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Long-term outcome after intraoperative radiotherapy as a boost in breast cancer

Langzeitergebnisse nach intraoperativem Boost bei Brustkrebs

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Abstract

Purpose

To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost).

Methods

Retrospective analysis of 400 patients with an IORT boost with low-energy X‑rays (20 Gy), subsequent whole-breast irradiation (46–50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic.

Results

The median age was 63 years (30–85) and the median follow-up was 78 months (2–180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost.

Conclusion

IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.

Zusammenfassung

Ziel

Untersuchung der onkologischen Ergebnisse in der Langzeitnachsorge und der Häufigkeit chronischer Nebenwirkungen bei Patientinnen mit Brustkrebs, die eine intraoperative Strahlentherapie als vorgezogenen Boost (IORT-Boost) erhielten.

Methoden

Retrospektive Analyse von 400 Patientinnen mit IORT-Boost mit niederenergetischen Röntgenstrahlen (20 Gy), anschließender Ganzbrustbestrahlung (46–50 Gy) und einer jährlichen onkologischen Nachsorge. Die Nebenwirkungen wurden prospektiv über einen Zeitraum von bis zu 15 Jahren erhoben (LENT-SOMA-Skalen). Nebenwirkungen mit einer Bewertung von ≥Grad 2, die mindestens dreimal während der Nachbeobachtung auftraten, wurden als chronisch eingestuft.

Ergebnisse

Das mediane Alter betrug 63 Jahre (Spanne 30–85 Jahre) und die mediane Nachsorgezeit 78 Monate (Spanne 2–180 Monate) nach IORT-Boost. Bei 15 Patientinnen trat ein Lokalrezidiv auf. Dies resultierte in einer lokalen Rezidivrate von 2,0 %, 6,6 % und 10,1 % nach jeweils 5, 10 und 15 Jahren. Die Gesamtüberlebensrate lag bei 92,1 %, 81,8 % bzw. 80,7 % nach jeweils 5, 10 und 15 Jahren. Die häufigsten hochgradigen Nebenwirkungen waren Fibrose (21 %) und Schmerzen (8,6 %). Die meisten Nebenwirkungen traten innerhalb der ersten 3 Jahre auf. Die kumulativen errechneten Raten für eine chronische Fibrose lagen bei 19,1 % und 21,1 % nach 5 und ≥8 Jahren, für chronische Schmerzen bei 8,6 % nach ≥4 Jahren, für ein chronisches Brustödem bei 2,4 % nach ≥2 Jahren, für ein chronisches Lymphödem des Arms bei 0,0 % nach 5 und 10 Jahren und für eine chronische Hyperpigmentierung bei 0,5 % nach ≥2 Jahren. Die Ausprägung an Nebenwirkungen war ähnlich oder fiel geringer aus als die erwarteten Effekte nach einem perkutenen Boost.

Schlussfolgerung

Der IORT-Boost scheint eine hocheffiziente und sichere Methode für einen vorgezogenen Boost des Tumorbetts bei Hochrisikopatienten mit Brustkrebs zu sein.

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References

  1. Anonymous (1995) LENT SOMA scales for all anatomic sites. Int J Radiat Oncol Biol Phys 31:1049–1091

    Article  Google Scholar 

  2. Aziz MH, Schneider F, Clausen S et al (2011) Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x‑rays? Radiat Oncol 6:174

    Article  Google Scholar 

  3. Bartelink H, Horiot JC, Poortmans PM et al (2007) 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. J Clin Oncol 25:3259–3265

    Article  Google Scholar 

  4. Bartelink H, Maingon P, Poortmans P et al (2015) Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol 16:47–56

    Article  Google Scholar 

  5. Benda RK, Yasuda G, Sethi A et al (2003) Breast boost: are we missing the target? Cancer 97:905–909

    Article  Google Scholar 

  6. Blank E, Kraus-Tiefenbacher U, Welzel G et al (2010) Single-center long-term follow-up after intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage x‑rays. Ann Surg Oncol 17(Suppl 3):352–358

