Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 1, pp. 41–48, 2007Copyright � 2007 Elsevier Inc.

Printed in the USA. All rights reserved0360-3016/07/$–see front matter

doi:10.1016/j.ijrobp.2007.01.070

CLINICAL INVESTIGATION Breast

TARGET VOLUME DELINEATION FOR PARTIAL BREAST RADIOTHERAPYPLANNING: CLINICAL CHARACTERISTICS ASSOCIATED WITH LOW

INTEROBSERVER CONCORDANCE

ROSS P. PETERSEN, B.SC.,*y PAULINE T. TRUONG, M.D., C.M.,*y HOSAM A. KADER, M.B., B.S.,*y

ERIC BERTHELET, M.D.,*y JUNELLA C. LEE, B.SC.,*y MICHELLE L. HILTS, PH.D.,*z

ADAM S. KADER, B.SC.,*y WAYNE A. BECKHAM, PH.D.,*z AND IVO A. OLIVOTTO, M.D.*y

*Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, yUniversity of BritishColumbia, and zUniversity of Victoria, Victoria, BC, Canada

Purpose: To examine variability in target volume delineation for partial breast radiotherapy planning and evalu-ate characteristics associated with low interobserver concordance.Methods and Materials: Thirty patients who underwent planning CT for adjuvant breast radiotherapy formed thestudy cohort. Using a standardized scale to score seroma clarity and consensus contouring guidelines, three radi-ation oncologists independently graded seroma clarity and delineated seroma volumes for each case. Seroma geo-metric center coordinates, maximum diameters in three axes, and volumes were recorded. Conformity index (CI),the ratio of overlapping volume and encompassing delineated volume, was calculated for each case. Cases withCI #0.50 were analyzed to identify features associated with low concordance.Results: The median time from surgery to CT was 42.5 days. For geometric center coordinates, variations from themean were 0.5–1.1 mm and standard deviations (SDs) were 0.5–1.8 mm. For maximum seroma dimensions, var-iations from the mean and SDs were predominantly <5 mm, with the largest SDs observed in the medial–lateralaxis. The mean CI was 0.61 (range, 0.27–0.84). Five cases had CI #0.50. Conformity index was significantly asso-ciated with seroma clarity ( p < 0.001) and seroma volume ( p < 0.002). Features associated with reduced concor-dance included tissue stranding from the surgical cavity, proximity to muscle, dense breast parenchyma, andbenign calcifications that may be mistaken for surgical clips.Conclusion: Variability in seroma contouring occurred in three dimensions, with the largest variations in themedial–lateral axis. Awareness of clinical features associated with reduced concordance may be applied towardtraining staff and refining contouring guidelines for partial breast radiotherapy trials. � 2007 Elsevier Inc.

Breast cancer, Partial breast radiotherapy, Target volume, Interobserver variability, Conformity index.

INTRODUCTION

Prospective randomized trials are in progress to evaluate the

efficacy of adjuvant partial breast radiotherapy (PBRT) after

breast-conserving surgery in patients with early-stage breast

cancer. The hypothesis that irradiation of the postsurgical

excision cavity with a margin of adjacent breast tissue offers

equivalent local control compared with standard whole breast

radiotherapy is based on studies demonstrating that approxi-

mately 70–80% of in-breast recurrences occur at or near the

tumor bed (1–4). Radiation treatment targeted to a limited

volume using accelerated fractionation schedules over

shorter durations has the potential to reduce normal tissue

toxicities and improve convenience for breast cancer

patients. Currently available PBRT modalities include

41

interstitial brachytherapy (5–9), MammoSite balloon catheter

systems (10–12), computerized tomography (CT)-based con-

formal external beam techniques (13–15), proton beams (16),

and intraoperative electron beam therapy (17). Regardless of

the PBRT modality of choice, accurate delineation of target

volumes is critical because these volumes provide the basis

for all subsequent planning decisions.

