Electrons for intraoperative radiotherapy in selected breast-cancer patients: late results of the Montpellier phase II trial

Claire Lemanski, David Azria, Sophie Gourgou-Bourgade, Norbert Ailleres, Aurelie Pastant, Philippe Rouanet, Pascal Fenoglietto, Jean-Bernard Dubois, Marian Gutowski, Claire Lemanski, David Azria, Sophie Gourgou-Bourgade, Norbert Ailleres, Aurelie Pastant, Philippe Rouanet, Pascal Fenoglietto, Jean-Bernard Dubois, Marian Gutowski

Abstract

Background: The Montpellier cancer institute phase II trial started in 2004 and evaluated the feasibility of intraoperative radiotherapy (IORT) technique given as a sole radiation treatment for patients with an excellent prognostic and very low recurrence risk.

Methods: Forty-two patients were included between 2004 and 2007. Inclusion criteria were patients ≥ 65 years old, T0-T1, N0, ductal invasive unifocal carcinoma, free-margin > 2 mm. IORT was delivered using dedicated linear accelerator. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electrons. In vivo dosimetry was performed for all patients. Primary end-point was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, specific and overall survival.

Results: At inclusion, median age was 72 years (range, 66-80). Median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Late cosmetic results were good at 5 years despite the poor agreement of accuracy assessment between patients and physicians. Four patients (9.5%) experienced a local failure and underwent salvage mastectomy. The 5 year-disease free survival is 92.7% (range 79.1-97.6). All patients are still alive with a median follow-up of 72 months (range 66-74).

Conclusion: Our results confirm with a long-term follow-up that exclusive partial breast IORT is feasible for early-breast cancer in selected patients. IORT provides good late cosmetics results and should be considered as a safe and very comfortable "one-step" treatment procedure. Nevertheless, patient assessments are essential for long-term quality results.

Figures

Figure 1
Figure 1
Consort diagram. * Eleven 11 patients received IORT but definitive pathology results did not strictly follow the inclusion criteria: positive sentinel nodes were found on the definitive pathology reports for 6 patients; lobular carcinoma was found for 2 patients; bifocality was found in 1 patient; and margins IORT in breast cancer were <2 mm for 2 patients. These two patients with close margins underwent radical mastectomy. After IORT, the 11 patients did not receive any additional external RT and were followed according to the protocol. **The main reasons for nondelivery of IORT (n=41) were: (i) pT/pN restaging during the IORT pathology assessment (n =29), (ii) operative room availability (n = 6), (iii) machine disorder (n = 3), (iv) anesthesia complications (n = 2), (v) informed consent withdrawal (n= 1).
Figure 2
Figure 2
Photographies of patient #1 with 60 months of follow-up.
Figure 3
Figure 3
Photographies of patient #2 with 60 months of follow-up.
Figure 4
Figure 4
Photographies of patient #3 with 60 months of follow-up.
Figure 5
Figure 5
Photographies of patient #4 with 60 months of follow-up.