    Article  Google Scholar 

  7. Chang DW, Te Marvelde L, Chua BH (2014) Prospective study of local control and late radiation toxicity after intraoperative radiation therapy boost for early breast cancer. Int J Radiat Oncol Biol Phys 88:73–79

    Article  Google Scholar 

  8. Collette S, Collette L, Budiharto T et al (2008) Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC Trial 22881-10882 ‘boost versus no boost’. Eur J Cancer 44:2587–2599

    Article  Google Scholar 

  9. Early Breast Cancer Trialists’ Collaborative Group, Darby S, Mcgale P et al (2011) 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 378:1707–1716

    Article  Google Scholar 

  10. Ebner F, Schramm A, Bottke D et al (2016) Comparison of seroma production in breast conserving surgery with or without intraoperative radiotherapy as tumour bed boost. Arch Gynecol Obstet 294:861–866

    Article  CAS  Google Scholar 

  11. Fastner G, Sedlmayer F, Merz F et al (2013) IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: long term results of an ISIORT pooled analysis. Radiother Oncol 108:279–286

    Article  Google Scholar 

  12. Holland R, Veling SH, Mravunac M et al (1985) Histologic multifocality of Tis, T1–2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer 56:979–990

    Article  CAS  Google Scholar 

  13. Kindts I, Laenen A, Depuydt T et al (2017) Tumour bed boost radiotherapy for women after breast-conserving surgery. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD011987.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kindts I, Verhoeven K, Laenen A et al (2019) A comparison of a brachytherapy and an external beam radiotherapy boost in breast-conserving therapy for breast cancer: local and any recurrences. Strahlenther Onkol 195:310–317

    Article  Google Scholar 

  15. Kolberg HC, Loevey G, Akpolat-Basci L et al (2017) Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy. Strahlenther Onkol 193:62–69

    Article  Google Scholar 

  16. Kraus-Tiefenbacher U, Bauer L, Kehrer T et al (2006) Intraoperative radiotherapy (IORT) as a boost in patients with early-stage breast cancer—acute toxicity. Onkologie 29:77–82

    PubMed  Google Scholar 

  17. Kraus-Tiefenbacher U, Bauer L, Scheda A et al (2006) Long-term toxicity of an intraoperative radiotherapy boost using low energy X‑rays during breast-conserving surgery. Int J Radiat Oncol Biol Phys 66:377–381

    Article  Google Scholar 

  18. Lemanski C, Azria D, Thezenas S et al (2006) Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results. Int J Radiat Oncol Biol Phys 64:1410–1415

    Article  Google Scholar 

  19. Piroth MD, Baumann R, Budach W et al (2019) Heart toxicity from breast cancer radiotherapy. Strahlenther Onkol 195:1–12

    Article  Google Scholar 

  20. Sperk E, Astor D, Keller A et al (2014) A cohort analysis to identify eligible patients for intraoperative radiotherapy (IORT) of early breast cancer. Radiat Oncol 9:154

    Article  Google Scholar 

  21. Turesson I, Nyman J, Holmberg E et al (1996) Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys 36:1065–1075

    Article  CAS  Google Scholar 

  22. Vaidya JS, Baum M, Tobias JS et al (2006) Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost. Int J Radiat Oncol Biol Phys 66:1335–1338

    Article  Google Scholar 

  23. Vaidya JS, Baum M, Tobias JS et al (2011) Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. Int J Radiat Oncol Biol Phys 81:1091–1097

    Article  Google Scholar 

  24. Wenz F, Blank E, Welzel G et al (2012) Intraoperative radiotherapy during breast-conserving surgery using a miniature x‑ray generator (Intrabeam(R)): theoretical and experimental background and clinical experience. Womens Health 8:39–47

    Google Scholar 

  25. Wenz F, Welzel G, Blank E et al (2010) Intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage X‑rays: the first 5 years of experience with a novel approach. Int J Radiat Oncol Biol Phys 77:1309–1314

    Article  Google Scholar 

  26. Wenz F, Welzel G, Keller A et al (2008) Early initiation of external beam radiotherapy (EBRT) may increase the risk of long-term toxicity in patients undergoing intraoperative radiotherapy (IORT) as a boost for breast cancer. Breast 17:617–622

