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The American Brachytherapy Society consensus statement for accelerated partial breast irradiation

Open AccessPublished:April 24, 2013DOI:https://doi.org/10.1016/j.brachy.2013.02.001

      Abstract

      Purpose

      To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer.

      Methods and Materials

      Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience.

      Results

      Increasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selection for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age (≥50 years old), tumor size (≤3 cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment.

      Conclusions

      These guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection.

      Keywords

      Introduction

      Breast-conserving therapy (BCT) represents one of the seminal treatment breakthroughs in the management of breast cancer. With more than 20-year followup, multiple randomized trials have found comparable outcomes between BCT and mastectomy, allowing women to choose to preserve their breast without compromising their ability to be cured of their cancer (
      • Fisher B.
      • Anderson S.
      • Bryant J.
      • et al.
      Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
      ,
      • Van Dongen J.A.
      • Voogd A.C.
      • Fentiman I.S.
      • et al.
      Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial.
      ,
      • Veronesi U.
      • Cascinelli N.
      • Mariani L.
      • et al.
      Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.
      ). Beyond simply preserving the breast, BCT has been associated with improved quality of life, including social functioning, body image, and physical functioning, compared with mastectomy (
      • Arndt V.
      • Stegmaier C.
      • Ziegler H.
      • et al.
      Quality of life over 5 years in women with breast cancer after breast-conserving therapy versus mastectomy: A population-based study.
      ). Radiation therapy (RT) represents an integral part of BCT as multiple trials have documented increased rates of ipsilateral breast tumor recurrence (IBTR) in women undergoing breast-conserving surgery (BCS) without RT; even among women considered at low risk for IBTR, RT has been associated with a significant reduction in IBTR (Table 1 ) with a meta-analysis confirming these findings and identifying a breast cancer mortality benefit (
      • Fisher B.
      • Anderson S.
      • Bryant J.
      • et al.
      Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
      ,
      • Fisher B.
      • Bryant J.
      • Dignam J.J.
      • et al.
      Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.
      ,
      • Fyles A.W.
      • McCready D.R.
      • Manchul L.A.
      • et al.
      Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer.
      ,
      • Hughes K.S.
      • Schnaper L.A.
      • Berry D.
      • et al.
      Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.
      ,
      • Veronesi U.
      • Marubini E.
      • Mariani L.
      • et al.
      Radiotherapy after breast-conserving surgery in small breast carcinoma: Long-term results of a randomized trial.
      ,
      • Darby S.
      • McGale P.
      • et al.
      Early Breast Cancer Trialists’ Collaborative Group (EBCTG)
      Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data on 10,801 women in 17 randomised trials.
      ). One factor that often prevents women from receiving BCS followed by adjuvant RT is the length of treatment required. Traditional whole-breast irradiation (WBI) typically requires 5–6 ½ weeks with studies demonstrating that 25% or more of women fail to receive adjuvant radiation after BCS (
      • Hershman D.L.
      • Buono D.
      • McBride R.B.
      • et al.
      Surgeon characteristics and receipt of adjuvant radiotherapy in women with breast cancer.
      ,
      • Voti L.
      • Richardson L.C.
      • Reis I.
      • et al.
      The effect of race/ethnicity and insurance in the administration of standard therapy for local breast cancer in Florida.
      ). Accelerated partial breast irradiation (APBI) represents a technique that allows for the delivery of adjuvant therapy after BCS in 1 week or less with multiple techniques available at this time to deliver APBI; intraoperative partial breast irradiation is an another alternative that delivers a single fraction of RT in the perioperative period. APBI allows for women who may otherwise forgo adjuvant RT the ability to complete treatment in an efficient manner and is increasingly being used with a 10-fold increase noted between 2002 and 2007 (
      • Husain Z.A.
      • Mahmood U.
      • Hanlon A.
      • et al.
      Accelerated partial breast irradiation via brachytherapy: A patterns-of-care analysis with ASTRO consensus groupings.
      ).
      Table 1Breast-conserving therapy with or without RT
      TrialNumber of patientsTrial randomizationFollowup (mo)Limiting factorsLocal recurrence
      RT (%)No RT (%)
      NSABP B-06
      • Fisher B.
      • Anderson S.
      • Bryant J.
      • et al.
      Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
      1851Lumpectomy ± RT2481439
      NSABP B-21
      • Fisher B.
      • Bryant J.
      • Dignam J.J.
      • et al.
      Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.
      1009Lumpectomy + tamoxifen ± RT87T < 1 cm316
      Canadian Multi-Institutional
      • Fyles A.W.
      • McCready D.R.
      • Manchul L.A.
      • et al.
      Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer.
      769Tamoxifen ± RT66>50 y old.67.7
      CALGB 9343
      • Hughes K.S.
      • Schnaper L.A.
      • Berry D.
      • et al.
      Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.
      636Tamoxifen ± RT126>70 y old17
      Milan
      • Veronesi U.
      • Marubini E.
      • Mariani L.
      • et al.
      Radiotherapy after breast-conserving surgery in small breast carcinoma: Long-term results of a randomized trial.
      580Quadrantectomy ± RT109T ≤ 2.5 cm5.823.5
      RT = radiation therapy; NSABP = National Surgical Adjuvant Breast and Bowel Project; CALGB = Cancer and Leukemia Group B; T = tumor size.
      With the increased use of APBI, evidence-based guidelines are necessary to guide clinicians with regard to appropriate patient evaluation and selection. Although the American Brachytherapy Society (ABS) has previously provided guidelines for APBI, these guidelines have been updated to reflect the significant increase in published data and changes in clinical practice since the previous publication (

      American Brachytherapy Society: Breast Brachytherapy Task Group. Breast Brachytherapy. American Brachytherapy Society Web site. Available at: http://www.americanbrachytherapy.org/guidelines/abs_breast_brachytherapy_taskgroup.pdf. Updated February 1, 2007. Accessed August 22, 2012.

      ).

      Methods and materials

      The ABS guidelines for APBI were composed by members of the ABS with expertise in breast cancer and in particular breast brachytherapy. The goals of this effort were to update the previous guidelines based on a review of new data addressing the efficacy and toxicity of APBI. Clinical guideline development was initiated with a systematic review of the literature with a focus on randomized trials, multi-institution series, and single institution reports addressing clinical outcomes and toxicities. Five randomized trials were identified along with 41 nonrandomized studies (Phase I/II, single institution, and multi-institution). Although randomized trials were evaluated, because of the short followup of more recent trials, outdated or nonstandard techniques of older trials, and a lack of power in several trials, focus was placed on nonrandomized data when creating the final guidelines. Current recommendations or guidelines previously published (by other societies) were evaluated as well. Following a discussion of the literature, the revised guidelines were established by consensus among the authors based on the review of the literature on the topic and their expert opinions. When evaluating the data available and establishing guidelines, the study design and limitations of studies were also taken into consideration. Furthermore, guidelines were made with the knowledge that current guidelines may be changed moving forward based on future published data, in particular data from randomized trials.

      Evaluation of specific guideline recommendations

      With regard to age criteria for the application of APBI, this guideline remains unchanged because of a lack of significant new data supporting a change in the recommendation. Specifically, no APBI studies were identified that conclusively established age as risk factor for an increased risk of IBTR when applying the technique beyond that already identified when using BCT in general with standard WBI.
      When evaluating tumor size, the threshold was kept at 3 cm, consistent with the previous ABS guidelines and other consensus guidelines and inclusion criteria for randomized trials. No data were identified to suggest that APBI should or could be applied after neoadjuvant chemotherapy for patients with tumors >3 cm. Similarly, when evaluating nodal status, only node-negative patients were included consistent with the previous ABS guidelines and other consensus guidelines.
      For surgical margins, the recommendation was based on recently published data and confirmed with other consensus guidelines. Specifically, very few published studies were identified that conclusively established (or suggested) that APBI could be applied safely in other clinical settings (i.e., focally positive margins, etc.). The exclusion of lymphovascular space invasion (LVSI) was based on a combination of recently published APBI data and consensus agreement with previously published guidelines.
      For histology, a change was made to incorporate all invasive subtypes and ductal carcinoma in situ (DCIS) because no new data were identified establishing any other subtype that resulted in a higher risk of IBTR. Specifically, the inclusion of DCIS was based on a large number of new publications supporting the clinical efficacy of APBI in patients with DCIS. With regard to the invasive lobular carcinomas (ILC), although there still remains limited data regarding APBI and lobular carcinomas, the guideline was modified to include lobular carcinomas based on (1) the publication of two series confirming the efficacy of APBI in this population, (2) a lack of any modern APBI study finding increased recurrences with ILCs treated with APBI, and (3) extrapolation from series evaluating treatment of ILCs with standard BCT using WBI.
      With regard to estrogen receptor status, there was significant discussion regarding the inclusion of estrogen receptor–negative patients based on recently published data; however, these data are consistent with multiple other series in patients treated with mastectomy or BCT with WBI that have found that estrogen receptor negativity is associated with higher rates of local recurrence (LR). As such, it was felt that the biology of the tumor rather than the treatment modality (i.e., limiting RT to the vicinity of the lumpectomy cavity) is responsible for the higher rates of LR, and thus, the guideline was made to include estrogen receptor–negative patients. Finally, this report was reviewed and approved by the Board of Directors of the ABS.