References

    1. 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. 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;378:1707–1716.
    1. Fisher B, Wickerham DL, Deutsch M, Anderson S, Redmond C, Fisher ER. Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings. Semin Surg Oncol. 1992;8:153–160.
    1. Reitsamer R, Sedlmayer F, Kopp M, Kametriser G, Menzel C, Glueck S, Nairz O, Deutschmann H, Merz F, Peintinger F. Concepts and techniques of intraoperative radiotherapy (IORT) for breast cancer. Breast Cancer. 2008;15:40–46. doi: 10.1007/s12282-007-0001-4.
    1. Dubois JB, Hay M, Gely S, Saint-Aubert B, Rouanet P, Pujol H. IORT in breast carcinomas. Front Radiat Ther Oncol. 1997;31:131–137.
    1. Lemanski C, Azria D, Thezenas S, Gutowski M, Saint-Aubert B, Rouanet P, Fenoglietto P, Ailleres N, Dubois JB. Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results. Int J Radiat Oncol Biol Phys. 2006;64:1410–1415. doi: 10.1016/j.ijrobp.2005.10.025.
    1. Singletary SE, Greene FL. Revision of breast cancer staging: the 6th edition of the TNM classification. Semin Surg Oncol. 2003;21:53–59. doi: 10.1002/ssu.10021.
    1. Lemanski C, Azria D, Gourgon-Bourgade S, Gutowski M, Rouanet P, Saint-Aubert B, Ailleres N, Fenoglietto P, Dubois JB. Intraoperative radiotherapy in early-stage breast cancer: results of the montpellier phase II trial. Int J Radiat Oncol Biol Phys. 2010;76:698–703. doi: 10.1016/j.ijrobp.2009.02.039.
    1. Gatzemeier W, Orecchia R, Gatti G, Intra M, Veronesi U. Intraoperative radiotherapy (IORT) in treatment of breast carcinoma–a new therapeutic alternative within the scope of breast-saving therapy? Current status and future prospects. Report of experiences from the European Institute of Oncology (EIO), Mailand. Strahlenther Onkol. 2001;177:330–337. doi: 10.1007/PL00002415.
    1. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20:37–46. doi: 10.1177/001316446002000104.
    1. Gujral DM, Sumo G, Owen JR, Ashton A, Bliss JM, Haviland J, Yarnold JR. Ipsilateral breast tumor relapse: local recurrence versus new primary tumor and the effect of whole-breast radiotherapy on the rate of new primaries. Int J Radiat Oncol Biol Phys. 2011;79:19–25. doi: 10.1016/j.ijrobp.2009.10.074.
    1. Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004;351:971–977. doi: 10.1056/NEJMoa040587.
    1. 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. doi: 10.1200/JCO.2002.11.101.
    1. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513–520. doi: 10.1056/NEJMoa0906260.
    1. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008;371:1098–1107.
    1. 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. doi: 10.1023/A:1011136326943.
    1. Bourgier C, Marsiglia H, Taghian A. A mixed-modality 3d-conformal accelerated partial breast irradiation technique using opposed mini-tangent photon fields and en face electrons to minimize the lung exposure to radiation: in regard to Jain et al. (Int J Radiat Oncol Biol Phys 2009;75:82–88) Int J Radiat Oncol Biol Phys. 2010;76:956–957. doi: 10.1016/j.ijrobp.2009.10.026.
    1. Gruenberger T, Gorlitzer M, Soliman T, Rudas M, Mittlboeck M, Gnant M, Reiner A, Teleky B, Seitz W, Jakesz R. It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients. Breast Cancer Res Treat. 1998;50:37–46. doi: 10.1023/A:1006064608360.
    1. Ballard-Barbash R, Potosky AL, Harlan LC, Nayfield SG, Kessler LG. Factors associated with surgical and radiation therapy for early stage breast cancer in older women. J Natl Cancer Inst. 1996;88:716–726. doi: 10.1093/jnci/88.11.716.
    1. Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO) Int J Radiat Oncol Biol Phys. 2009;74:987–1001. doi: 10.1016/j.ijrobp.2009.02.031.
    1. Polgar C, Van Limbergen E, Potter R, Kovacs G, Polo A, Lyczek J, Hildebrandt G, Niehoff P, Guinot JL, Guedea F, Johansson B, Ott OJ, Major T, Strnad V. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence. Radiother Oncol. 2010;94:264–273. doi: 10.1016/j.radonc.2010.01.014.
    1. Azria D, Bourgier C. Partial breast irradiation: new standard for selected patients. Lancet. 2010;376:71–72. doi: 10.1016/S0140-6736(10)60898-7.
    1. 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, Sutterlin 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. doi: 10.1016/S0140-6736(10)60837-9.
    1. Wasser K, Ruch M, Brade J, Schoeber C, Kraus-Tiefenbacher U, Schnitzer A, Engel D, Wenz F, Sutterlin M, Schoenberg SO, Buesing KA. Do structural changes in the tumour bed after intraoperative radiotherapy (IORT) of breast cancer complicate the evaluation of mammograms in a long-term follow-up? Eur J Radiol. 2012;81:e255–e259. doi: 10.1016/j.ejrad.2011.02.016.
    1. Aziz MH, Schneider F, Clausen S, Blank E, Herskind C, Afzal M, Wenz F. Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays? Radiat Oncol. 2011;6:174. doi: 10.1186/1748-717X-6-174.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi