Partial Breast Re-Irradiation for Patients With Ipsilateral Breast Tumor Recurrence, After First Being Treated With Breast Conservation for Early Stage Breast Cancer: An Efficacy Trial Comparing Mammosite® and Intraoperative Radiation
Phase: NA
Conditions: Breast Cancer
Sponsor: Case Comprehensive Cancer Center

CASE 11107 Version date 5.29.2009 
Page 1 of 23 
 
CASE WESTERN RESERVE UNIVERSITY/UNIVERSITYHOSPITALS 
IRELAND CANCER CENTER 
______________________________________________________________________________________ 
 
STUDY NO: CASE 11107 
 
TITLE: Partial Breast Re-Irradiation for Patients with Ipsilateral Breast Tumor Recurrence, After First Being 
Treated with Breast Conservation for Early Stage Breast Cancer: An Efficacy Trial Comparing MammoSite® and 
Intraoperative Radiation 
 
 
PRINCIPAL INVESTIGATOR:  
Janice A. Lyons, MD 
 
 
Ireland Cancer Center 
 
 
University Hospitals of Cleveland  
Case Medical Center 
 
 
Department of Radiation Oncology  
11100 Euclid Avenue 
 
 
Cleveland, Ohio 44106 
 
 
(216) 844-2538  
 
 
 
CO-INVESTIGATORS: 
 
Robert Shenk, MD  
 
Paula Silverman, MD  
 
University Hospitals 
 
University Hospitals  
 
Case Medical Center 
  
Case Medical Center 
 
Department of Surgery  
 
Department of Medicine   
 
Rosemary Leeming, MD  
Joseph Baar, MD  
 
 
University Hospitals 
 
University Hospitals 
 
 
Case Medical Center 
  
Case Medical Center 
 
 
Department of Surgery 
 
Department of Medicine  
 
 
 
SPONSOR:  
 
 
Investigator-Initiated 
 
 
STATISTICIAN:  
 
Pingfu Fu, PH D 
Biostatistics and Informatics Core Facility 
Case Western Reserve University 
 
 
CLINICAL FACILITY:   
University Hospitals Ireland Cancer Center 
 
 
APPROVALS:   
 
Clinical Trials Development and Review Committee: March 3, 2008 
Case Cancer IRB: August 7, 2008 
 
 
STUDY COORDINATOR:  
Clinical Trials Core Facility 
University Hospitals Ireland Cancer Center 
Case Western Reserve University 
11100 Euclid Avenue 
Cleveland, Ohio 44106-5065 

CASE 11107 Version date 5.29.2009 
Page 2 of 23 
 
 
TABLE OF CONTENTS 
 
Section  
 
 
 
 
 
 
 
 
Page 
Schema  
 
1.0 Introduction  
 
 
 
 
 
 
 
4 
 
2.0 Objectives  
 
 
 
 
 
 
 
12 
 
3.0 Selection of Patients  
 
 
 
 
 
 
12 
 
4.0 Registration  
 
 
 
 
 
 
 
13 
 
5.0 Treatment Plan  
 
 
 
 
 
 
 
13 
 
6.0 Measurement of Effect   
 
 
 
 
 
15 
 
7.0 Study Parameters   
 
 
 
 
 
 
16 
 
8.0 Statistical Considerations  
 
 
 
 
 
16 
 
9.0 Records to be Kept  
 
 
 
 
 
 
17 
 
10.0 Patient Consent and Peer Judgment  
 
 
 
 
17 
 
11.0 References  
 
 
 
 
 
 
 
17 
 
Appendix I Cosmetic Guidelines 
 
 
 
 
 
21 
 
Appendix II  Patient Cosmesis/QOL form 
 
 
 
 
23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CASE 11107 Version date 5.29.2009 
Page 3 of 23 
 
SCHEMA 
 
Excisional Biopsy Followed by Partial Breast Irradiation for patients with ipsilateral breast tumor 
recurrence who were first treated with breast conserving surgery and whole breast radiation 
therapy. 
 
1. Intraoperative Radiation to a Dose of 21 Gy in a Single Fraction. 
 
OR 
 
2. MammoSite® Brachytherapy consisting of a dose of 34 Gy delivered over 10 fractions of 
3.4 Gy twice daily over 5 days, with at least 6 hours between fractions. 
 
Eligible patients include: 
 
Patients with a prior ipsilateral breast cancer (invasive, or in situ) initially treated with 
tylectomy and whole breast radiation (with or without tumor bed boost). 
 
Patients who have had at least five years of time elapsed since the end of the prior course 
of radiation. 
 
 
Patients with histologically confirmed recurrences comprised of ductal carcinoma in-situ, 
invasive ductal, medullary, papillary, colloid (mucinous), or tubular histologies. 
 
Patients with histologically confirmed unifocal recurrences measuring <3 cm. 
 
Patients with negative resection margins with at least a 2 mm margin from the invasive 
and in-situ cancer or a negative re-excision. 
 
Patients with invasive recurrences that have a negative re-staging work-up consisting of 
at least a CT chest/abdomen and bone scan. 
 
Hormonal therapy is allowed.  If chemotherapy is planned, it must begin no earlier than 
two weeks following completion of radiation.   
 
Patients must be > 18 years of age.  
 
Patients with a negative pregnancy test. 

CASE 11107 Version date 5.29.2009 
Page 4 of 23 
 
 
1.0 INTRODUCTION 
 
Despite widespread mammographic screening and increasingly aggressive treatment approaches, 
breast cancer continues to be a leading cause of both morbidity and mortality in the aging female 
population. Every year, approximately 180,000 women are diagnosed with breast cancer and 
about 40,000 women will die of this disease (1). Local treatment options have changed 
dramatically over the past several decades and increasing numbers of women are now effectively 
treated with breast conservation. Although treatment patterns vary on a geographical basis, 
studies show that in some settings, greater than 70% of women with breast cancer are now 
preserving their breasts (2).   
 
This shift away from mastectomy came after the publication of results from several prospective, 
randomized studies comparing mastectomy and conservative surgery followed by radiation (3-
10). These studies demonstrated similar survival and disease–free survival rates regardless of 
which treatment approach women chose. In 1992, the NIH Consensus Development Panel was 
convened to review these studies. This resulted in the 1992 Consensus Statement indicating that 
breast conservation and mastectomy were equivalent treatment options with respect to survival 
(11). The primary study done in the United States was the NSABP B-06 published with 12 year 
results in 1995 (5). This study randomized patients between three arms: mastectomy, 
conservative surgery alone and conservative surgery followed by radiation treatments. Although 
the overall survival was similar in all three arms, there were dramatic differences in the local 
recurrence rates. The conservative surgery alone arm had a local recurrence rate of 39% 
compared to 10% local recurrence rate in the mastectomy and conservative surgery plus 
radiation arms.  Now with 20 years of follow-up from B-06, the rate of an ipsilateral breast 
tumor recurrence (IBTR) is approximately 14% (12).  This information led to a standard 
recommendation in the United States that all patients undergoing breast conservation receive 
post-operative radiation as part of their care (11). 
 
