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A phase II trial to evaluate single-dose stereotactic body radiation therapy (SBRT) prior to surgery for early-stage breast carcinoma: SIGNAL (stereotactic image-guided neoadjuvant ablative radiation then lumpectomy) trial

  • Study Protocol
  • Published:
Journal of Radiation Oncology

Abstract

Background

Breast-conserving therapy has become a preferred option in the treatment of early breast cancer. Current breast-conserving therapy includes 3–5 weeks of external beam radiotherapy to the whole breast, sometimes followed by a 1–2-week boost to the tumor bed. However, the duration of the radiation regimen can be prohibitive for the elderly, infirm or immobile patients, those patients who live far from the cancer center, or those who have difficulty taking an extended leave of absence. We propose to treat these patients with a single dose of radiation preoperatively, thereby shortening the total treatment time.

Methods

This is a single-arm phase II case series trial, conducted on 120 patients with early breast cancer who will be accrued from multidisciplinary breast cancer clinics. These patients will have research biopsies taken at the time of enrollment and will undergo radiation planning with CT simulation and PET/MRI. A single dose of 21 Gy will then be delivered in the prone position to the tumor. A second research biopsy will be taken, then lumpectomy will be performed. This entire procedure will be completed within 1 week (7 days). The primary endpoint is rate of toxicity (≥grade 2 fibrosis), and secondary endpoints include cosmetic results, quality of life, and rate of recurrence.

Discussion

This study will assess the toxicity associated with using a single preoperative dose of radiation as a replacement for standard adjuvant radiotherapy in breast-conserving therapy. Results of this trial will guide the design of a possible phase III study.

Trial registration: Clinicaltrials.gov identifier: NCT02212860

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References

  1. Blichert-Toft M, Brincker H, Andersen JA, Andersen KW, Axelsson CK, Mouridsen HT, Dombernowsky P, Overgaard M, Gadeberg C, Knudsen G, Borgeskov S, Bertelsen S, Knudsen JB, Hansen JB, Poulsen PE, Willumsen H, Schousen P, Froberg D, Ornsholt J, Andersen M, Olesen S, Skovgaard S, Oster M, Schumacher H, Lynderup EK, Holm CN (1988) A Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma: preliminary results. Acta Oncol 27:671–677

    Article  PubMed  CAS  Google Scholar 

  2. Fisher B, Redmond C, Poisson R, Margolese R, Wolmark N, Wickerham L, Fisher E, Deutsch M, Caplan R, Pilch Y, Glass A, Shibata H, Lerner H, Terz J, Sidorovich L (1989) Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 320(13):822–828

    Article  PubMed  CAS  Google Scholar 

  3. Lichter AS, Lippman ME, Danforth DN Jr, d'Angelo T, Steinberg SM, deMoss E, MacDonald HD, Reichert CM, Merino M, Swain SM (1992) Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute. J Clin Oncol 10(6):976–983

    PubMed  CAS  Google Scholar 

  4. Sarrazin D, Le MG, Arriagada R, Contesso G, Fontaine F, Spielmann M, Rochard F, Le Chenalier T, Lacour J (1989) Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 14(3):177–184

    Article  PubMed  CAS  Google Scholar 

  5. van Dongen JA, Bartelink H, Fentiman IS, Lerut T, Mignolet F, Olthuis G, van der Schueren R, Sylvester R, Winter J, van Zijl K (1992) Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. JNCI Monogr 11:15–18

    Google Scholar 

  6. Veronesi U, Banfi A, Del Vecchio M, Saccozzi R, Clemente C, Greco M, Luini A, Marubini E, Muscolino G, Rilke F, Sacchini V, Salvadori B, Zecchini A, Zucali R (1986) Comparison of Halsted mastectomy with quadrantectomy, axillary dissection, and radiotherapy in early breast cancer: long-term results. Eur J Cancer Clin Oncol 22(9):1085–1089

    Article  PubMed  CAS  Google Scholar 

  7. Plataniotis GA, Theofanopoulou M-A, Sotiriadou K, Theodorou K, Mavroidis P, Kyrgias G (2009) Palliative hypofractionated radiotherapy for non-small-cell lung cancer (NSCLC) patients previously treated by induction chemotherapy. J Thorac Dis 1(1):5–10

