Advertisement

A phase II study investigating the acute toxicity of targeted intraoperative radiotherapy as tumor-bed boost plus whole breast irradiation after breast-conserving surgery in Korean patients

  • Sung Gwe Ahn
  • Soong June Bae
  • Hak Woo Lee
  • Chang Ik Yoon
  • Jun Won Kim
  • Ik Jae Lee
  • Joon Jeong
Clinical trial
  • 28 Downloads

Abstract

Background

There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer.

Methods

This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991).

Results

Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5–21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications.

Conclusions

Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Keywords

Breast cancer Intra-operative radiotherapy Whole breast irradiation Tumor-bed boost TARGIT Toxicity 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The institutional review boards approved the trial according to their local laws and regulations (IRB No 3-2013-0299). All patients gave written informed consent, and the trial was conducted in compliance with the Helsinki Declaration.

Supplementary material

10549_2018_5038_MOESM1_ESM.tif (2.3 mb)
Volumetry by preoperative magnetic resonance imaging. a Manual measurement of breast and tumor portion on axial breast MRI images. b 3D volume of breast tissue portion. c 3D volume of tumor portion. Supplementary material 1 (TIF 2341 KB)
10549_2018_5038_MOESM2_ESM.tif (314 kb)
The applicator size and duration of TARGIT. Supplementary material 2 (TIF 313 KB)
10549_2018_5038_MOESM3_ESM.tif (4.9 mb)
Two cases with complications. a Wound dehiscence. A 52-year-old female did not have a medical history of diabetes mellitus and had a low body mass index (18.68) and low breast volume (401.703 cc). Wound dehiscence with discharge was first noted on POD #15. Wound revision under local anesthesia was performed on POD #27. b Wound infection. A 76-year-old female had a medical history of diabetes mellitus, a high body mass index (33.85), and a high breast volume (1441.18 cc). A wound infection was first noted after the 2nd cycle of docetaxel-cyclophosphamide chemotherapy. This patient was treated with antibiotics for 1 week. Supplementary material 3 (TIF 4989 KB)
10549_2018_5038_MOESM4_ESM.tif (1 mb)
Comparison of age and body mass index (BMI) according to the incidence of complications using the Student t-test. a Comparison of mean age between the non-complication and complication groups (p < 0.001). b Comparison of mean BMI between the non-complication and complication groups (p = 0.001). c Comparison of mean breast volume between the non-complication and complication groups (p = 0.017). d Comparison of mean tumor volume between the non-complication and complication groups (p = 0.094). e Comparison of the mean tumor-volume ratio between the non-complication and complication groups (p = 0.696). Supplementary material 4 (TIF 1054 KB)
10549_2018_5038_MOESM5_ESM.docx (14 kb)
Supplementary material 5 (DOCX 13 KB)