The term breast conserving therapy (BCT) indicates breast cancer treatment that involves 
resection of the cancer with a rim of normal tissue, axillary lymph node dissection for those with 
invasive cancer, and breast radiotherapy.  The major advantage of BCT is related to the superior 
cosmetic result and reduced psychological and emotional trauma resulting from this procedure 
compared to mastectomy.  
 
Standard therapy after tumor excision generally includes five weeks of external beam XRT to the 
whole breast (45-50 Gy) followed by a boost to the tumor bed with either an additional 8 to 10 
fractions (days) of external beam XRT or a two to three day interstitial implant. The rationale for 
this approach is based upon two principles. First, higher doses of XRT are given to the 'tumor 
bed' in an attempt to control residual small foci of cancer that may be left behind after excision 
alone. Second, whole breast XRT is used to eliminate possible areas of occult multicentric in situ 
or infiltrating cancer in remote areas of the breast. That such remote, multicentric areas of cancer 
exist has long been established.  However, the biological significance of these areas of occult 
cancer is unknown and the necessity to prophylactically treat the entire breast has recently been 
questioned. For instance, there are now at least five prospective randomized trials that have been 

CASE 11107 Version date 5.29.2009 
Page 5 of 23 
 
conducted comparing the outcome of patients treated with excisional biopsy alone or followed 
by whole breast XRT (5,13-17). In all of these trials, the majority of recurrences in the breast of 
patients who did not receive XRT occurred at or in the area of the tumor bed. Thus, it would 
appear that XRT after tumor excision exerts its maximal effect upon reducing breast cancer 
recurrence at or near the tumor site (17).   
 
One possible attraction for many women who select breast conservation as their treatment, is that 
if it “fails,” only then would they have to have a mastectomy—i.e. they have an initial 
opportunity to save their breast.  The psychological impact of losing one’s breast is difficult for 
some women to accept.  The term “salvage” mastectomy has been applied to the setting in which 
a patient who was initially treated with partial mastectomy and radiation therapy, and who 
develops an ipsilateral breast tumor recurrence (IBTR) then undergoes a mastectomy.  The 
reasons behind the idea of a salvage mastectomy are several—first, since radiation treatments for 
breast cancer currently target the whole breast for the majority of the treatment period, by re-
irradiating the breast, one would risk the possibility of unacceptable tissue damage, including 
necrosis and increased incidence of secondary malignancies.  Just like all normal tissues, normal 
breast tissue has a limit as to how much radiation it may receive before the damage becomes 
irreparable.  Second, the breasts of many patients who develop an IBTR may not be able to 
accommodate a second lumpectomy—i.e., cosmetic outcome can be affected, particularly with 
inferiorly located recurrences.  Finally, studies have shown that patients who elect to have their 
IBTR removed with a lumpectomy (without repeat radiation) may have recurrence rates that can 
be as high as 35%, which is unacceptably high for most women (18).  When counseling a woman 
considering a salvage mastectomy, it must be made clear that re-recurrence rates (i.e. a 2nd 
recurrence, this one after the mastectomy) have ranged from 2-32% of patients (19, 20). 
 
Overall survival after mastectomy for an IBTR in a patient previously treated with breast 
conservation ranges from 52-84% at 5 years, (21, 22).  As one might expect, invasive 
recurrences have a poorer prognosis than do noninvasive (23).  Deaths after a noninvasive IBTR 
occur infrequently—deaths after an invasive recurrence occur more frequently and are often 
associated with metastatic disease.  Having an IBTR increases the rate of developing distant 
metastases, as well as increases the risk of dying, when compared to women without an IBTR 
(24). 
 
Many studies have observed that if a patient were to experience an IBTR, the majority of time it 
would be located in the vicinity of the original primary.  But, as breast cancer can be 
multicentric, by repeating breast conservation surgery, one might “miss” residual tumor left in 
other areas of the breast.  The National Surgical Adjuvant Breast and Bowel Project (NSABP) 
protocol B-06 (25), among other things, looked at 110 mastectomy specimens in women whose 
breast cancer had been treated with breast conservation.  They found that 14% of IBTR’s were 
multicentric, however the clinical significance of this multicentricity is unclear.  Since many of 
these patients did not receive adjuvant radiation initially (i.e. were randomized to lumpectomy 
alone), it is likely that this percentage overestimates the risk of multicentricity in IBTR as it is 
possible that those receiving adjuvant radiation may have a lower incidence of having a 
multicentric recurrence. 
 

CASE 11107 Version date 5.29.2009 
Page 6 of 23 
 
While the majority of IBTR’s occur near the location of the original primary, it is clear that a 
breast cancer can manifest in any location in the breast.  The addition of radiation as well as an 
increase in the amount of time from the original course of radiation in increases the likelihood 
that an in breast recurrence represents a new primary breast cancer.  Interestingly, studies have 
shown that the clinical behavior of where the breast recurrences occur differ.  Huang and 
colleagues at MD Anderson performed a retrospective chart review of patients treated with 
breast conservation, who went on to develop an IBTR as their first recurrence (19).  A true 
recurrence was defined as a cancer with identical histology to the patient’s primary, or one in 
which was located within 3 cm of the original tumor—all other IBTR were considered new 
primaries.  They found that new primaries had statistically significant increased overall survival 
(77% vs 46%, p = 0.0002), increased cause specific survival (83% vs 49%, p = 0.0001) and 
increased distant disease free survival at 10 years (77% vs 26%, p < 0.0001), when compared to 
true recurrences.  This suggests for advocates of accelerated partial breast irradiation (treating 
just the site of surgery rather than the whole breast), that if one were to have a recurrence outside 
of the radiation field, as suggested by Huang et al, their prognosis might be better. 
 
A corollary can be made to an IBTR in a patient previously treated with breast conservation, that 
it may be possible, with modern diagnostic equipment, including breast MRI, to identify patients 
with known unifocal IBTR that may be able to be treated with focal radiation, thus avoiding a 
mastectomy. There is very little data in the literature looking at re-irradiation for patients with 
ipsilateral breast cancer recurrences.  The largest of which is at report is from The University of 
Pittsburgh.  Deutsch et al, treated 39 patients with repeat radiation therapy for breast cancer—31 
invasive and 8 in situ cancers.  Patients were treated with en-face electrons to a total dose of 
5000cGy, directed only at the cavity of the IBTR excision (i.e. partial breast with linac).  At last 
follow-up (median 51.5 months, range 1-180 months), 76.9% of patients had an intact breast free 
of tumor.  At 5 years, overall survival was 78% and disease free survival was 69%.  Importantly, 
no late sequelae of repeat radiation therapy developed other than skin pigmentation changes—
cosmetic outcome was reported as good to excellent in 69% of patients (26).  There were no rib 
fractures, pulmonary problems or secondary malignances, despite areas of the breast being 
exposed to more than 10,000 cGy.  All patients except one finished the radiation treatments (RT 
was discontinued for nonmedical reasons).  Distant metastases developed in 8 women (2 with 
concerning bone scans at the time of diagnosis of IBTR), and 7 of these women died 21-71 
months after re-irradiation.  Two of the women who developed distant metastases first developed 
a contralateral breast cancer.  Eight women developed a 2nd IBTR after re-irradiation (2 of which 
had positive axillary lymph nodes), and only 3 of which were in the same quadrant as the first. 
 
