brachytherapy in the treatment of breast cancer...breast brachytherapy techniques vary widely, and...

Brachytherapy in the Treatment of Breast CancerPublished on Cancer Network (http://www.cancernetwork.com)

Brachytherapy in the Treatment of Breast CancerReview Article [1] | February 01, 2001 | Breast Cancer [2], Brachytherapy [3]By Subir Nag, MD [4], Robert R. Kuske, MD [5], Frank A. Vicini, MD [6], Douglas W. Arthur, MD [7],and Robert D. Zwicker, PhD [8]

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionatedtreatments. In

Introduction

Breast brachytherapy has been in use for most of the 20th century. In the 1920s, Keynes usedinterstitial radium needles to implant the entire breast, and frequently, the peripheral lymph nodes,to treat cancer of the breast.[1] With the advent of megavoltage radiation, external-beam radiationtherapy (EBRT) was used to treat the whole breast, with brachytherapy being utilized as a boost forunresected tumors. The high total doses resulted in poor cosmetic results, and therefore, the trendwas to perform lumpectomy followed by EBRT and lower doses of brachytherapy.[2,3]

Published reports, however, showed that lumpectomy (with biopsy-negative margins) followed byEBRT without an intersitial boost was as effective as mastectomy.[4] This raised the question ofwhether boosts were necessary. In addition to these reports, the widespread availability of the lessinvasive electron-beam boost led to a decline in the role of brachytherapy boost in treating primarybreast cancers.

Whole-breast EBRT involves a 6-week course of fractionated treatments. In contrast, brachytherapycan be completed in a 4- to 5-day treatment course.[5-7] This feature has renewed interest in breastbrachytherapy as a sole treatment modality after lumpectomy. The American Brachytherapy Society(ABS) recognizes that EBRT is the standard radiation modality used in the treatment of breastcancer. Brachytherapy is an alternative that is being investigated for specific circumstances.

The ABS Guidelines for Brachytherapy

Breast brachytherapy techniques vary widely, and few radiation oncologists have extensiveexperience in this realm. Because limited guidelines exist for the clinical use of this therapy,[8] theABS formed a panel to issue guidelines specifically for the use of brachytherapy in breast carcinoma.

The ABS panel consisted of selected ABS members with expertise in breast brachytherapy. The panelperformed a literature review, and supplemented with their clinical experience and biomathematicalmodeling, formulated specific recommendations and directions for future investigations in breastbrachytherapy. Technical details were also included to benefit readers who may not be able to findsuch details in standard textbooks.

Recommendations were made by consensus and supported by evidence in the literature wheneverpossible. The ABS’s categories of consensus are similar to those used by the NationalComprehensive Cancer Network.[9] Unless specifically noted, these recommendations generallyreflect a category 2 consensus. Definitions of categories 1 through 3 are as follows:

Category 1: There is uniform panel consensus based on high-level evidence that therecommendation is appropriate.

Category 2: There is panel consensus based on lower-level evidence, including nonpublishedclinical experience, that the recommendation is appropriate. There is no major disagreement amongpanel members.

Category 3: There is major disagreement among panel members that the recommendation is

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appropriate.

The initial report was revised due to additional comments of external experts who were not membersof the panel. These reviewers are listed in the acknowledgments below. The Board of Directors of theABS approved the final document.

Please note: These guidelines represent a consensus of the authors regarding a currently accepted treatment. These guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient’s treatment. The American Brachytherapy Society makes no warranties of any kind regarding the use of these guidelines and disclaims any responsibility for their application in any way.

General Considerations Regarding Technique

Clinical Target Volume

The ABS recommends precise definition and meticulous delineation of the clinical target volume.There are various methods of identifying this parameter, including the use of surgical clips,computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, nonionic radio-opaquecontrast material, and/or direct visualization at the time of surgery.[8,10-12] Patients should be seenby both a surgeon and radiation oncologist before treatment.

