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Comparison of conventional and hypofractionated radiation after mastectomy in locally advanced breast cancer: a prospective randomised study on dosimetric evaluation and treatment outcome

Published online by Cambridge University Press:  17 January 2020

Sumana Maiti
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Suman Meyur*
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Bidhan Chandra Mandal
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Lekshmi R Shenoi
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Susmita Biswas
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
Siddhartha Basu
Affiliation:
Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India
*
Author for correspondence: Dr Suman Meyur, Department of Radiotherapy and Oncology, Institute of Post-Graduate Medical Education and Research, Kolkata, India. Mobile: +91 9674457101. E-mail: [email protected]

Abstract

Background:

Although hypofractionated radiotherapy has been standardised in early breast cancer, even in post-mastectomy no such consensus has been developed for locally advanced breast cancer (LABC), probably due to complex planning and field matching. This study is directed towards dosimetric evaluation and comparison of toxicity, response and disease-free survival (DFS) comparison between hypofractionation and conventional radiotherapy in post-mastectomy LABC.

Methodology:

In total, 222 female breast cancer patients were randomly assigned to be treated with either hypofractionated radiotherapy (n = 120) delivering 40 Gy in 15 fractions over 3 weeks or conventional radiotherapy (n = 102) with 50 Gy in 25 fractions over 5 weeks after modified radical mastectomy (MRM) along with neoadjuvant and/or adjuvant chemotherapy. All patients were planned with treatment planning software and assessed regularly during and after treatment.

Results:

Median follow-up period was 178 weeks in conventional arm (CRA) and 182 weeks in hypofractionation arm (HFA). There exists a dosimetric difference between the two arms of treatment, in spite of similar dose coverage [planning treatment volume (PTV) D90 92·04% in CRA versus 92·5% in HFA; p = 0·49], average dose in HFA is less than that of CRA (p < 0·001); so is the maximum clinical target volume (CTV) dose (p < 0·001). Similarly, average lung dose in HFA arm is significantly lower than CRA (9·9 versus 10·84; p = 0·06), but the V20Gy of lung and V30Gy of heart had no difference. The toxicity of radiation was comparable with similar mean time to produce toxicity [CRA: 7 W, HFA: 10 W; hazard ratio 0·64, 95% confidence interval (CI) = 0·28–1·45]. Three-year recurrence event was alike in two arms (CRA: 4·9%, HFA: 5·8%; p = 0·76). Mean DFS in CRA is 230 weeks and that of HFA is 235 weeks with hazard ratio 1·01 (95% CI = 0·32–3·19; p = 0·987).

Conclusion:

Though biologically effective dose (BED) in hypofractionation is lesser than that of conventional fractionation, there are indistinguishable toxicity, locoregional recurrence, distant failure rate and DFS between the two modalities.

Type
Original Article
Copyright
© The Authors, 2020. Published by Cambridge University Press