      Results

      Prior published guidelines

      In an effort to guide clinicians, guidelines or consensus statements have been previously published by groups, including the American Society for Radiation Oncology, Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology, American Society of Breast Surgeons (ASBS), and aforementioned ABS guidelines (

      American Brachytherapy Society: Breast Brachytherapy Task Group. Breast Brachytherapy. American Brachytherapy Society Web site. Available at: http://www.americanbrachytherapy.org/guidelines/abs_breast_brachytherapy_taskgroup.pdf. Updated February 1, 2007. Accessed August 22, 2012.

      ,
      • Smith B.D.
      • Arthur D.W.
      • Buchholz T.A.
      • et al.
      Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO).
      ,
      • Polgar C.
      • Van Limbergen E.
      • Potter R.
      • et al.
      Patient selection for accelerated partial-breast irradiation (APBI) after breast conserving surgery: Recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009).
      ,

      The American Society of Breast Surgeons. Consensus statement for accelerated partial breast irradiation. Am Soc Breast Surgeons Web site. Available at: https://www.breastsurgeons.org/statements/PDF_Statements/APBI.pdf. Updated August 15, 2012. Accessed August 22, 2012.

      ).

      Clinical outcomes

      Clinical outcomes by technique are presented in Table 2 (
      • Ribeiro G.G.
      • Magee B.
      • Swindell R.
      • et al.
      The Christie Hospital breast conservation trial: An update at 8 years from inception.
      ,
      • Dodwell D.J.
      • Dyker K.
      • Brown J.
      • et al.
      A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.
      ,
      • Polgar C.
      • Fodor J.
      • Major T.
      • et al.
      Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma—5-year results of a randomized trial.
      ,
      • Vaidya J.S.
      • Joseph D.J.
      • Tobias J.S.
      • et al.
      Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised non-inferiority phase 3 trial.
      ,
      • Livi L.
      • Buonamici F.B.
      • Simontacchi G.
      • et al.
      Accelerated partial breast irradiation with IMRT: New technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial.
      ,
      • Fentiman I.S.
      • Poole C.
      • Tong D.
      • et al.
      Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.
      ,
      • King T.A.
      • Bolton J.S.
      • Kuske R.R.
      • et al.
      Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer.
      ,
      • Krishnan L.
      • Jewell W.R.
      • Tawfik O.W.
      • et al.
      Breast conservation therapy with tumor bed irradiation alone in a selected group of patients with stage I breast cancer.
      ,
      • Arthur D.W.
      • Koo D.
      • Zwicker R.D.
      • et al.
      Partial breast brachytherapy after lumpectomy: Low-dose-rate and high-dose-rate experience.
      ,
      • Perera F.
      • Yu E.
      • Engel J.
      • et al.
      Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years' minimum follow-up.
      ,
      • Fentiman I.S.
      • Deshmane V.
      • Tong D.
      • et al.
      Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial.
      ,
      • Poti Z.
      • Nemeskeri C.
      • Fekeshazy A.
      • et al.
      Partial breast irradiation with interstitial 60Co brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.
      ,
      • Slampa P.
      • Soumarova R.
      • Ruzickova J.
      • et al.
      Pilot study of sole conformal perioperative interstitial brachyradiotherapy of early stage breast carcinoma using high-dose rate afterloading.
      ,
      • Stevens M.J.
      • Cooper S.G.
      • Cross P.
      • et al.
      Accelerated partial breast irradiation using interstitial high dose rate iridum brachytherapy: Early Australian experience and review of the literature.
      ,
      • Kaufman S.A.
      • DiPetrillo T.A.
      • Price L.L.
      • et al.
      Long-term outcome and toxicity in a Phase I/II trial using high-dose-rate multicatheter interstitial brachytherapy for T1/2 breast cancer.
      ,
      • Patel R.R.
      • Christensen M.E.
      • Hodge C.W.
      • et al.
      Clinical outcome analysis in “high-risk” versus “low-risk” patients eligible for national surgical adjuvant breast and bowel B-39/radiation therapy oncology group 0413 trial: Five-year results.
      ,
      • Gomez-Iturriaga A.
      • Pina L.
      • Cambeiro M.
      • et al.
      Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy.
      ,
      • White J.R.
      • Winter K.A.
      • Kuske R.A.
      • et al.
      Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.
      ,
      • Johansson B.
      • Karlsson L.
      • Liljegren G.
      • et al.
      Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-2 breast cancer: First long time results from a clinical study.
      ,
      • Yoshida K.
      • Nose T.
      • Masuda N.
      • et al.
      Preliminary result of accelerated partial breast irradiation after breast-conserving surgery.
      ,
      • Polgar C.
      • Major T.
      • Fodor J.
      • et al.
      Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study.
      ,
      • Hattangadi J.A.
      • Powell S.N.
      • Macdonald S.M.
      • et al.
      Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.
      ,
      • Strnad V.
      • Hildebrandt G.
      • Potter R.
      • et al.
      Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery.
      ,
      • Shah C.
      • Antonucci J.V.
      • Wilkinson J.B.
      • et al.
      Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis.
      ,
      • Richards G.M.
      • Berson A.M.
      • Rescigno J.
      • et al.
      Acute toxicity of high-dose-rate intracavitary brachytherapy with the MammoSite applicator in patients with early-stage breast cancer.
      ,
      • Dowlatshahi K.
      • Snider H.C.
      • Gittleman M.A.
      • et al.
      Early experience with balloon brachytherapy for breast cancer.
      ,
      • Tsai P.I.
      • Ryan M.
      • Meek K.
      • et al.
      Accelerated partial breast irradiation using the MammoSite device: Early technical experience and short-term clinical follow-up.
      ,
      • Niehoff P.
      • Ballardini B.
      • Polgar C.
      • et al.
      Early European experience with the MammoSite radiation therapy system for partial breast brachytherapy following breast conservation operation in low-risk breast cancer.
      ,
      • Niehoff P.
      • Polgar C.
      • Ostertag H.
      • et al.
      Clinical experience with the MammoSite radiation therapy system for brachytherapy of breast cancer: Results from an international phase II trial.
      ,
      • Benitez P.R.
      • Keisch M.E.
      • Vicini F.
      • et al.
      Five-year results: The initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.
      ,
      • Chao K.K.
      • Vicini F.A.
      • Wallace M.
      • et al.
      Analysis of treatment efficacy, cosmesis, and toxicity using the MammoSite breast brachytherapy catheter to deliver accelerated partial-breast irradiation: The William Beaumont Hospital experience.
      ,
      • Cuttino L.W.
      • Keisch M.
      • Jenrette J.M.
      • et al.
      Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.
      ,
      • Vicini F.
      • Beitsch P.
      • Quiet C.
      • et al.
      Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation.
      ,
      • Vicini F.A.
      • Keisch M.
      • Shah C.
      • et al.
      Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy.
      ,
      • Leonard C.
      • Carter D.
      • Kercher J.
      • et al.
      Prospective trial of accelerated partial breast intensity-modulated radiotherapy.
      ,
      • Hepel J.T.
      • Tokita M.