The optimum volume to be treated by breast brachytherapy is controversial; treating too small avolume would result in high recurrence rates.[13,14] The ABS currently recommends a 2-cm marginaround the lumpectomy cavity. This results in the irradiation of a large volume, but reduces localrecurrence. Only controlled clinical trials will be able to demonstrate whether it is possible to treat asmaller volume and still obtain good local control.

The clinical target volume is defined as the volume encompassed by an irregularly shaped surfaceapproximately 2 cm outside of the excision cavity, unless extending the margin would go beyond thebreast tissue.[8] If the skin restricts the superficial margin, then the superficial target margin isredefined as 0.5 cm below the skin surface. Similarly, if the chest wall restricts the deep margin, thenew deep-target margin boundary would be redefined as the surface of the chest wall.

The margin can be modified under special circumstances, depending on the tumor size and extent ofsurgical resection (consensus category 3). For brachytherapy, the clinical target volume is the sameas the planning-target volume. In order to guarantee adequate coverage, the treated volume isideally larger than the target volume.[8]

Treatment Planes

The ABS recommends using a minimum of two planes, unless the amount of breast tissue limits thetarget volume to less than a 2-cm thickness. For a larger target volume (> 2.5- to 3-cm thickness),additional planes should be considered.

Optimized values of interplanar spacing for a range of biplanar implant sizes are available.[15-17]Within a given plane, the separation between catheters is 1.0 to 1.5 cm. Ideally, the catheters shouldextend 1 to 2 cm beyond the edge of the clinical target volume. Coverage of the target volume alongthe length of the catheters is determined by the length of the active sources or dwell positions alongeach catheter. They should also extend 1 to 2 cm beyond the target volume.

To allow for this, skin entry and exit points should extend 2 to 4 cm beyond the edge of the targetvolume. This will allow a "dead space" of 1 to 2 cm from the last radioactive sources to the skin,which minimizes the risk of skin hyperpigmentation and telangiectasia.[8] To minimize the risk of ahigh dose to the ribs, a minimum distance of 0.5 cm between catheters in the deep plane and theribs is suggested.

If a wide separation between catheters or planes is noted, or if a peripheral edge at the clinicaltarget volume is not covered by the prescription isodose curve, it is preferable to insert additionalcatheters to avoid underdosage. Similarly, if the target volume is thicker on one side, additionalcrossing catheters may be required to adequately cover the thicker side. A less desirable alternativewould be a higher weighting (increased dwell times) on the thicker side. However, this may lead to

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problematic local high-dose regions surrounding these catheters.

Catheter Concerns

The ABS deems the use of rigid templates as optional. The advantage of templates is that they effectprecise geometric source distributions. However, this strategy may produce coverage problems incases of curved, irregularly shaped target volumes. The freehand technique, especially with an openwound, permits catheter placement that conforms to the shape of the lumpectomy cavity.Nonetheless, this may result in less uniform isodose distributions.

The ABS recommends the appropriate use of dose optimization in high-dose-rate therapy. However,optimization should not be used to compensate for inadequate or improper catheter placement. It ispreferable to have too many catheters implanted rather than too few. Since the catheters arecommonly left in place for 1 to 2 weeks when brachytherapy is used as a sole modality, the ABSrecommends appropriate catheter care to reduce the risk of infection and minimize discomfort.[8]The ABS recommends adequate treatment planning to ensure dose coverage and dose homogeneitywithin the clinical target volume. These characteristics define the quality of a breast implant.Iridium-192 is the most commonly used isotope for both low-dose-rate and high-dose-rate breastbrachytherapy. The ABS recommends the following procedures for calibration and quality assuranceof high-dose-rate units as specified by the device manufacturer, license conditions, and nationalprofessional organizations.[16-21] The ABS also recommends in-house calibration of low-dose-ratesources as specified by the American Association of Physicists in Medicine (AAPM).[18,22]

For large numbers of brachytherapy sources, it is recommended that at least 10% of sources bechecked for consistency with the manufacturer’s stated value. Tolerance levels for possiblediscrepancies and specifications for well counters used for this purpose are available in theliterature. The AAPM recommendation should also be followed for source-activity specification anddose-calculation formalism.[22]

High-Dose-Rate Implants

Due to the flexibility of dwell-time optimization, a high dose rate can provide greater dosehomogeneity than a low dose rate. For high-dose-rate implants, it is possible to optimize dosehomogeneity by requiring that a uniform dose be delivered in the plane midway between andparallel to the implant planes. To achieve this with biplanar implants, the separation between theideally positioned catheter planes can be calculated as the target thickness divided by the squareroot of 2.[16] Dwell times in this case will assume a Manchester-type configuration,[23] with longerdwell times near the edges of the implanted planes. Foreknowledge of the optimal interplanarseparation will provide the clinician with a concrete physics-based plan of action with which to beginthe procedure. Although the actual centering and dimensions of the implant will deviate from theideal, small deviations are not expected to have a great impact on the clinical effectiveness of thetreatment.[16]

For any given set of dose constraints, dwell-time optimization programs can often yield a widedisparity in dwell times between neighboring dwell positions. This, in turn, can lead to intense localhot spots. Dwell times should be examined before treatment to avoid such extreme variations.

Non-CT-Based Treatment

For non-CT-based treatment planning, the ABS recommends that either orthogonal or twovariable-angle films of the implanted breast�with dummy seeds in each catheter�be obtained fordosimetry calculations. Additional film, with planes parallel and perpendicular to the implant plane,should be produced to aid in visualization of the target dimensions and to determine the relationshipwith the chest wall and position of clips. These films are used to define the clinical target volume andproduce computer-generated isodose curves.

Commonly obtained calculation planes are the central transverse, extreme transverse, coronal, andsagittal planes. The coronal and sagittal planes are orthogonal to the central transverse plane and toeach other, but may not correspond to the strict anatomic definition of "coronal" and "sagittal." For

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the purpose of breast brachytherapy, these calculation planes are defined as follows[8]:

Central Transverse Plane: The plane through the geometric center of the implant, slicingperpendicularly through the catheters.

Extreme Transverse Planes: Located 1 cm proximal from each edge of the clinical target volume,and parallel to the central transverse plane.

Coronal Plane: The plane midway between the two implant planes (or between any two, if thereare more), and parallel to them. Note that this need not be coronal in strict anatomic terms.

Sagittal Plane: The plane perpendicular to the other two planes and passing through the implantcenter. Note that this need not be sagittal in strict anatomic terms.

It should be recognized that each isodose plot provides only two-dimensional (2D) information that isrelevant to its corresponding calculation plane.

Image-Based Treatment Planning

The ABS considers image-based treatment planning to be ideal due to the additional information thatcan be obtained. If image-based planning is available, isodose plots on all CT cuts or a representativeselection of CT cuts should be generated. If possible, three-dimensional (3D) images of the targetand relevant isodose surfaces should be examined.

A dose-volume histogram of the clinical target volume provides useful information and should beused whenever available to aid in the assessment of dose coverage and homogeneity.[24] Adose-volume histogram of the skin can be useful for predicting cosmesis.

The plan evaluation should include an assessment of target volume coverage, including adetermination or estimate of the fraction of the target volume that is receiving the prescription dose(V100). If 3D planning is available, the percentage volume of target contained within various isodosesurfaces (eg, V200, V150, V100, V90, V80 ) should be obtained and correlated with the outcome. There was noconsensus (category 3) regarding the acceptable value for V100. However, it was felt that one should beconcerned if the V100 is significantly less than 90%. The actual volume of the target volume (incubic centimeters) should be obtained and recorded.

Several schemes have been put forward to plan and evaluate interstitial iridium-192 implants and toassess dose homogeneity within an implant.[25-29] For 2D planning, the isodose plots of the centralreference plane can be used to determine the mean central dose (or dose rate)�a measurement thatis geometrically identical to the basal dose (or dose rate) of the Paris System.[25]

Dose-Homogeneity Index

The International Commission on Radiation Units and Measurement defines the dose homogeneityindex as the ratio of the minimum target dose to the mean central dose.[30] The Radiation TherapyOncology Group (RTOG) defines the dose homogeneity index as the ratio of the prescribed dose tothe mean central dose.[8] The ABS recommends the use of the RTOG definition, since its value isdependent on the choice of the prescription isodose line. The maximum dose to skin forbrachytherapy as a boost is typically kept below 50% of the implant dose. For implant only, the ABSsuggests keeping the skin dose limited to the prescribed dose.

