IMRT sparing of normal tissues in locoregional treatment of breast cancer

Jean-Michel Caudrelier, Joanne Meng, Bernd Esche, Laval Grimard, Terrence Ruddy, Kayvan Amjadi, Jean-Michel Caudrelier, Joanne Meng, Bernd Esche, Laval Grimard, Terrence Ruddy, Kayvan Amjadi

Abstract

Purpose: This clinical study was designed to prospectively evaluate the acute and moderately-late cardiac and lung toxicities of intensity modulated radiation therapy delivered by helical tomotherapy (IMRT-HT) for locoregional breast radiation treatment including the internal mammary nodes (IMN).

Material/methods: 30 patients with stage III breast cancers have been accrued in this study. All patients received adjuvant chemotherapy. Target volumes were defined as follows: the PTV included breast/chest wall, axillary level II, III, infra/supraclavicular, IM nodes CTVs plus 3 mm margins. The heart with subunits and the lungs were defined as critical organs. Dose to PTV was 50 Gy in 25 fractions. Acute toxicities were assessed every week and 2 weeks post treatment using the CTCAE v3.0.scale. The moderately-late toxicities were assessed clinically plus by cardiac myoview perfusion tests scheduled at baseline, 3 and 12-month follow-up, as well a CT chest at the 6 month follow-up. The data analysis is descriptive.

Results: All participants completed the 5-week course of radiation without interruption. Skin erythema was modest and mainly grade 1-2 between the 3rd and the 5th week of radiation treatment. Only 4/30 patients experienced grade 3 skin reactions, mostly seen 2 weeks post radiation. Only 5 patients demonstrated grade 1 or 2 dyspnea, but 3 of them already had symptoms pre-radiation treatment. With a median follow-up of 58 (24-76) months, there have been infrequent moderately-late side effects. Most were grade 1 and were sometimes present at the baseline assessment. Cardiac myoview tests done at baseline and 1-year follow-up for 15 out of 18 left sided breast cancers did not show any abnormalities related to radiation. The 6-month follow-up chest CT-scans done for 25 out of 30 patients showed minimal anterior lung fibrosis for 7 patients and were completely normal for the other 18. No locoregional recurrence has been recorded and the 5-year survival is 78% (95% CI: 70-97%).

Conclusion: IMRT-HT for locoregional breast radiation is very well tolerated with minimal acute or moderately-late side effects. Cardiac and respiratory tests did not show any strong evidence of significant treatment related abnormalities.

Trial registration: clinicaltrials.gov: http://NCT00508352.

