The emerging role of brachytherapy in the management of patients with breast cancer

The Emerging Role of Brachytherapy in the Management of Patients with Breast Cancer Frank Vicini, Kathy Baglan, Larry Kestin, Peter Chen, GregoryEdrnundson, and Alvaro Martinez Brachytherapy remains an important treatment option in the overall management of patients with breast cancer. In patients treated with breast conserving therapy (BCT), prospective randomized trials have established the advantage of a boost in most patients. Interstitial brachytherepy has consistently been shown to provide an important option to boost patients, and in certain clinical settings it may provide a more appropriate means of dose delivery. The concept of delivering partial breast irradiation with accelerated treatment schedules has now provided brachytherapy a new and

exciting role in the management of patients treated with BCT. There are now data available from several phase 1/11studies suggesting that brachytherapy alone can be used safely and reproducibly in this setting in order to reduce the time, inconvenience, and toxicity associated with traditional radiation therapy. Although preliminary results with brachytherapy alone are encouraging, proper patient selection and optimal dosimetric guidelines must be employed in order to achieve success when used in this setting. Copyright © 2002 by W.B. Saunders Company

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used safely and reproducibly in this setting in order to reduce the time, inconvenience, and toxicity of traditional radiation therapy (RT). 4-18 In this article, the emerging use of brachytherapy as the sole radiation treatment modality will be reviewed as well as its application when used as a boost with BCT.

rachytherapy has been used for well over 70 years to treat patients with various stages of breast cancer. However, the degree of importance of this method of radiation delivery in the overall management of breast cancer patients has varied markedly over time. The history of the use of brachytherapy for breast cancer has been extensively reviewed by several authors and will not be expanded upon in this article. 1-3 Regardless of how brachytherapy is incorporated into the management of patients, its main advantage is the ability to tightly conform doses to a specified volume while reducing exposure to nearby normal tissues. These optimal physical properties are one of the primary advantages exploited when brachytherapy is used to boost patients after standard whole-breast external beam radiation therapy (EBRT). Although currently limited in terms of the frequency of its use, brachytherapy as boost treatment continues to remain an attractive treatment option in selected patients. Perhaps the most intriguing new role for brachytherapy is when it is used as the sole radiation modality after lumpectomy in patients treated with breast conserving therapy (BCT). There are now data available from several phase I/II trials suggesting that brachytherapy can be

From the Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI. Address reprint requests to Frank A. Vicini, MD, 3601 West Thirteen Mile Road Royal Oak, MI 48073. E-mail:[email protected] Copyright © 2002 by W..B. Saunders Company 1053-4296/02/1201-0004535.00/0 do#l O.lO53/srao.2002.28662

Brachytherapy as Boost Treatment The advantage in delivering a higher dose or boost of RT to the tumor bed after lumpectomy in patients treated with BCT has recently been supported by several large, prospective randomized trials. 19-21 As a result, brachytherapy has remained an important option in the overall management of breast cancer patients ( Table 1). Even though EBRT is currently used to boost the majority of patients treated with BCT (due to the ease of its use), there are certain clinical, pathologic, or treatment related situations where brachytherapy has been suggested as a more efficacious means of delivering a boost. These situations include: Patients with large breasts and/or deep-seated tumors where the integral dose with EBRT would be markedly greater than with brachytherapy, ~,~5,22,23 and patients with close, positive, or uncertain margins (or those with an extensive intraductal component). These patients are believed to require slightly higher tumor bed doses due to an increased probability of having marked subclinical disease remaining after lumpectomy. Brachytherapy (particularly low-dose rate (LDR) brachytherapy) has been suggested to provide a more radiobiologically ef-

Seminars in Radiation Oncolog~,, Vol 12, No 1 (January), 2002.'pp 31-39

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Vicini et al

32

Table 1. Studies of Brachytherapy as Boost Treatment with Breast Conserving Therapy Number of Patient~