Brachytherapy as the Sole Modality for Subclinical Disease

For more than a century, the management of breast cancer was based on the premise that theentire breast should be treated. The published literature, however, indicates that the vast majority ofrecurrences occur in the vicinity of the surgical excision site�both with and without whole-breastirradiation.[31-36]

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Remote relapse rates are approximately 0% to 3.5% in trials with lumpectomy alone or lumpectomyand breast irradiation.[31-37] These published trials did not exclude patients with biologicallysignificant multicentric breast disease. Therefore, it has been hypothesized that the primary benefitof breast irradiation following tumor excision exists in its effects on the breast tissue immediatelysurrounding the lumpectomy cavity.

Numerous clinical trials have been undertaken to evaluate the treatment of breast cancer bybrachytherapy alone (Table 1).[5,8,10,38-43] Whereas most of the early results are comparable tostandard breast conservation, some reported results are not. These differences emphasize theimportance of patient selection and treatment approach.

The ABS recognizes that EBRT is the standard radiation modality used in the treatment of breastcancer. At the present time, the use of brachytherapy as a sole modality should be consideredinvestigational and should be performed in the context of a controlled clinical trial. The ABSacknowledges the significant increase in the use of brachytherapy as the sole treatment in themanagement of early-stage breast cancer after lumpectomy. In view of promising early results, theABS encourages the enrollment of these patients in clinical trial protocols in order to address theissues raised in this report.

The ABS recommends the routine use of dose-volume histograms and the dose homogeneity index(as defined by the RTOG) as tools to ensure reproducible brachytherapy and to allowinterinstitutional comparison. To demonstrate that a 4- to 5-day brachytherapy regimen is anacceptable alternative to the standard 6 weeks of EBRT, the ABS recommends adherence to theseguidelines. If accelerated treatment using brachytherapy yields comparable local control andcosmetic outcome, it would likely improve the quality of life for women with breast cancer. Just asimportantly, it would also extend the option of breast conservation to more women.

With the successful completion of the RTOG 95-17 phase II brachytherapy trial, the ABS recommendsthe initiation of a randomized clinical trial comparing brachytherapy alone to whole-breast EBRT. Anaccelerated (4- to 5-day) brachytherapy treatment course can be an attractive alternative to 6weeks of EBRT, especially in the following groups:

patients living a long distance from radiation oncology treatment facilities

patients who lack transportation

professional women whose schedules will not accommodate a 6-week course of therapy

elderly, frail patients in poor health who may not be able to travel for a prolonged course ofdaily treatment

women with large breasts who may have unacceptable toxicity with EBRT.

Patient Selection Criteria

Patients who are not acceptable candidates for breast-conserving therapy should not be consideredfor brachytherapy alone.[13,31,44-46] The ABS recommends that to be considered for treatmentwith brachytherapy as a sole modality, patients should have T1/2, N0 histologically confirmed,unifocal, invasive ductal carcinoma of the breast, with a lesion < 3 cm, treated with lumpectomy andaxillary dissection.

The ideal patient has negative surgical margins of excision. However, patients with close, butnegative, inked histologic margins of lumpectomy or reexcision specimen are appropriate candidates

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as well.

