,
December 8–10, 2002
P. Wallner, D. Arthur, H. Bartelink, J. Connolly, G. Edmundson, A. Giuliano,
N. Goldstein, J. Hevezi, T. Julian, R. Kuske, A. Lichter, B. McCormick,
R. Orecchia, L. Pierce, S. Powell, L. Solin, F. Vicini, T. Whelan, J. Wong,
C. N. Coleman
For the Workshop Participants
Breast conserving surgery followed by radiation therapy has
been accepted as an alternative to mastectomy in the man-
agement of patients with early-stage breast cancer. Over the
past decade there has been increasing interest in a variety of
radiation techniques designed to treat only the portion of the
breast deemed to be at high risk for local recurrence
(partial-breast irradiation [PBI]) and to shorten the dura-
tion of treatment (accelerated partial-breast irradiation
[APBI]). To consider issues regarding the equivalency of the
various radiation therapy approaches and to address future
needs for research, quality assurance, and training, the Na-
tional Cancer Institute, Division of Cancer Treatment and
Diagnosis, Radiation Research Program, hosted a Workshop
on PBI in December 2002. Although 5- to 7-year outcome
data on patients treated with PBI and APBI are now becom-
ing available, many issues remain unresolved, including clin-
ical and pathologic selection criteria, radiation dose and
fractionation and how they relate to the standard fraction-
ation for whole breast irradiation, appropriate target vol-
ume, local control within the untreated ipsilateral breast
tissue, and overall survival. This Workshop report defines
the issues in relation to PBI and APBI, recommends param-
eters for consideration in clinical trials and for reporting of
results, serves to enhance dialogue among the advocates of
the various radiation techniques, and emphasizes the impor-
tance of education and training in regard to results of PBI
and APBI as they become emerging clinical treatments. [J
Natl Cancer Inst 2004;96:175–84]
Over the past few years, a number of studies (1–13) have
detailed the rationale for and the various technical consider-
ations of partial-breast irradiation (PBI), which is defined as
radiation of the site of excision and adjacent breast tissue only.
PBI can consist of brachytherapy or external modalities. Accel-
erated partial-breast irradiation (APBI) is defined as radiation
that employs fractions higher than 1.8–2.0 Gy per day over a
period of less than 5–6 weeks and uses any of four techniques:
1) brachytherapy implant, 2) external beam with 3D-conformal
radiation therapy (3D-CRT)/intensity-modulated radiation ther-
apy (IMRT), 3) the MammoSite device (a registered trademark
of Proxima Therapeutics, Alpharetta, GA), or 4) intra-operative
radiation therapy (IORT). Several clinical reports (1–13) of
nonrandomized treatment groups with 7–8 year follow-up inter-
vals have produced substantial interest and discussion of PBI/
APBI in lay and medical circles. The efficacy of breast conserv-
ing therapy (BCT) compared with mastectomy has been
supported and validated by recent publications (14,15) contain-
ing 20-year follow-up data from large, well-controlled, random-
ized phase III clinical trials. Such studies have demonstrated the
importance of long-term data in determining the ultimate effi-
cacy of a treatment.
It is recognized that BCT was introduced into clinical practice
by single institution studies and that early data from BCT trials
indicated that such an approach might be comparable to mas-
tectomy. General acceptance of BCT did not occur, however,
until the National Surgical Adjuvant Breast and Bowel Project
(NSABP) published the results of its B-06 trial (14). Deciding on
when exciting early results are sufficiently mature to allow
practitioners and patients to consider utilizing a new treatment
Author affiliations: Radiation Research Program, National Cancer Institute,
National Institutes of Health, Bethesda, MD (PW, CNC); Department of Radi-
ation Oncology, Virginia Commonwealth University-MCV Campus, Richmond,
VA (DA); Antoni van Leeuwenhoek Ziekenhuis Department of Radiotherapy,
Netherlands Cancer Institute, Amsterdam, The Netherlands (HB); Department of
Pathology, Beth Israel Deaconess Medical Center, Boston, MA (JC); Depart-
ment of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (GE,
NG, FV, JW); John Wayne Cancer Institute, Santa Monica, CA (AG); Cancer
Therapy and Research Center, San Antonio, TX (JH); Department of Human
Oncology, Allegheny General Hospital, Pittsburgh, PA (TJ); Arizona Oncology
Services, Scottsdale, AZ (RK); Department of Radiation Oncology, University
of Michigan Medical School, Ann Arbor, MI (AL, LP); Department of Radiation
Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (BM);
Radiotherapy Department, European Institute of Oncology, Milan, Italy (RO);
Department of Radiation Oncology, Massachusetts General Hospital, Boston,
MA (SP); Department of Radiation Oncology, University of Pennsylvania
School of Medicine (LS); Supportive Cancer Care Research Unit, Hamilton
Regional Cancer Center, Hamilton, ON, Canada (TW).
Address for reprints: Kathy Horvath, RRP, DCTD, NCI, 6130 Executive
Boulevard, EPN Room 6015A, Rockville, MD 20892.
Correspondence to: C. N. Coleman, MD, Division of Cancer Treatment and
Diagnosis, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm.
B3B69, MSC 1002, Bethesda, MD 20892 (e-mail: email@example.com).
See “Notes” following “References.”
Journal of the National Cancer Institute, Vol. 96, No. 3, © Oxford University
Press 2004, all rights reserved.
Journal of the National Cancer Institute, Vol. 96, No. 3, February 4, 2004COMMENTARY 175
by guest on October 30, 2015
approach in routine practice is a complex issue beyond the scope
of this summary. However, broad interest in PBI makes this an
opportune time to build on the experience now available in the
use of BCT and PBI.
To address issues regarding the equivalency of the various
radiation therapy approaches, the National Cancer Institute
(NCI), Division of Cancer Treatment and Diagnosis, Radiation
Research Program, hosted a Workshop in Bethesda, MD, from
December 8 through December 10, 2002. The intent of the
Workshop was to review the current “State of the Art and the
Science” related to PBI and APBI and to consider the need for
additional research, training, quality assurance, and procedure
standardization. It must be emphasized that it was not the pur-
pose of the Workshop nor is it the role of the NCI to determine
treatment policy or consider reimbursement issues. It is further
emphasized that consensus on emerging treatment regimens is
not always achievable but that an open exchange of information
and expert opinion are critical to the evolution of patient care.
Workshop participants included individuals representing all
clinical specialties involved in the care of patients with early-
stage breast cancer, including experts in various radiation on-
cology approaches and representatives of cooperative clinical
trial groups and agencies (see Appendix 1 for the full list of
participants). Formal presentations by participants reviewed is-
sues in regard to BCT, including pathology and radiation biol-
ogy. Given that much of the PBI and APBI data are not yet
published, experts from Europe, Canada, and the United States
presented preliminary unpublished information from their geo-
graphic region to facilitate access to such information. These
presentations were followed by open-ended discussions and a
breaking-up of participants into three working groups that were
assigned the task of further examining specific aspects of the
issues relating to PBI and APBI and of making specific sets of
recommendations. This Workshop report represents the opinions
of the participants and illustrates that the field of PBI and APBI
is in rapid development. Because it is not possible to provide a
complete and balanced reference list and because it was the goal
of the Workshop to expeditiously produce a report, only a
limited number of references are included.