A group in France utilized post-operative brachytherapy in a small series of patients who opted 
for repeat breast conservation after IBTR—some refused mastectomy, and some were not 
candidates—they were treated to a dose of 30 Gy (dose rate not mentioned) (27).  Four (26%) of 
patients developed a 2nd IBTR at a median follow-up of 4 years.  There are several criticisms of 
this study, including the lack of reporting of margin status, or brachytherapy dose rate.  Three 
patients had “major” cosmetic sequelae (one with locally treated skin necrosis), but cosmetic 
analyses/comment is only available for 8/15 patients involved in the study. 
 
A group from Austria utilized pulse-dose-rate brachytherapy to treat IBTR, obviating the need 
for mastectomy.  At first, patients were treated with whole breast radiotherapy followed by a 

CASE 11107 Version date 5.29.2009 
Page 7 of 23 
 
brachytherapy boost, but over time treatment was changed to brachytherapy alone.  
Brachytherapy dose for the group who also received EBRT ranged from 12.5 to 28.0 Gy (mean 
22.4 Gy), whereas in the group that received brachytherapy alone, it ranged from 40.2 to 50.0 Gy 
(mean 46.5) (28).  At a median follow-up of 59 months, 12 of the 17 women were alive and had 
no evidence of local tumor.  Twenty-four percent of patients (4) experienced a 2nd IBTR—all 
within the 1st year and all in the group who received both EBRT and brachytherapy.  There have 
been no 2nd IBTR’s in the group receiving brachytherapy alone, suggesting increased local 
control with increasing brachy dose.  Often dose escalation, with the hope of increasing local 
control, cannot be maximized due to toxicities of normal tissues.  In this study, no patients had 
unacceptable cosmetic results; it was good or excellent in one third of patients. 
 
Recent interest in accelerated partial breast irradiation relies on the principle that since the most 
frequent location of an ipsilateral breast cancer recurrence is in the tumor bed, by targeting this 
area one can minimize the cumulative dose to the whole breast (and therefore 
complications/toxicities that may arise from increased dose to the breast  There is also the 
possibility that if a patient were to develop an ipsilateral breast cancer recurrence following 
accelerated partial breast irradiation that it may be possible to resect this recurrence and then 
treat the whole breast with radiation.  This study attempts to clarify the feasibility and efficacy of 
using accelerated partial breast irradiation in patients who have already received whole breast 
irradiation.  It only seems natural, that one might consider utilizing partial breast to treat an in-
breast recurrence in someone who, for whatever reason, refuses mastectomy, or is not a 
candidate for one.  By utilizing various techniques of partial breast irradiation, treatment can be 
targeted to only the surgical lumpectomy cavity.  Partial breast irradiation can be accomplished 
by a multitude of techniques, including 3-D conformal external beam radiation, MammoSite 
catheter brachytherapy, multi-catheter brachytherapy and intra-operative radiation therapy.   
 
There are currently several groups studying the efficacy of lumpectomy bed irradiation alone in 
the management of early stage breast cancer patients (29-38). Both interstitial brachytherapy 
techniques as well as external beam irradiation protocols have been implemented (See Table 1). 
Preliminary results from these trials are very encouraging and the techniques have been shown to 
be safe, tolerable, and highly reproducible. In 1993, Vicini et al. initiated a pilot trial of low dose 
rate (LDR) brachytherapy as the sole radiation modality with BCT (32).  As of February 2001, 
120 patients have been treated on this protocol. With a median follow-up of 85 months, only 3 
patients have developed a local recurrence (five-year actuarial rate of 1%) and cosmetic results 
were judged as good to excellent in 98% patients (verbal communication). In addition, no 
adverse sequelae were noted on the protocol. More recently, a second protocol employing high 
dose rate (HDR) brachytherapy (in the same subset of patients) was also initiated at the same 
institution (39).  Although results were preliminary, no adverse sequelae were noted. 
 
Table 1: Breast conserving therapy with lumpectomy plus partial breast irradiation 
Institution 
# Pt 
Med 
F/U 
(mos) 
Scheme 
(cGy) 
Total Dose 
(cGy) 
% 
LR 
% Good 
/Excellent 
Cosmetic 
results 
HDR Series* 
 
 
 
 
 
 
Ochsner Clinic29 
26 
20 
400 x 8 
3200 
0 
67 

CASE 11107 Version date 5.29.2009 
Page 8 of 23 
 
Royal Devon/Exeter  45 
18 
1000 x 2 
2000 
8.8 
95 
Hospital, Exeter, 
 
 
700 x 4 
2800 
 
 
England30 
 
 
600 x 6 
3600 
 
 
Orszagos Onkologiai  41 
17 
520 x 7 
3640 
2.4 
Not stated 
Intezet, Budapest, 
Hungary37 
 
 
433 x 7 
3030 
 
 
London Regional 
Cancer Center, 
London, Ontario33,36 
39 
20 
372 x 10 
3720 
2.6a 
Not stated 
William Beaumont  
79 
48 
400 x 8 
3200 
1 
98 
Hospital39 
 
 
340 x 10 
3400 
 
 
LDR Series** 
 
 
 
 
 
 
Ochsner Clinic29 
26 
20 
 
4500 
0 
78 
Guy’s Hospital31,40 
27 
72 
40 cGy/hr 
5500 
37a 
83 
Cionini et al35 
90 
27 
 
5000-6000 
4.4a 
Not stated 
William Beaumont 
Hospital34 
120 
85 
52 cGy/hr 
4992 
1 
98 
External Beam 
Series 
 
 
 
 
 
 
Christie Hospital38,41 
353 
65 
500 
4000 
19.6a
--- 
William Beaumont 
Hospital 
31 
12 
385 x 10 
3850 
0 
100 
European Institute of 
Oncology42 
86 
8 
2100 x 1 
2100 
--- 
--- 
 
aSeven year rate    
*HDR = High dose rate brachytherapy                       
**LDR = Low dose rate brachytherapy

CASE 11107 Version date 5.29.2009 
Page 9 of 23 
 
 
 
Intra-operative Partial Breast Irradiation Experience 
 
Over the last several years, increasing interest in the use of intraoperative radiation (IORT) in the 
setting of breast conservation has developed. The rationale of IORT is relatively simple. Rather 
than using external beam radiation to treat the entire breast post-operatively, radiation is applied 
directly to the surgical tumor bed through the open surgical incision. There are several 
advantages to this approach. First, the radiation dose is applied directly to the tumor bed with 
little chance for geographical miss. There is also less irradiation of normal tissues. The radiation 
is done at the time of surgery, therefore, there is no delay between surgery and the initiation of 
radiation. This results in a shorter overall treatment course and potentially less cost involved. 
This approach has been utilized with intraoperative brachytherapy as well. An advantage of 
utilizing intraoperative electron beam therapy over brachytherapy may be increased dose 
homogeneity seen with intraoperative treatment compared to brachytherapy.  There is also 
decreased risk to hospital personnel compared to brachytherapy due to decreased radiation 
exposure and decreased requirements for shielding.   
 