Margins are generally considered positive if a tumor exists at the inked resection margin; marginsare deemed close, but negative, if the tumor exists within 2 mm of the inked margin; and marginsare considered negative if the tumor is at least 2 mm from the inked edge.[8,47-49]

Special Circumstances: The treatment of node-positive patients is controversial. Some panelmembers feel that patients with less than four positive axillary nodes with no extracapsularextension (with at least eight sampled axillary lymph nodes), or a negative sentinel node, could alsobe considered for brachytherapy as the sole modality (category 3). Patients must have negativepostlumpectomy or postreexcision mammography if they had presented with malignancy-associatedmicrocalcifications. There should be no remaining suspicious microcalcifications in the breast beforebrachytherapy.[32]

Insufficient evidence exists regarding the use of brachytherapy in patients with invasive lobularhistology. Some panel members expressed concern about biologically significant multicentricity andmultifocality with this histology (category 3).[6,50] Treatment of patients with ductal carcinoma insitu (DCIS) by this modality is also controversial, but considered acceptable by the panel as long asthe other selection criteria are met. Specifically, small, unifocal DCIS that is excised with clearmargins appears to have recurrence rates and patterns of failure that are similar to those of invasivecancer (category 3).[51]

Patients with collagen-vascular diseases, Paget’s disease of the nipple, or significant skininvolvement are poor candidates for breast-conservation therapy. Moreover, patients with a breastthat is technically unsuitable for brachytherapy should not be considered for such treatment.

Dose of Sole-Modality Brachytherapy

The ABS recognizes that an optimal dose has not been established, and that the following range ofdoses may be appropriate:

Low Dose Rate: The ABS recommends a dose range of 45 to 50 Gy to the clinical targetvolume.[7,8,10] Traditionally, the dose has been administered at about 10 Gy/d, at a rate of 30 to 70cGy/h.[52]

High Dose Rate: The ABS recommends a total dose of 34 Gy in 10 fractions to the clinical targetvolume.[8,10,53] Treatments of 3.4 Gy are generally administered at two fractions per day,separated by at least 6 hours. This dose�which was originally derived using the linear quadraticmodel to determine the biological equivalence of a 45-Gy low dose rate[54]�was used in the phase IIRTOG trial.[8] However, since the actual alpha/beta ratio of breast tissues and tumors is not known,it should be realized that these doses may not be exactly bioequivalent to the corresponding dosesof the low dose rate.

Pulsed Dose Rate: The pulsed dose rate is rarely used in the United States. That said, doses usedfor this schedule are similar to those employed for the low dose rate.

Despite the common use of a brachytherapy boost following EBRT to the whole breast, its necessityremains controversial. A randomized trial from Lyon, France, addressing this issue demonstrated asmall but statistically significant improvement in local control with the addition of a boost.[55]Another randomized trial from Nice, France, showed improvement in local control, but this differencewas not statistically significant.[56] Results are awaited from the European Organization forResearch and Treatment of Cancer (EORTC) randomized trial consisting of approximately 5,500patients. Other studies have not shown any improvement with a brachytherapy boost.[48]

If a boost is deemed necessary, either EBRT or brachytherapy can deliver the desired dose.[57-61]Acceptable local control and cosmetic results have been reported (Table 2).[52,57-59,62-69] Thecost and time required (for both the patient and physician) for these two boosting techniques differgreatly. In addition, brachytherapy adds the risk of an invasive procedure with an outcome that ishighly dependent upon the expertise of the physician/physicist team.[10,58] Therefore,

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brachytherapy should be used selectively as a boosting technique.

Benefits of Brachytherapy Boost

Brachytherapy can deliver a higher dose to the clinical target volume with a lower dose to the skin,and as a result, it has the potential for an improved cosmetic result.[57,70] Situations in which ahigher dose may be required because of a larger tumor burden include[57-59,61]:

close, positive, or unknown margins

an extensive intraductal component (category 3)

a younger patient.

In addition, brachytherapy has been considered potentially advantageous over EBRT when thelocation/shape of the clinical target volume allows brachytherapy to provide better coverage whilereducing the surrounding normal tissue dose. Examples include deep tumors in a large breast or aclinical target volume of irregular thickness.[57-59,61]

The brachytherapy boost can be administered before or after EBRT. There is generally a 1- to 2-weekgap between the EBRT and brachytherapy. The ABS does not favor one method of sequencing overthe other. The ABS recommends defining the clinical target volume for boost as it would be definedwith brachytherapy alone.

