Skip to main content

Advertisement

SpringerLink
Log in

Effectiveness and safety of intraoperative radiotherapy (IORT) with low-energy X-rays (INTRABEAM®) for accelerated partial breast irradiation (APBI)

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate treatment outcomes in patients with early-stage breast cancer (ESBC) treated with targeted intraoperative radiation therapy (IORT) administered as accelerated partial breast irradiation (APBI).

Methods

Between December 2014 and May 2019, 50 patients diagnosed with ESBC were treated with a 50 kilovoltage (kV) X-ray source with a single dose of 20 Gy using the Intrabeam® radiotherapy delivery system. All patients were followed prospectively to assess local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), radiation-induced toxicity, and cosmetic outcomes. We also evaluated the prognostic implications of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).

Results

Median follow-up was 53 months. Mean patient age was 70 years. The mean duration of radiation delivery was 22.25 min. Two patients developed a recurrence. One death was recorded. Elevated pretreatment NLR levels were a significant risk factor for mortality (p = 0.0026). The most common treatment-related toxicities were breast induration (30%) and seroma (18%). Five-year LC, DFS, CSS, and OS rates were 97.1%, 93.9%, 100%, and 94.4%, respectively. Cosmesis was excellent or good in most cases (94%).

Conclusion

These findings confirm the effectiveness of a single dose of 20 Gy of IORT with the Intrabeam device as APBI. The toxicity profile was good with excellent cosmesis. These results provide further support for the clinical use of APBI in well-selected patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MMA. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173.797 patients. Br Med J. 2015;6(351):4901. https://doi.org/10.1136/bmj.h4901.

    Article  CAS  Google Scholar 

  2. Fisher E, Anderson S, Redmond C, Fisher B. Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Semin Surg Oncol. 1992;8(3):161–6. https://doi.org/10.1002/cncr.20153.

    Article  CAS  PubMed  Google Scholar 

  3. Veronesi U, Luini A, del Vecchio M, Greco M, Galimberti V, Merson M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med. 1993;328(22):1587–91. https://doi.org/10.1056/NEJM199306033282202.

    Article  CAS  PubMed  Google Scholar 

  4. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10.801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16. https://doi.org/10.1016/S0140-6736(11)61629-2.

    Article  CAS  PubMed  Google Scholar 

  5. Bennion NR, Baine M, Granatowicz A, Wahl AO. Accelerated partial breast radiotherapy: a review of the literature and future directions. Gland Surg. 2018;7(6):596–610. https://doi.org/10.21037/gs.2018.11.05.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98. https://doi.org/10.1056/NEJMoa1209825.

    Article  CAS  PubMed  Google Scholar 

  7. Hoekstra N, Fleury E, Merino Lara TR, van der Baan P, Bahnerth A, Struik G, et al. Long-term risks of secondary cancer for various whole and partial breast irradiation techniques. Radiother Oncol. 2018;128(3):428–33. https://doi.org/10.1016/j.radonc.2018.05.032.

    Article  PubMed  Google Scholar 

  8. Polgár C, Major T, Takácsi-Nagy Z, Fodor J. Breast-conserving surgery followed by partial or whole breast irradiation: twenty-year results of a phase 3 clinical study. Int J Radiat Oncol Biol Phys. 2021;109(4):998–1006. https://doi.org/10.1016/j.ijrobp.2020.11.006.

    Article  PubMed  Google Scholar 

  9. Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a ran. Lancet. 2016;387(10015):229–38. https://doi.org/10.1016/S0140-6736(15)00471-7.

    Article  PubMed  Google Scholar 

  10. Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155–64. https://doi.org/10.1016/S0140-6736(19)32514-0.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165–72. https://doi.org/10.1016/S0140-6736(19)32515-2.

    Article  PubMed  Google Scholar 

  12. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017;390(10099):1048–60. https://doi.org/10.1016/S0140-6736(17)31145-5.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Li X, Sanz J, Foro P, Martínez A, Zhao M, Reig A, et al. Long-term results of a randomized partial irradiation trial compared to whole breast irradiation in the early stage and low-risk breast cancer patients after conservative surgery. Clin Transl Oncol. 2021;23(10):2127–32. https://doi.org/10.1007/s12094-021-02618-5.

    Article  CAS  PubMed  Google Scholar 

  14. Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020;38(35):4175–83. https://doi.org/10.1200/JCO.20.00650.

    Article  PubMed  Google Scholar 

  15. Orecchia R, Veronesi U, Maisonneuve P, Galimberti VE, Lazzari R, Veronesi P, et al. Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial. Lancet Oncol. 2021;22(5):597–608. https://doi.org/10.1016/S1470-2045(21)00080-2.

    Article  PubMed  Google Scholar 

  16. Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, et al. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT—a randomised clinical trial. BMJ. 2020;19:370. https://doi.org/10.1136/bmj.m2836.