Boost Type

Boost Dose

Total Dose

145

~92Ir

20 Gy

->60 Gy

194 122

~92Ir ~2~I

15 Gy 15-20 Gy

de la Rochefordiere et al 2~ Frazier et aF3; Vicini et a122 Vicini et al 2z

232 Hennequin et a129 Manning et a156 Mansfield et a124

Moreno et a157 Perez et al 2~

Pierquin et al 3° Sarin et a131 Deore et a127 Touboul et a132 Wazer et a125

106 18 stage I stage II stage I stage II 530 81 TI 38 T2 371 T1 122 T2 138 TI/2 only

378 276 266 150

273 169 127 67

Electron HDR ~9~Ir HDR 192Ir 192Ir 192Ir Electron Electron 192Ir 192Ir 192Ir Electron Electron ~9~Ir

192Ir ~92Ir 192Ir Electron

15 Gy 5 Gy x 2 2.5 Gy bid X 6 15-20 Gy 15-20 Gy 20 Gy 20 Gy 10-27 Gy 10-20 Gy 10-20 Gy 10-20 Gy 10-20 Gy 25 Gy

15-30 15-25 20 10-20

Gy Gy Gy Gy

fective dose than EBRT in this setting while producing a more acceptable cosmetic result. 22,24 Arguments have persisted through the years as to the true physical and/or radiobiologic advantages of brachytherapy in these settings. 24-39 Excellent reviews can be found in the literature, l-3,15,4° Regardless of one's opinion, if a boost is deemed necessary and if it has been determined that brachytherapy is the optimal method of RT delivery for a particular patient, the American Brachytherapy Society (ABS) recently published a set of guidelines/recommendations for use in these patients. 2 The most important points in these guidelines that should be considered when brachytherapy is used as a boost with BCT are summarized below.

(1) Precise definition and meticulous delineation of the clinical target volume (CTV) for boost treatment with brachytherapy is critical in order to ensure optimal results. A 2-cm margin around the lumpectomy cavity is suggested unless the skin surface or chest wall are limiting. Ideally, surgical clips should be placed at the boundaries of the lumpectomy cavity at the time of surgery in order to aid in the localization of the tumor bed for implantation and to establish adequate dosimetric coverage for quality assurance purposes. 41,42It

->60 Gy ->60 Gy ->60 Gy (60-72.2 Gy) 55 Gy 65 60-65 60-65 65 65 -60-70 60-70 60-70 60-70 70

Gy Gy Gy Gy Gy

60-75 60-75 70 60-70

Gy Gy Gy Gy

Gy Gy Gy Gy Gy

5-yr Local Control

Other Follow-up Local Control

Good~Excellent Cosmetic Results

94%

--

95%

96% 97%

85% (13-yr) 95% (13-yr)

89% 94%

95%

94% (13-yr)

89%

95%

63%

-93% 93% 95% 87% 95% 96% 89% 95% 91% 8% (TI) 12% (T2)

-100% (minimum 40 mo follow-up) 85% (10-~x) 93% (10-yr) 85% (10-yr) 74% (10-yr) 92% (7-yr) 96% (10-yr) 84% (10-yr) 92% (10-yr) 83% (10-yr) ---

14% 94% 96% 97%

--91% (7-yr) 97% (7-yr)

68% >90% >90% >90°/0 >90% 81% 79% 84% 74% 87% (T1) 59% (T2) 81% 62% 90% 78%

cannot be overemphasized that clinical estimates of the lumpectomy bed are insufficient to guarantee accurate identification and coverage of the appropriate boost volume. 41 (2) As has also been pointed out by others, the ABS recommends a minimum of 2 planes for most brachytherapy implants, unless the amount of breast tissue limits the target volume to less than a 2-cm thickness. Ideally, catheters should extend 1 to 2 cm beyond the edge of the CTV. If a wide separation between either catheters/needles or planes is noted, it is preferable to insert additional catheters/needles rather than to alter the weighting of sources to dosimetrically correct a suboptimal implant. (3) The ABS strongly recommends adequate treatment planning to ensure dose coverage and dose homogeneity within the CTV. Criteria to judge the quality of implants have been summarized by others. 1,2,15 (4) A total dose of 10 to 20 Gy (at 30 to 70 cGy/h) prescribed to the CTV for LDR implants (depending of course on the adequacy of surgical margins and the total EBRT dose) is the generally recommended dose for boosting patients (Table 1). For high dose rate (HDR) implants, the optimal

Role of Brachytherapy in Managing Breast Cancer

dose has not yet been established. 15,33 However, the ABS recommends that a dose-fractionation scheme be used that yields early and late effects approximately equivalent to those of a 10- to 20-Gy LDR implant. 43 Because most radiation oncologists do not have extensive experience in breast brachytherapy, it seems advisable to adopt the ABS guidelines which were developed by a panel of breast brachytherapy experts after a careful review of all the available literature. L2 It should also be noted that new techniques have been designed to ensure accurate and reproducible breast implants. 1,16,44 Many of these techniques were developed for use with brachytherapy as the sole radiation modality after lumpectomy (see below). However, it is strongly suggested that these methods of implantation be adopted even in the boost setting. Given the fact that a boost will likely persist as an integral part of the overall management of most patients treated with BCT, properly applied breast brachytherapy will remain an important technique to optimize efficacy in certain subsets of patients.

Brachytherapy as the Sole Radiation Modality The combination of lumpectomy followed by RT, referred to as BCT is now widely accepted as an equivalent treatment option to mastectomy for most women with clinical stage I/II invasive breast cancer. One question that has remained unanswered, however, is whether or not the entire breast needs to be treated or only a more limited volume of tissue surrounding the tumor bed. Traditionally, patients treated with BCT have been irradiated to the entire breast. However, most of the potential long-term complications and time constraints of BCT result from either whole-breast or nodal irradiation. In addition, giving radiotherapy to the entire breast essentially precludes giving further RT in the event that a patient develops a new primary tumor. In recognition of the problems outlined above, the option of partial-breast irradiation (PBI) has been explored. This concept lends itself to much shorter treatment schemes than whole breast irradiation, as the toxicities to the breast and surrounding tissues should be lessened by treating only a portion of the breast. In addition, if a

33

markedly shortened treatment scheme could be shown to produce equivalent outcome to traditional 6 weeks of whole-breast irradiation, it would substantially improve the quality of life of patients and allow easier integration of radiotherapy with chemotherapy. Just as important, a logistically simpler and quicker treatment could potentially increase the breast conservation option to more women and reduce the costs of post lumpectomy radiation. To this end, several groups began to explore accelerated treatment schemes in the 1980s and 1990s. Both EBRT and brachytherapy were employed. 6,7,11,13-15,17,t8,45-5° The success of these early phase IA and III studies has been inconsistent and will be reviewed below with special emphasis on the optimal brachytherapy techniques and selection criteria required to produce acceptable results.

Randomized Studies Comparing Partial Breast Irradiation to Whole Breast RT There have been only 2 randomized trials comparing PBI with whole-breast RT. The first, conducted from 1982-1987 at the Christie Hospital in Manchester, England, randomized 708 patients to receive irradiation to the entire breast and regional lymph nodes without a boost (40 Gy in 15 fractions over 21 days with a 4-MV linear accelerator) or treatment to the involved quadrant (40 Gy to 42.5 Gy in 8 fractions delivered over 10 days typically with 10 MeV electrons to an average field size of 8 × 6 cm, prescribed to the 100% isodose line) without whole-breast or nodal RT. 47-49,51 Axillary dissections were not performed, and systemic therapy was not given. More importantly, specimen margins were not evaluated microscopically, and in 42% of patients the pathologic tumor size was not recorded. With a median follow-up of 65 months, the incidences of tumor recurrence in the breast, as a first site of failure by 7 years, were 7% (26 out of 355) in the whole-breast RT arm and 14% in the PBI arm, respectively. The 5-year actuarial local recurrence rates were 8% and 17%, respectively; the 7-year rates were 11% and 20%, respectively. O f interest in this trial was the fact that the difference in outcome between whole-breast RT and PBI was primarily restricted to patients with infiltrating lobular histology (ILH). The respective 7-year actuarial recurrence rates in these patients were 8% and 34% vs 11% and 15% in

