Objective: Partial-breast irradiation (PBI) with external-beam radiotherapy has produced higher than expected rates of fair-to-poor cosmesis. Worsened outcomes have been correlated with larger volumes of breast tissue exposed to radiation. A novel breast-specific stereotactic radiotherapy (BSRT) device (BSRTD) has been developed at our institution and has shown promise in delivering highly conformal dose distributions. We compared normal tissue sparing with this device with that achieved with intensity-modulated radiation therapy (IMRT)-PBI. Methods: Fifteen women previously treated with breast conservation therapy were enrolled on an institutional review board-approved protocol. Each of them underwent CT simulation in the prone position using the BSRTD-specific immobilization system. Simulated postoperative and preoperative treatment volumes were generated based on surgical bed/clip position. Blinded planners generated IMRT-PBI plans and BSRT plans for each set of volumes. These plans were compared based on clinically validated markers for cosmetic outcome and toxicity using a Wilcoxon rank-sum test. Results: The BSRT plans consistently reduced the volumes receiving each of several dose levels (Vx) to breast tissue, the chest wall, the lung, the heart, and the skin in both preoperative and postoperative settings (p < 0.05). Preoperative BSRT yielded particularly dramatic improvements. Conclusion: The novel BSRTD has demonstrated significant dosimetric benefits over IMRT-PBI. Further investigation is currently proceeding through initial clinical trials.

1.
American Cancer Society: Cancer Facts and Figures 2015. Atlanta, American Cancer Society, 2015.
2.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-1241.
3.
Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, Salvadori B, Zucali R: Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 2001;12:997-1003.
4.
Malmström P, Holmberg L, Anderson H, Mattsson J, Jönsson PE, Tennvall-Nittby L, Balldin G, Lovén L, Svensson JH, Ingvar C, Möller T, Holmberg E, Wallgren A: Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening. Eur J Cancer 2003;39:1690-1697.
5.
Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD: Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group. Lancet 1996;348:708-713.
6.
Holli K, Hietanen P, Saaristo R, Huhtala H, Hakama M, Joensuu H: Radiotherapy after segmental resection of breast cancer with favorable prognostic features: 12-year follow-up results of a randomized trial. J Clin Oncol 2009;27:927-932.
7.
Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA: Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 2004;351:963-970.
8.
Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC: Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 2013;31:2382-2387.
9.
Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Nesbitt L, Paik S, Pisansky TM, Wolmark N: 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. J Clin Oncol 2002;20:4141-4149.
10.
Nattinger AB, Kneusel RT, Hoffmann RG, Gilligan MA: Relationship of distance from a radiotherapy facility and initial breast cancer treatment. J Natl Cancer Inst 2001;93:1344-1346.
11.
Nattinger AB, Hoffmann RG, Kneusel RT, Schapira MM: Relation between appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery. Lancet 2000;356:1148-1153.
12.
Polgár C, Fodor J, Major T, Sulyok Z, Kásler M: Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial. Radiother Oncol 2013;108:197-202.
13.
Ribeiro GG, Magee B, Swindell R, Harris M, Banerjee SS: The Christie Hospital breast conservation trial: an update at 8 years from inception. Clin Oncol (R Coll Radiol) 1993;5:278-283.
14.
Rodríguez N, Sanz X, Dengra J, Foro P, Membrive I, Reig A, Quera J, Fernández-Velilla E, Pera Ó, Lio J, Lozano J, Algara M: Five-year outcomes, cosmesis, and toxicity with 3-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2013;87:1051-1057.
15.
Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sütterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M: Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 2010;376:91-102.
16.
Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Leonardi MC, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B: Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol 2013;14:1269-1277.
17.
Livi L, Buonamici FB, Simontacchi G, Scotti V, Fambrini M, Compagnucci A, Paiar F, Scoccianti S, Pallotta S, Detti B, Agresti B, Talamonti C, Mangoni M, Bianchi S, Cataliotti L, Marrazzo L, Bucciolini M, Biti G: Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys 2010;77:509-515.