      • MacAusland S.G.
      • et al.
      Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation.
      ,
      • Jagsi R.
      • Ben-David M.A.
      • Moran J.M.
      • et al.
      Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation.
      ,
      • Vicini F.
      • Winter K.
      • Wong J.
      • et al.
      Initial efficacy results of RTOG 0319: Three-dimensional conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I/II breast carcinoma.
      ,
      • Chen P.Y.
      • Wallace M.
      • Mitchell C.
      • et al.
      Four-year efficacy, cosmesis, and toxicity using three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation.
      ,
      • Hardee M.E.
      • Raza S.
      • Becker S.J.
      • et al.
      Prone hypofractionated whole-breast radiotherapy without a boost to the tumor bed: Comparable toxicity of IMRT versus 3D conformal technique.
      ,
      • Mussari S.
      • Sabino Della Sala W.
      • Busana L.
      • et al.
      Full-dose intraoperative radiotherapy with electrons in breast cancer. First report on late toxicity and cosmetic results from a single-institution experience.
      ,
      • Beal K.
      • McCormick B.
      • Zelefsky M.J.
      • et al.
      Single-fraction intraoperative radiotherapy for breast cancer: Early cosmetic results.
      ,
      • Sacchini V.
      • Beal K.
      • Goldberg J.
      • et al.
      Study of quadrant high-dose intraoperative radiation therapy for early-stage breast cancer.
      ,
      • Veronesi U.
      • Orecchia R.
      • Luini A.
      • et al.
      Intraoperative radiotherapy during breast conserving surgery: A study on 1,822 cases treated with electrons.
      ,
      • Kimple R.J.
      • Klauber-DeMore N.
      • Kuzmiak C.M.
      • et al.
      Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer.
      ,
      • Elliott R.L.
      • DeLand M.
      • Head J.F.
      • Elliott M.C.
      Accelerated partial breast irradiation: Initial clinical experience with the Intrabeam System.
      ,
      • Kozak K.R.
      • Smith B.L.
      • Adams J.
      • et al.
      Accelerated partial breast irradiation using proton beams: Initial clinical experience.
      ,
      • Bush D.A.
      • Slater J.D.
      • Garberoglio C.
      • et al.
      Partial breast irradiation delivered with proton beam: Results of a Phase II trial.
      ). The top of this table focuses on the published randomized trials to date; although there is a paucity of randomized data, multiple randomized Phase III trials are currently accruing or are recently closed and an increasing number of prospective, multi-institution, and single institution retrospective series are being published at this time.
      Table 2Series evaluating clinical outcomes by partial breast technique
      TrialYear publishedNumber of patientsAPBI techniqueFollowup (mo)Findings
      Randomized
       Christie Hospital
      • Ribeiro G.G.
      • Magee B.
      • Swindell R.
      • et al.
      The Christie Hospital breast conservation trial: An update at 8 years from inception.
      1993708EBRT65LR 15% limited field vs. 11% WBI and increased LR with ILC and limited field
       United Kingdom
      • Dodwell D.J.
      • Dyker K.
      • Brown J.
      • et al.
      A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.
      2005174EBRTTrend toward increased LR with APBI (12% vs. 4%)
       Hungary
      • Polgar C.
      • Fodor J.
      • Major T.
      • et al.
      Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma—5-year results of a randomized trial.
      2007258Interstitial/electron66No difference in LR (4.7% vs. 3.4%) and HDR associated with improved cosmesis
       TARGIT
      • Vaidya J.S.
      • Joseph D.J.
      • Tobias J.S.
      • et al.
      Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised non-inferiority phase 3 trial.
      20102232IntraoperativeNo difference in LR between intraoperative therapy and WBI; recent update demonstrates increase in IBTR for IORT cohort
       Florence
      • Livi L.
      • Buonamici F.B.
      • Simontacchi G.
      • et al.
      Accelerated partial breast irradiation with IMRT: New technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial.
      2010259EBRT (IMRT)Grade ½ skin toxicity 41% WBI vs. 5.8% APBI
      Nonrandomized
       Guy's Hospital
      • Fentiman I.S.
      • Poole C.
      • Tong D.
      • et al.
      Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.
      199627Interstitial (HDR)7237% IBTR at 8 y
       Oschner Clinic
      • King T.A.
      • Bolton J.S.
      • Kuske R.R.
      • et al.
      Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer.
      200050Interstitial (HDR)75No difference in outcomes and toxicities between APBI and EBRT cohort
       University of Kansas
      • Krishnan L.
      • Jewell W.R.
      • Tawfik O.W.
      • et al.
      Breast conservation therapy with tumor bed irradiation alone in a selected group of patients with stage I breast cancer.
      200124Interstitial (HDR)470% IBTR at 4 y
       Virginia Commonwealth
      • Arthur D.W.
      • Koo D.
      • Zwicker R.D.
      • et al.
      Partial breast brachytherapy after lumpectomy: Low-dose-rate and high-dose-rate experience.
      200344Interstitial (HDR/LDR)420% LR at 4 y, 80% excellent/good cosmesis, and 90% with HDR
       Ontario
      • Perera F.
      • Yu E.
      • Engel J.
      • et al.
      Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years' minimum follow-up.
      200339Interstitial (HDR)915-y IBTR 16.2% and 5% in-field
       Guys' Hospital
      • Fentiman I.S.
      • Deshmane V.
      • Tong D.
      • et al.
      Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial.
      200450Interstitial (HDR-Cs)7518% IBTR, 7/9 IBTR in-field, and 80% excellent/good
       Hungary
      • Poti Z.
      • Nemeskeri C.
      • Fekeshazy A.
      • et al.
      Partial breast irradiation with interstitial 60Co brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.
      200470Interstitial (60Co)14427/34 Disease free and 50% poor cosmesis
       Czech Republic
      • Slampa P.
      • Soumarova R.
      • Ruzickova J.
      • et al.
      Pilot study of sole conformal perioperative interstitial brachyradiotherapy of early stage breast carcinoma using high-dose rate afterloading.
      200525Interstitial (HDR)110% IBTR at 1 y
       Australia
      • Stevens M.J.
      • Cooper S.G.
      • Cross P.
      • et al.
      Accelerated partial breast irradiation using interstitial high dose rate iridum brachytherapy: Early Australian experience and review of the literature.
      20067Interstitial (HDR)43No LR
       Tufts University
      • Kaufman S.A.
      • DiPetrillo T.A.
      • Price L.L.
      • et al.
      Long-term outcome and toxicity in a Phase I/II trial using high-dose-rate multicatheter interstitial brachytherapy for T1/2 breast cancer.
      200732Interstitial (HDR)70.55-y IBTR 6.1% and beyond 5 y 90% excellent cosmesis
       University of Wisconsin
      • Patel R.R.
      • Christensen M.E.
      • Hodge C.W.
      • et al.
      Clinical outcome analysis in “high-risk” versus “low-risk” patients eligible for national surgical adjuvant breast and bowel B-39/radiation therapy oncology group 0413 trial: Five-year results.
      2008273247-Interstitial (HDR), 26 MammoSite48.55-y LR 2.2% low risk vs. 6.4% high risk (<50 y, ER−, and LN+)
       Spain
      • Gomez-Iturriaga A.
      • Pina L.
      • Cambeiro M.
      • et al.
      Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy.
      200826Interstitial (HDR)536-y LR 0% and 87.5% excellent/good cosmesis
       RTOG 9517
      • White J.R.
      • Winter K.A.
      • Kuske R.A.
      • et al.
      Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.
      200899Interstitial (HDR/LDR)735-y IBTR 3% (HDR) and 6% (LDR)