A potential caveat in PBRT planning is interobserver

inconsistencies in delineating the target volume. Although

the optimal target volume for PBRT remains to be estab-

lished, most series in the PBRT literature have defined the

postoperative seroma or tumor bed as the volume on which

subsequent planning and prescription decisions are based

(5–19). As margins are added to the seroma volume to create

the clinical and planning target volumes, variations in its

Reprint requests to: Pauline T. Truong, M.D., C.M., British Co-lumbia Cancer Agency, Vancouver Island Centre, 2410 Lee Ave.,Victoria, BC V8R 6V5, Canada. Tel: (250) 519-5575; Fax: (250)519-2018; E-mail: ptruong@bccancer.bc.ca

Presented in part at the 2007 United Kingdom Radiation Oncol-ogy Conference, March 18–21, 2007, Edinburgh, Scotland.

Conflict of interest: none.Received Nov 9, 2006, and in revised form Jan 27, 2007.

Accepted for publication Jan 31, 2007.

42 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 1, 2007

delineation may ultimately result in critical differences in the

treatment volume. This could potentially undermine the ef-

fectiveness of PBRT and compromise the validity of trials’

results.

Studies evaluating contouring practices in breast cancer

(20–22) and other tumor sites (23–27) have shown that var-

iability in target volume delineation occurs frequently in

radiation treatment planning. Contouring guidelines and

computer-based educational tools have been demonstrated

to be practical measures that can improve consistency (20,

23–26). Another potential measure to improve consistency

is to evaluate geometric parameters and clinical features

that may be associated with greater observer variability.

Awareness of these characteristics may then be applied to re-

fining contouring protocols and in training radiation oncolo-

gists and radiation therapy staff who participate in trials of

PBRT.

The present analysis aimed to evaluate variability in CT-

based delineation of the seroma volume for PBRT planning

and to describe clinical characteristics associated with low

interobserver concordance.

METHODS AND MATERIALS

Patient cohortThirty patients with early-stage breast cancer treated with breast-

conserving surgery who underwent planning CT for adjuvant breast

RT at the British Columbia (BC) Cancer Agency, Vancouver Island

Centre, between June 2002 and April 2005 formed the study cohort.

The median age at diagnosis was 67 years (range, 47–80 years). All

patients had invasive or in situ ductal carcinoma, pathologic tumor

size <3 cm (median, 1.15 cm; range, 0.2–2.2 cm), negative sentinel/

axillary nodes, and clear surgical margins, defined as tumor >2 mm

from inked margins, after partial mastectomy.

Radiotherapy planningAll patients underwent planning CT using a CT scan unit (Hi-

Speed FX/I; GE Medical Systems, Milwaukee, WI). The median

time from surgery to CT was 42.5 days (range, 20–77 days). Patients

were imaged in the supine treatment position with the ipsilateral arm

abducted using a breast board and arm rest immobilization system.

Before CT scanning, the ipsilateral breast tissue and the breast sur-

gical scar were marked with lead wire by trained radiotherapy staff.

Computed tomography images were obtained using a 5-mm inter-

slice thickness from above the suprasternal notch to the mid-

abdomen. Images were transferred to a treatment-planning system

(Varian Eclipse, version 7.3.10; Varian Medical Systems, Palo

Alto, CA) for contouring. The ipsilateral breast, chest wall, pector-

alis major muscle, lungs, and heart were contoured on each slice by

an experienced dosimetrist.

Seroma clarityA Seroma Clarity Scale was developed to standardize grading of

the clarity and ease of delineation of the seroma volume (19). This

numeric scale ranged from 0 to 5, with 0 representing no visible se-

roma and 5 representing a clear, homogenous seroma with sharp

boundaries (Fig. 1). Three radiation oncologists, each with at least

10 years of experience treating breast cancer, served as observer

subjects for this analysis. The radiation oncologists independently

assigned a seroma clarity score for each case. Means and standard

deviations (SDs) in seroma clarity scores were calculated for the

study cohort.

