The goal in APBI is to deliver a homogeneous dose of radiation in a short period of time to the tumor bed with additional margin. This may be achieved using several distinct radiotherapy techniques and include multicatheter interstitial brachytherapy, single lumen balloon catheter brachytherapy, intracavitary multiple lumen catheter brachytherapy, 3D-CRT, and IORT. Each technique is vastly different from the others in terms of degree of invasiveness, radiation delivery, operator proficiency, acceptance among radiation oncologists, and length of treatment. However, each technique is able to deliver a homogeneous dose of radiation to the target area, which in theory is radiobiologically equivalent to conventional protracted WBI with respect to local tumor control, as well as acute and long-term toxicity.
There is a considerable amount of phase I and II data available investigating APBI with similar local control rates as compared to WBI at 5 years. However, most of these data evolved from patients who received multicatheter interstitial breast brachytherapy, which is an intricate, labor-intensive procedure that requires skill on the part of the radiation oncologist. More recently, the intracavitary catheters, such as the MammoSite balloon catheter, external beam radiotherapy, and IORT, have been investigated as alternative methods of APBI.
Multicatheter Interstitial Brachytherapy
Multicatheter interstitial brachytherapy has been the longest-used APBI technique that originated as a technique for delivering a tumor bed boost following WBI (Table 95-2). Through this approach, flexible afterloading catheters are placed through the breast tissue in several planes, to ensure adequate coverage of the lumpectomy cavity with margin (Fig. 95-1). Generally, these catheters are placed at 1 to 1.5 cm intervals, in several planes, for a total of 10 to 20 catheters to ensure a homogeneous dose covering the target area. Low-activity sources with dose rates in the range of 0.4 to 2 Gy/h are used in low dose rate (LDR) brachytherapy, while high-activity sources with dose rates greater than 12 Gy/h are used in high dose rate (HDR) brachytherapy. Medium dose rate (MDR) and pulsed dose rate (PDR) brachytherapy have also been investigated as alternative methods. With respect to APBI, LDR sources are implanted for approximately 2 to 5 days while the patient is admitted as an inpatient, while HDR brachytherapy allows for an outpatient treatment, fractionated over the course of a week, with a treatment time on the order of seconds to minutes. Implants are carried out using iridium 192 (192Ir) sources of uniform or varying source activities. Remote afterloading with HDR brachytherapy allows for flexibility in treatment planning, given programmable dwell times for each catheter.
Table 95-2 Multicatheter Interstitial Brachytherapy Accelerated Partial Breast Irradiation Studies |Favorite Table|Download (.pdf)
Table 95-2 Multicatheter Interstitial Brachytherapy Accelerated Partial Breast Irradiation Studies
|Series||No. of Patients||Dose Rate||APBI Scheme (Dose [Gy] × Fraction No.)||Median FU (mo)||TR/MM (%)||Regional Nodal Failure (%)||Good/Excellent Cosmesis (%)|
|Oschner Clinic 37,38||84|
4.0 × 8
45 × 1
|New Orleans, LA|
|William Beaumont Hospital39||199|
4.0 × 8 or
3.4 × 10
|Royal Oaks, MI||50 × 1|
3.4 × 10
45 × 1
|NIO I45,46||45||HDR||4.33 × 7 or||84||0||NR||84|
|Budapest, Hungary||5.2 × 7|
|NIO II47||126||HDR||5.2 × 7||36||1.2||NR||86|
Multicatheter interstitial implant. (Courtesy of Douglas Arthur. Reprinted with permission. ©2008 American Society of Clinical Oncology. All rights reserved.)
The Oschner Clinic in New Orleans, Louisiana, first investigated the use of LDR and HDR interstitial implants following lumpectomy in patients with DCIS or invasive ductal histology, with a tumor size less than 4 cm, negative margins, and 0 to 3 positive axillary nodes.37 They randomized 50 patients in block fashion to either LDR (45 Gy over 3.5-6 days) or HDR (32 Gy over 4 days in 8 fractions). The target volume included the lumpectomy cavity with 2 cm of circumferential breast tissue. In their original report with a median follow-up of 75 months, there was only 1 breast recurrence (2%) and 3 regional nodal failures (6%), with only 1 nodal failure among the 9 patients with positive nodes upon study entry.
In a retrospective, case-control study, King et al identified patients who met the eligibility criteria for the brachytherapy trial but who received WBI.38 They matched these patients to brachytherapy-treated patients according to characteristics based on tumor size, breast size, and pathologic stage. Using this case-control cohort, they found no difference in breast recurrences (2% vs 5%) and locoregional recurrences (8% vs 5%) in patients treated with APBI and WBI, respectively. There was also a nonsignificant difference in cosmesis rated as good or excellent at 20 months between the APBI and WBI groups (75% and 85%, respectively).
The William Beaumont Hospital group has the largest experience using interstitial brachytherapy with the longest reported follow-up of 199 patients with early-stage breast cancer (JNCI).39 Eighty percent of these patients were treated on institutional protocols with the following criteria: invasive ductal histology, tumor size less than 3.0 cm, negative margins (2 mm or more), age more than 40 years, and negative lymph nodes. The other 20% were treated with APBI for "compassionate" reasons and included patients with close margins, DCIS, participation in other studies, and timing of radiotherapy after lumpectomy. The median age was 65 years and 12% of patients had 1 to 3 positive lymph nodes. One hundred twenty patients were treated with LDR brachytherapy, receiving 50 Gy over 96 hours, while the rest of the cohort underwent HDR brachytherapy, receiving either 32 Gy in 8 fractions or 34 Gy over 10 fractions. The target volume included the lumpectomy cavity with a 1 to 2 cm margin for all patients. The group also included a matched pair analysis to compare the rate of local recurrence between APBI and WBI. At 60 months, they reported a 1% local recurrence rate in both the APBI and WBI groups. There was also no difference in distant metastases, disease-free survival, cause-specific survival, or overall survival between the 2 groups. Furthermore, in patients with 60-month follow-up, 99% of patients reported their cosmesis to be good or excellent.
The RTOG conducted the first multi-institutional trial (RTOG 95-17) consisting of interstitial brachytherapy to treat early-stage breast cancer patients.40 This was a phase I/II trial to determine the feasibility, reproducibility, toxicity, cosmesis, local control, and survival of patients treated with lumpectomy and axillary lymph node evaluation followed by APBI using interstitial brachytherapy. One hundred women were enrolled and 99 were found to be eligible. Eighty-seven patients were T1 and 20 patients had 1 to 3 positive lymph nodes. Thirty-three patients were treated using LDR (45 Gy over 4.5 days) and 66 using HDR (34 Gy over 10 fractions in 5 days). With a median follow-up of 3.7 years, 3 patients developed an in-breast recurrence and 3 patients experienced a nodal failure. In a recent update presented at the American Society of Therapeutic Radiation Oncology in November 2006 with a median follow-up of 6 years, 3% and 6% of patients treated with HDR and LDR experienced an in-breast failure, with the majority of failures being classified as a true recurrence/marginal miss.41 The authors concluded that "multicathether partial breast brachytherapy on this trial experienced excellent in-breast control rates."
There have been several European groups that have investigated the efficacy of multicatheter interstitial brachytherapy to deliver APBI. Many of the early studies were fraught with poor patient selection and outdated treatment planning modalities.42-44 For the purpose of this discussion, we will focus on the more recent European studies, including 1 prospective, randomized controlled study comparing WBI to APBI using interstitial brachytherapy. The National Institute of Oncology (NIO) in Budapest, Hungary, has much experience in the use of HDR interstitial implants to provide APBI.45,46 They treated women of any age with pathologic T1 tumors (in situ carcinoma and invasive lobular carcinoma were excluded) with negative margins and lymph nodes that were pathologically negative (or <2 mm micrometastases). Forty-five patients were treated to a total of 30.3 Gy (n = 8) or 36.4 Gy (n = 37) in 7 fractions over 4 days. The authors included a control group of patients who met the eligibility criteria during the same time period and were treated with WBI. With a median follow-up of 7 years, the actuarial ipsilateral failure rate was reported as 9% (n = 3) in the APBI group and 12% in the WBI group. All patients treated with APBI who experienced a recurrence were subsequently treated with lumpectomy followed by 46 to 50 Gy WBI, providing a 100% mastectomy-free recurrence rate. The NIO then conducted a single institution randomized study between 1998 and 2004 of patients more than 40 years with the same eligibility criteria as described above.47 Two hundred fifty-five patients were randomized to 50 Gy WBI (n = 129) or APBI (n = 126) using HDR multicatheter interstitial brachytherapy (36.4 Gy in 7 fractions over 4 days). Patients who were not suitable for implantation received EBRT using an enface electron field of 50 Gy prescribed to the 80% isodose. With a median follow-up of 3 years, the local recurrence rates were reported as 1.3% and 1.9% for APBI and WBI, respectively (p = .99). There was no difference in cause-specific survival, disease-free survival, and distant metastases-free survival. However, they reported fewer grade 2 to 3 skin side effects in patients treated with APBI as compared to WBI (3% vs 17%, p < .001). At 5 years, the actuarial rate of ipsilateral breast failure was 5.5% and 4.4% in PBI and WBI arms, respectively (p = .65). The long-term cosmetic results being rated as good/excellent were 79% and 59% in the PBI and WBI arms, respectively (p = .001).
Single Lumen Balloon Catheter Brachytherapy
The MammoSite balloon brachytherapy device (MammoSite Radiation Therapy System [RTS]; Hologic, Bedford, Massachusetts) was introduced in 2002 and is a form of intracavitary brachytherapy that is simpler in its technique and treatment planning as compared to interstitial brachytherapy (Fig. 95-2). The apparatus consists of a double lumen catheter that is 15 cm in length and 6 mm in diameter. The catheter contains a central lumen that allows for a HDR 192Ir source, and a small adjacent lumen for filling the distally located balloon. This spherical MammoSite balloon catheter is available in 2 sizes when inflated, either 4 to 5 cm or 5 to 6 cm in diameter, for variability in the dimensions of a lumpectomy cavity. An elliptically shaped MammoSite balloon catheter is also available that is a fixed 4 × 6 cm in diameter ellipsoid when inflated.
MammoSite balloon brachytherapy. (Courtesy of Douglas Arthur. Reprinted with permission. ©2008 American Society of Clinical Oncology. All rights reserved.)
The MammoSite catheter is implanted after lumpectomy, at the time of surgery directly into the cavity; after surgery under ultrasound guidance through a small, separate incision; or after surgery directly into the cavity through the healing lumpectomy wound. The manufacturer of the MammoSite catheter has also produced a simpler and less expensive balloon catheter called the Cavity Evaluation Device (CED). This allows the surgeon, without wasting a MammoSite device because of poor conformance or inadequate balloon-to-skin distance, to check balloon-cavity conformance and to ensure adequate skin-to-balloon distance while in the operating room. Also, to preclude wasting a MammoSite catheter from disqualifying final nodal and margin histology, the CED may be left in the breast for a few days until the final pathology is reported. If the patient remains a candidate for brachytherapy, the CED may then be exchanged for a MammoSite catheter in the surgeon's office or outpatient clinic under local anesthesia.
After catheter placement, computed tomography (CT) of the breast is performed prior to initiation of treatment to determine that the balloon-to-skin distance is 5 mm or more, the conformity of the balloon to the walls of the lumpectomy cavity is more than 90%, and there is symmetry between the balloon and the center shaft of the catheter (Fig. 95-2). These guidelines were developed by the ASBS to ensure proper patient selection for this technique.
The ASBS published the outcomes of insertion techniques of a registry trial of 1403 patients who received MammoSite breast brachytherapy.48 The trial, initiated in May 2002 by the manufacturer who relinquished control of the trial in November 2003, accrued patients from 87 institutions over 30 months. Patients were enrolled per the American Brachytherapy Society eligibility criteria listed earlier in this review. A total of 1237 (87%) patients received APBI via MammoSite, 43 (3%) patients received a boost via MammoSite, and 123 (9%) patients underwent catheter explantation. Explantation was performed for poor skin spacing (35%), irregular cavity (28%), positive margins (9%), and balloon failure (9%). Recently published 3-year data on 1440 early-stage breast cancer patients (1449 cases) treated with MammoSite in the ASBS registry trial with a median follow-up of 30.1 months revealed a 1.6% rate of ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for invasive breast cancer and 0.59% for DCIS).49 The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively.
Cuttino et al presented a pooled analysis of 9 institutions of patients with stage 0, I, and II breast carcinoma with MammoSite between 2000 and 2004 at the American Society of Therapeutic Radiation Oncology annual meeting in November 2006.50 All 483 patients received 34 Gy in 10 fractions over 5 days. The median follow-up was 2 years, and all patients had a minimum follow-up of 1 year. They found a 1.2% (n = 6) in-breast failure rate; however, only 0.4% of all patients experienced a failure that was characterized as a true recurrence or marginal miss. Cosmetic results were reported as good/excellent in 91% of patients. Administration of prophylactic antibiotics, skin spacing more than 5 mm, and use of multiple dwell positions contributed to less dermatologic toxicity in terms of severe acute skin reactions, severe hyperpigmentation, and grade 3/4 acute skin reactions.
A multi-institutional phase II clinical trial was conducted from May 2003 to January 2006 to evaluate the utility of MammoSite in patients with DCIS.51 Eligibility criteria included the following: age 45 years or more, unicentric pure DCIS, 1 mm or more margins, tumor size upto 5 cm, clinically node negative, and a postlumpectomy mammogram showing complete resolution of any suspicious microcalcifications. One hundred and thirty-three patients were enrolled, with 117 patients receiving the MammoSite implant. Seventeen patients underwent removal of the implant for various reasons, including suboptimal skin distance, positive margins, and irregular cavity. Thus, 100 patients completed treatment with a median follow-up period of 9 months. Two patients experienced an ipsilateral breast recurrence, with 1 being a true recurrent/marginal miss. Ninety-eight percent of patients reported a good/excellent cosmetic result and there was a 4% infection rate, consistent with the other series. Details of these studies can be found in Table 95-3.
Table 95-3 Mammosite Brachytherapy Accelerated Partial Breast Irradiation Studies |Favorite Table|Download (.pdf)
Table 95-3 Mammosite Brachytherapy Accelerated Partial Breast Irradiation Studies
|Series||No. of Patients||Dose Rate||APBI Scheme (Dose [Gy] × Fraction No.)||Median FU (mo)||TR/MM (%)||Infection Rate (%)||Explantation Rate (%)||Good/Excellent Cosmesis (%)|
|ASBS Registry Trial48,71||1403||HDR||3.4 × 10||15||0.1||8||9||98|
|Cuttino et al50||483||HDR||3.4 × 10||12||0.4||NR||NR||91|
|Benitez et al51||100||HDR||3.4 × 10||9.5||2||4||14.5||98|
Intracavitary Multiple Lumen Catheter Brachytherapy
Given the limitations of single lumen balloon catheters in shaping the radiation dose in the treatment region, many patients with inadequate skin spacing (less than 5-7 mm) or deep-set lesions near the chest wall are often found not to be candidates for this procedure. Given these considerations, intracavitary multiple lumen catheters were developed to allow for greater flexibility in treatment planning, thereby increasing the number of patients eligible for intracavitary brachytherapy. Two devices are currently available: (1) the Strut-Adjusted Volume Implant (SAVI) breast brachytherapy device (Cianna Medical; Aliso Viejo, California), which has 6, 8, or 10 peripheral source channels (Fig. 95-3); and (2) the Contura multi-lumen balloon applicator (SenoRx Inc; Irvine, California), which has 5 fixed lumens in the shaft: 1 centered and 4 offset by 5 mm (Fig. 95-3).
A. Strut-Adjusted Volume Implant (SAVI) breast brachytherapy device. (Courtesy of the Texas Cancer Clinic and Cianna Medical, Aliso Viejo, California.)B. Contura multi-lumen balloon applicator. (Courtesy of SenoRx.)
Like the MammoSite catheter, the SAVI and Contura devices are implanted after lumpectomy, either at the time of surgery directly into the cavity or after surgery under ultrasound guidance through a small, separate incision (Fig. 95-4). However, if placement at the time of surgery is preferred, use of the temporary CED catheter described previously allows exchange for the SAVI or Contura device in the office or clinic after brachytherapy eligibility is confirmed by viewing the final pathology report.
Contura multi-lumen balloon applicator. (Courtesy of the Texas Cancer Clinic.)
Clinical studies evaluating toxicity and local control rates involving both devices are in the beginning phases. However, dosimetric studies have shown that the flexibility of treatment planning with intracavitary multiple lumen catheters create a greater potential for optimization of dose delivery, thereby reducing toxicity in patients with lesions close to skin or rib.52,53 This flexibility benefits patients who are unable to meet dosimetric requirements using a single lumen catheter (Fig. 95-5).
Isodose comparison between a single-dwell (left) and a multicatheter/dwell plan (right). The minimum balloon-to-skin distance is 3 mm. The PTV is shown in light purple. Using multiple catheters and dwell positions reduces the maximum skin dose from 195% to 135% (blue). Per the NSABP B-39 protocol, the maximum allowable skin dose is 145%. (Courtesy of Frank Vicini.)
3D Conformal External Beam Radiotherapy
This technique, although the most widely used form of radiation therapy to treat carcinomas of all types, has the least amount of data supporting its role in APBI. 3D-CRT is a noninvasive method of delivering APBI that provides increased dose homogeneity leading to theoretical potential for better cosmetic outcomes compared with the other techniques (Figs. 95-6, 95-7 and 6418152). Furthermore, 3D-CRT is a technique that is less operator dependent than interstitial brachytherapy techniques and may include patients who do not meet eligibility criteria for intracavitary devices like MammoSite. In addition, cost analysis studies have indicated that 3D-CRT may be cheaper than brachytherapy techniques that do not require an extra surgical procedure or inpatient hospitalization.54,55 With the emergence of CT-based simulation, easier identification of the tumor bed and calculation of doses to critical normal structures has also led to an interest in delivering APBI using 3D-CRT.
Three-dimensional conformal radiation therapy plan using a 4-field external beam technique using different beam angles to deliver a conformal dose of radiation to the tumor bed.
Amount of normal tissue receiving 90% of prescribed dose: whole-breast irradiation versus partial breast irradiation (3D-CRT).
External beam radiation for partial breast. A. Typical 4-field arrangement for left-sided breast cancer. B. Corresponding transverse CT image through center of treatment area of breast.
Vicini et al at the William Beaumont Hospital first used 3D-CRT to deliver APBI in a select group of patients using active breathing control to account for movement of the breast secondary to respiration.56 They found this technique to be feasible and initiated a phase I/II trial further investigating the role of 3D-CRT in patients who met the eligibility criteria for RTOG 95-17.57 Thirty-one patients were enrolled and underwent CT-based planning. The clinical target volume (CTV) was defined as the lumpectomy cavity plus a 1 to 1.5 cm margin, limited by the skin surface and chest wall. A 1-cm margin was added to form the planning target volume (PTV). The first 5 patients received 34 Gy over 10 twice-daily fractions, while the remainder of the patients received 38.5 Gy over 10 twice-daily fractions. With a median follow-up of 10 months, there were no recurrences and a 100% rating of good/excellent cosmesis. The technical aspects of this study were found to be feasible and easily reproducible.
The RTOG conducted a phase I/II trial to evaluate the feasibility and reproducibility of 3D-CRT in delivering APBI.58 They enrolled 58 patients with stage I or II invasive ductal carcinoma with lesions upto 3 cm and negative surgical margins. After lumpectomy, the surgical cavity was defined on CT scan and this was denoted as the gross tumor volume (GTV). An expansion of 1.0 to 1.5 cm was added to form the CTV. The CTV was restricted to within 5 mm of the skin surface and lung–chest wall interface. An additional margin of more than 1.0 cm was provided to form the PTV, to account for penumbra. However, a separate PTV structure was formed to exclude this volume to within 5 mm of the skin surface and lung–chest wall interface and was used for the dose volume histogram (DVH) analysis. A total of 38.5 Gy was delivered in 10 fractions over 5 days. Patients were not treated using active breathing control. Port films and orthogonal pair films were taken 4 times during the course of therapy. The dose volume constraints were as follows: less than 50% of the ipsilateral breast should receive less than 50% of the prescribed dose and 25% of the ipsilateral whole breast should receive the prescribed dose; the contralateral breast received less than 3% of the prescribed dose; less than 10% of the ipsilateral lung could receive 30% of the prescribed dose; less than 10% of the contralateral lung could receive 5% of the prescribed dose; less than 5% of the heart could receive a maximum of 5% of the prescribed dose for right-sided lesions, and for left-sided lesions the volume of lung receiving 5% of the dose should be less than conventional WBI; finally, the maximum dose to the thyroid could be 3% of the prescribed dose. The primary end point of the study was to determine if 3D-CRT was reproducible, which was confirmed by the authors, as there were only 4 cases with major variations in the first 42 evaluable plans. All 4 of these major variations arose from the strict DVH constraints on the ipsilateral lung. The results of this study served as the foundation for the NSABP B-39/RTOG 0413 clinical trial that opened in 2005.
Formenti et al at the New York University designed a phase I/II study in 2000 evaluating the role of APBI delivered using 3D-CRT to patients lying in the prone position. Advocates of the prone position state that it reduces normal tissue motion secondary to respiration and cardiac systole, and further allows for the removal of the heart and lungs from the treatment field. This group treated 78 patients with a median follow-up of 28 months, which is the longest published follow-up of APBI using 3D-CRT.59 There were no recurrences to date, and cosmesis was rated as good/excellent in 92% of patients. Details on the experience with 3D-CRT are listed in Table 95-4.