References

    1. Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomized trials—early breast cancer trialists’ collaborative group. N Engl J Med. 1995;333:1444–1455.
    1. Early Breast Cancer Trialists’ Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355:1757–1770.
    1. Hooning MJ, Aleman BM, van Rosmalen AJ, Kuenen MA, Klijn JG, van Leeuwen FE. Cause-specific mortality in long-term survivors of breast cancer: a 25-year follow-up study. Int J Radiat Oncol Biol Phys. 2006;64:1081–1091. doi: 10.1016/j.ijrobp.2005.10.022.
    1. Henson KE, McGale P, Taylor C, Darby SC. Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer. Br J Cancer. 2013;108:179–182. doi: 10.1038/bjc.2012.575.
    1. Nixon AJ, Manola J, Gelman R. No long-term increase in cardiac related mortality after breast-conserving surgery and radiation therapy using modern techniques. J Clin Oncol. 1998;16:1374–1379.
    1. Vallis KA, Pintilie M, Chong N, Holowaty E, Douglas PS, Kirkbride P, Wielgosz A. Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer. J Clin Oncol. 2002;20:1036–1042. doi: 10.1200/JCO.20.4.1036.
    1. Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99:365–375. doi: 10.1093/jnci/djk064.
    1. Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, Solin LJ. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24:4100–4106. doi: 10.1200/JCO.2005.05.1037.
    1. Correa CR, Litt HI, Hwang WT, Ferrari VA, Solin LJ, Harris EE. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol. 2007;25:3031–3037. doi: 10.1200/JCO.2006.08.6595.
    1. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–998. doi: 10.1056/NEJMoa1209825.
    1. Taghian A, Jagsi R, Makris A, Goldberg S, Ceilley E, Grignon L, Powell S. Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: practice is culture driven rather than evidence based. Int J Radiat Oncol Biol Phys. 2004;60:706–714. doi: 10.1016/j.ijrobp.2004.04.027.
    1. Whelan TJOI, Ackerman I, Chapman JW, Chua B, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Craighead P, Nolan MC, Bowen J, McCready DR, Pritchard KI, Leine MN, Parulekar W. NCIC-CTG MA.20: an intergroup trial of regional nodal irradiation in early breast cancer. J Clin Oncol ASCO Annual Meeting Proceed (Post-Meeting Edition) 2011. p. 29.
    1. Poortmans PSH, Kirkove C, Budach V, Maingon P, Valli MC, Collette S, Fourquet A, Bartelink H, van den Bogaert W. Irradiation of the internal mammary and medial supraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC radiation oncology and breast cancer groups phase III trial 22922/10925. Eur J Cancer. 2013;8(Suppl 2)
    1. Cho BC, Hurkmans CW, Damen EMF, Zipj LJ, Mijnheer BJ. Intensity modulated versus non-intensity modulated radiotherapy in the treatment of the left breast and upper internal mammary lymph node chain: a comparative planning study. Radiother Oncol. 2002;62:127–136. doi: 10.1016/S0167-8140(01)00472-8.
    1. Thilmann C, Sroka-Perez G, Krempien R, Hoess A, Wannenmacher M, Debus J. Inversely planned intensity modulated radiotherapy of the breast including the internal mammary chain: a plan comparison study. Technol Cancer Res Treat. 2004;31:69–75.
    1. Cozzi L, Fogliata A, Nicolini G, Bernier J. Clinical experience in breast irradiation with intensity modulated photon beams. Acta Oncol. 2005;44:467–474. doi: 10.1080/02841860510029879.
    1. Fogliata A, Nicolini G, Alber M, Asell M, Dobler B, El-Haddad M, Hårdemark B, Jelen U, Kania A, Larsson M, Lohr F, Munger T, Negri E, Rodrigues C, Cozzi L. IMRT for breast. A planning study. Radiother Oncol. 2005;76:300–310. doi: 10.1016/j.radonc.2005.08.004.
    1. Krueger EA, Fraass BA, McShan DL, Marsh R, Pierce LJ. Potential gains for irradiation of chest wall and regional nodes with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2003;56:1023–1037. doi: 10.1016/S0360-3016(03)00183-4.
    1. Chui CS, Hong L, McCormick B. Intensity-modulated radiotherapy technique for three-field breast treatment. Int J Radiat Oncol Biol Phys. 2005;62:1217–1223. doi: 10.1016/j.ijrobp.2005.03.040.
    1. Popescu CC, Olivotto I, Patenaude V, Wai E, Beckham WA. Inverse-planned, dynamic, multi-beam, intensity-modulated radiation therapy (IMRT): a promising technique when target volume is the left breast and internal mammary lymph nodes. Med Dosim. 2006;31:283–291. doi: 10.1016/j.meddos.2006.05.003.
    1. Goddu SM, Chaudhari S, Mamalui-Hunter M, Pechenaya OL, Pratt D, Mutic S, Zoberi I, Jeswani S, Powell SN, Low DA. Helical tomotherapy planning for left-sided breast cancer patients with positive lymph nodes: comparison to conventional multiport breast technique. Int J Radiat Oncol Biol Phys. 2009;73:1243–1251. doi: 10.1016/j.ijrobp.2008.11.004.
    1. Popescu CC, Olivotto IA, Beckham WA, Ansbacher W, Zavgorodni S, Shaffer R, Wai ES, Otto K. Volumetric modulated arc therapy improves dosimetry and reduces treatment time compared to conventional intensity-modulated radiotherapy for locoregional radiotherapy of left-sided breast cancer and internal mammary nodes. Int J Radiat Oncol Biol Phys. 2010;76:287–295. doi: 10.1016/j.ijrobp.2009.05.038.
    1. Caudrelier JM, Morgan SC, Montgomery L, Lacelle M, Nyiri B, Macpherson M. Helical tomotherapy for locoregional irradiation including the internal mammary chain in left-sided breast cancer: dosimetric evaluation. Radiother Oncol. 2009;90:99–105. doi: 10.1016/j.radonc.2008.09.028.
    1. Pignol JP, Olivotto I, Rakovitch E, Gardner S, Sixel K, Beckham W, Vu TT, Truong P, Ackerman I, Paszat L. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol. 2008;26:2085–2092. doi: 10.1200/JCO.2007.15.2488.
    1. Marks LB, Yu X, Vujaskovic Z, Small W Jr, Folz R, Anscher MS. Radiation-induced lung injury. Semin Radiat Oncol. 2003;13:333–345. doi: 10.1016/S1053-4296(03)00034-1.
    1. Miles EF, Larrier NA, Kelsey CR, Hubbs JL, Ma J, Yoo S, Marks LB. Intensity-modulated radiotherapy for resected mesothelioma: the duke experience. Int J Radiat Oncol Biol Phys. 2008;71:1143–1150. doi: 10.1016/j.ijrobp.2007.11.011.
    1. Willner J, Jost A, Baier K, Flentje M. A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer treated with 3-D conformal radiotherapy. StrahlentherOnkol. 2003;179:548–556.
    1. Marks LB, Bentzen SM, Deasy JO, Kong FM, Bradley JD, Vogelius IS, El Naqa I, Hubbs JL, Lebesque JV, Timmerman RD, Martel MK, Jackson A. Radiation dose-volume effects in the lung. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S70–S76.
    1. Marks LB, Yu X, Prosnitz RG, Zhou SM, Hardenbergh PH, Blazing M, Hollis D, Lind P, Tisch A, Wong TZ, Borges-Neto S. The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys. 2005;63:214–223. doi: 10.1016/j.ijrobp.2005.01.029.
    1. Seddon B, Cook A, Gothard L, Salmon E, Latus K, Underwood SR, Yarnold J. Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy. Radiother Oncol. 2002;64:53–63. doi: 10.1016/S0167-8140(02)00133-0.
    1. Lind PA, Pagnanelli R, Marks LB, Borges-Neto S, Hu C, Zhou SM, Light K, Hardenbergh PH. Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution. Int J Radiat Oncol Biol Phys. 2003;55:914–920. doi: 10.1016/S0360-3016(02)04156-1.
    1. Kapur A, Latus KA, Davies G, Dhawan RT, Eastick S, Jarritt PH, Roussakis G, Young MC, Anagnostopoulos C, Bomanji J, Costa DC, Pennell DJ, Prvulovich EM, Ell PJ, Underwood SR. A comparison of three radionuclide myocardial perfusion tracers in clinical practice: the ROBUST study. Eur J Nucl Med Mol Imaging. 2002;29:1608–1616. doi: 10.1007/s00259-002-0998-8.

Source: PubMed

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