Seroma volume delineationThe consensus guidelines used in this study to contour the seroma

volume have been previously published (20). These guidelines were

derived from the PBRT literature and from consensus discussions

among BC Cancer Agency radiation oncologists participating in

PBRT trials (20). Using these guidelines, each of the three radiation

oncologists independently delineated the seroma volume for each

case using Varian Eclipse software. The observers were permitted

to adjust the CT window settings and magnification views at their

discretion. Clinical records, including surgical and pathology re-

ports, mammography, and other imaging modalities, were available

to each observer.

Variations from the means and SDsThe seroma contours were analyzed for general trends by exam-

ining seroma volumes, geometric center coordinates, and maximum

dimensions in the anterior–posterior, medial–lateral, and superior–

inferior axes using the statistics function of the workstation. Seven

variables were examined: seroma volume, seroma center coordi-

nates in the three axes, and maximum seroma dimensions in the

three axes. These measurements were performed for 30 cases,

each contoured by three observers, yielding 630 measurements for

analysis. The means and SDs of each variable were calculated for

each patient. The average variation from the mean was calculated

for each observer with the corresponding SDs. Individual observer’s

seroma volumes were plotted as a function of the mean seroma

volumes of the group.

Conformity indexTo examine case-specific interobserver variability, we used the

Conformity Index (CI), defined by Struikmans et al. (21) as the ratio

of overlapping volume to encompassing delineated volume (Figs. 2a

and 2b). A CI of 1 indicates 100% concordance, a CI of 0.50 indi-

cates that the observers agreed on 50% of the encompassing delin-

eated volume, and a CI of 0 indicates no concordance (Fig. 2a).

The CI of the three observers was computed for each case (illustra-

tive case, Fig. 2b). In cases with CI #0.50, an investigator indepen-

dent of the contouring radiation oncologists reviewed each case to

identify clinical features that may have contributed to the observed

low concordance.

Associations between CI and patient age, pathologic tumor size,

time interval from surgery to CT, mean seroma clarity score, and

mean seroma volume were tested using Pearson correlation statis-

tics. Statistical significance was defined as a p value of <0.05. All

statistical analyses were performed using commercial software

(SPSS 11.0, Chicago, Illinois).

RESULTS

Seroma claritySeroma clarity grading using the Seroma Clarity Scale was

reproducible among the observers. The mean (SD) seroma

clarity score for the patient cohort was 3.74 (0.68). In 8 of

30 cases, the scores were the same among all three observers;

16 of 30 cases differed by 1 point; and the remaining 6 cases

differed by 2 points. No deviation greater than 2 points was

observed.

Partial breast contouring variability d R. P. PETERSEN et al. 43

Fig. 1. British Columbia Cancer Agency Seroma Clarity Scale. 0 = no visible seroma, 1 = scar/shadow, 2 = seroma identifi-able but with significant uncertainties, 3 = seroma identifiable with minor uncertainties, 4 = seroma easily identifiable, gen-erally homogenous with slightly blurred margin, 5 = seroma easily identifiable, homogenous with sharp boundaries.

Seroma volumesThe mean seroma volume was 48.7 cm3 (range, 10.3–

189.3 cm3). Figure 3 presents the plot of each observer’s con-

toured volume relative to the mean volume of the group. No

trends were identified in terms of any observer characteristi-

cally contouring smaller or larger volumes relative to the

mean of the group.

Seroma geometric center coordinates and maximumdimensions

Table 1 summarizes the average variations from the mean

and the SDs for each observer’s identification of the seroma

geometric center coordinate. Variations from the mean and

SDs were <2 mm in all dimensions. The largest SDs in geo-

metric center coordinates were noted in the medial–lateral

axis (range, 1.2–1.8 mm).

Table 2 summarizes the average variations from the mean

and standard deviations for the maximum seroma diameters

in three axes. Variations from the mean were <5 mm in all di-

mensions. The SDs in maximum seroma diameters were larg-

est in the medial–lateral axis (range, 4.3–7.7 mm), compared

with the superior–inferior axis (range, 2.4–3.4 mm) or the

anterior–posterior axis (range, 1.8–3.3 mm).