34

Vicini et a/

patients with infiltrating ductal histology (IDH). Of note, 64% of local failures in the IDH patients receiving PBI were in the same quadrant as the primary tumor compared with only 38% in patients with ILH on the PBI arm. In addition, the failure rate outside of the quadrant of the original tumor for patients with IDH was only 5.5%. The above findings using EBRT to deliver PBI emphasize several points. First, in order for the concept of PBI to work, proper patient selection is critical. Because RT is limited to the region of the tumor bed, it is mandatory patients have adequate surgical margins to ensure optimal excision prior to RT. As noted above, specimen margins were not a selection criterion in the Christie Hospital trial suggesting their patients may not have been optimal candidates for PBI. Second, care must be taken to exclude patients with a higher probability of harboring clinically occult multicentric disease or tumor extending a marked distance from the surgical bed. This suggests that patients with ILH or an extensive intraductal component (EIC) are probably not good candidates for PBI. Finally, in order for PBI to achieve a maximal success rate, adequate coverage of the CTV and planning target volume must be assured. To this end, dose volume histogram analyses must be undertaken in order to ultimately correlate tumor control rates with the dose delivered to the CTV. The techniques used in the Christie Hospital trial were simply not capable of providing this critical information. Even though normal tissue toxicity was comparable between the 2 arms of the trial, doses to the CTV, normal breast, lung, heart, and contralateral breast were not given. In addition, the impacts of breathing motion and treatment set-up uncertainties were not taken into consideration in this trial. Given the fact that only 8 fractions were used in the PBI arm, these issues are critical. At the present time, EBRT techniques capable of delivering PBI in an accurate and reproducible fashion have simply not been developed. The second randomized trial comparing whole-breast RT to PBI used primarily brachytherapy as the mode of RT delivery. Seventy-two patients with T1 breast cancer treated at the National Institute of Oncology in Budapest, Hungary were randomized between whole-breast irradiation (50 Gy in 25 fractions in 37 patients) or PBI (using 7 × 5.2 Gy HDR interstitial brachy-

therapy in 26 patients or 50 Gy in 25 fractions using wide field electron therapy in 9 patients). At a median follow-up of 21 months, no local or regional recurrences were observed. Three patients (4.2%) developed distant metastases (1 in the whole-breast RT arm and 2 in the PBI arm). There were no marked differences in the 2 arms regarding the incidence of telegiectasia, fibrosis, or fact necrosis. 7 Whether or not brachytherapy will provide a better control rate in the breast in the Hungarian trial vs the Manchester EBRT trial remains to be seen. Fortunately, quantitative assessment of implant quality with both dose volume histograms and dose nonuniformity ratios were used in the Hungarian trial. This should theoretically provide (with extended follow-up) a more objective interpretation of control rates in the breast. N o n r a n d o m i z e d Studies o f Partial Breast Irradiation

Nearly all nonrandomized studies of PBI have been performed with interstitial implantation with LDR or HDR radioactive sources. Results in these studies have varied substantially due to both patient selection factors and differences in quality control between trials. Data are now available from at least 8 different institutions throughout North America and Europe. 4-7,1°,11,13-18,46,50,52Outcome, treatment techniques, and patient selection criteria in all of these studies are outlined in Table 2. A complete assessment of the largest trials with the longest follow-up and most stringent enrollment and treatment criteria are presented below. O c h s n e r Clinic

From January 1992 through October 1993, 50 patients with breast cancer were assigned (in a block-randomized fashion) to receive either a LDR implant (45 Gy given over 3.5 to 6 days) or HDR implant (32 Gy in 8 fractions given over 4 days in twice-daily treatments). 12,14,52All patients had tumors smaller than 4 cm with negative margins. Both node-positive and node-negative patients were eligible as well as patients with ductal carcinoma-in-situ (DCIS). At a median follow-up of 75 months, 1 breast recurrence (2%), and 3 regional nodal failures (6%) were noted. The single local recurrence developed near the surgical scar 78 months after treatment. Two patients developed symptomatic fat necrosis re-