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References

Huang, L, Chen, S, Yang, WT, Shao, Z. Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy. Oncotarget 2017; 8(24): 39703.CrossRefGoogle ScholarPubMed
Barrett, A, Dobbs, J, Morris, S, Roques, T. Breast. In: Jamieson, G, Senior, E, Silman, J, Walker, J, Townson, H, Ross, J (eds). Practical Radiotherapy Planning, 4th edition. London, UK: Hodder Arnold, 2009: 265282.CrossRefGoogle Scholar
Ragaz, J, Olivotto, IA, Spinelli, JJ et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005; 97(2): 116126.CrossRefGoogle ScholarPubMed
Overgaard, M, Nielsen, HM, Overgaard, J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b and c randomized trials. Radio Oncol 2007; 82(3): 247253.CrossRefGoogle ScholarPubMed
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Darby, S, McGale, P et al. 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 randomized trials. Lancet 2011; 378: 17071716.Google Scholar
McGale, P, Taylor, C, Correa, C et al. Effects of radiotherapy after mastectomy and axillary surgery on 10 years recurrence and 20 years breast cancer mortality: meta-analysis of individual patients data for 8135 woman in 22 randomized trials. Lancet 2014; 383: 21272135.Google Scholar
MacDonald, SM, Harris, EE, Arthur, DW et al. ACR appropriateness criteria® locally advanced breast cancer. Breast J 2011; 17(6): 579585.CrossRefGoogle ScholarPubMed
Trialists’ Group TS. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 2008; 371(9618): 10981107.CrossRefGoogle Scholar
Jones, B, Dale, RG, Deehan, C, Hopkins, KI, Morgan, DA. The role of biologically effective dose (BED) in clinical oncology. Clin Oncol (R Coll Radiol) 2001; 13: 7181.Google Scholar
Shaltout, EA, El Razek, A. Adjuvant postmastectomy hypofractionated radiotherapy in Egyptian cancer patients: a 2 years follow-up. Annlas Oncol 2012; 23: 3436.Google Scholar
Whelan, T, Mackenzies, R, Julian, J. Randomized trial of breast irradiation schedules after lumpectomy for woman with lymph node- negative brest cancer. J Natl Cancer Inst 2002; 94: 11431150.CrossRefGoogle Scholar
Whelan, TJ, Pignol, JP, Levine, MN et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010; 362(6): 513520.CrossRefGoogle ScholarPubMed
Owen, JR, Ashton, A, Bliss, JM et al. Effect of radiotherapy fraction size on tumor control in patients with early stage breast cancer after local tumor excision: longterm results of a randomized trial. Lancet Oncol 2006; 7(6): 467471.CrossRefGoogle Scholar
Yarnold, J, Ashton, A, Bliss, J. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer : long-term results of a randomized trial. Radiothr Oncol 2005; 75: 917.CrossRefGoogle Scholar
Bentzen, SM, Agrawal, RK, Aird, EG et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 2008; 9(4): 331341.Google Scholar
Bentzen, SM, Agrawal, RK, Aird, EG et al. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 2008; 371(9618): 10981107.Google ScholarPubMed
Clark, RM, Whelan, T, Levine, M. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node negative breast cancer: an update. Ontario Clinical Oncology Group. J Natl Cancer Inst 1996; 88: 16591664.CrossRefGoogle ScholarPubMed
Overgarrd, M, Bentzen, SM, Christensen, JJ, Madsen, EH. The value of the NSD formula in equation of acute and late radiation complications in normal tissue following 2 and 5 fractions per week in breast cancer patients treated with post mastectomy irradiation. Radiother Oncol 1987; 9: 111.CrossRefGoogle Scholar
Ollivotto, IA, Weir, LM, Kim-Sing, C. Late cosmetic results of short fractionation for breast conservation. Radiother Oncol 1996; 41: 713.CrossRefGoogle Scholar
Wang, SL, Fang, H, Song, YW et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for PTS with risk breast cancer:a randomized, non-inferiority, open –level phase 3 trial. Lancet Oncol 2019; 20(3): 352360.CrossRefGoogle Scholar
Recht, A, Edge, SB, Solin, LJ et al. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19(5): 15391569.CrossRefGoogle ScholarPubMed
Yarnold, J. Early and locally advanced breast cancer: diagnosis and treatment National Institute for Health and Clinical Excellence guideline 2009. Clin Oncol 2009; 21(3): 159160.CrossRefGoogle ScholarPubMed
Smith, BD, Bentzen, SM, Correa, CR et al. Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys 2011; 81(1): 5968.CrossRefGoogle ScholarPubMed
Goetz, MP, Gradishar, WJ, Anderson, BO et al. NCCN guidelines insights: breast cancer, Version 3.2018: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2019; 17(2): 118126.CrossRefGoogle Scholar
Yamauchi, C, Sekiguchi, K, Nishioka, A et al. The Japanese Breast Cancer Society Clinical Practice Guideline for radiation treatment of breast cancer. Breast Cancer 2016; 23(3): 378390.CrossRefGoogle ScholarPubMed
Oken, M, Creech, R, Tormey, D et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649655.CrossRefGoogle ScholarPubMed
Breast cancer atlas for radiation therapy planning: consensus definitions. https://www.rtog.org/CoreLab/ContouringAtlases/BreastCancerAtlas.aspx. Accessed on 21st September 2019.Google Scholar
National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. NIH publication # 09-7473. Published 29 May 2009. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf. Accessed on 21st September 2019.Google Scholar
Cox, JD, Stetz, J, Pajak, TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31(5): 13411346.CrossRefGoogle Scholar
EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale, P, Taylor, C et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014; 383(9935): 21272135.Google ScholarPubMed
Khan, AJ, Poppe, MM, Goyal, S et al. Hypofractionated postmastectomy radiation therapy is safe and effective: first results from a prospective phase II trial. J Clin Oncol 2017; 35(18): 20372043.CrossRefGoogle ScholarPubMed
Yarnold, J, Bentzen, SM, Coles, C, Haviland, J. Hypofractionated whole-breast radiotherapy for women with early breast cancer: myths and realities. Int J Radiat Oncol Biol Phys 2011; 79(1): 19.CrossRefGoogle ScholarPubMed
Youssef, A, Stanford, J. Hypofractionation radiotherapy vs. conventional fractionation for breast cancer: a comparative review of toxicity. Cureus 2018; 10(10): e3516.Google Scholar
Darby, SC, Ewertz, M, McGale, P et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013; 368(11): 987998.CrossRefGoogle ScholarPubMed
Bhattacharyya, M, Kalita, AK, Medhi, PP et al. Hypofractionated radiotherapy in post mastectomy locally advanced breast cancer: a study from a regional cancer center in North East India. Int J Res Med Sci 2018; 6(12): 39423948.CrossRefGoogle Scholar
Rastogi, K, Jain, S, Bhatnagar, AR, Bhaskar, S, Gupta, S, Sharma, N. A comparative study of hypofractionated and conventional radiotherapy in postmastectomy breast cancer patients. Asia Pac J Oncol Nurs 2018; 5: 107113.Google ScholarPubMed