      3%/9% Grade ¾ toxicity with HDR/LDR
       Sweden
      • Johansson B.
      • Karlsson L.
      • Liljegren G.
      • et al.
      Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-2 breast cancer: First long time results from a clinical study.
      200950Interstitial (PDR)867-y LR 4% and 56% excellent/good cosmesis
       Japan
      • Yoshida K.
      • Nose T.
      • Masuda N.
      • et al.
      Preliminary result of accelerated partial breast irradiation after breast-conserving surgery.
      200945Interstitial (HDR)4% LR
       Hungary
      • Polgar C.
      • Major T.
      • Fodor J.
      • et al.
      Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study.
      201045Interstitial (HDR)13312-y IBTR 9.3% and 78% excellent/good cosmesis
       MGH
      • Hattangadi J.A.
      • Powell S.N.
      • Macdonald S.M.
      • et al.
      Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.
      201150Interstitial (LDR)13412-y LR 15%
       German–Austrian
      • Strnad V.
      • Hildebrandt G.
      • Potter R.
      • et al.
      Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery.
      2011274Interstitial (HDR/PDR)635-y LR 2% and 90% excellent/good cosmesis
       William Beaumont
      • Shah C.
      • Antonucci J.V.
      • Wilkinson J.B.
      • et al.
      Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis.
      2011199Interstitial (HDR)126No difference in LR between APBI (5.0%) and WBI (3.8%) at 12 y
       St. Vincent
      • Richards G.M.
      • Berson A.M.
      • Rescigno J.
      • et al.
      Acute toxicity of high-dose-rate intracavitary brachytherapy with the MammoSite applicator in patients with early-stage breast cancer.
      200432Balloon1186% Excellent/good cosmesis and 25% acute erythema/desquamation
       Rush
      • Dowlatshahi K.
      • Snider H.C.
      • Gittleman M.A.
      • et al.
      Early experience with balloon brachytherapy for breast cancer.
      2004112Balloon<1 yWell tolerated and 4/112 punctured or ruptured balloon
       Kaiser Permanente
      • Tsai P.I.
      • Ryan M.
      • Meek K.
      • et al.
      Accelerated partial breast irradiation using the MammoSite device: Early technical experience and short-term clinical follow-up.
      200651Balloon160% LR and 95.6% excellent/good cosmesis
       Multi-Institution
      • Niehoff P.
      • Ballardini B.
      • Polgar C.
      • et al.
      Early European experience with the MammoSite radiation therapy system for partial breast brachytherapy following breast conservation operation in low-risk breast cancer.
      200644Balloon1482% Skin discoloration/inflammation and 18% telangiectasias
       Germany
      • Niehoff P.
      • Polgar C.
      • Ostertag H.
      • et al.
      Clinical experience with the MammoSite radiation therapy system for brachytherapy of breast cancer: Results from an international phase II trial.
      200632Balloon2026% Telangiectasias, 56% hyperpigmentation, and 91% erythema
       MammoSite Initial Trial
      • Benitez P.R.
      • Keisch M.E.
      • Vicini F.
      • et al.
      Five-year results: The initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.
      200770Balloon5-y LR 0% and 83.3% excellent/good cosmesis
       William Beaumont
      • Chao K.K.
      • Vicini F.A.
      • Wallace M.
      • et al.
      Analysis of treatment efficacy, cosmesis, and toxicity using the MammoSite breast brachytherapy catheter to deliver accelerated partial-breast irradiation: The William Beaumont Hospital experience.
      200780Balloon223-y IBTR 2.9%, 88.2% excellent/good cosmesis, and decreased cosmesis with <7 mm spacing
       Multi-Institution
      • Cuttino L.W.
      • Keisch M.
      • Jenrette J.M.
      • et al.
      Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.
      2008483Balloon241.2% IBTR and 91% excellent/good cosmesis
       ASBS Registry
      • Vicini F.
      • Beitsch P.
      • Quiet C.
      • et al.
      Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation.
      ,
      • Vicini F.A.
      • Keisch M.
      • Shah C.
      • et al.
      Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy.
      20111440Balloon545-y IBTR 2.6%, 5.4%, and 5.3% by risk group and 90.4% excellent/good cosmesis
       Rocky Mountain
      • Leonard C.
      • Carter D.
      • Kercher J.
      • et al.
      Prospective trial of accelerated partial breast intensity-modulated radiotherapy.
      200755EBRT (IMRT)100% LR and 54/64 excellent/good cosmesis
       Tufts University
      • Hepel J.T.
      • Tokita M.
      • MacAusland S.G.
      • et al.
      Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation.
      200960EBRT1510% Moderate/severe late toxicity, 25% Grades 2–4 fibrosis, and 81.7% excellent/good cosmesis
       University of Michigan
      • Jagsi R.
      • Ben-David M.A.
      • Moran J.M.
      • et al.
      Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation.
      201034EBRT (IMRT)247/32 Unacceptable cosmesis
       RTOG 0319
      • Vicini F.
      • Winter K.
      • Wong J.
      • et al.
      Initial efficacy results of RTOG 0319: Three-dimensional conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I/II breast carcinoma.
      201052EBRT544-y IBTR 6% and 4% Grade 3 toxicity
       William Beaumont
      • Chen P.Y.
      • Wallace M.
      • Mitchell C.
      • et al.
      Four-year efficacy, cosmesis, and toxicity using three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation.
      201094EBRT504-y IBTR 1.1% and 89% excellent/good cosmesis
       NYU
      • Hardee M.E.
      • Raza S.
      • Becker S.J.
      • et al.
      Prone hypofractionated whole-breast radiotherapy without a boost to the tumor bed: Comparable toxicity of IMRT versus 3D conformal technique.
      201297EBRT (prone)92% Grade ½ dermatitis and IMRT reduces acute toxicity vs. 3D-CRT
       Italy
      • Mussari S.
      • Sabino Della Sala W.
      • Busana L.
      • et al.
      Full-dose intraoperative radiotherapy with electrons in breast cancer. First report on late toxicity and cosmetic results from a single-institution experience.
      200647Intraoperative484-y LR 0%
       Memorial Sloan-Kettering
      • Beal K.
      • McCormick B.
      • Zelefsky M.J.
      • et al.
      Single-fraction intraoperative radiotherapy for breast cancer: Early cosmetic results.
      ,
      • Sacchini V.
      • Beal K.
      • Goldberg J.
      • et al.
      Study of quadrant high-dose intraoperative radiation therapy for early-stage breast cancer.
      200750IntraoperativeNo LR and volume <47 cm3 associated with improved cosmetic outcomes
       Milan
      • Veronesi U.
      • Orecchia R.
      • Luini A.
      • et al.
      Intraoperative radiotherapy during breast conserving surgery: A study on 1,822 cases treated with electrons.
      20101822Intraoperative363-y LR 2.3%
       University of North Carolina
      • Kimple R.J.
      • Klauber-DeMore N.
      • Kuzmiak C.M.
      • et al.
      Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer.
      201171Intraoperative423-y LR 5.2% and IBTR 8%
       Baton Rouge
      • Elliott R.L.
      • DeLand M.
      • Head J.F.
      • Elliott M.C.
      Accelerated partial breast irradiation: Initial clinical experience with the Intrabeam System.
      201167Intraoperative0% LR, 11/67 required WBI, and 4/67 mastectomy
       MGH
      • Kozak K.R.
      • Smith B.L.
      • Adams J.
      • et al.
      Accelerated partial breast irradiation using proton beams: Initial clinical experience.
      200620Protons12No LRs, 100% excellent/good cosmesis at 12 mo, 79% moderate/severe skin color change, and 22% moist desquamation
       Loma Linda
      • Bush D.A.
      • Slater J.D.
      • Garberoglio C.
      • et al.
      Partial breast irradiation delivered with proton beam: Results of a Phase II trial.
      201150Protons485-y LR 0% and reduction in dose to contralateral breast, heart, and lungs
      APBI = accelerated partial breast irradiation; EBRT = external beam radiation therapy; LR = local recurrence; WBI = whole-breast irradiation; ILC = invasive lobular carcinoma; HDR = high-dose rate; TARGIT = targeted intraoperative radiotherapy; IMRT = intensity-modulated radiation therapy; IBTR = ipsilateral breast tumor recurrence; LDR = low-dose rate; RTOG = Radiation Therapy Oncology Group; PDR = pulsed dose rate; MGH = Massachusetts General Hospital; ASBS = American Society of Breast Surgeons; NYU = New York University; 3D-CRT = three-dimensional conformal radiotherapy.
      Interstitial APBI represents the technique with the longest followup to date. Multiple series have reported outcomes with more than 10-year followup to date (
      • Fentiman I.S.
      • Poole C.
      • Tong D.
      • et al.
      Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.
      ,
      • King T.A.
      • Bolton J.S.
      • Kuske R.R.
      • et al.
      Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer.
      ,
      • Krishnan L.
      • Jewell W.R.
      • Tawfik O.W.
      • et al.
      Breast conservation therapy with tumor bed irradiation alone in a selected group of patients with stage I breast cancer.
      ,
      • Arthur D.W.
      • Koo D.
      • Zwicker R.D.
      • et al.
      Partial breast brachytherapy after lumpectomy: Low-dose-rate and high-dose-rate experience.
      ,
      • Perera F.
      • Yu E.
      • Engel J.
      • et al.
      Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years' minimum follow-up.
      ,
      • Fentiman I.S.
      • Deshmane V.