Role of Brachytherapy in Managing Breast Cancer

35

Table 2. Studies Of Partial Breast Irradiation Number of Patients External Beam Series Ribeiro et a147,48; Magee et a149,51 HDR Series Clarke et aP 5

Median Follow-up (too)

353

65

45

18

Kuske et allm52; King et a114 Perera et a116,17 Polgar et al 7,8

26

75

39 72

20 21

Vicini et al 6

54

>36

RTOG 95-17 ~ Wazer et al TM LDR Series Cionini et a113 Fentiman et a145,46 Krishnan 5° Kuske et all2.s2; King et a114 Vicini et al 5,6 RTOG 95-171~

68 30

Not Stated 24

90 27 25 25 120 31

27 72 47 75 >36 Not Stated

Scheme

Total D o s e

500-531cGy × 8 1000 cGy × 2 700 cGy X 4 600 cGy × 6 400 cGy X 8 372 cGy X 10 520 cGy X 7 433 cGy X 7 400 cGy X 8 340 cGy × 10 340 cGy X 10 340 cGy X 10

4,000-4,250cGy 2,000 cGy 2,800 cGy 3,600 cGy 3,200 cGy 3,720 3,640 3,030 3,200 3,400 3,400 3,400

cGy cGy cGy cGy cGy cGy cGy

Local Good~Excellent Recurrence CosmeticResults

25%]"

Not Stated

8.8%

95%

<2%:[:

75%

2.6%* 2.8%

Not Stated 98%

0%

>90%

Not Stated Not Stated

Not Stated Not Stated

-40 cGy/hr ---

5,000-6,000 cGy 5,500 eGy 2,000-2500 cGy 4,500 eGy

4.4%* 37%* 0% <2%$

Not Stated 83% 100% 75%

52 cGy/hr 42 cGy/hr

4,992 cGy 4,500 cGy

0% Not Stated

>90% Not Stated

*7-yr rate t8-yr rate ~not specified whether the one ipsi|ateral breast recurrence occurred in the LDRorHDRbrachytherapy group

quiring surgery, and about 70% of patients had good or excellent cosmetic results. A recent update of the Oschner Clinic trial compared outcome in their 51 brachytherapy cases with a group of 94 EBRT patients who met eligibility criteria for the brachytherapy study but were treated with traditional whole-breast EBRT during the same time period. 14 These retrospectively selected patients were identified as controls and matched for pathologic stage, tumor size, and breast size. At a median, follow-up of 75 months, the 2 groups were similar for grade III treatment toxicities, local/regional recurrence rates, and cosmesis scores.

RTOG 95-17 Study of Brachytherapy as the Sole Method of Radiation The (Radiation Therapy Oncology Group) RTOG recently completed accrual of a prospective phase II cooperative group trial of PBI with interstitial brachytherapy as the sole method of radiation therapy in patients treated with BCT. 11 The trial

was designed to test the feasibility, reproducibility, toxicity, cosmesis, local control, and disease free survival of brachytherapy alone for select patients treated with lumpectomy and axillary dissection. Between August 1997 and March 2000, 100 patients were accrued of whom 99 met all eligibility criteria. Thirty-one patients were treated with low-dose rate brachytherapy (45 Gy in 4.5 days) and 68 with high-dose rate brachytherapy (34 Gy in 10 fractions over 5 days). The target volume was defined as 2-cm peripheral, 1-cm deep, and 1-cm superficial to the surgical clips (or to the skin surface and no deeper than the pectoralis fascia). Two plane implants were used in 74 patients, > 2 in 24 and a 1 plane implant in only a single patient. Quality assurance (QA) was evaluated prospectively by a rapid turnaround review of isodose curves with clips and target volume displayed prior to initiation of treatment. A retrospective clinical and dosimetry review was recently completed by the study chair (R Kuske, personal communication May 2001),

Vicini et al

36

RTOG dosimetry office staff, and Radiological Physics Center (RPC) staff. I° On QA review, an amazing 95 patients were treated per protocol with only 4 minor protocol deviations and no major deviations. Adequate coverage of the target volume was achieved in 97% of patients with acceptable dose homogeneity in 99%. These incredible dose specification and QA results serve as a model for future trials of interstitial breast brachytherapy and clearly lay the foundation for the proper application of brachytherapy for PBI. It is anticipated that this highly successful brachytherapy trial will soon be followed by a phase III study comparing PBI to conventional whole-breast RT.