Table 95-4 3D Conformal Radiation Therapy Accelerated Partial Breast Irradiation Studies |Favorite Table|Download (.pdf)
Table 95-4 3D Conformal Radiation Therapy Accelerated Partial Breast Irradiation Studies
|Series||No. of Patients||APBI Scheme (Dose [Gy] × Fraction No.)||Position||Median FU (mo)||TR/MM (%)||Mean % of Breast Receiving 100% Dose||Good/Excellent Cosmesis (%)|
|RTOG 03-1958||46||3.85 × 10||Supine||NR||NR||NR||NR|
|William Beaumont Hospital56,57||31||3.4 × 10 or||Supine||10||0||23||100|
|Royal Oaks, MI||31||3.85 × 10|
|NYU59||78||6.0 × 5||Prone||28||0||26||92|
|New York, NY|
Intraoperative radiotherapy is a method of delivering a single dose of radiation directly to the tumor bed or to the exposed tumor at the time of surgery. For most tumor sites, it can be used adjuvantly after surgery or as a boost, to be followed by fractionated external beam radiotherapy for either palliative or curative intent. The objective of IORT is to deliver a high single dose of electrons or low-energy photons to the exposed target volume while displacing critical, dose-limiting structures. Traditionally, patients were transported from the operating room to the radiotherapy suite during surgery, or surgery was performed in the radiotherapy suite. However, there are several devices now available that function as mobile IORT machines such as the Intrabeam (Carl Zeiss AG; Oberkochen, Germany), which produces 50 kVp x-rays; and the Mobetron System (Oncology Care Systems Group of Siemens Medical Systems, Intraop Medical Inc; Santa Clara, California) and Novac 7 System (Hitesys spA; Aprilia, Italy), both of which produce electrons between 4 and 12 MeV. While the use of IORT has mainly been studied in depth treating abdominal, genitourinary, and gynecologic malignancies and sarcomas, the experience in breast cancer is limited. Recently, it was actively explored in Europe as part of BCT due to longer treatment delays secondary to rising costs and poor access to health care. Advocates of IORT affirm that a geographical miss, which may occur with standard external beam radiotherapy, are avoided by this technique, where the surgical bed is visualized at the time of radiation therapy. Importantly, before radiotherapy is limited solely to the tumor bed using IORT, obtaining negative margins, which is dependent on histology, accurate patient selection, and the skill of the surgeon, is crucial to the success of IORT.
The theoretical benefit of IORT is the delivery of a large single dose of radiation, either with x-rays or electrons. Large single doses of radiation are thought to be more effective on "late-responding" tissues such as lung and spinal cord, which have a low α/β ratio (2.0-6.3 and 1.7-4.9, respectively).60 Breast tissue and tumors are thought to have an α/β ratio of 10. The linear-quadratic model, which uses values of α and β to determine relative effectiveness of a fractionation scheme on early- and late-responding tissues, may not be reliable to use with single fraction sizes greater than 6 to 8 Gy.61 Given this, estimates of single fraction sizes comparable to the standard 60 Gy delivered over 30 fractions are thought to be 20 to 22 Gy.61,62 However, the late effect on breast tissue using large single fraction sizes is unknown.
There are several prospective series of patients where IORT was used to deliver radiotherapy as a part of BCT. A study by Veronesi et al at the European Institute of Oncology examined 237 patients with tumors less than 2 cm who received quandrantectomy followed by immediate IORT using the Novac 7, with 222 patients receiving 21 Gy using 3- to 9-MeV electrons.62 With a mean follow-up of 19 months, 2.5% of patients developed adverse effects secondary to IORT and only 1.3% patients developed a recurrence in the ipsilateral breast, all of which were outside of the treatment field. The European Institute of Oncology has met its goal of accruing 824 patients randomized to either WBI plus boost or a single dose of 21 Gy using IORT. The results from this trial are eagerly awaited. Another study conducted by the University College of London examined 185 patients with early-stage breast cancer who received IORT using the Intrabeam system.61,63 The prescribed dose was one 5 to 20 Gy fraction at a depth of 1 and 0.2 cm, respectively. Twenty-two patients received IORT alone, while 163 patients received it as a boost prior to WBI. Their data has not been reported in full, but preliminarily only 2 recurrences were noted and cosmetic outcomes were described as being good. This group is also accruing 1600 patients to a randomized study designed to test equivalence comparing WBI plus boost to single fraction IORT.