      • Tong D.
      • et al.
      Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial.
      ,
      • Poti Z.
      • Nemeskeri C.
      • Fekeshazy A.
      • et al.
      Partial breast irradiation with interstitial 60Co brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.
      ,
      • Slampa P.
      • Soumarova R.
      • Ruzickova J.
      • et al.
      Pilot study of sole conformal perioperative interstitial brachyradiotherapy of early stage breast carcinoma using high-dose rate afterloading.
      ,
      • Stevens M.J.
      • Cooper S.G.
      • Cross P.
      • et al.
      Accelerated partial breast irradiation using interstitial high dose rate iridum brachytherapy: Early Australian experience and review of the literature.
      ,
      • Kaufman S.A.
      • DiPetrillo T.A.
      • Price L.L.
      • et al.
      Long-term outcome and toxicity in a Phase I/II trial using high-dose-rate multicatheter interstitial brachytherapy for T1/2 breast cancer.
      ,
      • Patel R.R.
      • Christensen M.E.
      • Hodge C.W.
      • et al.
      Clinical outcome analysis in “high-risk” versus “low-risk” patients eligible for national surgical adjuvant breast and bowel B-39/radiation therapy oncology group 0413 trial: Five-year results.
      ,
      • Gomez-Iturriaga A.
      • Pina L.
      • Cambeiro M.
      • et al.
      Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy.
      ,
      • White J.R.
      • Winter K.A.
      • Kuske R.A.
      • et al.
      Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.
      ,
      • Johansson B.
      • Karlsson L.
      • Liljegren G.
      • et al.
      Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-2 breast cancer: First long time results from a clinical study.
      ,
      • Yoshida K.
      • Nose T.
      • Masuda N.
      • et al.
      Preliminary result of accelerated partial breast irradiation after breast-conserving surgery.
      ,
      • Polgar C.
      • Major T.
      • Fodor J.
      • et al.
      Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study.
      ,
      • Hattangadi J.A.
      • Powell S.N.
      • Macdonald S.M.
      • et al.
      Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.
      ,
      • Strnad V.
      • Hildebrandt G.
      • Potter R.
      • et al.
      Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery.
      ). A randomized trial from Hungary randomized 258 women with T1N0-1mi, Grades 1–2 nonlobular breast cancer with negative surgical margins to WBI or partial breast irradiation (high-dose rate, HDR, accelerated [36.4 Gy/7 fx, 69% of patients] or electrons standard fractionation to a limited field [50 Gy/25 fx, 31% of patients]). At 5 years, no difference in LR was noted (3.4% vs. 4.7%), and rates of excellent/good cosmesis were significantly improved with HDR-based APBI compared with electrons (81% vs. 70%) (
      • Polgar C.
      • Fodor J.
      • Major T.
      • et al.
      Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma—5-year results of a randomized trial.
      ). Ten-year results have recently been presented, and the key findings remain unchanged. Although a few smaller and older series have published poor outcomes or cosmesis, multiple more recent and larger series have demonstrated excellent outcomes including a nonrandomized matched-pair analysis which found no difference in IBTR, regional recurrence (RR), or survival between patients undergoing interstitial APBI or WBI at 12 years (
      • Fentiman I.S.
      • Poole C.
      • Tong D.
      • et al.
      Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.
      ,
      • Fentiman I.S.
      • Deshmane V.
      • Tong D.
      • et al.
      Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial.
      ,
      • Poti Z.
      • Nemeskeri C.
      • Fekeshazy A.
      • et al.
      Partial breast irradiation with interstitial 60Co brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.
      ,
      • Shah C.
      • Antonucci J.V.
      • Wilkinson J.B.
      • et al.
      Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis.
      ). The Radiation Therapy Oncology Group (RTOG) trial 9517 was a Phase I/II trial of 99 patients undergoing interstitial APBI with either HDR or low-dose-rate brachytherapy. At 5/10 years, the rates of IBTR were 4.7%/5.9%, with 3–9% rates of Grades 3 and 4 toxicity (
      • White J.R.
      • Winter K.A.
      • Kuske R.A.
      • et al.
      Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.
      ).
      Balloon-based APBI emerged with the introduction of the MammoSite applicator (Hologic, Inc, Bedford, MA). A prospective trial of 70 patients at 5 years showed no LRs developed, and more than 80% of patients had excellent/good cosmesis. These outcomes have been confirmed by the larger ASBS Cancer MammoSite Registry Trial of 1440 women. This study, with 54-month followup, found the 5-year actuarial rate of IBTR to be 3.8% with 90.6% of patients reporting excellent/good cosmesis at 60 months (
      • Vicini F.
      • Beitsch P.
      • Quiet C.
      • et al.
      Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation.
      ,
      • Vicini F.A.
      • Keisch M.
      • Shah C.
      • et al.
      Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy.
      ). A retrospective multi-institutional analysis of nearly 500 patients with 24-month followup demonstrated a 1.2% IBTR with more than 90% of patients having excellent/good cosmesis (
      • Cuttino L.W.
      • Keisch M.
      • Jenrette J.M.
      • et al.
      Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.
      ). Although there are no published randomized comparisons of balloon APBI with WBI, a retrospective matched-pair analysis comparing outcomes from the ASBS Registry with those of WBI patients from the SEER database found no difference in rates of RR or survival at 5 years (
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Comparison of survival and regional failure between accelerated partial breast irradiation and whole breast irradiation.
      ).
      External beam RT has also been developed as a method to deliver APBI. Two older randomized trials from the United Kingdom found increased rates of LR with partial breast techniques that are inconsistent with today's standard techniques (
      • Ribeiro G.G.
      • Magee B.
      • Swindell R.
      • et al.
      The Christie Hospital breast conservation trial: An update at 8 years from inception.
      ,
      • Dodwell D.J.
      • Dyker K.
      • Brown J.
      • et al.
      A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.
      ). A more recent prospective trial from Italy found reduced rates of acute toxicities with intensity-modulated RT–based APBI (
      • Livi L.
      • Buonamici F.B.
      • Simontacchi G.
      • et al.
      Accelerated partial breast irradiation with IMRT: New technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial.
      ). RTOG 0319 was a Phase I/II trial of 52 patients undergoing external beam RT APBI and found the 4-year rate of IBTR to 6%, with only 4% of patients developing Grade 3 toxicity. Although two recent series have documented increased rates of toxicity and poor cosmesis, an interim analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/RTOG 0413 trial evaluating the 1386 patients receiving three-dimensional conformal radiotherapy APBI found no significant toxicity issues at 41 months with a 3% rate of Grade 3 or more fibrosis (
      • Hepel J.T.
      • Tokita M.
      • MacAusland S.G.
      • et al.
      Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation.
      ,
      • Jagsi R.
      • Ben-David M.A.
      • Moran J.M.
      • et al.
      Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation.
      ,
      • Julian T.B.
      • Constantino J.P.
      • Vicini F.A.
      • et al.
      Early toxicity results with 3D conformal external beam (CEBT) from the NSABP B-39/RTOG 0413 accelerated partial breast irradiation (APBI) trial.
      ). On the contrary, recent analysis of the Randomized Trial of Accelerated Partial Breast Irradiation Trial comparing external beam APBI and WBI found that this form of APBI was associated with an increased rate of adverse cosmesis and Grade ½ toxicities with short-term followup (
      • Whelan T.J.
      • Olivotto I.
      • Parpia S.
      • et al.
      Interim toxicity results from RAPID: A randomized trial of accelerated partial breast irradiation (APBI) using 3D conformal external beam radiation therapy (3D CRT).
      ).
      Intraoperative therapy, although included in Table 2 as a partial breast technique, should not be grouped with other APBI modalities in terms of outcomes, toxicities, and guidelines recommendations because of significant differences in the technique. Although initial outcomes from a randomized noninferiority trial comparing intraoperative radiation therapy (IORT) with WBI found no difference in outcomes at 4 years, a more recent update suggested a 2% higher rate of IBTR compared with WBI, whereas updates from the Milan trial have found higher than the expected rates of IBTR (
      • Vaidya J.S.
      • Joseph D.J.
      • Tobias J.S.
      • et al.
      Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised non-inferiority phase 3 trial.
      ,
      • Vaidya J.S.
      “Targeted intraoperative radiotherapy for early breast cancer: TARGIT-A trial-updated analysis of local recurrence and first analysis of survival”.
      ,
      • Orecchia R.
      Eliot trials in Milan: Results.
      ).

