Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years

Paola Pinnarò, Antonella Soriani, Valeria Landoni, Carolina Giordano, Maria Papale, Annelisa Marsella, Laura Marucci, Giorgio Arcangeli, Lidia Strigari, Paola Pinnarò, Antonella Soriani, Valeria Landoni, Carolina Giordano, Maria Papale, Annelisa Marsella, Laura Marucci, Giorgio Arcangeli, Lidia Strigari

Abstract

Background: Accelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule.

Methods: From October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed.

Results: After a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (<1/cm2) limited to the boost area was evident in 2 out of 39 patients. The compliance with the treatment was excellent (100%).

Conclusion: The radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results.

Figures

Figure 1
Figure 1
Skin acute toxicity based on ctc v.2 criteria versus toxicity grade observed for the 39 patients.
Figure 2
Figure 2
Skin late toxicity based on ctc v.2 criteria versus toxicity grade for the 39 patients.
Figure 3
Figure 3
Minimum (broken line), mean (solid line), maximum (dotted line) cumulative lung dose volume histograms for hypofractionated breast radiotherapy. Filled circles indicate dose volume constraints used for planning, equivalent to V20 Gy<12.5%, V13<14.5% and V10<16% respectively at 2 Gy/fr regime considering an α/β value for the lung equal to 3 Gy.

References

    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. 2000;12:997–1003. doi: 10.1023/A:1011136326943.
    1. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–1241. doi: 10.1056/NEJMoa022152.
    1. Early Breast Cancer Trialist's Collaborative Group. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087–2106.
    1. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radioll. 1989;62:679–94. doi: 10.1259/0007-1285-62-740-679.
    1. Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, Lada B, Lukka H, Perera F, Fyles A, Laukkanen E, Gulavita S, Benk V, Szechtman B. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst. 2002;94:1143–1150.
    1. Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson J, Haviland J, Bentzen S, Owen R. Fractionation sensitivity and dose response of late dverse effects in the breast after radiotherapy for early breast cancer: Long term results of a randomized trial. Radiother Oncol. 2005;75:9–17. doi: 10.1016/j.radonc.2005.01.005.
    1. Owen JR, Ashton A, Bliss JM, Homewood J, Harper C, Hanson J, Haviland J, Bentzen SM, Yarnold JR. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: Long term results of randomized trial. Lancet. 2006;7:467–471. doi: 10.1016/S1470-2045(06)70699-4.
    1. The START Trialists' Group. The UK Standardisation of breast radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomized trial. Lancet Oncol. 2008;9:331–341. doi: 10.1016/S1470-2045(08)70077-9.
    1. The START Trialists' Group. The UK Standardisation of breast radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomized trial. Lancet. 2008;371:1098–1107. doi: 10.1016/S0140-6736(08)60348-7.
    1. Brenner DJ. Hypofractionation for prostate cancer radiotherapy - What are the issues? Int J Radiat Oncol Biol Phys. 2003;57:912–914.
    1. Withers HR, Thames HD, Peters LJ. A new isoeffect curve for change in dose per fraction. Radiother Oncol. 1983;1:187–91. doi: 10.1016/S0167-8140(83)80021-8.
    1. Steel GG. Basic clinical radiobiology. 3. London: Arnold; 2002. pp. 134–146.
    1. Ivaldi GB, Leonardi MC, Orecchia R, Zerini D, Morra A, Galimberti V, Gatti G, Luini A, Veronesi P, Ciocca M, Sangalli C, Fodor C, Veronesi U. Preliminary results of electron intraoperative therapy boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women. Int J Radiat Oncol Biol Phys. 2008;72(2):485–93. Epub 2008 Apr 11.
    1. Koukourakis MI, Giatromanolaki A, Kouroussis C, Kakolyris S, Sivridis E, Frangiadaki C, Retalis G, Georgoulias V. Tumor and Angiogenesis Research Group. Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients. Int J Radiat Oncol Biol Phys. 2002;52(1):144–55.
    1. Manavis J, Ambatzoglou J, Sismanidou K, Koukourakis MI. Computed tomography (CT) scan evaluation of late toxicity following hypofractionated/accelerated radiotherapy with cytoprotection (HypoARC) in breast cancer patients treated with conservative surgery. Am J Clin Oncol. 2006;29(5):479–83. doi: 10.1097/01.coc.0000227482.36289.f2.
    1. International Commission on Radiation Units and Measurements. Prescribing, recording and reporting photon beam therapy: ICRU report 50 Bethesda: International Commission on Radiation Units and Measurements. 1993.
    1. Yorke ED, Jackson A, Rosenzweig KE, Braban L, Leibel SA, Ling CC. Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study. Int J Radiat Oncol Biol Phys. 2005;63:672–682.
    1. Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, Perez CA. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC) Int J Radiat Oncol Biol Phys. 1999;45:323–329.
    1. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal Official Statement of the European Respiratory Society. Eur Respir J. 1993;6(Suppl 16):5–40.
    1. Prediletto R, Paoletti P, Fornai E, Perissinotto A, Petruzzelli S, Formichi B, Ruschi S, Palla A, Giannella-Neto A, Giuntini C. Natural course of treated pulmonary embolism Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram. Chest. 1990;97(3):554–61. doi: 10.1378/chest.97.3.554.
    1. COMMON TOXICITY CRITERIA (CTC)
    1. LENT SOMA. Tables Radiother Oncol. 1995. pp. 17–60.
    1. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.02.
    1. Nishioka A, Ogawa Y, Hamada N, Terashima M, Inomata T, Yoshida S. Analysis of radiation pneumonitis and radiation-induced lung fibrosis in breast cancer patients after breast conservation treatment. Oncol Rep. 1999;6:513–517.
    1. Wennberg B, Gagliardi G, Sundbom L, Svane G, Lind P. Early response of lung in breast cancer irradiation: radiologic density changes measured by ct and symptomatic radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2002;52:1196–1206. doi: 10.1016/S0360-3016(01)02770-5.
    1. Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM, Asrari F, Pilepich MV, Gagnon JD, Wong G. Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307–10.
    1. Lind PA, Rosfors S, Wennberg B, Glas U, Bevegård S, Fornander T. Pulmonary function following adjuvant chemotherapy and radiotherapy for breast cancer and the issue of three-dimensional treatment planning. Radiother Oncol. 1998;49:245–54. doi: 10.1016/S0167-8140(98)00121-2.
    1. Dörr W, Bertmann S, Herrmann T. Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects. Strahlenther Onkol. 2005;181(9):567–73. doi: 10.1007/s00066-005-1457-9.
    1. Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J. Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst. 1996;88(13):918–22. doi: 10.1093/jnci/88.13.918.
    1. Yerushalmi R, Kramer MR, Rizel S, Sulkes A, Gelmon K, Granot T, Neiman V, Stemmer SM. Decline in pulmonary function in patients with breast cancer receiving dose-dense chemotherapy: a prospective study. Ann Oncol. 2009;20(3):437–40. doi: 10.1093/annonc/mdn652. Epub 2009 Jan 12.

Source: PubMed

3
Abonnieren