Efficacy and Safety of Hypofractionation Radiotherapy versus Conventional Whole Breast Radiotherapy for Early Stage Breast Cancer after Breast Conserving Surgery: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 GANYu-hong ¹ , WANGXiao-hu ² , TIANJin-hui ^2,3 , GELong ³ , LIURei-feng ² , YANGYan ² ,  ZHANGQiu-ning ²

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China;
2. Tumor Hospital of Gansu Province, Lanzhou 730000, China;
3. Evidence-based Medicine Centre of Lanzhou University, Lanzhou 730000, China;

Corresponding?author：

ZHANGQiu-ning, Email: zqn168@sina.com

Keywords：

Breast neoplasm; Breast conserving surgery; Hypofractionation radiotherapy; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160161

Video：

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Objective To systematically evaluate the efficacy, cosmetic outcome and adverse reaction of hypofractionation radiotherapy (HRT) versus conventional radiotherapy (CRT) for early stage breast cancer after breast conserving surgery. Methods The databases including CNKI, CBM, VIP, PubMed, EMbase and The Cochrane Library (Issue 1, 2015) were searched from the inception to May 2015 to collect the randomized controlled trials (RCTs) related to HRT versus CRT for early stage breast cancer after breast conserving surgery. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. Results Six RCTs involving 8 240 patients were included. Meta-analyses results showed, there were no statistical differences between the HRT group and the CRT group in local-regional recurrence rate (5 year: RR=1.01, 95%CI 0.73 to 1.40, P=0.94; 10 year: RR=1.04, 95%CI 0.86 to 1.26, P=0.67), mortality (5 year: RR=0.95, 95%CI 0.85 to 1.08, P=0.45; 10 year: RR=0.97, 95%CI 0.86 o 1.09, P=0.61), photographic breast appearance (RR=0.98, 95%CI 0.91 to 1.05, P=0.56), the incidence of lung fibrosis (5 year: RR=1.07, 95%CI 0.66 to 1.72, P=0.78; 10 year: RR=1.05, 95%CI 0.62 to 1.77, P=0.86), the incidence of rib fracture (5 year: RR=1.00, 95%CI 0.60 to 1.68, P=0.99; 10 year: RR=1.19, 95%CI 0.70 to 2.00, P=0.52), and the incidence of ischemic of heart (5 year: RR=0.88, 95%CI 0.54 to 1.45, P=0.62; 10 year: RR=0.86, 95%CI 0.54 to 1.37, P=0.53). Conclusion HRT could provide similar tumor control as CRT without serious toxicity. Meanwhile HRT is superior to CRT in terms of patient convenience and costs, it should be promoted as adjuvant treatment for early stage breast cancer after breast conserving surgery.

Citation： GANYu-hong, WANGXiao-hu, TIANJin-hui, GELong, LIURei-feng, YANGYan, ZHANGQiu-ning. Efficacy and Safety of Hypofractionation Radiotherapy versus Conventional Whole Breast Radiotherapy for Early Stage Breast Cancer after Breast Conserving Surgery: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2016, 16(9): 1047-1055. doi: 10.7507/1672-2531.20160161 Copy

1.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2.	Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): 279-289.
3.	Fisher B, Anderson S, Bryant J, et al. 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.
4.	Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med, 1993, 328: 1587-1591.
5.	Clark RM, Whelan T, Levine M, et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst, 1996, 88: 1659-1664.
6.	Forrest AP, Stewart HJ, Everington D, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet, 1996, 348: 708-713.
7.	EBCTCG (Early Breast Cancer Trialists' Collaborative Group). 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: 2127-2135.
8.	Virnig B, Habermann E, Al-Raie W, et al. Increased use of breast-conserving surgery: preferred treatment or failure to provide adequate local therapy? Breast Cancer Res Treat, 2007, 106: Suppl 1: S188.
9.	Mouw KW, Harris JR. Breast Hypofractionation in the era of modulated radiotherapy (RT). 2013, 22 Suppl 2: S129-136.
10.	Bentzen SM, Baumann M. The linear-quadratic model in clinical practice. In: Steel GG, ed. Basic clinical radiobiology, 3rd edn. London: Arnold, 2002: 134-146.
11.	Thames HD, Hendry JH, Moore JV, et al. The high steepness of dose-response curves for late-responding normal tissues. Radiother Oncol, 1989, 15: 49-53.
12.	Rew DA, Wilson GD. Cell production rates in human tissues and tumors and their significance. Part II: clinical date J. Eur J Surg Oncol, 2000, 26(4): 405-417.
13.	Owen J, Ashton A, Bliss J, et al. Effect of radiotherapy fraction size on tumor control in patients with early-stage breast cancer after local tumor excision: long-term results of a randomized trial. Lancet Oncol, 2006, 7(6): 467-471.
14.	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): 331-341.
15.	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): 1098-1107.
16.	Yarnold J, Ashton A, Bliss J, et al. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol, 2005, 75(1): 9-17.
17.	Whelan T, Piganol J, Levine M, et al. Long term results of hypofractionated radiation therapy for breast cancer. N Engl J Med, 2010, 362(6): 51-20.
18.	The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results. In: Haviland JS, Agrawal R, Aird E, et al, editors. CTRC-AACR San Antonio Breast Cancer Symposium December 4-8, 2012.
19.	王淑蓮, 李曄雄, 余子豪, 等.早期乳腺癌患者根治術后的放射治療.中華腫瘤志, 2002, 24(1): 68-70.
20.	趙淑紅, 王宏, 張潤莉, 等.早期乳腺癌保乳術后大分割放療的研究.中國醫藥導報, 2013, 10(24): 17-19.
21.	Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. Natl Cancer Inst, 2002, 794(15): 1143-1150.
22.	FAST Trialists group, Agrawal RK, Alhasso A, et al. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol, 2011, 100(1): 93-100.
23.	Baillet F, Housset M, Maylin C, et al. The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients. Int J Radiat Oncol Biol Phys, 1990, 19(5): 1131-1133.
24.	Higgins JPT, Altman DG, Sterne JAC, et al. Chapter 8: Assessing risk of bias in included studies//Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available at: www.cochrane-handbook.org.
25.	冶秀鵬, 馬小萍, 包慎, 等.早期乳腺癌保乳術后大分割放療的Meta分析.現代腫瘤醫學, 2015, 23(16): 2292-2300.
26.	Arenault T, Parpia S, Reiter H, et al. Acute Toxicity and Quality of Life of Hypofractionated Radiation Therapy for Breast Cancer. Int J Radiat Oncol Biol Phys, 2015, 93(3): S59.
27.	Pignol JP, Olivotto I, Rakovitch E, et al. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol, 2008, 26(13): 2085-2092.

