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Accelerated partial breast irradiation: Initial experience with the Intrabeam System
Surgical Oncology (2011) 20, 73e79
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journal homepage: www.elsevier.com/locate/suronc
REVIEW
Accelerated partial breast irradiation: Initial experience with the Intrabeam System R.L. Elliott*, M. DeLand, J.F. Head, M.C. Elliott Elliott, Elliott, Head Breast Cancer Research and Treatment Center, Baton Rouge, LA 70816, USA Accepted 11 November 2009
KEYWORDS Breast irradiation; Intraoperative radiotherapy; Intrabeam System; Breast surgery
Abstract Failure after breast conserving surgery (BCS) and total breast irradiation usually occurs at the site of the original tumor. This has caused an increased interest in accelerated partial breast irradiation (APBI), because if radiation is delivered directly to the tumor bed there should be better local control. Patients greater than age 50 with core biopsy confirmed invasive ductal carcinoma were enrolled. They had preoperative ultrasound defining margins of less than 3.5 cm. Intraoperative ultrasound was also performed in an effort to ensure good surgical margins. After excision of the tumor, intraoperative radiotherapy (IORT) with the Intrabeam System was delivered to the tumor bed. The procedure has been performed on 67 patients. Sixty-one patients had it with the original surgery, while 6 had the procedure after re-exploration of the segmental mastectomy site. Because of the final pathology (surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomy and 11 received total breast irradiation. When total breast irradiation is done the IORT serves as the radiation boost. The cosmetic results have been good to excellent, and there have been no serious surgical or radiation complications. To date there have been no local failures. IORT with the Intrabeam System is feasible, user friendly, versatile, with few complications, good cosmetic results, and great patient acceptance. It is practical and excellent for breast IORT in the community setting. ª 2009 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 * Correspondence to: Robert L. Elliott, EEH, Breast Cancer Research and Treatment Center, 17050 Medical Center Drive, 4th Floor, Baton Rouge, LA 70816, USA. Tel.: þ1 225 755 3070; fax: þ1 225 906 2620. E-mail address: [email protected] (R.L. Elliott). 0960-7404/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2009.11.001
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R.L. Elliott et al. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .78 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 Authorship statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79
Introduction Breast conserving surgery (BCS) is usually followed by total breast irradiation. However, recently there has been tremendous interest in accelerated partial breast irradiation (APBI). The rational is that local recurrences after BCS and total breast irradiation usually occur at the site of the original tumor [1]. Therefore, it is logical that if radiation is delivered directly to the tumor bed, comparable control to total breast irradiation might be achieved. The feasibility and efficacy of APBI with limited field radiation therapy in the management of early-stage breast cancer have been very nicely reported by Vincini et al.[2] Recently Sanders et al. [3] reported on APBI in early-stage breast cancer and compared the different methods of delivering the radiation. They stated APBI is very feasible in carefully selected patients with early-stage breast cancer. Chen et al. [4] have reported on the long-term cosmetic results and toxicity after APBI with an interstitial brachytherapy technique. Since the interstitial brachytherapy APBI procedure has shown efficacy with minimal toxicity, newer methods of performing APBI have evolved. Interstitial catheter brachytherapy is the oldest and most studied method of APBI and has been widely used in the United States [5]. Some other APBI techniques being used and evaluated in trials are: MammoSite intracavitary brachytherapy (Proxima Therapeutics; Alpharetta, GA, USA), three-dimensional conformal APBI, Intrabeam intraoperative soft X-rays, breast preserving in situ IORT with the Mobetron (Intraop Medical Inc; Norcross, GA), and intraoperative single fraction electron beam (ELIOT). We believe that the APBI procedure should be convenient, economical, versatile, easy to use, appropriate for the community setting, and require little active involvement on behalf of the patient. For these reasons we chose the Intrabeam intraoperative radiation system (IORT). The purpose of this communication is to present our initial experience in selected breast cancer patients using the Intrabeam System.
Methods In October 2004 we began a prospective clinical trial of the Intrabeam intraoperative radiation procedure (IORT) in postmenopausal women with invasive ductal carcinomas of the breast <3.5 cm in diameter. All patients, enrolled through July 2008, had a preoperative diagnosis obtained by ultrasound directed or stereotactic core needle biopsy. The tumor biology (such as, estrogen and progesterone receptor status, Her-2-neu and Ki-67) was known in most patients
prior to the procedure. All patients had digital mammography, real time ultrasound and dedicated breast magnetic resonance imaging (MRI) to rule out multicentric disease. After proper staging to rule out systemic disease the patients were educated about the procedure, shown a PowerPoint Presentation of the procedure and informed of the TARGIT Trial. They were then seen in consultation by the radiation oncologist. The patients in this private community practice did not want to be randomized to a trial, and all wanted to avoid total breast irradiation if possible. They were advised that, if the final pathology report was unfavorable, then a mastectomy or total breast irradiation would be recommended. They knew that if they had to have total breast irradiation that the Intrabeam IORT would serve as the radiation boost. After informed consent patients were taken to the operating room (OR) where they had sentinel node biopsy by the radioactive colloid injection method, ultrasound directed segmental mastectomy, and Intrabeam IORT. The pathologist evaluated surgical margins by touch prep intraoperatively. Before proceeding with the Intrabeam IORT, the surgeon confirms that there is residual tissue of at least 1 cm from the surgical margin to the skin and chest wall. The radiation time was dictated by the size of the Intrabeam radiation probe applicator needed to fill the biopsy cavity. The study was approved by the Mastology Research Institute Institutional Review Board and meets all guidelines of the responsible government agency. The Intrabeam System has a miniature X-ray source which is lightweight (1.6 kg) with a small control consol. The X-ray source is combined with a balanced floor stand with 6 degrees of freedom allowing flexibility of positioning to the patient on the operating table (Fig. 1). It allows excellent positioning with ergonomic features for easily guiding the X-ray source to the target. The miniature X-ray source has a probe that is 10 cm long and 3.2 mm in diameter. Within the probe electrons of desired energy are accelerated down the probe and forced to strike a gold target. This results in production of an isotropic dose distribution of radiation around the probe tip. Spherical applicators (Fig. 2) are fixed at the end of the source and range in size from 1.5 cm to 5 cm. The applicators are placed in the segmental mastectomy cavity (Fig. 3) to achieve a homogeneous dose distribution on its surface and thus to the surface of the tumor cavity (Fig. 3). This produces a better tissue-radiation source interface. Prior to insertion of the applicator into the surgical cavity it is very important to obtain meticulous hemostasis and to confirm that there is residual tissue of at least 1 cm from the skin and chest wall. Low energy photons (50 kVP) are produced by the X-ray system and they have a steep dose fall-off in
Accelerated partial breast irradiation
75 applicator is from 15 GY at the surface to 5 GY at 1 cm to less than half that at 2 cm. The IORT procedure has increased our overall operating time by about 35 min. After the radiation is delivered the applicator is removed, the wound is irrigated and closed in the usual way.