The Mobetron is a lightweight, mobile, self-shielded linear accelerator. It provides electrons with 
energies of 4, 6, 9, or 12 MeV capable of penetrating to a depth of approximately 1, 2, 3, and 4 
cm to the 80% isodose line, respectively. Treatment is delivered through applicators with 
dimensions from 3-10 cm. The applicators may be either flat or beveled at 30 degrees. The unit 
weighs 1/6 of what a conventional accelerator does allowing it to be moved from room to room. 
There is minimal x-ray contamination eliminating the need for a shielded operating room and a 
beam stopper attached to the unit provides the necessary shielding from X-rays generated by the 
patient during treatment. The control panel for the Mobetron is located outside of the operating 
room during treatment and the patient may be directly observed through the windows during the 
treatment (36). The Mobetron is present at only a handful of institutions both inside and outside 
of the USA. It is currently being utilized in a variety of tumor sites to provide intraoperative 
radiation. 
 
Intra-operative external beam irradiation has also recently been explored as an additional method 
of delivering post-lumpectomy partial breast irradiation in an accelerated fashion. Veronesi et al 
from the European Institute of Oncology in Milan, Italy recently published their preliminary 
results from a phase I/II dose escalation study of single-fraction irradiation given immediately 
after quadrantectomy (42). With minimal toxicity in the first 86 patients treated with dose levels 
of 17-19-21 Gy per fraction using 3 - 9 MeV electrons, the authors have now proceeded with a 
phase III trial comparing standard whole breast irradiation (50 Gy plus a 10 Gy boost) to a 21 Gy 
intraoperative 
single fraction. As of February 2002, > 250 patients have been enrolled in this 
equivalency trial with an accrual goal of over 800 patients (verbal communication). 
Vaidya et al recently published their experience with intra-operative partial breast radiation 
therapy as boost treatment (43).  In a pilot study of 35 patients, the post-operative tumor bed 
boost was replaced with an intra-operative 5 Gy fraction of radiation therapy delivered with the 
Photon Radiosurgery System. This device emits soft X-rays from a ball-shaped applicator 

CASE 11107 Version date 5.29.2009 
Page 10 of 23 
 
applied directly against the lumpectomy cavity. With a median follow-up of 24 months, there 
have been no major complications. A phase III trial has recently been initiated. 
 
MammoSite® Brachytherapy Experience 
 
One of the primary disadvantages of conventional breast brachytherapy is the complexity and 
reproducibility of the procedure.  Breast brachytherapy is used either to deliver a localized boost 
dose of radiation to the lumpectomy cavity or to deliver the primary radiation to the lumpectomy 
cavity.  In clinical practice, a typical boost prescription is 10 – 25 Gy, a short, intense treatment 
to the tissue around the lumpectomy cavity.   The boost dose is generally followed by external 
beam radiation to the whole breast.   A typical primary breast brachytherapy treatment dose is 
between 32 and 34 Gy.  Conventional breast brachytherapy is an invasive procedure and consists 
of the placement of up to 20 needles or catheters around the site of the tumor removal.  These 
needles or catheters are loaded with a radiation source for a period of 4-5 days. After completion 
of radiation the needles or catheters are removed (43). Even using the best imaging available, the 
technique is difficult and requires a great deal of experience and skill to position the needles or 
catheters to cover the required treatment area adequately.  
 
The MammoSite® applicator was developed to address these disadvantages.  The MammoSite® 
allows an easier implant and reproducible radiation delivery to the target tissue area.  The 
MammoSite® is a nylon tube (for the radiation source to travel in) with a balloon attached at the 
end to expand and conform to the cavity.  The MammoSite® applicator is inserted into the cavity 
created by the tumor removal surgery, either at the time of lumpectomy or post lumpectomy.  
The MammoSite® applicator is then inflated and expands to fill the cavity.  The radiation can 
then be delivered using commercially available radioactive sources using the center nylon tube 
of the MammoSite® applicator.  This central source creates a symmetrical radiation delivery 
from the inside of the cavity to the adjacent tissues where residual cancer is most likely to exist 
while reducing damaging radiation delivery to the surrounding vital organ structures.   
 
In a Phase II clinical trial with the MammoSite®, 43 patients received radiation therapy as 
primary treatment. Short-term cosmesis has been good to excellent on the Harvard Scale in 88% 
of the women treated.  Patients experienced only mild to moderate side effects, including skin 
erythema (57%), dry desquamation (13%) and moist desquamation (5%) short term that were 
related to the radiation therapy dose. The study demonstrated that the device was safe and well 
tolerated which resulted in FDA clearance of the device on May 6, 2002 (44, 45). The safety and 
effectiveness of the MammoSite® Radiation Therapy System (RTS) as a replacement for whole 
breast irradiation in the treatment of breast cancer is currently being investigated.  
 
 
 
 
 
Current Trial Design 
 
Patients enrolled in this protocol will be selected to insure that their cancers have been 
adequately excised and that tumor bed irradiation alone will be feasible.  Depending on 
individual patient characteristics (for example, proximity of the tumor cavity to the skin, 

CASE 11107 Version date 5.29.2009 
Page 11 of 23 
 
patient’s ability to tolerate another surgical procedure) a decision will be made jointly by the 
breast surgeon, radiation oncologist and medical oncologist at our multi-disciplinary conference 
as to which method of partial breast irradiation is best suited for the patient.  Practical 
considerations will also be taken into account, in the decision of which type of radiation to 
offer—that said, provided a patient is medically eligible for either type of radiation, she will be 
given the opportunity to decide which treatment she would like.  Some patients may not be 
deemed medically fit to undergo another surgical procedure, and might then be offered 
MammoSite based APBI, because the catheter does not necessarily have to be placed in the 
operating room.  Another example in which one therapy might be more advisable than another, is 
woman who has a history of immune deficiency and resultant life threatening infections—rather 
than leaving a MammoSite catheter with an open wound for more than one week, one might opt 
for a single treatment in the operating room at the time of lumpectomy.  One endpoint of the 
study will be to evaluate which patients are best suited for treatment by each of the available 
partial breast irradiation options. 
 
The aim of the study will be to evaluate patient acceptance of the concept of partial breast re-
irradiation for an IBTR, in the hope that there will be an alternative treatment to the recognized 
standard of care (mastectomy).  We will also evaluate cosmetic outcome following the 
procedure.  Long term outcome data regarding further in-breast recurrences as well as tumor bed 
recurrence will also be recorded and analyzed. 
 
 

CASE 11107 Version date 5.29.2009 
Page 12 of 23 
 
 
 
 
 
 
 
2.0 OBJECTIVES 
2.1 To determine the in breast recurrence rate following repeat radiation to the breast.  These 
patients will be followed for a period of five years following completion of radiation to 
determine these rates. 
2.2 To determine the cosmetic outcome resulting from partial breast re-irradiation using 
different techniques, including both physician and patient rated scales. 
2.3 To determine patient satisfaction of partial breast re-irradiation as it pertains to their overall 
treatment experience as measured by a questionnaire. 
2.4 To determine if there are patient factors illuminated during a discussion of informed 
consent, which limit a patient’s suitability to receive partial breast re-irradiation delivered 
by a particular technique. 
2.5 To evaluate tylectomy wound healing and overall complication rate after partial breast re-
irradiation. 
2.6 To determine ipsilateral breast tumor recurrence rates as well as tumor bed recurrence rates.  
These patients will be followed for a period of five years following completion of the 
second course of radiation to determine these rates. 
 