References

  1. 1.
    Arndt V, Stegmaier C, Ziegler H et al (2008) Quality of life over 5 years in women with breast cancer after breast-conserving therapy versus mastectomy: a population-based study. J Cancer Res Clin Oncol 134(12):1311–1318.  https://doi.org/10.1007/s00432-008-0418-y CrossRefPubMedGoogle Scholar
  2. 2.
    Darby S, McGale P, Correa C 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(9804):1707–1716.  https://doi.org/10.1016/s0140-6736(11)61629-2 CrossRefPubMedGoogle Scholar
  3. 3.
    Veronesi U, Luini A, Del Vecchio M et al (1993) Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 328(22):1587–1591.  https://doi.org/10.1056/nejm199306033282202 CrossRefPubMedGoogle Scholar
  4. 4.
    Fisher ER, Anderson S, Redmond C et al (1992) Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Semin Surg Oncol 8(3):161–166PubMedGoogle Scholar
  5. 5.
    Clark RM, McCulloch PB, Levine MN et al (1992) Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 84(9):683–689CrossRefGoogle Scholar
  6. 6.
    Boyages J, Recht A, Connolly JL et al (1990) Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 19(1):29–41CrossRefGoogle Scholar
  7. 7.
    Baum M, Vaidya JS, Mittra I (1997) Multicentricity and recurrence of breast cancer. Lancet 349(9046):208.  https://doi.org/10.1016/s0140-6736(05)60950-6 CrossRefPubMedGoogle Scholar
  8. 8.
    Vaidya JS, Vyas JJ, Chinoy RF et al (1996) Multicentricity of breast cancer: whole-organ analysis and clinical implications. Br J Cancer 74(5):820–824CrossRefGoogle Scholar
  9. 9.
    Strnad V, Ott OJ, Hildebrandt G et al (2016) 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 randomised, phase 3, non-inferiority trial. Lancet 387(10015):229–238.  https://doi.org/10.1016/s0140-6736(15)00471-7 CrossRefPubMedGoogle Scholar
  10. 10.
    Vaidya JS, Wenz F, Bulsara M et al (2014) 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 383(9917):603–613.  https://doi.org/10.1016/s0140-6736(13)61950-9 CrossRefPubMedGoogle Scholar
  11. 11.
    Veronesi U, Orecchia R, Maisonneuve P et al (2013) Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol 14(13):1269–1277.  https://doi.org/10.1016/s1470-2045(13)70497-2 CrossRefPubMedGoogle Scholar
  12. 12.
    Vaidya JS, Joseph DJ, Tobias JS et al (2010) Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 376(9735):91–102.  https://doi.org/10.1016/s0140-6736(10)60837-9 CrossRefPubMedGoogle Scholar
  13. 13.
    Fastner G, Reitsamer R, Ziegler I et al (2015) IOERT as anticipated tumor bed boost during breast-conserving surgery after neoadjuvant chemotherapy in locally advanced breast cancer—results of a case series after 5-year follow-up. Int J Cancer 136(5):1193–1201.  https://doi.org/10.1002/ijc.29064 CrossRefPubMedGoogle Scholar
  14. 14.
    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(2):279–286.  https://doi.org/10.1016/j.radonc.2013.05.031 CrossRefPubMedGoogle Scholar
  15. 15.
    Forouzannia A, Harness JK, Carpenter MM et al (2012) Intraoperative electron radiotherapy boost as a component of adjuvant radiation for breast cancer in the community setting. Am Surg 78(10):1071–1074PubMedGoogle Scholar
  16. 16.
    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(4):1091–1097.  https://doi.org/10.1016/j.ijrobp.2010.07.1996 CrossRefPubMedGoogle Scholar
  17. 17.
    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.  https://doi.org/10.1245/s10434-010-1265-z CrossRefPubMedGoogle Scholar
  18. 18.
    Lee JJB, Choi J, Ahn SG et al (2017) In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost. Radiat Oncol J 35(2):121–128.  https://doi.org/10.3857/roj.2017.00150 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kawamura M, Itoh Y, Sawaki M et al (2015) A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome. Radiat Oncol 10:150.  https://doi.org/10.1186/s13014-015-0469-6 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pan L, Zheng W, Ye X et al (2014) A novel approach of INTRABEAM intraoperative radiotherapy for nipple-sparing mastectomy with breast reconstruction. Clin Breast Cancer 14(6):435–441.  https://doi.org/10.1016/j.clbc.2014.04.002 CrossRefPubMedGoogle Scholar
  21. 21.
    Bulman AS, Cassoni AM, Ellis H (1985) The functional results following primary treatment of breast cancer with breast conservation. Eur J Surg Oncol 11(3):247–249PubMedGoogle Scholar
  22. 22.
    Habibollahi F, Mayles HM, Mayles WP et al (1988) Assessment of skin dose and its relation to cosmesis in the conservative treatment of early breast cancer. Int J Radiat Oncol Biol Phys 14(2):291–296CrossRefGoogle Scholar
  23. 23.
    Fernando IN, Ford HT, Powles TJ et al (1996) Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: a prospective study of treatment practice at the Royal Marsden Hospital. Clin Oncol (R Coll Radiol) 8(4):226–233CrossRefGoogle Scholar
  24. 24.
    Vrieling C, Collette L, Fourquet A et al (2000) The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC ‘boost vs. no boost’ trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. Radiother Oncol 55(3):219–232CrossRefGoogle Scholar
  25. 25.
    Twardella D, Popanda O, Helmbold I et al (2003) Personal characteristics, therapy modalities and individual DNA repair capacity as predictive factors of acute skin toxicity in an unselected cohort of breast cancer patients receiving radiotherapy. Radiother Oncol 69(2):145–153CrossRefGoogle Scholar
  26. 26.
    Moody AM, Mayles WP, Bliss JM et al (1994) The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity. Radiother Oncol 33(2):106–112CrossRefGoogle Scholar
  27. 27.
    Pignol JP, Olivotto I, Rakovitch E et al (2008) A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol 26(13):2085–2092.  https://doi.org/10.1200/jco.2007.15.2488 CrossRefPubMedGoogle Scholar
  28. 28.
    Vaidya JS, Baum M, Tobias JS et al (2001) Targeted intra-operative radiotherapy (Targit): an innovative method of treatment for early breast cancer. Ann Oncol 12(8):1075–1080CrossRefGoogle Scholar
  29. 29.
    Shah C, Vicini F, Shaitelman SF et al (2017) The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation. Brachytherapy.  https://doi.org/10.1016/j.brachy.2017.09.004 CrossRefPubMedGoogle Scholar
  30. 30.
    Vaidya JS (2017) A comparison of intra-operative radiotherapy boost with external beam radiotherapy boost in early breast cancer (TARGIT-B). https://clinicaltrials.gov/ct2/show/NCT01792726. Accessed 26 Dec 2017

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Surgery, Gangnam Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Department of Radiation Oncology, Gangnam Severance Hospital, College of MedicineYonsei UniversitySeoulRepublic of Korea

Personalised recommendations