Results
Figure 1 Intrabeam stand with radiation probe and applicator in position in the patient.
soft tissue. Therefore, no special shielding is required and the procedure can be performed in any operating room without modification. The prescription dose of radiation is 5 GY at 10 mm from the surface of the applicator (dose determined for use in TARGIT Trial). The exact length of the treatment period is determined by the applicator size, which range from 2.5 to 5.0 cm in this study. It takes 17.70, 22.80, 19.00, 24.30, 29.70, and 36.45 min with the 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 cm applicators, respectively, to provide the prescribed IORT dose, which is directed and targeted to the tissues at the highest risk of recurrence. It is important to approximate the cavity tissue around the applicator with a purse string suture (Fig. 4) and sometimes a few interrupted sutures are placed to ensure applicator and tissue approximation. Skin edges are everted to keep the skin edges 1 cm away from the applicator surface (Fig. 5). There is a rapid fall-off dose so there is minimal effect on surrounding tissue. The fall-off of the X-ray dose on a 3.5 cm diameter
Figure 2 Tray showing all of the different size Intrabeam radiation applicators.
The Intrabeam IORT procedure has been performed in 67 patients. The median age of the patients was 60.0 years (10 patients less than 50 years old and 57 patients 50 years or older). The median tumor size was 1.2 cm with 50 T1 tumors and 10 T2 tumors. The IORT was done as part of the original segmental mastectomy procedure in 61 patients, while in the other 6 patients it was done after excision of the primary tumor with re-exploration of the segmental mastectomy site. Nodal status was determined by sentinel node biopsy (6 patients with positive nodes and 55 patients with negative nodes). Because of the final pathology report (positive surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomies and 11 patients went on to have total breast external beam radiation. The reasons for mastectomy were: (1) one patient with positive margins after re-excision, (2) two patients that did not want to have total breast radiation, and (3) one patient with recurring lymphangitis. Total external beam radiation was recommended in 11 patients because of involved lymph nodes, extensive intraductal component, and incidental invasive lobular carcinomas. The type of systemic therapy was individualized and based on nodal status and tumor biology (Table 1). A small subset of 11 patients did receive adjuvant chemotherapy, while all 37 patients with positive estrogen receptors were placed on hormonal therapy with either an antiestrogen or an aromatase inhibitor (Table 1). The majority of patients were in this category confirming the favorable tumor biology and prognostic features of the tumors in patients eligible for this procedure. There were very few serious surgical or radiation complications (Table 2), but all patients had post-operative seromas proven by ultrasound. The seromas were symptomatic (pain and swelling) in 25% (17 of 67) of the patients, and were managed by aspiration. It usually required three aspirations to resolve the seromas by six weeks. There was one patient with a chronic seroma that developed a draining sinus requiring excision. Another patient had recurring bouts of lymphangitis and later came to mastectomy while another had significant radiation fibrosis (Table 2). The post-operative cosmetic results have been acceptable, and no patients have had serious surgical deformity. All patients developed some induration at the operative site. However, only one patient had severe fibrosis and fat necrosis requiring excision at 18 months. One patient had mild increased pigmentation of the skin at the surgery site secondary to radiation and two patients had very minimal telangiectasia. Cosmetic results have been evaluated at three months, six months, and annually. Physician evaluation of the cosmetic results by the Harvard criteria yielded excellent to good results in 85% (57 of 67) of the patients and fair to poor results in 15% (10 of 67) of the patients. There have been no serious systemic effects or other toxicities.
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Figure 3 Shows the radiation probe and applicator inserted in the segmental mastectomy cavity.
The effect of the procedure on follow-up digital mammograms is easily visualized (Fig. 6), and has persisted for the length of the follow-up. Some patients have been followed for over four years (median follow-up of 28.2 months), and as yet, there have been no local failures (Table 2). One patient has died from metastatic disease without local recurrence, and one patient died from cardiovascular disease (NED for breast cancer). However, the follow-up is not long enough to assess the efficacy of the Intrabeam IORT procedure in preventing local recurrence.
Discussion The use of APBI is supported by the fact that the majority of local failures in the breast occur at the operative site [1,2,6,7]. Vicini et al. [2] have reported on one of the largest series of patients treated with limited field radiation therapy by the interstitial catheter brachytherapy
Figure 4 Surgeon placing purse string suture to approximate cavity tissue around the probe.
R.L. Elliott et al.
Figure 5 Shows the applicator in place ready for radiation to be delivered. Skin edges are approximated but are more than 1 cm away from applicator.
technique. Their report suggested that the procedure is adequate in controlling residual disease in appropriately selected patients. This raised the question of whether total breast irradiation is always necessary in selected low risk patients. Veronesi et al. [8] have published a preliminary report of IORT in conservatively treated limited stage breast cancer. They used the intraoperative single fraction electron beam procedure (ELIOT), which delivers a very high dose of electrons to the quadrectomy site. They are pleased with their initial results and follow-up, and are continuing their study in appropriate patients. Orecchia [1] and colleagues reported an update on the (ELIOT) procedure in patients with early-stage breast cancer and stated that it was feasible and appropriate in a select group of patients. They predicted that the use of the procedure will become widespread in the immediate future. Kraus-Frefenbacher et al [9] have used the Intrabeam System for IORT of breast cancer. They found it to be a feasible method to deliver a single high radiation dose to breast cancer patients. They had no acute side effects or complications during the first post-operative days or after 12 months. They felt the treatment was well tolerated and did not cause greater tissue damage than expected. Herskind et al. [10] have also studied extensively the radiobiological aspects of intraoperative radiotherapy with isotropic low-energy X-rays in early-stage breast cancer with the Intrabeam System. They found that the relative biological effectiveness for tumor cells was higher than for late-reacting tissue, and the applicator diameter was an important parameter in determining the range of tumor cell control in the irradiated tumor bed. Vaidya and his group [11,12] have reported on targeted IORT (TARGIT Trial) and found it yielded low recurrence rates when given as a boost. They felt the Intrabeam System was a simpler and more direct method to deliver radiation to the operative site. It can be done at the time of surgery and it adds only 20e40 min of time to the operation. In these particular studies the intraoperative radiotherapy was used as a tumor bed boost prior to external beam total breast irradiation.