William Beaumont Hospital The largest published brachytherapy experience with PBI is currently by William Beaumont Hospital. 4-6,53,54 From January 1993 through January 2000, 174 patients were treated with PBI on 1 of 3 different Institutional Review Board (IRB) approved protocols using either a LDR implant (120 patients, 50 Gy at 52 cGy/hr) or a HDR implant (54 patients [ 46 treated with 400 cGy × 8 and 8 with 340 cGy × 10]). Thirty-two patients (18%) were followed for > 5 years, and 65 patients (37%) for > 4 years. The median follow-up for all patients was 36 months. No local and one regional recurrence were noted. The 5-year actuarial regional recurrence rate was 1%. Three patients failed distantly for a 5-year actuarial rate of 3%. No adverse sequelae were noted and cosmetic results were judged good/excellent in 90% of patients. In order to estimate the expected rate of local recurrence in patients with similar prognostic factors treated with traditional whole breast EBRT, all 174 brachytherapy patients were matched from a reference group of 1388 patients treated with standard BCT at the same institution. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, and tamoxifen use. Median follow-up was 36 months for both groups of patients. No statistically significant differences were noted between patients treated with brachytherapy or EBRT in the rates of local recurrence (0% vs 1%, p = 0.31), locoregional failure (1% vs 2%, p = 0.61), distant metastases (3% vs 6%, p = 0.24), disease free survival (91%

vs 87%, p = 0.55), overall survival (93% vs 90%, p = 0.66), or cause specific survival (99% vs 97%, p = 0.28).

Literature Analysis/Recommendations The above findings regarding PBI using interstitial brachytherapy appear to suggest that this treatment technique is viable and may provide a new application for the use of brachytherapy implants in the management of patients with breast cancer. However, in order for this new technique to ultimately prove successful, the following recommendations/guidelines will need to be followed.

(1) It is critical that proper patient selection be employed when treating patients with brachytherapy limited to the region of the lumpectomy cavity. Patients with probable muhicentric disease, inadequately excised tumors, an EIC component, or ILH are clearly not optimal for this t r e a t m e n t approach and probably accounted for part of the suboptimal results observed in the Guy's Hospital and Christie Hospital trials. 45-48 Eligibility criteria as outlined in the R T O G 95-17 protocol, 11 the William Beaumont Hospital Experience, 4 or the Oschner Clinic Experience should be followed in order to ensure optimal results. 55 (2) Since radiation is given in larger than standard doses per fraction, strict implant quality criteria must be followed in order to avoid telengiectasias, fat necrosis, fibrosis, or myositis. The thorough guidelines on this issue developed in the RTOG 95-17 protocol and the William Beaumont Hospital experience should be followed if these techniques are to be used. 4AIJ8,53 (3) It is not adequate to simply provide a detailed description of the dosimetric quality of an interstitial implant, unless it can be correlated with the ultimate coverage of the CTV and PTV. As we have previously shown, acceptable coverage is not always intuitive necessitating the need to evaluate target volume coverage with dose volume histogram analyses. 53,54 This will ultimately be required in order to correlate tumor control rates with coverage of the lumpectomy cavity region. This is especially important because the necessary margin around the lumpectomy cavity

Role of Brachytherapy in Managing Breast Cancer

(4)

is not defined, and the radiobiologically comparable hypofractionated dose has not been established. Like all surgical procedures, breast brachytherapy requires a substantial degree of expertise in order to achieve good results. It is critical that physicians a t t e m p t i n g to deliver PBI with an interstitial implant be well versed in the technical requirements for this procedure. Several articles have described CT-based methods to ensure optimal coverage of the l u m p e c t o m y cavity. 16,44 Fortunately, even simpler implantation techniques have now been developed that are more user friendly and likely to result in an acceptable result.