CI and characteristics associated with reducedconcordance

Figure 4 presents the distribution of CIs for the patient

cohort. The mean CI was 0.61 (range, 0.27–0.84). Five cases

44 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 1, 2007

Fig. 2. (a) Conformity index (CI) = ratio of overlapping volume to encompassing delineated volume. Diagrammaticrepresentation of CI 0, 0.5, and 1. (b) Illustrative case of seroma contouring performed by three observers.

had CI #0.50. Screen captures of illustrative cases with low

CI are presented in Figs. 5a–5c. Clinical features associated

with reduced concordance in these five cases included the fol-

lowing: low seroma clarity score, tissue stranding from the

surgical cavity, proximity to the pectoralis muscle, dense

breast parenchyma, and presence of benign calcifications

that were mistaken for surgical clips.

In the Pearson correlation analysis, CI was significantly as-

sociated with seroma clarity score (r = 0.78, p < 0.001) and

seroma volume (r = 0.55, p < 0.002). No significant correla-

tion was found between CI and patient age at diagnosis,

pathologic tumor size, or time interval from surgery to CT

(all p > 0.05).

Fig. 3. Plot of individual observer’s seroma volumes as a functionof the mean seroma volumes. The solid line indicates the linearrelationship between the mean and the observer’s volumes.

DISCUSSION

Despite the proliferation of innovative PBRT techniques

and increased efforts to translate technological advances

into patient benefits, data addressing the pitfalls of variability

in PBRT target volume definition remain sparse. With the im-

plementation of any new radiotherapeutic approach, all clini-

cians will require training and will undergo a learning curve.

This study demonstrated that in PBRT target volume defini-

tion, the use of consensus guidelines resulted in good inter-

observer concordance for the majority of cases, but there

remained specific situations in which higher variability oc-

curred. The recognition of clinical features associated with

low concordance can serve to raise awareness of potential

caveats in PBRT volume contouring. This knowledge can

be used to train staff and to refine contouring protocols to

improve the consistency of seroma contouring.

Table 1. Seroma geometric center coordinates: averagevariations from the mean and standard deviations, in

millimeters

Observer Medial–lateral Superior–inferior Anterior–posterior

1 1.0 (1.8) 0.6 (0.8) 0.5 (0.6)2 1.1 (1.2) 0.5 (0.6) 0.5 (0.5)3 0.9 (1.2) 0.5 (0.5) 0.5 (0.5)

Values in parentheses are standard deviation.

Partial breast contouring variability d R. P. PETERSEN et al. 45

In the present study’s examination of seroma geometric

center coordinates and maximum diameters, the largest

SDs were noted in the medial–lateral axis. Potential sources

of contouring discrepancies in this axis include seroma vol-

umes with indistinct borders and low clarity scores, tissue ex-

tensions from the tumor bed, and dense breast parenchyma

(Figs. 5a–5c). In the examination of cases with low CI,

although dense extensions from the tumor bed may occur in

any dimension, they were prominent in the medial–lateral di-

rection (Fig. 5b). The consensus adopted by our institution

was that such extensions or stranding likely represented sur-

gical disturbance rather than the tumor bed and hence were

not to be included in contouring the seroma. However, we

acknowledge that uncertainty can arise, and the question of

whether all tissue extensions should be included as part of

the target volume remains controversial. Another clinical

characteristic noted to contribute to greater contouring varia-

tions in the medial–lateral axis was the presence of dense

breast parenchyma. Dense parenchyma, especially when ad-

jacent to the tumor bed, may often appear on CT as lateral

densities merging with the tumor bed (Fig. 5c). Determina-

tion of the boundaries between normal dense breast tissue

and the tumor bed can thus be difficult. Objective evaluation

of tissue radiodensity using the Hounsfield Unit measure-

ment tool in RT planning systems may be helpful in such

a situation.