Publications showing inferior cosmetic outcomes after brachytherapy boost have lacked thenecessary attention to technical details such as dose homogeneity.[63,66,68,69,71] Recentexperiences have demonstrated equivalent or superior results to electron-beam boosting�despitethe higher doses. Various low-dose-rate boost doses and high-dose-rate fractionation schemes havebeen used.

Dose of Brachytherapy After Whole-Breast EBRT

Following 45 to 50 Gy of EBRT to the whole breast, doses for brachytherapy are as follows:

Low Dose Rate: The ABS recommends a total dose of 10 to 20 Gy (at 30 to 70 cGy/h) prescribed tothe clinical target volume�depending on the surgical margins and EBRT dose.

High Dose Rate: Data on the use of a high dose rate as a boost are limited. The ABS recommendsthat a dose-fractionation scheme be used that yields early and late effects approximately equivalentto those of a 10- to 20-Gy low dose rate. Examples of fractionation schemes that have been used areincluded in Table 2.

Pulsed Dose Rate: The pulsed dose rate is rarely used in the United States. Doses are similar tothose used for the low-dose rate.[72]

Biomathematical models are often used to estimate equivalent high-dose-rate regimens.[53,54] Forexample, linear quadratic modeling has suggested[73] that a high-dose-rate regimen of 5 fractionsof 310 cGy per fraction should approximate the early and late effects of a 20-Gy low dose ratedelivered at 0.5 Gy/h.

The actual alpha/beta ratio of breast tissues and tumors is not known. Nevertheless, such estimatescan now be useful in reinforcing the clinician’s judgment, and may one day be improved when morereliable values of the model parameters for breast tissue become known. Although biomathematicalmodels[53,54] can be used to estimate the appropriate dose, there is no standardized high-dose-ratefractionation schedule that can be recommended.

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Brachytherapy for Recurrence After Breast Conservation

Literature is sparse on the use of brachytherapy to treat recurrence after breast-conservationtherapy. Maulard et al[74] treated 15 patients with tumorectomy and 30 Gy of perioperativelow-dose-rate brachytherapy (with catheters being placed at the time of surgery). They reported alocal recurrence in four patients (26%), an overall 5-year survival rate of 61%, and a disease-freesurvival rate of 33%.

The 30-Gy dose that Maulard et al used was lower than the usual 40 to 50 Gy used by radiationoncologists to treat microscopic disease. It is possible that the investigators could have achievedgreater local control if they had administered a higher dose (40 to 50 Gy) followingtumorectomy.[75] Maulard et al also treated 23 patients with larger tumors using brachytherapyalone (without tumorectomy) at 60 to 70 Gy in two implants, achieving an overall survival of50%.[74]

The ABS feels that mastectomy remains the treatment standard for local recurrence afterbreast-conservation therapy. Due to the paucity of published data, the ABS cannot make a firmrecommendation on the use of brachytherapy in recurrent breast cancers.

However, brachytherapy may provide a viable option for women with a strong desire for breastconservation, assuming appropriate selection and treatment techniques are exercised. The ABSbelieves that complete excision should precede brachytherapy.

The clinical target volume should be defined as previously detailed in these recommendations.Factors to be considered include time to recurrence, late effects from prior radiation, and a strongdesire on the part of the patient to preserve her breast. After adequate excision of the recurrence,management should proceed as outlined in the section entitled, "Brachytherapy as the Sole Modalityfor Subclinical Disease."

Conclusions

These guidelines have been established for the use of brachytherapy in the treatment of breastcancer; they will be modified as further clinical results become available. Practitioners andcooperative groups are encouraged to use these guidelines to formulate their treatment anddose-reporting policies. However, the responsibility for medical decisions ultimately rests with thetreating radiation oncologist. References: 1. Keynes G: The treatment of primary carcinoma of the breast with radium. Acta Radiol 10:393-402,1929.

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3. Pierquin B, Owen R, Maylin C, et al: Radical radiation therapy of breast cancer. Int J Radiat OncolBiol Phys 6:17-24, 1980.