3.0 PATIENT SELECTION 
3.1  
Eligibility Criteria 
3.1.1  Patients’ recurrences must have histologically confirmed ductal carcinoma in-situ, 
invasive ductal, medullary, papillary, colloid (mucinous), or tubular histologies. 
3.1.2 Lesion size < 3 cm treated with a tylectomy.  Patients with clinically and radiographically 
negative axillas should not undergo an axillary lymph node dissection unless they did not 
have prior axillary lymph node sampling (i.e. previous cancer was DCIS).  
3.1.3 Unifocal breast cancer recurrence. 
3.1.4 Negative resection margins with at least a 2 mm margin from invasive and in-situ cancer 
or a negative re-excision. 
3.1.5 Hormonal therapy is allowed.  If chemotherapy is planned, the radiation is delivered first 
and chemotherapy must begin no earlier than two weeks following completion of 
radiation.   
3.1.6 Patients must be > 18 years of age.  
3.1.7 Signed study-specific informed consent prior to study entry. 
 
3.2 
Ineligibility Criteria 
3.2.1 Patients with distant metastatic disease 
3.2.2 Patients with invasive lobular carcinoma, extensive lobular carcinoma in-situ, extensive 
ductal carcinoma in-situ (spanning more than 3 cm), or nonepithelial breast malignancies 
such as lymphoma or sarcoma. 
3.2.3 Patients with multicentric carcinoma (tumors in different quadrants of the breast or 
tumors separated by at least 4 cm). Palpable or radiographically suspicious contralateral 

CASE 11107 Version date 5.29.2009 
Page 13 of 23 
 
axillary, ipsilateral or contralateral supraclavicular, infraclavicular, or internal mammary 
lymph nodes unless these are histologically or cytologically confirmed negative. 
3.2.4 Extensive intraductal component (EIC) by the Harvard definition, i.e. 1) more than 25% 
of the invasive tumor is DCIS and DCIS present in adjacent breast tissue.  Presence of an 
EIC increases the chance of local recurrence, and as such, one might not be a candidate 
for repeat breast conservation. 
3.2.5 Patients with Paget’s disease of the nipple. 
3.2.6 Patients with skin involvement. 
3.2.7 Patients with collagen vascular disorders, specifically systemic lupus erythematosis, 
scleroderma, or dermatomyositis. 
3.2.8 Patients with psychiatric, neurologic, or addictive disorders that would preclude obtaining 
informed consent. 
3.2.9 Other malignancy, except non-melanomatous skin cancer, < 5 years prior to participation 
in this study. 
3.2.10 Patients who are pregnant or lactating due to potential fetal exposure to radiation and 
unknown effects of radiation on lactating females. 
3.2.11 Patients with known BRCA 1/BRCA 2 mutations. 
 
 
4.0 REGISTRATION PROCEDURES 
Investigators will register patients by contacting the Cancer Center Clinical Trials Unit study 
coordinator. Patients will be registered by the study coordinator online via the Clinical Trials 
Unit Oncore database. A registration card, copy of the informed consent, and copy of the signed 
eligibility checklist must be completed prior to a patient starting 
treatment. 
 
5.0 TREATMENT PLAN 
Patients enrolled on the study will receive partial breast irradiation delivered as 1) a single intra-
operative dose of 21 Gy or 2) MammoSite® brachytherapy consisting of a dose of 34 Gy in 10 
fractions delivered over 5 days.  Patients will be followed for a period of five years following 
completion of radiation. 
 
5.1 
Surgery 
5.1.1 Patients will undergo excisional biopsy or needle localization removal of the tumor. 
5.1.2 Patients with margins < 2 mm undergo re-excision of the biopsy 
cavity. 
5.1.3 For patients undergoing IORT, the skin around the excision site will be dissected and 
small skin flaps will be raised. The breast tissue is then loosely sutured so that the lateral 
margins are brought into apposition. The applicator will then be positioned to encompass 
the entire tumor bed with a 1 cm margin. After radiation has been delivered, sutures will 
be removed and the tumor bed will bed closed in the typical fashion. 
 
5.2 
Radiation Therapy – Consultation via presentation at our multi-disciplinary breast 
conference between the surgeon, radiation oncologist and medical oncologist will take place to 
determine suitability for undergoing partial breast radiation and a recommendation will be made 
as to which modality is best suited for the patient.  Clinical characteristics, including but not 

CASE 11107 Version date 5.29.2009 
Page 14 of 23 
 
limited to, distance of tumor from skin, patient’s ability to tolerate another surgical procedure, 
patient’s ability to come into the radiation department twice daily for treatment, will be 
considered in making this decision.  All patients will be seen in consultation by the radiation 
oncologist prior to enrollment. 
5.2.1  Intraoperative Radiation: 
5.2.1a  Applicator selection should allow for treatment of the tumor bed with a 1 cm radial 
margin. 
5.2.1b Dosimetry on all applicators should be available to the radiation oncologist upon 
request in the operating room. 
5.2.1c Energy of electrons should be such that the tumor cavity with a 1 cm margin will be 
covered by the 90% line. The energy of the electrons will be at the discretion of the 
radiation oncologist and determined at the time of treatment to ensure proper coverage 
of the tumor cavity. 
5.2.1d A dose of 21 Gy will be prescribed to the 90% isodose line. 
 
5.3.1  MammoSite® Brachytherapy: 
5.3.1a  Applicator Placement:  
5.3.1a1 The MammoSite® applicator may be placed either at the time of surgery or in a separate 
procedure using ultrasound guidance after surgery.   The MammoSite® applicator should 
be selected to best fit the cavity created by the surgical removal of the tumor.   
5.3.1a2 The balloon of the MammoSite® applicator should be inflated with a saline/contrast 
mixture (maximum of 25% contrast) to fill the cavity at the time of placement.  The 
balloon will remain inflated throughout the duration of the radiation and will be removed 
after the last fraction.   
5.3.1a3 Post implant imaging should be performed after insertion of the MammoSite® to 
evaluate the patient for skin spacing, symmetry and conformance of the applicator. 
5.3.1b Treatment Planning 
5.3.1b1 CT image is recommended for treatment planning.  Standard brachytherapy treatment 
planning will be conducted using commercially available software and equipment.  The 
treatment should be performed using available high dose rate (HDR) brachytherapy.  
5.3.1b2 CT imaging or plain orthogonal x-rays will be performed prior to treatment to ensure 
adequacy of implant. 
5.3.1c Brachytherapy Treatment: 
5.3.1c1 Brachytherapy should start between 3 - 7 days after implant.   
5.3.1c2 The dose is 34 Gy prescribed to a depth of 1 cm from the balloon surface delivered over 
10 fractions of 3.4 Gy over 5-10 days.  The fractions are delivered twice a day with at 
least six hours separating each fraction.   
5.3.1c3 All treatments should be done using a commercially available HDR and 192 Ir  radioactive 
sources. 
5.3.1d Applicator Removal: 
5.3.1d1 The removal of the applicator should be scheduled after the completion of 
brachytherapy.   
5.3.1d2 The applicator should be removed using standard sterile technique.   
5.3.1d3 The applicator exit/entrance site should be dressed according to standard medical 
practice.   
 