Our data demonstrated that although the largest SDs were

in the medial–lateral axis, variability in the other axes also

Table 2. Maximum seroma dimensions: average variationfrom the mean and standard deviations, in millimeters

Observer Medial–lateral Superior–inferior Anterior–posterior

1 2.7 (4.5) 2.6 (2.9) 1.8 (2.2)2 3.2 (4.3) 4.1 (3.4) 3.2 (3.3)3 3.4 (7.7) 3.2 (2.4) 2.4 (1.9)

Values in parentheses are standard deviation.

occurred. A relatively large deviation from the mean of 4

mm was noted in the superior–inferior axis for one observer.

With a CT interslice thickness of 5 mm, the observer may

have experienced uncertainty regarding whether an addi-

tional contour was warranted in the superior and inferior

limits. Studies of various tumor sites, including prostate

and lung cancer (27, 28), have suggested that the selection

of CT slice thickness can impact volume definitions. In a se-

ries reporting reproducibility among three radiation oncolo-

gists performing CT-based prostate organ contouring in 40

cases, the use of a 5-mm CT slice thickness was implicated

as a factor contributing to difficulties in localizing the pros-

tate apex and poor demarcation between the prostate base

and seminal vesicles (27). Another series, which compared

the use of 1.25-mm and 5-mm CT slice thicknesses in sub-

jects with pulmonary nodules, reported that reduced slice

thickness improved detection of small nodules and inter-

observer agreement (28). These data support the suggestion

that reducing interslice thickness can correspondingly reduce

interobserver variability, a strategy that warrants investiga-

tion in the setting of PBRT planning.

In the present analysis, the anterior–posterior axis was

associated with the smallest degree of contouring variability.

A potential explanation for this observation may be that the

skin and the chest wall provided clear boundaries in this dimen-

sion for the majority of cases and that the anterior–posterior

dimension is generally the smallest breast dimension on a

supine CT scan. Variability in the anterior–posterior axis

arose when the seroma abutted the pectoralis major muscle

(Fig. 5a). There is no need to include the pectoralis muscle

in the seroma definition if the surgical margins are clear

and cancer has not invaded the muscle. Difficulty in demar-

cating the interface between seroma and muscle can lead to

a failure to exclude muscle from the target volume and can

contribute to greater interobserver discrepancies. Review of

the operative and pathology reports may be helpful in these

situations to determine the extent of surgery and to verify

whether fascia and/or muscle were removed at the time of

0

2

4

6

8

10

12

14

0-0.10 0.11-0.20

0.21-0.30

0.31-0.40

0.41-0.50

0.51-0.60

0.61-0.70

0.71-0.80

0.81-0.90

0.91-1.00

Conformity Index

# of

Pat

ient

s

Fig. 4. Distribution of conformity indices for the study cohort.

46 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 1, 2007

Fig. 5. Illustrative cases with low conformity indices. (a) Computed tomography transverse plane showing a seroma abut-ting the pectoralis major muscle (yellow contour) and the presence of a benign breast calcification (arrow). Failure toexclude muscle when contouring the seroma and misidentification of a benign breast calcification as a surgical clipcontributed to a low conformity index of 0.46. (b) Computed tomography transverse plane showing a seroma with tissueextension from the core volume. The inclusion of this tissue extension in the seroma definition by one observer reduced theconformity index to 0.50. (c) Computed tomography transverse plane showing a seroma located near the skin surface, withindistinct borders and dense surrounding breast parenchyma. The conformity index was 0.38.

surgery and to determine margin status. Seromas located

more anteriorly can also present challenges in contouring in

the anterior–posterior dimension (Fig. 5c). For example, if

the seroma was very close to the skin surface or was blurred

by dense tissue behind the nipple–areolar complex, clarity

can be poor, resulting in greater contouring variation.

Benign calcifications in the breast were identified as

a source of discrepancy in PBRT contouring. In one case,

two observers misidentified a benign breast calcification for

a surgical clip and included this in their contours, resulting

in larger volumes and reduced concordance (Fig. 5a). Mea-

sures that can reduce this pitfall include careful review of

mammographic and CT images of both breasts to look for

other benign calcifications and for artifacts associated with

metallic markers, verification of operative reports to confirm

surgical clip placement, and applying tools measuring radio-

density to distinguish calcifications from clips. Radio-opaque

surgical clips have been demonstrated to be useful in guiding

Partial breast contouring variability d R. P. PETERSEN et al. 47

PBRT volume definition (29) but were not used routinely by

surgeons referring patients with breast cancer to our center

during the era of this study. The pitfalls in seroma delineation

identified in our study support the contention that clip place-

ment may be of added value in PBRT volume localization.