    Article  Google Scholar 

  27. Wockel A, Festl J, Stuber T et al (2018) Interdisciplinary screening, diagnosis, therapy and follow-up of breast cancer. Guideline of the DGGG and the DKG (S3-level, AWMF registry number 032/045OL, december 2017)—part 1 with recommendations for the screening, diagnosis and therapy of breast cancer. Geburtshilfe Frauenheilkd 78:927–948

    Article  Google Scholar 

  28. Wong WW, Pockaj BA, Vora SA et al (2014) Six-year outcome of a prospective study evaluating tumor bed boost with intra-operative electron irradiation followed by whole-breast irradiation for early-stage breast cancer. Breast J 20:125–130

    Article  Google Scholar 

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Acknowledgements

The authors thank all patients and families participating in this study. Further, the authors thank the Clinical Trials Unit in Mannheim (Anette Kipke, Jennifer Mack, Stefanie Kolb and Christiane Zimmermann).

Funding

The authors thank the Ministry for Science and Arts for the personal grant for Elena Sperk during the conduct of the study.

Author information

Authors and Affiliations

  1. University Medical Center Mannheim, Medical Faculty Mannheim, Department of Radiation Oncology, Heidelberg University, Theodor-Kutzer-Ufer 1–3, 68167, Mannheim, Germany

    Matthias Pez, Anke Keller MSc, Grit Welzel MSc, Yasser Abo-Madyan MD, Michael Ehmann MD, Frank A. Giordano MD & Elena Sperk MD

  2. University Medical Center Mannheim, Medical Faculty Mannheim, Department of Gynecology and Obstetrics, Heidelberg University, Mannheim, Germany

    Benjamin Tuschy MD, Sebastian Berlit MD & Marc Sütterlin MD

  3. University Medical Center Freiburg, Freiburg, Germany

    Frederik Wenz MD

Authors
  1. Matthias Pez
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  2. Anke Keller MSc
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  4. Yasser Abo-Madyan MD
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  5. Michael Ehmann MD
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  10. Frank A. Giordano MD
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  11. Elena Sperk MD
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Corresponding author

Correspondence to Elena Sperk MD.

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Conflict of interest

M. Pez, A. Keller, B. Tuschy, and S. Berlit declare that they have no competing interests. G. Welzel reports non-financial support from Carl Zeiss Meditec AG and personal fees from Roche Pharma AG outside the submitted work. Y. Abo-Madyan reports honoraria from Carl-Zeiss Meditec outside the submitted work, honoraria from Merck-Serono outside the submitted work, personal fees from Elekta. M. Ehmann reports travel grants from Carl Zeiss meditec AG outside the submitted work. M. Sütterlin reports personal fees and travel grants from Carl Zeiss Meditec AG outside the submitted work. F. Wenz reports personal fees from Celgene GmbH, personal fees from Roche Pharma AG, personal fees from Eli Lilly and Company, personal fees from Ipsen Pharma GmbH, research and travel grants from Carl Zeiss Meditec AG and from ELEKTA AB outside the submitted work. F. Wenz also holds a patent in collaboration with Carl Zeiss Meditec AG. F.A. Giordano reports grants and personal fees from NOXXON Pharma AG, grants and personal fees from CARL ZEISS MEDITEC AG, personal fees from Bristol-Myers Squibb, personal fees from Roche Pharma AG, personal fees from MSD Sharp and Dohme GmbH, personal fees from AstraZeneca GmbH, outside the submitted work; F.A. Giordano is the founder of Implacit GmbH, and reports non-financial support (using software for free) from Oncare GmbH; In addition, F.A. Giordano has a patent (US 62/435405) pending. E. Sperk reports grants from the Ministry for Science and Arts during the conduct of the study; personal fees and travel grants from Zeiss Meditec AG, outside the submitted work.

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Pez, M., Keller, A., Welzel, G. et al. Long-term outcome after intraoperative radiotherapy as a boost in breast cancer. Strahlenther Onkol 196, 349–355 (2020). https://doi.org/10.1007/s00066-019-01525-7

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