Accelerated partial breast irradiation Table 1
77
Therapies and procedures combined with IORT.
Procedure
Number of patients
IORT only 15 IORT and hormonal therapy 30 IORT and chemotherapy 4 IORT, chemotherapy and 3 hormonal therapy IORT and total breast irradiation 4 IORT, total breast irradiation and 3 hormonal therapy IORT, total breast irradiation and 3 chemotherapy IORT, total breast irradiation, 1 chemotherapy and hormonal therapy IORT and mastectomy 4
Keisch [13] and his group have published their initial clinical experience with the MammoSite brachytherapy balloon in women with early-stage breast cancer treated with breast conserving therapy. It is an excellent report of the pros and cons, and details of the MammoSite brachytherapy procedure. Vicini et al. [14] have described their experience with three-dimensional conformal APBI as a part of breast conservation therapy. The results with both techniques are impressive and confirm that APBI is feasible, effective, well tolerated, with minimal toxicity and great patient acceptance. Ollila and his group reported on the feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively in the Annals of Surgical Oncology [15]. Their procedure is similar to the Veronesi (ELIOT) technique [16]; however, the high dose electron radiation is delivered to the tumor while the tumor is intact and before segmental mastectomy. Ollila’s group used a dedicated mobile, self-shielded, linear accelerator called the Mobetron (Intraop Medical Inc.; Norcross, GA). They elected to irradiate the tumor in situ to deliver treatment to an undisturbed tumor bed, thus allowing a smaller margin of adjacent breast tissue. It further allowed them to define target volume with preoperative ultrasound, as well as select cone size, cone angle, electron energy, and the incision site for each individual
Table 2
Adverse events.
Procedure
Number of patients
Significant wound problems Chronic seroma with draining sinus Recurring lymphangitis Radiation fibrosis
1 1 1
Recurrences Local Distant/systemic
0 2
Deaths Cardiac disease (no evidence of cancer) Systemic recurrence without local recurrence
1 1
tumor. They admit the drawback to their procedure is a smaller treated volume. The lower dose and smaller volume may result in better cosmesis, but could also result in increased risk of local recurrence. This, of course, is an issue that is being studied by the group. Their short term initial analysis and follow-up show acceptable toxicity and feasibility of their in situ IORT procedure, which to date has been well tolerated. The five year results of the initial clinical trial of the MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer has recently been reported by Benitez et al. [17]. Seventy patients were enrolled in a prospective study and 43 patients completed APBI with MammoSite brachytherapy after lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years. They concluded that MammoSite balloon brachytherapy, as the sole modality for delivering radiation to the tumor bed, achieved excellent local control in their patients with early-stage invasive ductal breast cancer. They experienced minimal toxicities and had good to excellent cosmetic results in 83.3% of patients. There were no local failures in the 36 patients that were followed for a median of 5.5 years. There were problems in some patients with cavity size amenable to balloon placement, inadequate skin spacing, and poor cavity conformance; however, there were no serious surgical complications with only two infections of mastitis and abscess. Seroma formation occurred in 32.6%, but only 12% were symptomatic requiring aspiration. The efficacy of the procedure will be determined by long-term follow-up. Sauer et al. [18] recently discussed an overview of the different methods of APBI and issued a consensus statement of three German Oncology Societies. They felt that APBI alone after BCS without breast irradiation is still experimental even in patients with low risk and favorable prognostic factors. The opinion was that for all the techniques described, the relative biological effectiveness, side effects, and long-term complication are not yet predictable. In their consensus statement they agreed to support randomized clinical trials with well-defined inclusion criteria and to discourage the use of APBI in other settings or as a routine tool. Progress in medical technology has made mobile miniature X-ray generators, such as the Intrabeam System, available for IORT in breast cancer therapy. This communication is about our experience with APBI in a select group of breast cancer patients using the Intrabeam System [19]. Wenz has previously reported his experience with the Intrabeam System and has found the system to be extremely versatile and easy to use [20]. We believe that for early-stage breast cancer in carefully selected patients it has many advantages over the other techniques of APBI. First, it is extremely versatile and easy to use. It requires no special operating rooms. It is also more economical than either the linear accelerator (Veronesi Technique [21]) or the Mobetron unit reported on by Ollila [15]. The Mobetron is mobile, but not nearly as mobile as the Intrabeam. The control consol and miniature X-ray source of the Intrabeam fit nicely in a traveling case and can be easily transported to another hospital in the same or adjacent city. All that would be required at the other site is a stand for the X-ray source. This is a tremendous
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R.L. Elliott et al.
Figure 6 Left digital mammogram one year post-segmental mastectomy and Intrabeam (IORT) showing post-surgical and radiation changes (arrows), a. craniocaudal view, b. mediolateral view.
advantage, allowing the system to be used at multiple sites without marked added expense. Another significant advantage for the Intrabeam System is that once the IORT is completed the radiation has been delivered and the patient does not have to make trips to the Radiation Center twice a day for 5 days, as with intracavitary techniques. Some patients may have to travel long distances to the Radiation Center or stay in a hotel. This traveling to a Radiation Center is a major inconvenience of these other techniques, and in fact for many patients this inaccessibility to a nearby Radiation Center is one of the reasons they choose total mastectomy over breast conserving procedures. If local recurrence remains low, then total breast irradiation might be avoided. The interstitial brachytherapy procedures, whether intracavitary or catheter (MammoSite or SAVI, respectively), still require the patient to go to the radiation center twice a day for 5 days, and they also involve another procedure on the patient to remove the interstitial devices. These are both inconvenient for the patient, and their absence in the Intrabeam IORT method are additional advantages of the Intrabeam IORT method. There is evidence that there is less damage to other organs, such as lung and heart (Herskind et al.[10]). There are also less systemic and local effects with less radiation-associated fibrosis. There has been tremendous patient satisfaction when compared to some of the other APBI procedures, and it is also extremely operator friendly. This along with its mobility, versatility and cost effectiveness make the Intrabeam IORT System one of the most attractive methods of offering APBI to appropriately selected breast cancer patients, especially in the community setting. The length of follow-up in our patients is too short to truly determine the efficacy of preventing local recurrence, but there is some evidence it is comparable to other techniques. If the ongoing trial data confirms efficacy of the Intrabeam method, then the great patient acceptance, ease of operator use, along with being the most convenient, flexible,
inexpensive and versatile APBI system available, will make it the APBI procedure of choice. Recently a consensus statement on accelerated partial breast irradiation (APBI) was published by the American Society for Radiation Oncology (ASTRO) [22]. The consensus panel did an excellent job of describing the selection of patients for APBI outside of a clinical trial, and also how to properly inform the patients. We agree with their selection criteria for the three groups described in the statement. From our experience with intraoperative APBI we believe that intraoperative APBI should also have selection criteria for (1) suitable group, (2) cautionary group and (3) unsuitable group to be used in patient selection outside of a clinical trial. Informed consent should also be complete as emphasized in the consensus statement. However, in two different sections of the consensus statement it is stated, ‘‘Determination of the selection criteria for intraoperative radiotherapy is beyond the scope of this consensus statement’’. The panel also recommended caution in the adoption of intraoperative APBI until more data becomes available. We believe that by applying well-defined criteria to patient selection for the more patient convenient intraoperative APBI, that the results will be comparable to other APBI techniques. Hopefully, more studies and data will soon be available for intraoperative APBI to answer this question.
Conclusion Partial breast irradiation by intraoperative radiotherapy (IORT) with an Intrabeam System was performed on 67 breast cancer patients after breast conserving surgery. Final pathology required 4 patients to have total mastectomies and 11 patients went on to have total breast irradiation with the IORT serving as the radiation boost. There have been no serious surgical or radiation complications, but most patients developed post-operative seromas that were easily managed by aspiration.
Accelerated partial breast irradiation
79
Conflict of interest statement
[8] Veronesi U, Orecchia R, Luini A, Gatti G, Intra M, Zurrida S, et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancer that are conservatively treated. Eur J Cancer 2001;37:2178e83. [9] Kraus-Tiefenbacher U, Scheda A, Steil V, Hermann B, Kehrer T, Bauer L, et al. Intraoperative radiotherapy (IORT) for breast cancer using the intrabeam system. Tumori 2005;91:339e45. [10] Herskind C, Steel V, Kraus-Tiefenbacher U, Wenz F. Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy x-rays for early-stage breast cancer. Rad Res 2005;163:208e15. [11] Vaidya JS, Baum M, Jobiar JS. Targeted intraoperative radiotherapy (TARGIT): an innovative method of treatment for early breast cancer. Ann Oncol 2001;12:1075e80. [12] Vaidya JS, Baum M, Jobiar JS. The novel technique of delivering targeted intraoperative radiotherapy (TARGIT) for early breast cancer. Eur J Surg Oncol 2002;28:447e54. [13] Keisch M, Vicini F, Kuske RR, Hebert M, White J, Quiet C, et al. Initial clinical experience with the mammosite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. Int J Rad Oncol Biol Phys 2002;55:289e93. [14] Vicini F, Winter K, Straube W, Wong J, Pass H, Rabinovitch R, et al. A phase I/II clinical trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319. Int J Rad Oncol Biol Phys 2005;63:1531e7. [15] Ollila DW, Klauber-DeMore N, Tesche LJ, Kuzmiak CM, Pavic D, Goyal LK, et al. Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively. Am J Surg Oncol 2007;14:660e9. [16] Veronesi U, Orecchia R, Luini A, Galimberti V, Gatti G, Intra M, et al. Full-dose intraoperative radiotherapy with electrons during breast conserving surgery: experience with 590 cases. Am J Surg 2005;242:101e6. [17] Benitez P, Keisch M, Vicini F, Stolier A, Scroggins T, Walker A, et al. Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in earlystage breast cancer. Am J Surg 2007;194:456e62. [18] Sauer R, Sautter-Bihl ML, Budach W, Feyer P, Harms W, Souchan R, et al. Accelerated partial breast irradiation: consensus statement of 3 German oncology societies. Cancer 2007;110:1187e94. [19] Elliott RL, DeLand M, Head JF, Elliott MC, Duhon J, Miller S, et al. Partial breast irradiation: initial experience with intraoperative radiotherapy using the intrabeam system in selected breast cancer patients. Ann Surg Oncol 2007;14S:21. [20] Wenz F. Intraoperative radiotherapy for early breast cancer. US Oncol 2006:41e3. [21] Veronesi U, Gatti G, Luini A, Intra M, Ciocca M, Sanchez D, et al. Full-dose intraoperative radiotherapy with electrons during breast conserving surgery. Arch Surg 2003;138:1253e6. [22] Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Rad Oncol Biol Phys 2009; 74:987e1001.
The authors declare that they do not have any conflict of interest.
Authorship statement Guarantor of the integrity of the study: Jonathan F. Head (JFH). Study concepts: Robert L. Elliott (RLE). Study design: JFH, RLE. Definition of the intellectual content: JFH, RLE. Literature research: RLE. Clinical studies: RLE, Maitland M. DeLand (MMD) and Mary C. Elliott (MCE). Data acquisition: RLE, JFH. Data analysis: RLE, JFH. Statistical analysis: RLE, JFH. Manuscript preparation: RLE, JFH, MMD, MCE. Manuscript editing: RLE, JFH. Manuscript review: RLE, JFH, MMD, MCE.
Acknowledgments Supported by funds from the Sallie Astor Burdine Breast Foundation, Baton Rouge, LA.