1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): 279-289.
3. Fisher B, Anderson S, Bryant J, et al. 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.
4. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med, 1993, 328: 1587-1591.
5. Clark RM, Whelan T, Levine M, et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst, 1996, 88: 1659-1664.
6. Forrest AP, Stewart HJ, Everington D, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet, 1996, 348: 708-713.
7. EBCTCG (Early Breast Cancer Trialists' Collaborative Group). 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: 2127-2135.
8. Virnig B, Habermann E, Al-Raie W, et al. Increased use of breast-conserving surgery: preferred treatment or failure to provide adequate local therapy? Breast Cancer Res Treat, 2007, 106: Suppl 1: S188.
9. Mouw KW, Harris JR. Breast Hypofractionation in the era of modulated radiotherapy (RT). 2013, 22 Suppl 2: S129-136.
10. Bentzen SM, Baumann M. The linear-quadratic model in clinical practice. In: Steel GG, ed. Basic clinical radiobiology, 3rd edn. London: Arnold, 2002: 134-146.
11. Thames HD, Hendry JH, Moore JV, et al. The high steepness of dose-response curves for late-responding normal tissues. Radiother Oncol, 1989, 15: 49-53.
12. Rew DA, Wilson GD. Cell production rates in human tissues and tumors and their significance. Part II: clinical date J. Eur J Surg Oncol, 2000, 26(4): 405-417.
13. Owen J, Ashton A, Bliss J, et al. Effect of radiotherapy fraction size on tumor control in patients with early-stage breast cancer after local tumor excision: long-term results of a randomized trial. Lancet Oncol, 2006, 7(6): 467-471.
14. 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): 331-341.
15. 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): 1098-1107.
16. Yarnold J, Ashton A, Bliss J, et al. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol, 2005, 75(1): 9-17.
17. Whelan T, Piganol J, Levine M, et al. Long term results of hypofractionated radiation therapy for breast cancer. N Engl J Med, 2010, 362(6): 51-20.
18. The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results. In: Haviland JS, Agrawal R, Aird E, et al, editors. CTRC-AACR San Antonio Breast Cancer Symposium December 4-8, 2012.
19. 王淑蓮, 李曄雄, 余子豪, 等.早期乳腺癌患者根治術后的放射治療.中華腫瘤志, 2002, 24(1): 68-70.
20. 趙淑紅, 王宏, 張潤莉, 等.早期乳腺癌保乳術后大分割放療的研究.中國醫藥導報, 2013, 10(24): 17-19.
21. Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. Natl Cancer Inst, 2002, 794(15): 1143-1150.
22. FAST Trialists group, Agrawal RK, Alhasso A, et al. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol, 2011, 100(1): 93-100.
23. Baillet F, Housset M, Maylin C, et al. The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients. Int J Radiat Oncol Biol Phys, 1990, 19(5): 1131-1133.
24. Higgins JPT, Altman DG, Sterne JAC, et al. Chapter 8: Assessing risk of bias in included studies//Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available at: www.cochrane-handbook.org.
25. 冶秀鵬, 馬小萍, 包慎, 等.早期乳腺癌保乳術后大分割放療的Meta分析.現代腫瘤醫學, 2015, 23(16): 2292-2300.
26. Arenault T, Parpia S, Reiter H, et al. Acute Toxicity and Quality of Life of Hypofractionated Radiation Therapy for Breast Cancer. Int J Radiat Oncol Biol Phys, 2015, 93(3): S59.
27. Pignol JP, Olivotto I, Rakovitch E, et al. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol, 2008, 26(13): 2085-2092.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Hypofractionation Radiotherapy versus Conventional Whole Breast Radiotherapy for Early Stage Breast Cancer after Breast Conserving Surgery: A Systematic Review

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