The CI was found to be a useful method to quantify inter-

observer variability and to highlight specific cases with low

concordance for further analysis. The mean CI of 0.61 (range,

0.27–0.84) found in the current study of three observers, each

contouring 30 partial breast volumes, was comparable to the

mean CI of 0.56 (range, 0.39–0.74), reported by Struikmans

et al. (21) in their study of five observers, each contouring 18

breast boost volumes. However, distinct from that study’s

identification of one observer who consistently contoured

smaller volumes with respect to the mean, no characteristic

tendency to contour smaller or larger volumes relative to

the mean was demonstrated among our subjects. The use of

consensus-based contouring guidelines may have contrib-

uted to the concordance of the individual’s volumes in the

majority of cases.

The ongoing randomized trials of PBRT, including the Na-

tional Surgical Adjuvant Breast and Bowel Project B39 trial,

the Canadian Randomized Trial of Accelerated Partial Breast

Irradiation, and the European Society of Therapeutic Radiol-

ogy and Oncology trial, require that subjects have clearly

identifiable excision cavities. The correlations between con-

touring concordance and seroma clarity score and seroma

volume demonstrated in the present analysis have clinical

implications in identifying appropriate PBRT candidates for

these trials. A seroma clarity score of 3 or less may serve to

flag cases that require consensus review of applied contours

before trial enrolment and randomization. When the seroma

volume is small, external review of applied contours may

also be helpful to avert potentially large shifts in the planning

target volume.

The present study did not demonstrate significant associa-

tions between CI and patient age, tumor size, or time interval

from surgery to CT. The vast majority of subjects in our study

cohort were aged >50 years with small tumors, and all under-

went planning CT within 11 weeks from surgery. The relative

homogeneity in these characteristics and small sample size

REFER

may have limited the power to detect statistically significant

associations between CI and these characteristics. In a study

evaluating seroma clarity and volume as a function of time

from surgery, Kader et al. (19) applied the same Seroma Clar-

ity Scale used in the present study to a series of 206 women

undergoing planning CT after breast-conserving surgery. The

mean seroma clarity score was 3.4 and most stable from 3 to 8

weeks after surgery. Thereafter, the mean seroma clarity

score decreased to 2.5 during weeks 9 to 14, and further

declined to 1.7 beyond 14 weeks from surgery. Seroma vol-

umes also progressively decreased with longer time from sur-

gery (19), a finding consistent with a study by Oh et al. (30).

These data and the present study’s demonstration of reduced

concordance with low seroma clarity and volume support the

suggestion that the optimal time to perform planning CT for

PBRT candidates is within 8 weeks from surgery to reduce

the likelihood of encountering difficulties in target volume

delineation associated with low seroma clarity and small

volume.

With continuing advances in imaging technology, the

application of modalities such as breast ultrasound (31–33)

and breast magnetic resonance imaging (33, 34) in PBRT

planning warrant investigation. Correlative studies to assess

relationships between the postoperative seroma and the

preoperative breast tumor as defined by mammography,

CT, or ultrasound are also warranted because they have the

potential to further improve accuracy in localizing the

PBRT target volume.

CONCLUSION

Variability in seroma contouring can occur in three dimen-

sions but was most prominent in the medial–lateral axis.

Clinical features associated with reduced interobserver con-

cordance included low seroma clarity score, small volume,

tissue extension from the surgical cavity, proximity to the

pectoralis muscle, dense breast parenchyma, and the pres-

ence of benign calcifications. Knowledge of these features

may be applied to train staff participating in PBRT trials

and to refine contouring guidelines and quality assurance

processes for PBRT protocols.

ENCES

1. Clark RM, McCullock PB, Levine MN, et al. Randomized clin-ical trial to assess the effectiveness of breast irradiation follow-ing lumpectomy and axillary dissection for node-negative breastcancer. J Natl Cancer Inst 1992;84:683–689.

2. Liljgren G, Homberg L, Bergh J, et al. 10 year results after sec-tor resection with or without postoperative radiotherapy forstage I breast cancer: A randomized trial. J Clin Oncol 1999;17:2326–2333.

3. Veronesi U, Marubini E, Mariani L, et al. Radiotherapy afterbreast-conserving surgery in small breast carcinoma: Longterm results of a randomized trial. Ann Oncol 2001;12:997–1003.

4. Smith TE, Lee D, Turner BC, et al. True recurrence vs. new pri-mary ipsilateral breast tumor relapse: An analysis of clinical andpathologic differences and their implications in natural history,

prognoses, and therapeutic management. Int J Radiat OncolBiol Phys 2000;48:1281–1289.

5. Baglan KL, Martinez AA, Frazier RC, et al. The use of high-dose-rate brachytherapy alone after lumpectomy in patients

with early-stage breast cancer treated with breast-conserving

therapy. Int J Radiat Oncol Biol Phys 2001;50:1003–1011.6. Arthur DW, Koo D, Zwicker RD, et al. Partial breast brachy-

therapy after lumpectomy: Low dose rate and high dose rate

experience. Int J Radiat Oncol Biol Phys 2003;56:681–689.7. Vicini FA, Arthur DW. Breast brachytherapy: North American

experience. Semin Radiat Oncol 2005;15:108–115.8. Vicini F, Winter K, Straube W, et al. A phase I/II trial to eval-

uate three-dimensional conformal radiation therapy confined to

the region of the lumpectomy cavity for stage I/II breast carci-noma: Initial report of feasibility and reproducibility of radiation

48 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 1, 2007

therapy oncology group (RTOG) study 0319. Int J RadiatOncology Biol Phys 2005;63:1531–1537.

9. Kuske RR, Winter K, Arthur DW, et al. Phase II trial of brachy-therapy alone after lumpectomy for select breast cancer: Toxic-ity analysis of RTOG 95-17. Int J Radiat Oncol Biol Phys 2006;65:45–51.

10. Keisch M, Vicini F, Kuske RR, et al. Initial clinical experiencewith the MammoSite breast brachytherapy applicator in womenwith early-stage breast cancer treated with breast-conservingtherapy. Int J Radiat Oncol Biol Phys 2003;55:289–293.

11. Harper JL, Jenrette JM, Vanek KN, et al. Acute complicationsof MammoSite brachytherapy: A single institution’s initial clin-ical experience. Int J Radiat Oncol Biol Phys 2005;61:169–174.

12. Dickler A, Kirk MC, Chu J, et al. The MammoSite breast bra-chytherapy applicator: A review of techniques and outcomes.Brachytherapy 2005;4:130–136.

13. Formenti SC, Truong MT, Goldberg JD, et al. Prone acceleratedpartial breast irradiation after breast-conserving surgery: Pre-liminary clinical results and dose-volume histogram analysis.Int J Radiat Oncol Biol Phys 2004;60:493–504.

14. Taghian AG, Kozak KR, Doppke KP, et al. Initial dosimetricexperience using simple three-dimensional conformal exter-nal-beam accelerated partial-breast irradiation. Int J RadiatOncol Biol Phys 2006;64:1092–1099.

15. Baglan KL, Sharpe MB, Jaffray D, et al. Accelerated partialbreast irradiation using 3D conformal radiation therapy (3D-CRT). Int J Radiat Oncol Biol Phys 2003;55:302–311.

16. Taghian AG, Kozak KR, Katz A, et al. Accelerated partialbreast irradiation using proton beam: Initial dosimetric experi-ence. Int J Radiat Oncol Biol Phys 2006;65:1572–1578.