18.
Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA: Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 2013;31:4038-4045.
19.
Hepel JT, Tokita M, MacAusland SG, Evans SB, Hiatt JR, Price LL, DiPetrillo T, Wazer DE: Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2009;75:1290-1296.
20.
Leonard KL, Hepel JT, Hiatt JR, Dipetrillo TA, Price LL, Wazer DE: The effect of dose-volume parameters and interfraction interval on cosmetic outcome and toxicity after 3-dimensional conformal accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2013;85:623-629.
21.
Smith GL, Xu Y, Buchholz TA, Giordano SH, Jiang J, Shih YC, Smith BD: Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer. JAMA 2012;307:1827-1837.
22.
Julian TB, Costantino JP, Vicini FA, White JR, Winter KA, Arthur DW, Kuske RR, Rabinovitch R, Curran WJ, Wolmark N: Early toxicity results with 3-D conformal external beam therapy (CEBT) from the NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial (abstract). Int J Radiat Oncol Biol Phys 2011;81(suppl 2):S7.
23.
Njeh CF, Saunders MW, Langton CM: Accelerated partial breast irradiation (APBI): a review of available techniques. Radiat Oncol 2010;5:90.
24.
Nichols EM, Dhople AA, Mohiuddin MM, Flannery TW, Yu CX, Regine WF: Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future. Int J Radiat Oncol Biol Phys 2010;77:197-202.
25.
Nichols EM, Feigenberg SJ, Marter K, Cheston SB, Lasio G, Tkaczuk K, Kesmodel S, Buras R, Regine WF: Preoperative radiation therapy significantly increases patient eligibility for accelerated partial breast irradiation using 3D-conformal radiotherapy. Am J Clin Oncol 2013;36:232-238.
26.
Yu CX, Shao X, Zhang J, Regine W, Zheng M, Yu YS, Deng J, Duan Z: GammaPod - a new device dedicated for stereotactic radiotherapy of breast cancer. Med Phys 2013;40:051703.
27.
Mutaf YD, Yu CX, Nichols EM, Yi B, Prado K, D'Souza W, Regine WF, Feigenberg SJ: Localization accuracy of a novel prone breast stereotactic immobilization and localization system (abstract). Med Phys 2013;40:93.
28.
Ödén J, Toma-Dasu I, Yu CX, Feigenberg SJ, Regine WF, Mutaf YD: Dosimetric comparison between intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod™. Phys Med Biol 2013;58:4409-4421.
29.
Kirby AM, Coles CE, Yarnold JR: Target volume definition for external beam partial breast radiotherapy: clinical, pathological and technical studies informing current approaches. Radiother Oncol 2010;94:255-263.
30.
Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H: Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-1076.
31.
Chang JY, Senan S, Paul MA, Mehran RJ, Louie AV, Balter P, Groen HJ, McRae SE, Widder J, Feng L, van den Borne BE, Munsell MF, Hurkmans C, Berry DA, van Werkhoven E, Kresl JJ, Dingemans AM, Dawood O, Haasbeek CJ, Carpenter LS, De Jaeger K, Komaki R, Slotman BJ, Smit EF, Roth JA: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-637.
32.
Yoo S, Blitzblau R, Yin FF, Horton JK: Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT. J Appl Clin Med Phys 2015;16:5126.
33.
Horton JK, Blitzblau RC, Yoo S, Geradts J, Chang Z, Baker JA, Georgiade GS, Chen W, Siamakpour-Reihani S, Wang C, Broadwater G, Groth J, Palta M, Dewhirst M, Barry WT, Duffy EA, Chi JT, Hwang ES: Preoperative single-fraction partial breast radiation therapy: a novel phase 1, dose-escalation protocol with radiation response biomarkers. Int J Radiat Oncol Biol Phys 2015;92:846-855.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.