References [1] Orecchia R, Ciocca M, Lazzari R, Garibaldi C, Leonardi MC, Luini A, et al. Intraoperative radiation therapy with electrons (ELIOT) in early stage breast cancer. Breast 2003;12: 483e90. [2] Vicini F, Kestin L, Chen P, Benitez P, Goldstein NS, Martinez A. Limited-field radiation therapy in the management of earlystage breast cancer. J Natl Cancer Inst 2003;95:1205e10. [3] Sanders ME, Scroggins T, Ompil FL, Li BD. Accelerated partial breast irradiation in early stage breast cancer. J Clin Oncol 2007;25:996e1002. [4] Chen PY, Vicini FA, Benitez P, Kestin LL, Wallace M, Mitchell C, et al. Long-term cosmetic results and toxicity after accelerated partial breast irradiation (a method of radiation delivery by interstitial brachytherapy for the treatment of early-stage breast carcinoma). Cancer 2006;106:991e9. [5] Kushe R. Accelerated partial breast irradiation: moving forward. Amer Soc Breast Dis 2006;4:1e6. [6] Vaidya JS, Baum M, Tobias JS, Massarut S, Wenz F, Murphy O, et al. Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost. Int J Rad Onco Biol Phys 2006;66:1335e8. [7] Petit JY, Veronesi U, Orecchia R, Luini A, Rey P, Intra M, et al. Nipple-sparing mastectomy in association with intraoperative radiotherapy (ELIOT): a new type of mastectomy for breast cancer treatment. Breast Cancer Res Treat 2006; 96:47e51.
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journal homepage: www.elsevier.com/locate/suronc
REVIEW
Accelerated partial breast irradiation: Initial experience with the Intrabeam System R.L. Elliott*, M. DeLand, J.F. Head, M.C. Elliott Elliott, Elliott, Head Breast Cancer Research and Treatment Center, Baton Rouge, LA 70816, USA Accepted 11 November 2009
KEYWORDS Breast irradiation; Intraoperative radiotherapy; Intrabeam System; Breast surgery
Abstract Failure after breast conserving surgery (BCS) and total breast irradiation usually occurs at the site of the original tumor. This has caused an increased interest in accelerated partial breast irradiation (APBI), because if radiation is delivered directly to the tumor bed there should be better local control. Patients greater than age 50 with core biopsy confirmed invasive ductal carcinoma were enrolled. They had preoperative ultrasound defining margins of less than 3.5 cm. Intraoperative ultrasound was also performed in an effort to ensure good surgical margins. After excision of the tumor, intraoperative radiotherapy (IORT) with the Intrabeam System was delivered to the tumor bed. The procedure has been performed on 67 patients. Sixty-one patients had it with the original surgery, while 6 had the procedure after re-exploration of the segmental mastectomy site. Because of the final pathology (surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomy and 11 received total breast irradiation. When total breast irradiation is done the IORT serves as the radiation boost. The cosmetic results have been good to excellent, and there have been no serious surgical or radiation complications. To date there have been no local failures. IORT with the Intrabeam System is feasible, user friendly, versatile, with few complications, good cosmetic results, and great patient acceptance. It is practical and excellent for breast IORT in the community setting. ª 2009 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 * Correspondence to: Robert L. Elliott, EEH, Breast Cancer Research and Treatment Center, 17050 Medical Center Drive, 4th Floor, Baton Rouge, LA 70816, USA. Tel.: þ1 225 755 3070; fax: þ1 225 906 2620. E-mail address: [email protected] (R.L. Elliott). 0960-7404/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2009.11.001
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R.L. Elliott et al. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .78 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 Authorship statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79
Introduction Breast conserving surgery (BCS) is usually followed by total breast irradiation. However, recently there has been tremendous interest in accelerated partial breast irradiation (APBI). The rational is that local recurrences after BCS and total breast irradiation usually occur at the site of the original tumor [1]. Therefore, it is logical that if radiation is delivered directly to the tumor bed, comparable control to total breast irradiation might be achieved. The feasibility and efficacy of APBI with limited field radiation therapy in the management of early-stage breast cancer have been very nicely reported by Vincini et al.[2] Recently Sanders et al. [3] reported on APBI in early-stage breast cancer and compared the different methods of delivering the radiation. They stated APBI is very feasible in carefully selected patients with early-stage breast cancer. Chen et al. [4] have reported on the long-term cosmetic results and toxicity after APBI with an interstitial brachytherapy technique. Since the interstitial brachytherapy APBI procedure has shown efficacy with minimal toxicity, newer methods of performing APBI have evolved. Interstitial catheter brachytherapy is the oldest and most studied method of APBI and has been widely used in the United States [5]. Some other APBI techniques being used and evaluated in trials are: MammoSite intracavitary brachytherapy (Proxima Therapeutics; Alpharetta, GA, USA), three-dimensional conformal APBI, Intrabeam intraoperative soft X-rays, breast preserving in situ IORT with the Mobetron (Intraop Medical Inc; Norcross, GA), and intraoperative single fraction electron beam (ELIOT). We believe that the APBI procedure should be convenient, economical, versatile, easy to use, appropriate for the community setting, and require little active involvement on behalf of the patient. For these reasons we chose the Intrabeam intraoperative radiation system (IORT). The purpose of this communication is to present our initial experience in selected breast cancer patients using the Intrabeam System.
Methods In October 2004 we began a prospective clinical trial of the Intrabeam intraoperative radiation procedure (IORT) in postmenopausal women with invasive ductal carcinomas of the breast <3.5 cm in diameter. All patients, enrolled through July 2008, had a preoperative diagnosis obtained by ultrasound directed or stereotactic core needle biopsy. The tumor biology (such as, estrogen and progesterone receptor status, Her-2-neu and Ki-67) was known in most patients
prior to the procedure. All patients had digital mammography, real time ultrasound and dedicated breast magnetic resonance imaging (MRI) to rule out multicentric disease. After proper staging to rule out systemic disease the patients were educated about the procedure, shown a PowerPoint Presentation of the procedure and informed of the TARGIT Trial. They were then seen in consultation by the radiation oncologist. The patients in this private community practice did not want to be randomized to a trial, and all wanted to avoid total breast irradiation if possible. They were advised that, if the final pathology report was unfavorable, then a mastectomy or total breast irradiation would be recommended. They knew that if they had to have total breast irradiation that the Intrabeam IORT would serve as the radiation boost. After informed consent patients were taken to the operating room (OR) where they had sentinel node biopsy by the radioactive colloid injection method, ultrasound directed segmental mastectomy, and Intrabeam IORT. The pathologist evaluated surgical margins by touch prep intraoperatively. Before proceeding with the Intrabeam IORT, the surgeon confirms that there is residual tissue of at least 1 cm from the surgical margin to the skin and chest wall. The radiation time was dictated by the size of the Intrabeam radiation probe applicator needed to fill the biopsy cavity. The study was approved by the Mastology Research Institute Institutional Review Board and meets all guidelines of the responsible government agency. The Intrabeam System has a miniature X-ray source which is lightweight (1.6 kg) with a small control consol. The X-ray source is combined with a balanced floor stand with 6 degrees of freedom allowing flexibility of positioning to the patient on the operating table (Fig. 1). It allows excellent positioning with ergonomic features for easily guiding the X-ray source to the target. The miniature X-ray source has a probe that is 10 cm long and 3.2 mm in diameter. Within the probe electrons of desired energy are accelerated down the probe and forced to strike a gold target. This results in production of an isotropic dose distribution of radiation around the probe tip. Spherical applicators (Fig. 2) are fixed at the end of the source and range in size from 1.5 cm to 5 cm. The applicators are placed in the segmental mastectomy cavity (Fig. 3) to achieve a homogeneous dose distribution on its surface and thus to the surface of the tumor cavity (Fig. 3). This produces a better tissue-radiation source interface. Prior to insertion of the applicator into the surgical cavity it is very important to obtain meticulous hemostasis and to confirm that there is residual tissue of at least 1 cm from the skin and chest wall. Low energy photons (50 kVP) are produced by the X-ray system and they have a steep dose fall-off in
Accelerated partial breast irradiation
75 applicator is from 15 GY at the surface to 5 GY at 1 cm to less than half that at 2 cm. The IORT procedure has increased our overall operating time by about 35 min. After the radiation is delivered the applicator is removed, the wound is irrigated and closed in the usual way.
Results
Figure 1 Intrabeam stand with radiation probe and applicator in position in the patient.
soft tissue. Therefore, no special shielding is required and the procedure can be performed in any operating room without modification. The prescription dose of radiation is 5 GY at 10 mm from the surface of the applicator (dose determined for use in TARGIT Trial). The exact length of the treatment period is determined by the applicator size, which range from 2.5 to 5.0 cm in this study. It takes 17.70, 22.80, 19.00, 24.30, 29.70, and 36.45 min with the 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 cm applicators, respectively, to provide the prescribed IORT dose, which is directed and targeted to the tissues at the highest risk of recurrence. It is important to approximate the cavity tissue around the applicator with a purse string suture (Fig. 4) and sometimes a few interrupted sutures are placed to ensure applicator and tissue approximation. Skin edges are everted to keep the skin edges 1 cm away from the applicator surface (Fig. 5). There is a rapid fall-off dose so there is minimal effect on surrounding tissue. The fall-off of the X-ray dose on a 3.5 cm diameter
Figure 2 Tray showing all of the different size Intrabeam radiation applicators.
The Intrabeam IORT procedure has been performed in 67 patients. The median age of the patients was 60.0 years (10 patients less than 50 years old and 57 patients 50 years or older). The median tumor size was 1.2 cm with 50 T1 tumors and 10 T2 tumors. The IORT was done as part of the original segmental mastectomy procedure in 61 patients, while in the other 6 patients it was done after excision of the primary tumor with re-exploration of the segmental mastectomy site. Nodal status was determined by sentinel node biopsy (6 patients with positive nodes and 55 patients with negative nodes). Because of the final pathology report (positive surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomies and 11 patients went on to have total breast external beam radiation. The reasons for mastectomy were: (1) one patient with positive margins after re-excision, (2) two patients that did not want to have total breast radiation, and (3) one patient with recurring lymphangitis. Total external beam radiation was recommended in 11 patients because of involved lymph nodes, extensive intraductal component, and incidental invasive lobular carcinomas. The type of systemic therapy was individualized and based on nodal status and tumor biology (Table 1). A small subset of 11 patients did receive adjuvant chemotherapy, while all 37 patients with positive estrogen receptors were placed on hormonal therapy with either an antiestrogen or an aromatase inhibitor (Table 1). The majority of patients were in this category confirming the favorable tumor biology and prognostic features of the tumors in patients eligible for this procedure. There were very few serious surgical or radiation complications (Table 2), but all patients had post-operative seromas proven by ultrasound. The seromas were symptomatic (pain and swelling) in 25% (17 of 67) of the patients, and were managed by aspiration. It usually required three aspirations to resolve the seromas by six weeks. There was one patient with a chronic seroma that developed a draining sinus requiring excision. Another patient had recurring bouts of lymphangitis and later came to mastectomy while another had significant radiation fibrosis (Table 2). The post-operative cosmetic results have been acceptable, and no patients have had serious surgical deformity. All patients developed some induration at the operative site. However, only one patient had severe fibrosis and fat necrosis requiring excision at 18 months. One patient had mild increased pigmentation of the skin at the surgery site secondary to radiation and two patients had very minimal telangiectasia. Cosmetic results have been evaluated at three months, six months, and annually. Physician evaluation of the cosmetic results by the Harvard criteria yielded excellent to good results in 85% (57 of 67) of the patients and fair to poor results in 15% (10 of 67) of the patients. There have been no serious systemic effects or other toxicities.
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Figure 3 Shows the radiation probe and applicator inserted in the segmental mastectomy cavity.
The effect of the procedure on follow-up digital mammograms is easily visualized (Fig. 6), and has persisted for the length of the follow-up. Some patients have been followed for over four years (median follow-up of 28.2 months), and as yet, there have been no local failures (Table 2). One patient has died from metastatic disease without local recurrence, and one patient died from cardiovascular disease (NED for breast cancer). However, the follow-up is not long enough to assess the efficacy of the Intrabeam IORT procedure in preventing local recurrence.
Discussion The use of APBI is supported by the fact that the majority of local failures in the breast occur at the operative site [1,2,6,7]. Vicini et al. [2] have reported on one of the largest series of patients treated with limited field radiation therapy by the interstitial catheter brachytherapy
Figure 4 Surgeon placing purse string suture to approximate cavity tissue around the probe.
R.L. Elliott et al.