CASE 11107 Version date 5.29.2009 
Page 15 of 23 
 
5.4 
Data Safety and Monitoring Plan 
This protocol will adhere to the policies of the Case Comprehensive Cancer Center Data 
and Safety Monitoring Plan, version 2 guidelines in accordance 
with NCI regulations. The Data and Safety Toxicity Committee will review all 
serious adverse events and toxicity reports as well as annual reviews. 
 
 
  
6.0 MEASUREMENT OF EFFECT 
The endpoints of this study are as follows: 
6.1  Determination ipsilateral breast tumor recurrence rates as well as tumor bed recurrence 
rates.  The breast quadrant of recurrence will be recorded.  Patients will be followed for a 
period of five years following completion of radiation. 
6.2  Cosmetic outcome as determined by an established scale employed by the radiation 
oncologist and the surgeon. 
6.3 
Patient satisfaction with the procedure as determined by a questionnaire to be completed 
by the patients. 
6.4  Wound healing and overall complication rate after partial breast re-irradiation. 
6.5  Determination of which patients are best suited for each individual technique of 
performing partial breast irradiation.  Measurement of this will be observational. 
 
  

CASE 11107 Version date 5.29.2009 
Page 16 of 23 
 
 
7.0 STUDY PARAMETERS 
 
Study Parameters 
Pre-Treatment 
Follow-up 
H&P/clinical evaluation 
X 
1 month after RT & Q3mos for one 
year, then annually for 5 years. 
Mammogram 
X 
Ipsilateral breast 6 mos after dx, 
bilateral annually 
CXR 
X 
Annually x 5 years 
CT chest/abdomen/pelvis 
X 
If clinically indicated 
Bone Scan 
X 
If clinically indicated 
Cosmetic Evaluation/QOL 
assessment 
X 
1 month after RT & Q3mos for one 
year, and at 5 years. 
Skin Assessment 
 
Last day of RT 
Breast MRI 
 
If clinically indicated 
 
8.0 STATISTICAL CONSIDERATIONS 
The primary objective is to determine the feasibility of partial breast irradiation after repeat 
breast-conserving surgery for an IBTR. Thirty patients will be enrolled for this study and we 
expect to finish the enrollment within 5 years. For the safety of patients, interim analyses will be 
performed after 6, 12, 18 and 24 patients have reached 3 months and 1 year post treatment 
period. The protocol will remain open to enrollment during the interim analyses. The trial will be 
stopped if: 
a) The 3 month adverse event rate is determined to be in excess of 10%. 
b) A one-year local recurrence rate is more than 5%. 
Assume the probability of 3 month adverse event (or 1 year local recurrence) is p, allowable 
maximum adverse event rate (or 1 year local recurrence rate) is p0and the type I error is α.. The 
early stopping rules are based on the following statistical hypothesis test: 
 
 
H0: p < p0 
vs 
HA: p > p0 
 
Based on the exact probability of Binomial distribution, we will reject the null hypothesis (i.e. 
stop the trial) if we observe k or more adverse events (local recurrences), where 
   
:
min{l
k 
i
n
i
l
i
p
p
i
n










)
1(
0
0
2
/


}, 
 
 
and n is the number of patients at the time of the interim analysis. 
 
The trial will be stopped if the 3 month adverse event rate is in excess of 10%. The trial will also 
be stopped if the 1-year local recurrence rate is more than 5%. The following table is based on α 
= 0.05. 

CASE 11107 Version date 5.29.2009 
Page 17 of 23 
 
 
 
 
Minimum number of 
adverse events during first 3 
months to stop the trial 
Minimum number of local 
recurrences during the first 
1 year to stop the trial 
Number of patients treated 
3 
2 
6 
4 
3 
12 
5 
4 
18 
6 
5 
24 
 
Safety analysis will be performed on all patients enrolled in the study. The incidence and its 
confidence interval of 3 month adverse events and 1year local recurrences will be estimated. The 
time to local recurrence is calculated from the date of completion of radiation. Data for patients 
who remain free of local disease are censored as of date when the last follow-up information is 
obtained. At the end of the study, the cumulative local recurrence rate will be estimated by 
Kaplan-Meier method (46) for all patients (intend-to-treat) and 5-year recurrence rate will be 
then obtained and compared with those in the literature. The overall incidence and its confidence 
interval of acute complications following lumpectomy will be estimated. Also, we will estimate 
the overall incidence and the degree of fibrosis as defined on four-level scale of cosmetic 
outcome in appendix I. 
 
9.0 RECORDS TO BE KEPT 
 
At time of registration – Patient consent form, signed eligibility checklist and registration card. 
 
Following breast conservation surgery for the second time, prior to beginning breast re-radiation, 
the cosmetic results of breast conservation will be assessed. Appendix I should be used. The 
same will be used to reassess the patient during radiation therapy, at one month post-radiation 
therapy, and every three months thereafter for one year, followed bi-annually for the remainder 
of the 5 year follow-up. 
 
Follow-up Form - at time of disease response assessment, every three months during the first 
year and every 6 months thereafter for 5 years. 
 
10.0 PATIENT CONSENT AND PEER JUDGEMENT 
All institutional, NCI, FDA, State and Federal regulations concerning informed consent and peer 
judgement will be fulfilled.  Typically, patients choosing to participate in this trial will be 
consented either at the time of consultation with, or shortly after their meeting with the radiation 
oncologist.  As the referral to the radiation oncologist can come at varying stages in the 
diagnostic/treatment process (i.e. right after biopsy, but before lumpectomy, or after lumpectomy 
and before chemotherapy etc…), his/her participation in out Multidisciplinary Tumor Board is 
paramount.  It is at these weekly meetings that treatment recommendations are formulated—if a 
patient is scheduled to have a lumpectomy and her case is presented at tumor board, then the 
radiation oncologist may then see the patient right before surgery and assess interest in the study 
prior to surgery.  That said, even if a patient has already had a lumpectomy with negative 

CASE 11107 Version date 5.29.2009 
Page 18 of 23 
 
margins, she may always be taken back to the operating room if she decides to be in this trial and 
if it is deemed that to perform the radiation, she needs to be taken to the OR (i.e. for IORT, or for 
MammoSite placement). 
 