Kuske recently described his novel m e t h o d of implantation, where a biologically compatible contrast m e d i u m is injected into the l u m p e c t o m y cavity u n d e r ultrasound guidance immediately prior to b r a c h y t h e r a p y c a t h e t e r placement.~ The contrast m e d i u m diffuses throughout the seroma fluid, d e m o n s t r a t i n g the entirety of the irregularly shaped l u m p e c t o m y cavity. Using real-time fluoroscopic or m a m m o g r a p h i c guidance, accurate coverage of the cavity with b r a c h y t h e r a p y catheters can then be verified prior to the completion of the implant procedure. This ingenious m e t h o d of breast b r a c h y t h e r a p y has the potential to both improve the quality of m a n y breast implants as well as to allow more physicians and institutions the opportunity to participate in protocols of PBI.

(5) Despite all the studies published on the use of PBI to treat patients with breast cancer, it is i m p o r t a n t to point out that data are still preliminary and that the technique should still be considered investigational. The optimal dose fractionation schedule has not yet been established, and the necessary m a r g i n of clinically uninvolved breast tissue that needs to be irradiated around the l u m p e c t o m y bed is uncertain. Even t h o u g h 5-year results appear acceptable in the O s c h n e r Clinic and William B e a u m o n t Hospital studies, a well conducted phase III trial should be completed in order to determine the long-term efficacy of this treatm e n t approach and the patients most suitable for its application.

37

Conclusions B r a c h y t h e r a p y remains an i m p o r t a n t t r e a t m e n t option in the overall m a n a g e m e n t of patients with breast cancer. In patients treated with BCT, large, prospective randomized trials have definitively established the advantage of a boost in most patients. Interstitial brachytherapy has consistently been shown to provide an i m p o r t a n t option to boost these patients and in certain clinical settings m a y actually provide a more appropriate means of dose delivery. The concept of delivering PBI with accelerated t r e a t m e n t schedules has now provided b r a c h y t h e r a p y a new and exciting role in the m a n a g e m e n t of patients treated with BCT. Although preliminary results are encouraging, improved dosimetric guidelines (as established in R T O G 95-17) and dose volume histogram D V H analyses (as suggested by the B e a u m o n t group) must be employed in order to achieve success when used in this setting.

Reference 1. Kuske RR: Breast brachytherapy. Hematol Oncol Clin North Am 13:543-558, 1999 2. Nag S, Kuske RR, Vicini FA, et al: Brachytherapy in the treatment of breast cancer. Oncology 15:195-202, 205, 2001 3. White JR, Wilson JF: Brachytherapy and breast cancer. Semin Surg Oncol 13: 190-195, 1997 4. Vicini FA, Chen PY, Fraile M, et ah Low-dose-rate brachytherapy as the sole radiation modality in the management of patients with early-stage breast cancer treated with breast-conserving therapy: preliminary results of a pilot trial. IntJ Radiat Oncol Biol Phys 38:301310, 1997 5. Vicini F, Kini VR, Chen P, et al: Irradiation of the tumor bed alone after lumpectomy in selected patients with early-stage breast cancer treated with breast conserving therapy.J Surg Oncol 70:33-40, 1999 6. Vicini FA, Baglan KL, Kestin LL, et al: Accelerated treatment of breast cancer. J Clin Oncol 19:1993-2001, 2001 7. Polgar C, Fodor J, Orosz Z, et ah Sole high-dose-rate brachytherapy of the tumor bed after conservative surgery for T1 breast cancer: 4 year results of a phase I-II study and initial findings of a randomized phase III trial. 2001. (Personal Communication, May 2001) 8. Polgar C, Major T, SomogyiA, et al: Sole brachytherapy of the tumor bed after breast conserving surgery: A new radiotherapeutic strategy for patients at low risk of local relapse. Neoplasma 46:182-189, 1999 9. Polgar C, Major T, Somogyi A, et al: [Brachytherapy of the tumor bed after breast conserving surgery: New radiotherapeutic option in the management of early breast cancer]. A tumoragy egyeduli brachyterapiaja emlomegtarto mutet utah: uj sugarterapias lehetoseg a korai emlorak kezeleseben. Orv Hetil 140: 1461-1466, 1999

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