    CAS  Google Scholar 

  8. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R (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

    Article  PubMed  CAS  Google Scholar 

  9. Dragun AE, Huang B, Tucker TC, Spanos WJ (2011) Disparities in the application of adjuvant radiotherapy after breast-conserving surgery for early stage breast cancer: impact on overall survival. Cancer 117(12):2590–2598

    Article  PubMed  Google Scholar 

  10. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR (2013) The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomized controlled trials. Lancet Oncol 14(11):1086–1094

    Article  PubMed  Google Scholar 

  11. Whelan TJ, Kim D, Sussman J (2008) Clinical experience using hypofractionated radiation schedules in breast cancer. Semin Radiat Oncol 18(4):257–264

    Article  PubMed  Google Scholar 

  12. Liljegren G, Holmberg L, Adami HO, Westman G, Graffman S, Bergh J (1994) Sector resection with or without postoperative radiotherapy for stage I breast cancer: five-year results of a randomized trial. Uppsala-Orebro Breast Cancer Study Group. J Natl Cancer Inst 86(9):717–722

    Article  PubMed  CAS  Google Scholar 

  13. Clark RM, McCulloch PB, Levine MN, Lipa M, Wilkinson RH, Mahoney LJ, Basrur VR, Nair BD, McDermot RS, Wong CS, Corbett PJ (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):683–689

    Article  PubMed  CAS  Google Scholar 

  14. Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabar L, Nordgren H, Adami HO (1999) 10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 17(8):2326–2333

    PubMed  CAS  Google Scholar 

  15. Schnitt SJ, Hayman J, Gelman R, Eberlein TJ, Love SM, Mayzel K, Osteen RT, Nixon AJ, Pierce S, Connolly JL, Cohen P, Schneider L, Silver B, Recht A, Harris JR (1996) A prospective study of conservative surgery alone in the treatment of selected patients with stage I breast cancer. Cancer 77(6):1094–1100

    Article  PubMed  CAS  Google Scholar 

  16. Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD (1996) Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group. Lancet 348(9029):708–713

    Article  PubMed  CAS  Google Scholar 

  17. Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B (2013) Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol 14(13):1269–1277

    Article  PubMed  Google Scholar 

  18. Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eidermann W, Keshtgar M, Dewar J, Kraus-Tieferbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum (2010) Targeted intraoperative radiotherapy versus whole breast breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 376(9735):91–102

    Article  PubMed  Google Scholar 

  19. Kimple RJ, Klauber-DeMore N, Kuzmiak CM, Pavic D, Lian J, Livasy CA, Esler L, Moore DT, Sartor CI, Ollila DW (2011) Cosmetic outcomes for accelerated partial breast irradiation before surgical excision of early-stage breast cancer using single-dose intraoperative radiotherapy. Int J Radiat Oncol Biol Phys 79(2):400–407

    Article  PubMed Central  PubMed  Google Scholar 

  20. Pierce LJ (2015) Radiation therapy techniques for newly diagnosed, non-metastatic breast cancer. UpToDate. http://www.uptodate.com/contents/radiation-therapy-techniques-for-newly-diagnosed-non-metastatic-breast-cancer. Accessed 1 June 2015

  21. Wallgren A, Arner O, Bergstrom J, Blomstedt B, Granberg PO, Karnstrom L, Raf L, Sifversward C (1978) Preoperative radiotherapy in operable breast cancer: results in the Stockholm breast cancer trial. Cancer 42:1120–1125

    Article  PubMed  CAS  Google Scholar 

  22. Horton JK, Blitzblau RC, Yoo S, Georgiade GS, Geradts J, Baker JA, Chang Z, Duffy E, Hwang ES (2013) Preoperative single-fraction partial breast radiation therapy: a novel phase 1 dose-escalation protocol and exploration of breast cancer radiation response. Int J Radiat Oncol Biol Phys 87(2):s229–S229

    Article  Google Scholar 

  23. 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 JTA, Hwang ES (2015) Preoperative single-fraction partial breast radiation therapy: a novel phase 1, dose-escalation protocol with radiation response biomarkers. Int J Radiat Oncol Biol Phys 92(4):846–855