11.0 REFERENCES 
1. 
CA CancerJ Clin 2001; 51:14-24. 
2.  
Foster S, Farwell M, Costanza M. Breast-Conserving Surgery for Breast Cancer: Patterns 
of Care in a Geographical Region and Estimation of Potential Applicability. Ann Surg 
Onc 1995; 2 (3):275-280. 
3.  
Veronesi U, Banfi A, DelVecchio M, et al. Comparison of Halsted Mastectomy with 
Quadrantectomy, Axillary Lymph Node Dissection and Radiotherapy in Early Breast 
Cancer: Long Term Results. Eur J Cancer Clin Oncol, 1986; 22:1085. 
4.  
Sarrazin D, Le MG, Arriagada R, et al. Ten-year Results of a Randomized Trial 
Comparing a Conservative Treatment to Mastectomy in Early Breast Cancer. Radiother 
Oncol, 1989; 14:177. 
5.  
Fisher B, Anderdon S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. 
Reanalysis and Results after 12 Years of Follow-up in a Randomized Clinical Trial 
Comparing Total Mastectomy with Lumpectomy with or without irradiation in the 
Treatment of Breast Cancer. N Engl J Med, 1995; 333:1456. 
6.  
Bader J, Lippman M, Swain S, et al. Preliminary Report of the NCI Early Breast Cancer 
Study: A Prospective Randomized Comparison of Lumpectomy and Radiation to 
Mastectomy for Stage I and II Breast Cancer. In J Radiat Oncol Biol Phy, 1987; 
13:160(abstract). 
7.  
Glatstein E, Straus K, Lichter A, et al. Results of the NCI Early Breast Cancer Trial. 
Proceedings of the NIH Consensus Development Conference-Early Stage Breast Cancer, 
June 1990, pp 32-33. 
8.  
Van Dongen JA. Randomized Clinical Trial to Assess the Value of Breast Conserving 
Therapy in Stage I and II Breast Cancer; EORTC Trial 10801. Proceedings of the NIH 
Consensus Development Conference-Early Stage Breast Cancer, June 1990, pp 25-27. 
9.  
Blichert-Toft M, Brickner H, Andersen JA, et al. A Danish Randomized Trial Comparing 
Breast-preserving Therapy with Mastectomy in Mammary Carcinoma. Acta Oncol, 1988; 
27:671. 
10.  
Blichert-Toft M. A Danish Randomized Trial Comparing Breast-preserving Therapy with 
Mastectomy in Mammary Carcinoma. Proceeding of the NIH Consensus Development 
Conference-Early Stage Breast Cancer, June 1990, pp 28-31. 
11.  
NIH Concensus Development Panel. Treatment of Early Stage Breast Cancer. J Natl 
Cancer Inst Monogr 1992; 11: 137-42. 
12.  
Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial 
comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the 
treatment of invasive breast cancer. N Engl J Med. 347: 1233-1241, 2002. 
13.  
Lilijegren G, Holmberg L, Adami H0, et al. Sector resection with or without 
postoperative radiotherapy for Stage I breast cancer. Five year results. J Natl Cancer Inst. 
86:717-722, 1994. 
14.  
Clark RM, McCulloch PB, Levine MN, et al. A randomized clinical trial to assess the 
effectiveness of breast irradiation following lumpectomy and axillary dissection for node 
negative breast cancer. J Natl Cancer Inst. 84:683-689, 1992. 

CASE 11107 Version date 5.29.2009 
Page 19 of 23 
 
15.  
Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast preserving surgery 
in women with localized cancer of the breast. N Engl J Med. 328:1557-1591, 1993. 
16.  
Forrest AP, Stewart HJ, Everington D, et al. Randomized controlled trial of conservation 
therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet. 348:708-713, 1996. 
17.  
Schnitt S, Hayman J, Gelman R, et al. A prospective study of conservative surgery alone 
in the treatment of selected patients with stage I breast cancer. Cancer. 77:1094-1100, 
1996. 
18. 
Keurer H, Arthur D, Haffty B. Repeat breast-conserving surgery for in-breast local breast 
carcinoma recurrence: the potential role of partial breast irradiation.  Cancer. 100: 2269-
2280, 2004. 
19. 
Huang E, Buchholz T, Meric F, et al. Classifying local disease recurrences after breast 
conservation therapy based on location and histology: new primary tumors have more 
favorable outcomes than true local disease recurrences. Cancer. 95: 2059-2067, 2002. 
20. 
Cajucom C, Tsangaris T, Nemoto T, et al. Results of salvage mastectomy for local 
recurrence after breast-conserving surgery without radiation therapy. Cancer.71: 1774-
1779, 1993. 
21. 
Kurtz J, Almaric R, Brandone H, et al. Local recurrence after breast-conserving surgery 
and radiotherapy. Frequency, time course, and prognosis. Cancer. 63: 2217-2225, 1989. 
22. 
Fowble B, Solin L, Schultz D, et al. Breast recurrence following conservative surgery and 
radiation: patterns of failure, prognosis, and pathologic findings from mastectomy 
specimens with implications for treatment. Int J Radiat Oncol Biol Phys. 19: 833-842, 
1990. 
23. 
Abner A, Recht A, Eberlin T, et al. Prognosis following salvage mastectomy for 
recurrence in the breast after conservative surgery and radiation therapy for early-stage 
breast cancer. J Clin Onc. 11: 44-48, 1993. 
24. 
Fisher B, Anderson S, Fisher E, et al. Significance of ipsilateral breast tumour recurrence 
after lumpectomy. Lancet. 338: 327-331, 1991. 
25. 
Fisher E, Sass R, Fisher B, et al. Pathologic findings from the National Surgical Adjuvant 
Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity. 
Cancer. 57: 1717-1724, 1986. 
26. 
Deutsch M. Repeat high-dose external beam irradiation for in-breast tumor recurrence 
after previous lumpectomy and whole breast irradiation. Int J Radiat Oncol Biol Phys. 53: 
687-691, 2002. 
27. 
Maulard C, Housset M, Brunel P,  et al. Use or perioperative or split-course interstitial 
brachytherapy techniques for salvage irradiation of isolated local recurrences after 
conservative management of breast cancer. Am J Clin Oncol. 18: 348-352, 1995. 
28. 
Resch A, Fellner C, Mock U, et al. Locally recurrent breast cancer: pulse dose rate 
brachytherapy for repeat irradiation following lumpectomy—a second chance to preserve 
the breast. Radiology. 225: 713-718, 2002. 
29.  
Kuske R, Bolton J, Wilenzick R, et al: Brachytherapy as the sole method of breast 
irradiation in Tis, T1, T2, N0,1 breast cancer (Abstract). Int J Radiat Oncol Biol Phys. 30 
(Suppl 1):245, 1994. 
30.  
Clarke DH, Vicini FA, Jacobs H, et al: High dose rate brachytherapy for breast cancer. 
In: Naq S, ed. High Dose Rate Brachytherapy: Armonk, NY: Futura Publishing Co, Inc; 
1994:321-329. 