      Patient evaluation

      Patient evaluation for APBI should be a multi-disciplinary approach that incorporates the breast surgeon, radiation oncologist, and medical oncologist. Ideally, the patient should be evaluated by a radiation oncologist before or within a few days of surgery. A detailed history should be performed to rule out absolute/relative contraindications for BCT in general or APBI including pregnancy, prior RT to the breast or chest, connective tissue disease, or strong family history (potentially requiring genetic testing). Breast examination should be performed to help guide clinicians as to whether a patient will be a good candidate for APBI. Mammograms should be reviewed and evaluated for multifocality or multicentricity and diffuse calcifications. Pathology reports from the biopsy and excision should be reviewed to assess tumor size, histology, grade, receptor status, margin status, presence of LVSI, presence of extensive intraductal component (EIC), and nodal status as all these factors can help to guide clinicians in recommending appropriate adjuvant therapy for their patients. Patients with calcifications associated with their disease should have a postoperative mammogram (

      National Comprehensive Cancer Network. Breast Cancer. NCCN Guidelines Web Site. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site. Updated July 11, 2012. Accessed August 22, 2012.

      ).

      Patient selection

      The following section provides a review of the literature used to guide patient selection criteria. Based on these studies and the consensus of the panel, the ABS acceptable criteria are presented in Table 3 .
      Table 3American Brachytherapy Society acceptable criteria for accelerated partial breast irradiation
      Criteria
      Age≥50 y old
      Size≤3 cm
      HistologyAll invasive subtypes and DCIS
      Estrogen receptorPositive/negative
      Surgical marginsNegative
      Lymphovascular space invasionNot present
      Nodal statusNegative
      DCIS = ductal carcinoma in situ.

      Histology

      To date, most randomized and prospective trials limited patient inclusion to ductal histologies with limited numbers of patients with lobular carcinoma (ILC) or DCIS treated on the initial studies.
      With regard to lobular histology, these patients were excluded from the randomized Hungarian and intraoperative radiotherapy trials but included in the Christie Hospital trial. This randomized trial which used electrons to deliver APBI found that in patients with ILC, APBI was associated with increased rates of LR (42% vs. 17%) and was confirmed by a smaller Swedish study (
      • Ribeiro G.G.
      • Magee B.
      • Swindell R.
      • et al.
      The Christie Hospital breast conservation trial: An update at 8 years from inception.
      ,
      • Johansson B.
      • Karlsson L.
      • Liljegren G.
      • et al.
      Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-2 breast cancer: First long time results from a clinical study.
      ). However, the data from the Christie trial are difficult to interpret in light of the outdated technique for target delineation, a treatment delivery technique that is no longer routinely used, and a lack of modern image guidance during treatment delivery. However, the more recent German–Austrian trial found no difference rates of LR between ILC and invasive duct carcinoma (IDC) patients (
      • Strnad V.
      • Hildebrandt G.
      • Potter R.
      • et al.
      Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery.
      ). The largest reported series comes from William Beaumont Hospital (WBH), which evaluated 16 ILC patients and found no difference in LR compared with IDC patients (0% vs. 2.5%) (
      • Shah C.
      • Wilkinson J.B.
      • Shaitelman S.
      • et al.
      Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma.
      ).
      DCIS remains a controversial topic because of limited data and its exclusion from the initial APBI trials. However, recent data from the ASBS MammoSite Registry Trial evaluated the 194 patients with DCIS treated and found a 5-year LR rate of only 3.4% (
      • Jeruss J.S.
      • Kuerer H.M.
      • Beitsch P.D.
      • et al.
      Update on DCIS outcomes from the American Society of Breast Surgeons accelerated partial breast irradiation registry trial.
      ). Also, data from WBH and Bryn Mawr Hospital have confirmed excellent results albeit with small numbers of patients (
      • Park S.S.
      • Grills I.S.
      • Chen P.Y.
      • et al.
      Accelerated partial breast irradiation for pure ductal carcinoma in situ.
      ,
      • Stull T.S.
      • Goodwin M.
      • Gracely E.J.
      • et al.
      A single-institution review of accelerated partial breast irradiation in patients considered “cautionary” by the American Society for Radiation Oncology.
      ). A recent pooled analysis of 300 DCIS patients treated with APBI found a 5-year IBTR rate of 2.6%; furthermore, this analysis identified no difference in IBTR between DCIS patients and suitable risk invasive patients (
      • Shah C.
      • Vicini F.
      • Wilkinson J.B.
      • et al.
      Should ductal carcinoma in situ be removed from the ASTRO Consensus Panel Cautionary Group for off-protocol use of accelerated partial breast irradiation (APBI)? A pooled analysis of outcomes for 300 patients with DCIS treated with APBI.
      ). ABS Guideline: All invasive subtypes and DCIS are acceptable.

      Discussion

      Previous ABS guidelines and other recommendations and trials have limited recommendations to only IDC. However, over the past several years, there have been a significant number of publications that allow for a change in the guideline. With regard to DCIS, more than five publications have now documented the efficacy of APBI in patients with DCIS including a pooled analysis of 300 patients. In light of these findings, DCIS has been included in acceptable histologies. Implicit in this recommendation is the acknowledgment that further data from phase III trials will be needed to conclusively establish the efficacy of APBI in patients with pure DCIS. Nonetheless, with no recent data documenting an increased risk of IBTR in these patients when treated with APBI, the panel felt that the inclusion of DCIS was appropriate.
      With regard to lobular histology, there remains a paucity of data specifically addressing the use of APBI in patients with this invasive carcinoma subtype. However, over the past few years, two small series have been published addressing the role of APBI in these patients (no series larger than 50 patients). Because no modern series have been published documenting higher rates of IBTR for ILCs and multiple series using WBI have found comparable outcomes between IDCs and ILCs, it was the consensus opinion that lobular carcinomas should be considered acceptable for treatment (
      • Vo T.N.
      • Meric-Bernstam F.
      • Yi M.
      • et al.
      Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma.
      ,
      • Moran M.S.
      • Yang Q.
      • Haffty B.G.
      • et al.
      Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): Analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p.53 as a function of histology.
      ,
      • Silverstein M.J.
      • Lewinsky B.S.
      • Waisman J.R.
      • et al.
      Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma?.
      ,
      • White J.R.
      • Gustafson G.S.
      • Wimbish K.
      • et al.
      Conservative surgery and radiation therapy for infiltrating lobular carcinoma of the breast. The role of preoperative mammograms in guiding treatment.
      ). Again, implicit in this recommendation is the acknowledgment that further data from Phase III trials (and other prospective data) will be needed to conclusively establish the efficacy of APBI in patients with ILC.

      Nodal status

      To date, limited data remain available on patients with node-positive disease treated with APBI despite node-positive patients being included in the Yorkshire Breast Cancer Group Trial, RTOG 9517, RTOG 0319, Oschner Clinic experience, University of Wisconsin experience, Kaiser Permanent experience, and intraoperative radiotherapy trial. Data from older series have confirmed that without axillary lymph node sampling, increased rates of locoregional recurrence can be expected in patients undergoing APBI (
      • Ribeiro G.G.
      • Magee B.
      • Swindell R.
      • et al.
      The Christie Hospital breast conservation trial: An update at 8 years from inception.
      ,
      • Dodwell D.J.
      • Dyker K.
      • Brown J.
      • et al.
      A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.
      ). Furthermore, a series of three patients from Tufts University found that two of three patients that were node positive treated with APBI subsequently developed an IBTR (
      • Kaufman S.A.
      • DiPetrillo T.A.
      • Price L.L.
      • et al.
      Long-term outcome and toxicity in a Phase I/II trial using high-dose-rate multicatheter interstitial brachytherapy for T1/2 breast cancer.
      ). A retrospective review of 39 node-positive patients treated with APBI at WBH found no difference in IBTR at 5 years compared with node-negative patients with increased rates of RR and distant metastases (DM) in node-positive patients (
      • Shah C.
      • Wilkinson J.B.
      • Shaitelman S.
      • et al.
      Impact of lymph node status on clinical outcomes after accelerated partial breast irradiation.
      ). Also, data from the high-risk series from the University of Wisconsin that included node-positive patients found no difference in outcomes compared with a low-risk cohort (
      • Patel R.R.
      • Christensen M.E.
      • Hodge C.W.
      • et al.
      Clinical outcome analysis in “high-risk” versus “low-risk” patients eligible for national surgical adjuvant breast and bowel B-39/radiation therapy oncology group 0413 trial: Five-year results.
      ). ABS Guideline: Off-protocol, patients should be node negative.

      Discussion

      At this time, there remains insufficient evidence to support treatment of node-positive patients with APBI (even with limited nodal involvement). Older series have identified higher rates of failure and the largest modern series consists of only 39 patients. Furthermore, in light of the recently reported randomized Phase III trial (MA.20) demonstrating improvements in disease-free survival with the addition of regional irradiation to whole-breast treatment, node-positive patients should not be offered APBI off-protocol (
      • Whelan T.J.
      • Olivotto I.
      • Ackerman I.
      • et al.
      NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer.
      ). Although currently accruing trials have included patients with limited nodal disease, it will be several years before mature data are available.

      Tumor size

      Although tumor size has been used in the past to risk stratify BCT patients, recent data suggest that it may not be associated with IBTR in patients undergoing APBI (
      • Kunkler I.H.
      • Kerr G.R.
      • Thomas J.S.
      • et al.
      Impact of screening and risk factors for local recurrence and survival after conservative surgery and radiotherapy for early breast cancer: Results from a large series with long-term follow-up.
      ,
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Predictors of local recurrence following accelerated partial breast irradiation: A pooled analysis.
      ). An analysis of more than 1800 patients treated with BCT and WBI found pathologic tumor size to be associated with IBTR and DM; however, a recent pooled analysis of outcomes from the ASBS Registry and WBH did not find tumor size to be associated with IBTR, with nearly 2000 patients evaluated (
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Predictors of local recurrence following accelerated partial breast irradiation: A pooled analysis.
      ). ABS Guideline: Tumor size should be less than or equal to 3cm (including pure DCIS).

      Discussion

      To date, limited research has been performed to determine the ideal tumor size criteria for patients undergoing APBI. As noted previously, because of paucity of data available, limited conclusions can be drawn. Furthermore, because of selection bias, published studies are of limited value with a preponderance of subcentimeter tumors. Based on these findings, and consistent with previously published consensus criteria and guidelines along with clinical trial inclusion criteria, the guideline remains 3 cm. In addition, the panel does not believe that APBI should be applied off-protocol in the neoadjuvant setting.

      Age

      Previous randomized trials of women undergoing BCT have documented increased rates of IBTR with younger women (
      • Veronesi U.
      • Marubini E.
      • Mariani L.
      • et al.
      Radiotherapy after breast-conserving surgery in small breast carcinoma: Long-term results of a randomized trial.
      ). An analysis of the Christie Hospital randomized trial with partial breast irradiation did not find age to be associated with breast recurrence on multivariate analysis (
      • Magee B.
      • Swindell R.
      • Harris M.
      • et al.
      Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: Results from a randomised trial.
      ). However, the pooled analysis previously discussed found a trend for increased rates of IBTR for patients under 50 years old (
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Predictors of local recurrence following accelerated partial breast irradiation: A pooled analysis.
      ). ABS Guideline: Patients should be 50 years or older.

      Discussion

      To date, limited research has been completed to determine the ideal age criteria for patients undergoing APBI. As noted previously, because of paucity of data available, limited conclusions can be drawn but in light of the pooled analysis finding a trend for increased rates of IBTR in patients under age 50 years and similar data seen in patients undergoing WBI, the guideline has been left at 50 years old. The panel did not believe that there were sufficient data to specifically exclude younger patients from being treated with APBI but felt that caution was still warranted. Nonetheless, implicit in this recommendation is the acknowledgment by the panel that further data from Phase III trials will be needed to conclusively establish the efficacy of APBI in younger patients. Although no recent data documenting an increased risk of IBTR in these patients when treated with APBI (beyond that seen when WBI is used) have been conclusively identified, the panel felt that the inclusion of women less than age 50 years was not appropriate at this time.

      Receptor status

      Increasing data have suggested that estrogen receptor negativity is associated with IBTR in women undergoing APBI. As previously mentioned, a pooled analysis of the ASBS registry and data from WBH found that the only factor associated with IBTR was estrogen receptor negativity (
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Predictors of local recurrence following accelerated partial breast irradiation: A pooled analysis.
      ). Also, a review of 106 patients with cautionary features (including estrogen receptor negativity) found that receptor negativity was associated with a higher rate of IBTR (11.8% vs. 2.2%) (
      • Stull T.S.
      • Goodwin M.
      • Gracely E.J.
      • et al.
      A single-institution review of accelerated partial breast irradiation in patients considered “cautionary” by the American Society for Radiation Oncology.
      ). An analysis of high-risk patients including estrogen receptor–negative patients from the University of California Irvine also found that estrogen receptor negativity was associated with a decrease in recurrence-free survival (
      • Wilder R.B.
      • Curcio L.D.
      • Khanijou R.K.
      • et al.
      Preliminary results with accelerated partial breast irradiation in high-risk breast cancer patients.
      ). This has also been noted in older women who traditionally have excellent outcomes; analysis of the 537 women from the ASBS registry over age 70 years found that estrogen receptor–negative patients had higher rates of LR and decreased survival compared with estrogen receptor–positive patients (
      • Khan A.J.
      • Vicini F.A.
      • Beitsch P.
      • et al.
      Local control, toxicity, and cosmesis in women >70 years enrolled in the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial.
      ). ABS Guideline: Estrogen receptor may be positive or negative.

      Discussion

      As noted previously, there are increasing numbers of small series identifying higher rates of IBTR in estrogen receptor–negative patients undergoing APBI compared with estrogen receptor–positive patients undergoing APBI. Although these studies suggest that estrogen receptor negativity is associated with higher rates of local failure, similar findings have been seen with WBI and mastectomy and therefore may be indicative of the biology of an estrogen receptor–negative tumor and not the treatment modality (
      • Hunt K.K.
      • Ballman K.V.
      • McCall L.M.
      • et al.
      Factors associated with local-regional recurrence after negative sentinel node dissection: Results of the ACOSOG Z0010 trial.
      ,
      • Tendulkar R.D.
      • Rehman S.
      • Shukla M.E.
      • et al.
      Impact of postmastectomy radiation on locoregional recurrence in breast cancer patients with 1-3 positive lymph nodes treated with modern systemic therapy.
      ,
      • Lowery A.J.
      • Kell M.R.
      • Glynn R.W.
      • et al.
      Locoregional recurrence after breast cancer surgery: A systematic review by receptor phenotype.
      ). To date, there are no data comparing local outcomes in estrogen receptor–negative patients receiving mastectomy, WBI, and APBI, and therefore, no data to suggest that rates of IBTR are higher in estrogen receptor–negative patients receiving APBI compared with those who receive WBI.

      Margins

      Although margin status has been associated with IBTR in patients undergoing WBI after BCS, limited data are available for patients undergoing APBI (
      • Park C.C.
      • Mitsumori M.
      • Nixon A.
      • et al.
      Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: Influence of margin status and systemic therapy on local recurrence.
      ). A recent analysis of the MammoSite Registry found that close and positive margins were associated with a trend for increased rates of IBTR (
      • Shah C.
      • Wilkinson J.B.
      • Lyden M.
      • et al.
      Predictors of local recurrence following accelerated partial breast irradiation: A pooled analysis.
      ). Furthermore, a series of 48 patients prospectively treated with multicatheter brachytherapy from Korea did find that recurrence was associated with patients with close surgical margins (<2 mm) (
      • Yeo S.G.
      • Kim J.
      • Kwak G.H.
      • et al.
      Accelerated partial breast irradiation using multicatheter brachytherapy for select early-stage breast cancer: Local control and toxicity.
      ). ABS Guideline: Surgical margins should be negative.

      Discussion

      Although limited, the evidence presented to date suggests that close/positive margins are associated with higher rates of IBTR in patients undergoing APBI. These findings are consistent with large studies of patients undergoing WBI, and as such, the guideline remains consistent with previous consensus statements and guidelines recommending negative surgical margins. Because of differences in pathologic assessment of surgical margins, a lack of consistent data identifying that a certain “ideal” margin exits, and the fact that NSABP continues to use a definition of “no tumor on ink,” the panel finds that the guideline should remain a negative margin.

      Other

      Factors often associated with IBTR include LVSI and multifocality. However, limited data exist examining these factors in APBI patients. A review of 106 cautionary risk patients did not find focal LVSI to be associated with IBTR, RR, or DM (
      • Stull T.S.
      • Goodwin M.
      • Gracely E.J.
      • et al.
      A single-institution review of accelerated partial breast irradiation in patients considered “cautionary” by the American Society for Radiation Oncology.
      ). Recent data from WBH evaluated patients with and without LVSI and found that LVSI was associated with increased rates of RR and DM and a decrement in disease-free survival with no impact on IBTR or survival (
      • Jawad M.S.
      • Wilkinson J.B.
      • Shah C.
      • et al.
      Impact of lymphovascular space invasion, extensive intraductal component, and multi-focality following accelerated partial breast irradiation.
      ). The same series evaluated the impact of EIC and multifocality and found no difference in rates of IBTR based on either factor; however, EIC was associated with higher rates of RR (
      • Jawad M.S.
      • Wilkinson J.B.
      • Shah C.
      • et al.
      Impact of lymphovascular space invasion, extensive intraductal component, and multi-focality following accelerated partial breast irradiation.
      ).
      With regard to tumor grade, the Early Breast Cancer Trialists Collaborative Group meta-analysis has found that in women undergoing BCT, tumor grade was associated with recurrence risk at 10 years; also, the European Organisation for Research and Treatment of Cancer (EORTC) boost trial found tumor grade to be one of the most important factors associated with LR (
      • Darby S.
      • McGale P.
      • et al.
      Early Breast Cancer Trialists’ Collaborative Group (EBCTG)
      Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data on 10,801 women in 17 randomised trials.
      ,
      • Bartelink H.
      • Horiot J.C.
      • Poortmans P.M.
      • et al.
      Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial.
      ). With regard to APBI, the Christie Hospital trial initially suggested that grade was associated with higher rates of breast recurrence (
      • Magee B.
      • Swindell R.
      • Harris M.
      • et al.
      Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: Results from a randomised trial.
      ). More recently, data from the ASBS registry found increasing grade to be associated with higher rates of RR (
      • Aburabia M.
      • Roses R.E.
      • Kuerer H.M.
      • et al.
      Axillary failure in patients treated with MammoSite accelerated partial breast irradiation.
      ). ABS Guideline: LVSI should not be present (because of differences in pathologic assessment for LVSI, the presence of LVSI [focal or diffuse] is a contraindication).

      Discussion

      LVSI has been found to be associated with IBTR in patients undergoing WBI; although small series evaluating the impact of LVSI in patients undergoing APBI have not found that LVSI impacts IBTR, only two reports have been published to date. Therefore, it is the consensus opinion that LVSI not be present. With regard to other factors including tumor grade and multifocality, limited data are available regarding these factors in patients treated with APBI and similarly when examining the literature on these features in patients undergoing WBI, controversy continues to exist; as such, they were not included in the guideline. With respect to EIC, data extrapolated from WBI series have confirmed that in negative surgical margin cases, that EIC is not a factor associated with IBTR (
      • Leong C.
      • Boyages J.
      • Jayasinghe U.W.
      • et al.
      Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma.
      ). As such, EIC was not included in the consensus guidelines at this time as the panel believes that it is not a factor that should be used to stratify patient in light of negative surgical margins.

      Technical guidelines

      Previous guidelines have been published with regard to dosimetric guidelines. Previously published guidelines had focused on target coverage (≥90% dose received by ≥90% target volume, V150 <70 cm3 [interstitial]/50 cm3 [balloon], V200 <20 cm3 [interstitial]/10 cm3 [balloon], and dose homogeneity index ≥0.75) and skin dose–volume histogram parameters (maximum ≤100% [interstitial], <145% [balloon] consistent with the constraints of the NSABP B-39 protocol) (

      American Brachytherapy Society: Breast Brachytherapy Task Group. Breast Brachytherapy. American Brachytherapy Society Web site. Available at: http://www.americanbrachytherapy.org/guidelines/abs_breast_brachytherapy_taskgroup.pdf. Updated February 1, 2007. Accessed August 22, 2012.

      ,
      • Smith B.D.
      • Arthur D.W.
      • Buchholz T.A.
      • et al.
      Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO).
      ). With the development of multilumen balloon catheters and novel external beam techniques including intensity-modulated RT and protons, dosimetric guidelines should be revised to reflect the improvements in target coverage and normal tissue constraints possible with these new techniques. Before treatment, all patients should undergo CT-based planning. Based on clinical experience, expansions of 1–2 cm should be used to expand the seroma cavity to an appropriate planning target volume. Target margins may be individualized based on treatment technique and pathologic features (e.g., surgical margin status). Prescriptions have varied in the literature, but the most common prescriptions used are 34 Gy in 10 fractions twice daily for interstitial and intracavitary treatment and 38.5 Gy in 10 fractions twice daily for external beam–based treatment. A comprehensive review of each technique and the corresponding formal dosimetric recommendations are beyond of the scope of this review, but for reference, the NSABP B-39 guidelines and those presented by Wazer et al. may be used (
      • Smith B.D.
      • Arthur D.W.
      • Buchholz T.A.
      • et al.
      Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO).
      ,
      • Wazer D.E.
      • Hepel J.T.
      A comparison of brachytherapy techniques for partial breast irradiation.
      ).
      It should also be noted that although the focus of these guidelines is APBI as a sole modality of treatment, that in appropriately selected cases, brachytherapy remains an excellent modality for boost following WBI as well. Brachytherapy for boost treatment is a well-documented and efficacious modality of treatment having been used in the EORTC randomized trial comparing mastectomy and BCT and the EORTC boost trial (
      • Van Dongen J.A.
      • Voogd A.C.
      • Fentiman I.S.
      • et al.
      Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial.
      ,
      • Bartelink H.
      • Horiot J.C.
      • Poortmans P.M.
      • et al.
      Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial.
      ). Furthermore, studies have demonstrated excellent long-term clinical outcomes with respect to tumor control and toxicities with multiple forms of brachytherapy boost; a recently published Phase II trial with 10-year followup had a 96% local control rate with 93% of patients having excellent/good cosmesis (
      • Guinot J.L.
      • Tortajada M.I.
      • Carrascosa M.
      • et al.
      Ten-year results of a phase II study with single fraction of high-dose-rate brachytherapy (FAST-boost) after whole breast irradiation in invasive breast carcinoma.
      ,
      • Schroeder T.M.
      • Liem B.
      • Sampath S.
      • et al.
      Early breast cancer with positive margins: Excellent local control with an upfront brachytherapy boost.
      ,
      • Pan Q.
      • Calitschi E.
      • Otmezguine Y.
      • et al.
      Long term results of exclusive radiotherapy and brachytherapy of breast cancer.
      ). Although brachytherapy boost has documented excellent clinical, toxicity, and cosmetic results with interstitial HDR and low-dose-rate brachytherapy, because of the technical challenges of performing interstitial brachytherapy, noninvasive image-guided breast brachytherapy (NIBB) has been developed recently. This technique, which consists of breast immobilization and mild compression, mammography-guided target delineation using 192Ir brachytherapy with specialized surface applicators, results in highly collimated photon emissions. A dosimetric study from Tufts University found improved dosimetric outcomes including lower skin V100/D90/D50 and reduced chest wall/lung dose using NIBB compared with electrons or three-dimensional conformal radiotherapy; these findings were confirmed by a multi-institutional registry study which documented no acute or late Grade 3 toxicities and 100% excellent/good cosmesis in a series of 146 patients (
      • Sioshansi S.
      • Rivard M.J.
      • Hiatt J.R.
      • et al.
      Dose modeling of noninvasive image-guided breast brachytherapy in comparison to electron beam boost and three-dimensional conformal accelerated partial breast irradiation.
      ,
      • Hamid S.
      • Rocchio K.
      • Arthur D.
      • et al.
      A multi-institutional study of feasibility, implementation, and early clinical results with noninvasive breast brachytherapy for tumor bed boost.
      ). This has led to the activation of a multi-institutional study to evaluate NIBB for APBI (

      National Institutes of Health. Partial breast irradiation using non-invasive machine for early stage breast cancer. Clinical Trials.gov. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01463007?term=APBI+breast&rank=12. Updated July 5, 2012. Accessed August 22, 2012.

      ). Although future studies are required to further evaluate NIBB, the role of brachytherapy as a boost technique has sufficient data available to support its continued use.

      Conclusions

      These guidelines have been updated to provide clinicians with appropriate patient selection criteria to allow APBI to be used in a manner that will optimize clinical outcomes and patient satisfaction. The panel recommends that the application of APBI in any of these settings should still be approached carefully (on a case-by-case basis) with the understanding that until mature Phase III trial results are available, patients and clinicians need to be cognizant of the limited long-term data establishing the efficacy of this treatment approach.

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