Figure 5 Shows the applicator in place ready for radiation to be delivered. Skin edges are approximated but are more than 1 cm away from applicator.
technique. Their report suggested that the procedure is adequate in controlling residual disease in appropriately selected patients. This raised the question of whether total breast irradiation is always necessary in selected low risk patients. Veronesi et al. [8] have published a preliminary report of IORT in conservatively treated limited stage breast cancer. They used the intraoperative single fraction electron beam procedure (ELIOT), which delivers a very high dose of electrons to the quadrectomy site. They are pleased with their initial results and follow-up, and are continuing their study in appropriate patients. Orecchia [1] and colleagues reported an update on the (ELIOT) procedure in patients with early-stage breast cancer and stated that it was feasible and appropriate in a select group of patients. They predicted that the use of the procedure will become widespread in the immediate future. Kraus-Frefenbacher et al [9] have used the Intrabeam System for IORT of breast cancer. They found it to be a feasible method to deliver a single high radiation dose to breast cancer patients. They had no acute side effects or complications during the first post-operative days or after 12 months. They felt the treatment was well tolerated and did not cause greater tissue damage than expected. Herskind et al. [10] have also studied extensively the radiobiological aspects of intraoperative radiotherapy with isotropic low-energy X-rays in early-stage breast cancer with the Intrabeam System. They found that the relative biological effectiveness for tumor cells was higher than for late-reacting tissue, and the applicator diameter was an important parameter in determining the range of tumor cell control in the irradiated tumor bed. Vaidya and his group [11,12] have reported on targeted IORT (TARGIT Trial) and found it yielded low recurrence rates when given as a boost. They felt the Intrabeam System was a simpler and more direct method to deliver radiation to the operative site. It can be done at the time of surgery and it adds only 20e40 min of time to the operation. In these particular studies the intraoperative radiotherapy was used as a tumor bed boost prior to external beam total breast irradiation.
Accelerated partial breast irradiation Table 1
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Therapies and procedures combined with IORT.
Procedure
Number of patients
IORT only 15 IORT and hormonal therapy 30 IORT and chemotherapy 4 IORT, chemotherapy and 3 hormonal therapy IORT and total breast irradiation 4 IORT, total breast irradiation and 3 hormonal therapy IORT, total breast irradiation and 3 chemotherapy IORT, total breast irradiation, 1 chemotherapy and hormonal therapy IORT and mastectomy 4
Keisch [13] and his group have published their initial clinical experience with the MammoSite brachytherapy balloon in women with early-stage breast cancer treated with breast conserving therapy. It is an excellent report of the pros and cons, and details of the MammoSite brachytherapy procedure. Vicini et al. [14] have described their experience with three-dimensional conformal APBI as a part of breast conservation therapy. The results with both techniques are impressive and confirm that APBI is feasible, effective, well tolerated, with minimal toxicity and great patient acceptance. Ollila and his group reported on the feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively in the Annals of Surgical Oncology [15]. Their procedure is similar to the Veronesi (ELIOT) technique [16]; however, the high dose electron radiation is delivered to the tumor while the tumor is intact and before segmental mastectomy. Ollila’s group used a dedicated mobile, self-shielded, linear accelerator called the Mobetron (Intraop Medical Inc.; Norcross, GA). They elected to irradiate the tumor in situ to deliver treatment to an undisturbed tumor bed, thus allowing a smaller margin of adjacent breast tissue. It further allowed them to define target volume with preoperative ultrasound, as well as select cone size, cone angle, electron energy, and the incision site for each individual
Table 2
Adverse events.
Procedure
Number of patients
Significant wound problems Chronic seroma with draining sinus Recurring lymphangitis Radiation fibrosis
1 1 1
Recurrences Local Distant/systemic
0 2
Deaths Cardiac disease (no evidence of cancer) Systemic recurrence without local recurrence
1 1
tumor. They admit the drawback to their procedure is a smaller treated volume. The lower dose and smaller volume may result in better cosmesis, but could also result in increased risk of local recurrence. This, of course, is an issue that is being studied by the group. Their short term initial analysis and follow-up show acceptable toxicity and feasibility of their in situ IORT procedure, which to date has been well tolerated. The five year results of the initial clinical trial of the MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer has recently been reported by Benitez et al. [17]. Seventy patients were enrolled in a prospective study and 43 patients completed APBI with MammoSite brachytherapy after lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years. They concluded that MammoSite balloon brachytherapy, as the sole modality for delivering radiation to the tumor bed, achieved excellent local control in their patients with early-stage invasive ductal breast cancer. They experienced minimal toxicities and had good to excellent cosmetic results in 83.3% of patients. There were no local failures in the 36 patients that were followed for a median of 5.5 years. There were problems in some patients with cavity size amenable to balloon placement, inadequate skin spacing, and poor cavity conformance; however, there were no serious surgical complications with only two infections of mastitis and abscess. Seroma formation occurred in 32.6%, but only 12% were symptomatic requiring aspiration. The efficacy of the procedure will be determined by long-term follow-up. Sauer et al. [18] recently discussed an overview of the different methods of APBI and issued a consensus statement of three German Oncology Societies. They felt that APBI alone after BCS without breast irradiation is still experimental even in patients with low risk and favorable prognostic factors. The opinion was that for all the techniques described, the relative biological effectiveness, side effects, and long-term complication are not yet predictable. In their consensus statement they agreed to support randomized clinical trials with well-defined inclusion criteria and to discourage the use of APBI in other settings or as a routine tool. Progress in medical technology has made mobile miniature X-ray generators, such as the Intrabeam System, available for IORT in breast cancer therapy. This communication is about our experience with APBI in a select group of breast cancer patients using the Intrabeam System [19]. Wenz has previously reported his experience with the Intrabeam System and has found the system to be extremely versatile and easy to use [20]. We believe that for early-stage breast cancer in carefully selected patients it has many advantages over the other techniques of APBI. First, it is extremely versatile and easy to use. It requires no special operating rooms. It is also more economical than either the linear accelerator (Veronesi Technique [21]) or the Mobetron unit reported on by Ollila [15]. The Mobetron is mobile, but not nearly as mobile as the Intrabeam. The control consol and miniature X-ray source of the Intrabeam fit nicely in a traveling case and can be easily transported to another hospital in the same or adjacent city. All that would be required at the other site is a stand for the X-ray source. This is a tremendous
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Figure 6 Left digital mammogram one year post-segmental mastectomy and Intrabeam (IORT) showing post-surgical and radiation changes (arrows), a. craniocaudal view, b. mediolateral view.