17. Veronesi U, Orecchia R, Luini A, et al. Full-dose intraoperativeradiotherapy with electrons during breast conserving surgery:Experience with 590 cases. Ann Surg 2005;242:101–106.

18. Vicini FA, Kestin LL, Goldstein N. Defining the clinical targetvolume for patients with early-stage breast cancer treated withlumpectomy and accelerated partial breast irradiation: A patho-logic analysis. Int J Radiat Oncol Biol Phys 2004;60:722–730.

19. Kader HA, Truong PT, Panades M, et al. Is breast seroma theappropriate guide for PTV determination in accelerated partialbreast irradiation planning? (Abstr.). Radiother Oncol 2004;72(Suppl. 1):S6.

20. Wong EK, Truong PT, Kader HA, et al. Consistency in seromacontouring for partial breast radiotherapy: Impact of guidelines.Int J Radiat Oncol Biol Phys 2006;66:372–376.

21. Struikmans H, Warlam-Rodenhuis C, Stam T, et al. Interob-server variability of clinical target volume delineation of glan-dular breast tissue and of boost volume in tangential breastirradiation. Radiother Oncol 2005;76:293–299.

22. Hurkmans CW, Borger HJ, Pieters RB, et al. Variability in tar-get volume delineation on CT scans of the breast. Int J RadiatOncol Biol Phys 2001;50:1366–1372.

23. Tai P, Van Dyk J, Battista JJ, et al. Improving the consistency incervical esophageal target volume definition by special training.Int J Radiat Oncol Biol Phys 2002;53:766–774.

24. Logue JP, Sharrock CL, Cowan RA, et al. Clinical variability oftarget volume description in conformal radiotherapy planning.Int J Radiat Oncol Biol Phys 1998;41:929–931.

25. van Sornsen de Koste JR, Senan S, Underberg RW, et al. Use ofCD-ROM-based tool for analyzing contouring variations ininvolved-field radiotherapy for Stage III NSCLC. Int J RadiatOncol Biol Phys 2005;63:334–339.

26. Steenbakkers RJ, Duppen JC, Fitton I, et al. Observer variationin target volume delineation of lung cancer related to radiationoncologist-computer interaction: A ‘Big Brother’ evaluation.Radiother Oncol 2005;77:182–190.

27. Berthelet E, Liu MCC, Agranovich A, et al. Computed tomog-raphy determination of prostate volume and maximum dimen-sions: A study of interobserver variability. Radiother Oncol2002;63:37–40.

28. Fischbach F, Knollmann F, Griesshaber V, et al. Detection ofpulmonary nodules by multislice computed tomography: Im-proved detection rate with reduced slice thickness. Eur Radiol2003;13:2378–2383.

29. Weed DW, Yan D, Martinez AA, et al. The validity of surgicalclips as a radiographic surrogate for the lumpectomy cavity inimage-guided accelerated partial breast irradiation. Int J RadiatOncol Biol Phys 2004;60:484–492.

30. Oh KS, Kong FM, Griffith KA, et al. Planning the breast tumorbed: Changes in the excision cavity volume and surgical scar lo-cation after breast-conserving surgery and whole-breast irradia-tion. Int J Radiat Oncol Biol Phys 2006;66:680–686.

31. Thompson M, Henry-Tillman R, Margulies A, et al. Hema-toma-directed ultrasound-guided (HUG) breast lumpectomy.Ann Surg Oncol 2007;14:148–156.

32. Della Sala SW, Pellegrini M, Bernardi D, et al. Mammographicand ultrasonographic comparison between intraoperative radio-therapy (IORT) and conventional external radiotherapy (RT) inlimited-stage breast cancer, conservatively treated. Eur J Radiol2006;59:222–230.

33. Li Y, Wang J, Holloway C, et al. Development of an MRI/x-ray/ultrasound compatible marker for pre-operative breasttumour localization. Phys Med Biol 2005;50:3349–3360.

34. Tardivon AA, Athanasiou A, Thibault F, et al. Breast imagingand reporting data system (BIRADS): Magnetic resonanceimaging. Eur J Radiol 2007;61:212–215.