4. Fisher B, Bauer M, Margolese R, et al: Five-year results of a randomized clinical trial comparingtotal mastectomy and segmental mastectomy with or without radiation in the treatment of breastcancer. N Engl J Med 312:665-673, 1985.

5. Kuske RR, Bolton JS, Wilenzick RM, et al: Brachytherapy as the sole method of breast irradiation inTIS, T1, T2, N0-1 breast cancer. Int J Radiat Oncol Biol Phys 30(S1):245, 1994.

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7. Vicini FA, Chen PY, Fraile M, et al: Low-dose-rate brachytherapy as the sole radiation modality inthe management of patients with early-stage breast cancer treated with breast-conserving therapy:Preliminary results of a pilot trial. Int J Radiat Oncol Biol Phys 38:301-310, 1997.

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20. Glasgow GP, Bourland JD, Grigsby PW, et al: Remote Afterloading Technology: A Report of AAPMTask Group No. 41. New York, American Institute of Physics, 1993.

21. Kubo HD, Glasgow GP, Pethel TD, et al: High dose rate brachytherapy treatment delivery: Reportof the AAPM Radiation Therapy Committee Task Group No. 59. Med Phys 25:375-403, 1998.

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25. Pierquin B, Dutreix CH, Paine D, et al: The Paris System in interstitial radiation therapy. ActaRadiol Oncol Radiat Phys Biol 17:33-48, 1978.

26. Saw CB, Suntharalingam N: Reference dose rates for single and double plane Ir-192 implants.Med Phys 15:391-396, 1988.

27. Waterman FM, Mansfield CM, Komarnicky L, et al: A dosimetry system for Ir-192 interstitial breastimplants performed at the time of lumpectomy. Int J Radiat Oncol Biol Phys 37:229-235, 1997.

28. Wong VYW, Leung TW, Wong CM: Relative dose uniformity assessment in interstitial implants. IntJ Radiat Oncol Biol Phys 44:1179-1184, 1999.

29. Zwicker RD, Schmidt-Ullrich R: Dose uniformity in a planar interstitial implant system. Int J RadiatOncol Biol Phys 31:149-155, 1994.

30. ICRU Report 58: Dose and volume specification for reporting interstitial therapy. Bethesda, Md,International Commission on Radiation Units and Measurements, 1997.

31. Fisher B, Anderson S: Conservative surgery for the management of invasive and non-invasivecarcinoma of the breast: NSABP trials. World J Surg 18:63-69, 1994.

32. Fowble B, Solin LJ, Schultz DJ, et al: Breast recurrence following conservative surgery andradiation: Patterns of failure, prognosis, and pathologic findings from mastectomy specimens withimplications for treatment. Int J Radiat Oncol Biol Phys 19:833-842, 1990.

33. Clark RM, McCulloch PB, Levine MN, et al: Randomized clinical trial to assess the effectiveness ofbreast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. JNatl Cancer Inst 84:683-689, 1992.

34. Fisher ER, Sass R, Fisher B, et al: Pathologic findings from the National Surgical Adjuvant BreastProject (Protocol 6): II. Relation of local breast recurrence to multicentricity. Cancer 57:1717-1724,1986.

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Source URL: http://www.cancernetwork.com/brachytherapy-treatment-breast-cancer-1

Links:[1] http://www.cancernetwork.com/review-article[2] http://www.cancernetwork.com/breast-cancer[3] http://www.cancernetwork.com/brachytherapy[4] http://www.cancernetwork.com/authors/subir-nag-md[5] http://www.cancernetwork.com/authors/robert-r-kuske-md[6] http://www.cancernetwork.com/authors/frank-vicini-md[7] http://www.cancernetwork.com/authors/douglas-w-arthur-md[8] http://www.cancernetwork.com/authors/robert-d-zwicker-phd

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http://www.cancernetwork.com/brachytherapy-treatment-breast-cancer-1

brachytherapy in the treatment of breast cancer...breast brachytherapy techniques vary widely, and...

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