    Article  Google Scholar 

  17. Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated partial breast irradiation: update of an ASTRO evidence-based consensus statement conflict of interest disclosure statement. Practical Radiat Oncol. 2017. https://doi.org/10.1016/j.prro.2016.09.007.

    Article  Google Scholar 

  18. Shah C, Vicini F, Shaitelman SF, Hepel J, Keisch M, Arthur D, et al. The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation. Brachytherapy. 2018;17(1):154–70. https://doi.org/10.1016/j.brachy.2017.09.004.

    Article  PubMed  Google Scholar 

  19. The American Society of Breast Surgeons. Consensus Guideline on Accelerated Partial Breast Irradiation Available at: https://www.breastsurgeons.org/docs/statements/Consensus-Statement-for-Accelerated-Partial-Breast-Irradiation.pdf. Accessed 10 May 2021.

  20. Shaitelman SF, Vicini FA, Beitsch P, Haffty B, Keisch M, Lyden M. Five-year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation: an analysis of patients treated on the American Society of Breast Surg. Cancer. 2010;116(20):4677–85. https://doi.org/10.1002/cncr.25383.

    Article  PubMed  Google Scholar 

  21. Vicini F, Arthur D, Wazer D, Chen P, Mitchell C, Wallace M, et al. Limitations of the American society of therapeutic radiology and oncology consensus panel guidelines on the use of accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2011;79(4):977–84. https://doi.org/10.1016/j.ijrobp.2009.12.047.

    Article  PubMed  Google Scholar 

  22. Laplana M, Cozzi S, Najjari D, Martín MI, Rodríguez G, Slocker A, et al. Five-year results of accelerated partial breast irradiation: a single-institution retrospective review of 289 cases. Brachytherapy. 2021;20(4):807–17. https://doi.org/10.1016/j.brachy.2021.02.003.

    Article  PubMed  Google Scholar 

  23. Cozzi S, Jamal DN, Slocker A, Laplana M, Tejedor AG, Krengli M, et al. Second breast-conserving therapy with interstitial brachytherapy (APBI) as a salvage treatment in ipsilateral breast tumor recurrence: a retrospective study of 40 patients. J Contemp Brachytherapy. 2019;11(2):101–7. https://doi.org/10.5114/jcb.2019.84689.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. https://doi.org/10.1093/jnci/dju124.

    Article  CAS  PubMed  Google Scholar 

  25. Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S, et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 2013;30(1):432. https://doi.org/10.1007/s12032-012-0432-4.

    Article  PubMed  Google Scholar 

  26. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6. https://doi.org/10.1016/0360-3016(95)00060-C.

    Article  CAS  PubMed  Google Scholar 

  27. Harris JR, Levene MB, Svensson G, Hellman S. Analysis of cosmetic results following primary radiation therapy for stages I and II carcinoma of the breast. Int J Radiat Oncol Biol Phys. 1979;5(2):257–61. https://doi.org/10.1016/0360-3016(79)90729-6.

    Article  CAS  PubMed  Google Scholar 

  28. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–106. https://doi.org/10.1016/S0140-6736(05)67887-7.

    Article  CAS  PubMed  Google Scholar 

  29. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013;14(11):1086–94. https://doi.org/10.1016/S1470-2045(13)70386-3.

    Article  PubMed  Google Scholar 

  30. Veronesi U, Stafyla V, Luini A, Veronesi P. Breast cancer: from “maximum tolerable” to “minimum effective” treatment. Front Oncology. 2012;2:125. https://doi.org/10.3389/fonc.2012.00125.

    Article  Google Scholar 

  31. Cozzi S, Laplana M, Najjari D, Slocker A, Encinas X, Pera J, et al. Advantages of intraoperative implant for interstitial brachytherapy for accelerated partial breast irradiation either frail patients with early-stage disease or in locally recurrent breast cancer. J Contemp Brachytherapy. 2018;10(2):97–104. https://doi.org/10.5114/jcb.2018.75594.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Vaidya JS, Wenz F, Bulsara M, Rey J, Tobias S, Joseph DJ, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT—a randomised trial. Lancet. 2014;383(9917):603–13. https://doi.org/10.1016/S0140-6736(13)61950-9.

    Article  PubMed  Google Scholar 

  33. Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, et al. 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(9735):91–102. https://doi.org/10.1016/S0140-6736(10)60837-9.

    Article  PubMed  Google Scholar 

  34. Fastner G, Gaisberger C, Kaiser J, Scherer P, Ciabattoni A, Petoukhova A, et al. ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy with electrons (IOERT) in breast cancer. Radiother Oncol. 2020;149:150–7. https://doi.org/10.1016/j.radonc.2020.04.059.