advantage, allowing the system to be used at multiple sites without marked added expense. Another significant advantage for the Intrabeam System is that once the IORT is completed the radiation has been delivered and the patient does not have to make trips to the Radiation Center twice a day for 5 days, as with intracavitary techniques. Some patients may have to travel long distances to the Radiation Center or stay in a hotel. This traveling to a Radiation Center is a major inconvenience of these other techniques, and in fact for many patients this inaccessibility to a nearby Radiation Center is one of the reasons they choose total mastectomy over breast conserving procedures. If local recurrence remains low, then total breast irradiation might be avoided. The interstitial brachytherapy procedures, whether intracavitary or catheter (MammoSite or SAVI, respectively), still require the patient to go to the radiation center twice a day for 5 days, and they also involve another procedure on the patient to remove the interstitial devices. These are both inconvenient for the patient, and their absence in the Intrabeam IORT method are additional advantages of the Intrabeam IORT method. There is evidence that there is less damage to other organs, such as lung and heart (Herskind et al.[10]). There are also less systemic and local effects with less radiation-associated fibrosis. There has been tremendous patient satisfaction when compared to some of the other APBI procedures, and it is also extremely operator friendly. This along with its mobility, versatility and cost effectiveness make the Intrabeam IORT System one of the most attractive methods of offering APBI to appropriately selected breast cancer patients, especially in the community setting. The length of follow-up in our patients is too short to truly determine the efficacy of preventing local recurrence, but there is some evidence it is comparable to other techniques. If the ongoing trial data confirms efficacy of the Intrabeam method, then the great patient acceptance, ease of operator use, along with being the most convenient, flexible,
inexpensive and versatile APBI system available, will make it the APBI procedure of choice. Recently a consensus statement on accelerated partial breast irradiation (APBI) was published by the American Society for Radiation Oncology (ASTRO) [22]. The consensus panel did an excellent job of describing the selection of patients for APBI outside of a clinical trial, and also how to properly inform the patients. We agree with their selection criteria for the three groups described in the statement. From our experience with intraoperative APBI we believe that intraoperative APBI should also have selection criteria for (1) suitable group, (2) cautionary group and (3) unsuitable group to be used in patient selection outside of a clinical trial. Informed consent should also be complete as emphasized in the consensus statement. However, in two different sections of the consensus statement it is stated, ‘‘Determination of the selection criteria for intraoperative radiotherapy is beyond the scope of this consensus statement’’. The panel also recommended caution in the adoption of intraoperative APBI until more data becomes available. We believe that by applying well-defined criteria to patient selection for the more patient convenient intraoperative APBI, that the results will be comparable to other APBI techniques. Hopefully, more studies and data will soon be available for intraoperative APBI to answer this question.
Conclusion Partial breast irradiation by intraoperative radiotherapy (IORT) with an Intrabeam System was performed on 67 breast cancer patients after breast conserving surgery. Final pathology required 4 patients to have total mastectomies and 11 patients went on to have total breast irradiation with the IORT serving as the radiation boost. There have been no serious surgical or radiation complications, but most patients developed post-operative seromas that were easily managed by aspiration.
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Conflict of interest statement
[8] Veronesi U, Orecchia R, Luini A, Gatti G, Intra M, Zurrida S, et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancer that are conservatively treated. Eur J Cancer 2001;37:2178e83. [9] Kraus-Tiefenbacher U, Scheda A, Steil V, Hermann B, Kehrer T, Bauer L, et al. Intraoperative radiotherapy (IORT) for breast cancer using the intrabeam system. Tumori 2005;91:339e45. [10] Herskind C, Steel V, Kraus-Tiefenbacher U, Wenz F. Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy x-rays for early-stage breast cancer. Rad Res 2005;163:208e15. [11] Vaidya JS, Baum M, Jobiar JS. Targeted intraoperative radiotherapy (TARGIT): an innovative method of treatment for early breast cancer. Ann Oncol 2001;12:1075e80. [12] Vaidya JS, Baum M, Jobiar JS. The novel technique of delivering targeted intraoperative radiotherapy (TARGIT) for early breast cancer. Eur J Surg Oncol 2002;28:447e54. [13] Keisch M, Vicini F, Kuske RR, Hebert M, White J, Quiet C, et al. Initial clinical experience with the mammosite breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. Int J Rad Oncol Biol Phys 2002;55:289e93. [14] Vicini F, Winter K, Straube W, Wong J, Pass H, Rabinovitch R, et al. A phase I/II clinical trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319. Int J Rad Oncol Biol Phys 2005;63:1531e7. [15] Ollila DW, Klauber-DeMore N, Tesche LJ, Kuzmiak CM, Pavic D, Goyal LK, et al. Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively. Am J Surg Oncol 2007;14:660e9. [16] Veronesi U, Orecchia R, Luini A, Galimberti V, Gatti G, Intra M, et al. Full-dose intraoperative radiotherapy with electrons during breast conserving surgery: experience with 590 cases. Am J Surg 2005;242:101e6. [17] Benitez P, Keisch M, Vicini F, Stolier A, Scroggins T, Walker A, et al. Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in earlystage breast cancer. Am J Surg 2007;194:456e62. [18] Sauer R, Sautter-Bihl ML, Budach W, Feyer P, Harms W, Souchan R, et al. Accelerated partial breast irradiation: consensus statement of 3 German oncology societies. Cancer 2007;110:1187e94. [19] Elliott RL, DeLand M, Head JF, Elliott MC, Duhon J, Miller S, et al. Partial breast irradiation: initial experience with intraoperative radiotherapy using the intrabeam system in selected breast cancer patients. Ann Surg Oncol 2007;14S:21. [20] Wenz F. Intraoperative radiotherapy for early breast cancer. US Oncol 2006:41e3. [21] Veronesi U, Gatti G, Luini A, Intra M, Ciocca M, Sanchez D, et al. Full-dose intraoperative radiotherapy with electrons during breast conserving surgery. Arch Surg 2003;138:1253e6. [22] Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Rad Oncol Biol Phys 2009; 74:987e1001.
The authors declare that they do not have any conflict of interest.
Authorship statement Guarantor of the integrity of the study: Jonathan F. Head (JFH). Study concepts: Robert L. Elliott (RLE). Study design: JFH, RLE. Definition of the intellectual content: JFH, RLE. Literature research: RLE. Clinical studies: RLE, Maitland M. DeLand (MMD) and Mary C. Elliott (MCE). Data acquisition: RLE, JFH. Data analysis: RLE, JFH. Statistical analysis: RLE, JFH. Manuscript preparation: RLE, JFH, MMD, MCE. Manuscript editing: RLE, JFH. Manuscript review: RLE, JFH, MMD, MCE.
Acknowledgments Supported by funds from the Sallie Astor Burdine Breast Foundation, Baton Rouge, LA.
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