Clinical Care and Research Considerations (A. Lichter)
Interest in the use of PBI and APBI has come from within the
radiation oncology community as well as from surgeons, med-
ical oncologists, and patients. The potential benefits of shorter
treatment schedules include patient convenience and the poten-
tial for increasing the possibility of BCT in patients for whom
the logistics of a longer course of radiation therapy precludes
that option. Potential benefit to the patient must be balanced with
the potential risk of recurrence within the untreated breast tissue
in the breast receiving PBI or APBI and the unknown long-term
cosmetic results and complications with accelerated radiation
techniques. An important practical consideration for the use of
PBI and/or APBI is the precise choice of technique, for example,
interstitial brachytherapy (i.e., high-dose rate and low-dose rate),
balloon-based brachytherapy (i.e., the MammoSite device), or
external-beam radiation therapy (i.e., 3D-CRT and IMRT or
IORT). Patient selection criteria remain to be fully defined,
including questions regarding age exclusions and applicability
of PBI and APBI with various primary tumor sizes, histopathol-
ogy (invasive lobular, extensive intraductal carcinoma, and duc-
tal carcinoma in situ [DCIS]), and positive axillary lymph-node
Additional concerns about the use of PBI and APBI relate to
an uncertainty in expected results because of a lack of long-term
data from large-scale multi-institutional randomized trials, lim-
ited efficacy data, and the lack of establishment of equivalency
of APBI and whole-breast irradiation (WBI) in the specifications
of the Food and Drug Administration (FDA) approval of the
MammoSite device. Notwithstanding these concerns, many ra-
diation oncology practice sites and healthcare providers have
received training from the manufacturer of the MammoSite
After being introduced by single-institution reports, random-
ized trials with large patient populations and adequate follow-up
have established the standard-of-care for early-stage breast can-
cer as a choice between modified radical mastectomy and breast
conservation surgery plus radiation therapy to the whole breast.
Given that PBI was only introduced in the last decade, the
analogous nature of the PBI and APBI results (i.e., in terms of
local control, survival, and cosmesis) has not yet been con-
firmed. The radiation oncology community may be asked to deal
with concerns regarding institutional review board approvals,
the development of specialty-based organizational guidelines for
appropriateness, and unresolved reimbursement issues.
Radiation Biology Implications (S. Powell)
The use of PBI has important implications in terms of the
biologic equivalent doses of the altered fractionation and pro-
traction schedules. The effectiveness of breast conservation sur-
gery plus radiation therapy is based on the delivery of 60 or more
Gy to the tumor bed in a 6-week period, where current results
have shown more than 95% local control at 10 years (16–30).
Therefore, adoption of a novel dose regimen for PBI has to be
performed with great caution in order to provide a biologically
equivalent radiation dose. The methods available for calculating
the dose equivalence of PBI and WBI are derived from clinical
data; however, the main limitations of this type of data are that
the ranges of radiation dose per fraction and the overall protrac-
tion time of treatment are similar and do not include regimens
used to date in PBI, thus, dose equivalence between WBI and
PBI has to be derived by extrapolation.
The linear quadratic model is most commonly used to predict
dose equivalence, and it is represented mathematically as fol-
lows: Effect ? e(?D??D2) , where D is the dose and ? and ? are
the linear and quadratic coefficients of dose dependence, respec-
tively. This equation can be adapted to calculate dose equiva-
lence as follows:
where D1is the total dose equivalent to the new total dose D2
and d1and d2are the radiation doses per fraction for the
reference and new radiation regimens, respectively. The ?/?
ratio was derived empirically for tumor tissues to be approxi-
mately 10 and for late normal tissue reactions to be in the range
of 2 to 4; for the following examples, a value of 3 will be used.
Two commonly used schedules for PBI are 34 Gy in 10 fractions
twice a day and 32 Gy in eight fractions twice a day. Using the
176 COMMENTARYJournal of the National Cancer Institute, Vol. 96, No. 3, February 4, 2004
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R. Kuske is a consultant for Nucletron Corporation (Columbia, MD), a maker
of brachytherapy equipment.
This Workshop was supported jointly by the Radiation Research Program,
Division of Cancer Treatment and Diagnosis and the Office of Women’s Health,
National Cancer Institute, National Institutes of Health, DHHS.
The organizers of the Bethesda workshop wish to acknowledge the assis-
tance of Ms. Kathy Horvath (Radiation Research Program, National Cancer
Institute, National Institutes of Health) for her role in planning and imple-
menting the workshop and Darrell Anderson, M.S., Anna Small Billman,
B.A., and Stephanie Loranger, PhD (all from The Scientific Consulting
Group, Inc., Gaithersburg, MD), for assistance in preparation of the work-
Manuscript received March 25, 2003; revised November 21, 2003; accepted
December 15, 2003.
184 COMMENTARY Journal of the National Cancer Institute, Vol. 96, No. 3, February 4, 2004
by guest on October 30, 2015