    Article  CAS  PubMed  Google Scholar 

  35. Small W Jr, Thomas TO, Alvarado M, Baum M, Bulsara M, Diaz R, et al. Commentary on “accelerated partial breast irradiation consensus statement: update of an ASTRO evidence-based consensus statement.” Practical Radiat Oncol. 2017;7(3):159–63. https://doi.org/10.1016/j.prro.2017.01.016.

    Article  Google Scholar 

  36. Vaidya JS. A comparison of intra-operative radiotherapy boost with external beam radiotherapy boost in early breast cancer (TARGIT B) Available at: https://clinicaltrials.gov/ct2/show/NCT01792726. Accessed 4 Jun 2021

  37. Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, et al. Effect of delayed targeted intraoperative radiotherapy vs whole-breast radiotherapy on local recurrence and survival: long-term results from the TARGIT—a randomized clinical trial in early breast cancer. JAMA Oncol. 2020;6(7): e200249. https://doi.org/10.1001/jamaoncol.2020.0249.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Balagamwala EHEH, Manyam BVBV, Leyrer CMCM, Karthik N, Smile T, Tendulkar RDRD, et al. Most patients are eligible for an alternative to conventional whole breast irradiation for early-stage breast cancer: a national cancer database analysis. Breast J. 2018;24(5):806–10. https://doi.org/10.1111/tbj.13051.

    Article  PubMed  Google Scholar 

  39. Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, et al. 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(19):2382–7. https://doi.org/10.1200/JCO.2012.45.2615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16(3):266–73. https://doi.org/10.1016/S1470-2045(14)71221-5.

    Article  PubMed  Google Scholar 

  41. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459–78. https://doi.org/10.1007/s10549-012-2114-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. AlOmeir O, Patel N, Donyai P. Adherence to adjuvant endocrine therapy among breast cancer survivors: a systematic review and meta-synthesis of the qualitative literature using grounded theory. Support Care Cancer. 2020;28(11):5075–84. https://doi.org/10.1007/s00520-020-05585-9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Belletti B, Vaidya JS, D’Andrea S, Entschladen F, Roncadin M, Lovat F, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res. 2008;14(5):1325–32. https://doi.org/10.1158/1078-0432.CCR-07-4453.

    Article  CAS  PubMed  Google Scholar 

  44. Linares-Galiana I, Berenguer-Frances MA, Cañas-Cortés R, Pujol-Canadell M, Comas-Antón S, Martínez E, et al. Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer. J Radiat Res. 2021;62(1):110–8. https://doi.org/10.1093/jrr/rraa083.

    Article  CAS  PubMed  Google Scholar 

  45. Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer. 2015;113(1):150–8. https://doi.org/10.1038/bjc.2015.183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wersal C, Keller A, Weiss C, Giordano FA, Abo-Madyan Y, Tuschy B, et al. Long-term changes in blood counts after intraoperative radiotherapy for breast cancer-single center experience and review of the literature. Transl Cancer Res. 2019;1(8):1882–903. https://doi.org/10.21037/tcr.2019.09.05.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Bradley Londres for professional English language editing. We also give special thanks to Dr. Cristina Gutiérrez for her support and help. Fees for medical editing were supported by the authors’ funds from Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. We also thank CERCA Programme/Generalitat de Catalunya for institutional support.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona, L’Hospitalet de Llobregat, Avinguda de la Gran Via de l’Hospitalet, 199-203, 08907, Barcelona, Spain

    Maria Laplana, Marta García-Marqueta, Evelyn Martínez-Pérez, Héctor Pérez-Montero, Irene Martínez-Montesinos, Marta Irene Martín & Ferran Guedea

  2. Department of Radiology, Imaging Diagnostic Institute, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    Juan José Sánchez-Fernández

  3. Department of Radiation Oncology, Catalan Institute of Oncology, University of Barcelona and Girona, Girona, Spain

    Arantxa Eraso

  4. Department of Medical Physics, Catalan Institute of Oncology, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    Pablo Saldaña & Roberto Martín

  5. Department of Gynecology, Bellvitge Hospital, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    Maria Jesús Pla & Amparo García-Tejedor

Authors
  1. Maria Laplana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta García-Marqueta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan José Sánchez-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Evelyn Martínez-Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Héctor Pérez-Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irene Martínez-Montesinos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arantxa Eraso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pablo Saldaña
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roberto Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marta Irene Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maria Jesús Pla
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Amparo García-Tejedor
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ferran Guedea
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Laplana.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

All procedures involved in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All the patients included in the study signed informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Laplana, M., García-Marqueta, M., Sánchez-Fernández, J.J. et al. Effectiveness and safety of intraoperative radiotherapy (IORT) with low-energy X-rays (INTRABEAM®) for accelerated partial breast irradiation (APBI). Clin Transl Oncol 24, 1732–1743 (2022). https://doi.org/10.1007/s12094-022-02823-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-022-02823-w

Keywords

Search

Navigation