    Article  PubMed  Google Scholar 

  24. Lea DE, Catchside DG (1942) The mechanism of the induction by radiation of chromosome aberrations in Tradescantia. J Genet 44:216–245

    Article  Google Scholar 

  25. Brenner DJ (2008) The linear-quadratic model in an appropriate methodology for determining isoeffective doses at large dose per fraction. Semin Radiat Oncol 18:234–239

    Article  PubMed Central  PubMed  Google Scholar 

  26. Pinnaro P, Arcangeli S, Giordano C, Arcangeli G, Impiombato FA, Pinzi V, Iaccarino G, Soriani A, Landoni A, Strigari L (2011) Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer. Radiat Oncol 6:155

    Article  PubMed Central  PubMed  Google Scholar 

  27. Collette S, Collette L, Budiharto T, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad W, Mueller RP, Kurtz J, Morgan DA, Dubois JB, Salamon E, Mirimanoff R, Bolla M, Van der Hulst M, Marlam-Rodenhuis CC, Bartelink H (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(17):2587–2599

    Article  PubMed  Google Scholar 

  28. Brant R. Inference for proportions: comparing two independent samples. http://www.stat.ubc.ca/∼rollin/stats/ssize/b2.html. Accessed 14 Jun 2015

  29. NSABP B-39, RTOG 0413 (2004) A randomized phase III study of conventional whole breast irradiation versus partial breast irradiation for women with stage 0, I, or II breast cancer. Clin Adv Hematol Oncol 4(10):719–21

    Google Scholar 

  30. Bondiau PY, Courdi A, Bahadoran P, Chamorey E, Queille-Roussel C, Lallement M et al (2013) Phase 1 clinical trial of stereotactic body radiation therapy concomitant with neoadjuvant chemotherapy for breast cancer. Int J Radiat Oncol Biol Phys 85(5):1193–9

    Article  PubMed  Google Scholar 

  31. Fritz P, Kraus H-J, Blaschke T, Muhlnickel W, Strauch K, Engel-Riedel W et al (2008) Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four-dimensional CT scans for treatment planning. Lung Cancer 60(2):193–9

    Article  PubMed  Google Scholar 

  32. Kimple RJ, Klauber-Demore N, Kuzmiak CM, Pavic D, Lian J, Livasy CA et al (2011) Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer. Ann Surg Oncol 18(4):939–945

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Schulich School of Medicine & Dentistry, Western University, London, ON, Canada

    Keegan Guidolin

  2. London Health Sciences Centre, London, ON, Canada

    Michael Lock, Brian Yaremko, Neil Gelman, Stewart Gaede, Jeffrey Cao, Leslie Scott & Muriel Brackstone

  3. St. Joseph’s Health Care, London, ON, Canada

    Anat Kornecki

  4. Moores Cancer Centre, University of California, San Diego, CA, USA

    Vitali Moiseenko

Authors
  1. Keegan Guidolin
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  2. Michael Lock
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Correspondence to Keegan Guidolin.

Ethics declarations

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. This trial protocol has been reviewed and approved by the Western University Human Subjects Research Ethics Board (study #105643). Protocol modifications recommended by the DSMC will be communicated directly to the Principal Investigator, the co-investigators, and the Office of Research Ethics within 24 h. Informed consent will be obtained from patients before enrollment in the study, by the care-providing surgeon at the time of surgical consult and confirmation of eligibility. All patients will be made aware of the standard treatment, which includes external beam radiotherapy (50 Gy/25 fractions). All confidential information collected throughout the duration of the study will be stored in a firewall-protected file. Access will be permitted to the investigators listed and the DSMC.

Conflict of interest

The authors declare that they have no competing interests.

Funding sources

Lawson Internal Research Fund, Lawson Health Research Institute, London, Canada—$15,000. Ontario Research Fund—$30,000.

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Guidolin, K., Lock, M., Yaremko, B. et al. A phase II trial to evaluate single-dose stereotactic body radiation therapy (SBRT) prior to surgery for early-stage breast carcinoma: SIGNAL (stereotactic image-guided neoadjuvant ablative radiation then lumpectomy) trial. J Radiat Oncol 4, 423–430 (2015). https://doi.org/10.1007/s13566-015-0227-2

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  • DOI: https://doi.org/10.1007/s13566-015-0227-2

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