CASE 11107 Version date 5.29.2009 
Page 20 of 23 
 
31.  
Fentiman IS, Poole C, Tong PJ, et al. Inadequacy of iridium implant as sole radiation 
treatment for operable cancer. Eur J Cancer. 32A(4):608-611, 1996. 
32.  
Vicini FA, Chen PY, Gustafson G, et al. Low dose rate brachytherapy as the sole 
radiation modality in the management of patients with early stage breast cancer treated 
with breast-conserving therapy: Preliminary results of a pilot trial. Int J Radiat Oncol Biol 
Phys. 38 (2):301-310, 1997. 
33.  
Perera F, Chisela F, Engel J, et al. Method of localization and implantation of the 
lumpectomy site for high dose rate brachytherapy after conservative surgery for T1 and 
T2 breast cancer. Int J Radiat Oncol Biol Phys. 31:959-965, 1995. 
34.  
Vicini FA, Kini VJ, Chen P, et al. Irradiation of the tumor bed alone after lumpectomy in 
selected patients with early-stage breast cancer treated with breast conserving therapy. J 
Surg Oncol. 70:33-40, 1999. 
35.   
Cionini L, Pacini P, Marzano S, et al. Exclusive brachytherapy after conservative surgery 
in cancer of the breast. Lyon Chir. 89-128, 1993. 
36.  
Perera F, Engel J, Holliday R, et al. Local resection and brachytherapy confined to the 
lumpectomy site for early breast cancer: a pilot study. J Surg Oncol. 65:263-267, 1997. 
37.  
Polgar C, Major T, Somogyi A, et al. Brachytherapy of the tumor bed after breast 
conserving therapy: new radiotherapeutic option in the management of early breast 
cancer. Orv Hetil. 140:1461-1466, 1999. 
38.  
Ribeiro GG, Magee B, Swindell R, Harris M, Banerjee SS. The Christie Hospital Breast 
Conservation Trial: An update at eight years from inception. Clin Oncol. 5:278-283, 
1993. 
39.  
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 50(4):1003-1011, 2001.  
40.  
Fentiman IS, Poole C, Tong D, et al: Iridium implant treatment without external 
radiotherapy for operable breast cancer. A pilot study. Eur J Cancer. 27:497-450, 1991. 
41.  
Ribiero GG, Dunn G, Swindell R, et al: Conservation of the breast using two different 
techniques: Interim report of a clinical trial. Clin Oncol (R Coll Radiol). 2:27-34, 1990. 
42.  
Veronesi U, Orechhia R, Luini A, et al. A preliminary report of intraoperative 
radiotherapy (IORT) in limitedstage breast cancers that are conservatively treated. Eur J 
Cancer 37:2178-2183, 2001. 
43.  
Vaidya JS, Baum M, Tobias JS, et al. Targeted intra-operative radiotherapy (Targit): An 
innovative method of treatment for early breast cancer. Ann Oncol 12:1075-1080, 2001. 
44.  
Formenti SC, Rosenstein B, Skinner KA, et al. T1 stage breast cancer: Adjuvant 
hypofractionated conformal radiation therapy to tumor bed in selected postmenopausal 
breast cancer patients-pilot feasibility study Radiology 222:171-178, 2002. 
45.  
Baglan K, Sharpe M, Jaffray D, et al Accelerated partial breast irradiation using three-
dimensional conformalradiation therapy (3D-CRT). (Submitted for publication). 
46. 
Kaplan EL and Meier P. Nonparametric estimation from incomplete observations.  
Journal of the American Statistical Association, 1958; 53: 457-481. 
 

CASE 11107 Version date 5.29.2009 
Page 21 of 23 
 
APPENDIX I 
 
COSMETIC GUIDELINES 
 
Patient #:  _____________________ 
 
 
Following breast conservation surgery, prior to beginning breast re-radiation, the cosmetic results of 
breast conservation will be assessed using these guidelines. The same guidelines will be used to reassess 
the patient during radiation therapy, at one month post-radiation therapy, and every three months 
thereafter for one year, then biannually for a total of 5 years. 
 
Circle the number next to the word that best describes the cosmetic result. 
 
1. EXCELLENT: When compared to the untreated breast or the original appearance of the treated 
breast, there is minimal or no difference in the size or shape of the treated breast. The way the breast 
fells (its texture) is the same or slightly different. There may be thickening, scar tissue, or fluid 
accumulation within the breast but not enough to change the appearance. 
 
2. GOOD: There is mild asymmetry between the breasts, which means that there is some acceptable 
difference in the size or shape of the treated breast as compared to the opposite breast or the appearance 
of the breast before treatment. There may be some mild reddening or darkening of the breast. The 
thickening or scar tissue within the breast causes a mild change in its shape or size. 
 
3. FAIR: Moderate deformity of the breast, with an obvious difference in the shape and size of the 
treated breast. This change involves ¼ or less of the breast. There can be moderate thickening or scar 
tissue of the skin and the breast, and there may be obvious color changes. 
 
4. POOR: Marked change in the appearance of the treated breast involving more than ¼ of the breast 
tissue. The skin change may be obvious and detract from the appearance. Severe scarring and thickening 
of the breast, which clearly alters its appearance may be present. In retrospect, the breast may have been 
better treated by a mastectomy. 
 
Code a response for each of the following items: 
1. None 
2. Yes, seen on close observation 
3. Yes, seen on casual observation 
_____ skin telangectasia 
_____ skin atrophy 
_____ hyperpigmentation 
_____ erythema 
_____ fibrosis 
_____ skin dimpling or indentation 
_____ other significant treatment effects 
specify:_______________________________________________________________ 
 
 
 
 
 

CASE 11107 Version date 5.29.2009 
Page 22 of 23 
 
During radiation therapy the patient will be evaluated weekly by the radiation oncologist. The following 
scale will be used to classify the acute skin reactions during treatment: 
1. no change noted 
2. faint erythema 
3. bright erythema 
4. dry desquamation with or without erythema 
5. small to moderate area of moist desquamation 
6. large area of moist desquamation 
7. ulceration, hemorrhage, or necrosis 
 
 
Signature of person completing the form:  _____________________________________   
 
 
Date:  _________________ 
 

CASE 11107 Version date 5.29.2009 
Page 23 of 23 
 
APPENDIX II 
 
Patient Cosmesis/QOL form 
 
Date Questionnaire Completed:  ________________   Patient #:  __________________________ 
 
My treatment was: (check one)  
○ One time radiation treatment during surgery 
○ MammoSite radiation after surgery 
 
Circle the number next to the word that best describes the cosmetic result. 
 
1. EXCELLENT: When compared to the untreated breast or the original appearance of the treated 
breast, there is minimal or no difference in the size or shape of the treated breast. The way the breast 
feels (its texture) is the same or slightly different. There may be thickening, scar tissue, or fluid 
accumulation within the breast but not enough to change the appearance. 
 
2. GOOD: There is slight difference in the size or shape of the treated breast as compared to the 
opposite breast or the appearance of the breast before treatment. There may be some mild reddening 
or darkening of the breast. The thickening or scar tissue within the breast causes a mild change in its 
shape or size. 
 
3. FAIR: There is an obvious difference in the shape and size of the treated breast. This change 
involves ¼ or less of the breast. There can be moderate thickening or scar tissue of the skin and the 
breast, and there may be obvious color changes. 
 
4. POOR: There is marked change in the appearance of the treated breast involving more than ¼ of the 
breast tissue. The skin change may be obvious and detract from the appearance. Severe scarring and 
thickening of the breast, which clearly alters its appearance, may be present. In retrospect, the breast 
may have been better treated by a mastectomy. 
 
My satisfaction about the treatment and results is: 
1. I am totally satisfied with the treatment and results. 
2. I am not totally satisfied but would choose the same treatment again. 
3. I am not totally satisfied and would choose the standard 5-6 week course of radiation if I had it to 
do all over again. 
4. I am dissatisfied with my treatment. 
 
Before any treatment to your breast, the size and shape of my breasts was: 
1. The same on both sides. 
2. Larger on the right side. 
3. Larger on the left side. 
 
The size of my breasts now is: 
1. The same on both sides. 
2. Larger on the right side. 
3. Larger on the left side.  
 
Signature of person completing the form:  _______________________________________________