Accelerated Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer; A Randomized Phase III Clinical Trial
-
Sare Hosseini
,
Mehri Shahabadi
,
Roham Salek
,
Azar Fanipakdel
,
Leila Ghofraniha
,
Fereshteh Ghaderi
,
Seyed Alireza Javadinia
Abstract
To compare the cosmetic outcome and acute cutaneous, cardiac, and pulmonary toxicity profile of accelerated hypofractionated and conventional whole breast radiotherapy (WBRT).This was a blocked randomized, clinical trial on women with early-stage node-negative invasive breast cancer after breast conservation surgery (BCS) with clear margins randomly assigned to receive WBRT either at a conventional dose of 50.0 grays (Gy) in 25 fractions (the conventional group) or at a dose of 42.5 Gy in 16 fractions (the hypofractionated group). Boost irradiation was permitted in both groups. Data were analyzed by SPSS V21.0 using Mann–Whitney U, independent-samples t- and Chi-Square/Fisher's exact tests at the level of P≤0.05.The median follows up was 16 months. Forty-one patients in the conventional WBRT arm and 45 patients in the hypofractionated WBRT group were enrolled. No significant difference was observed in terms of left and right ventricle systolic dysfunction and diastolic dysfunction. Pulmonary function tests after 6 and 12 months follow up, were comparable in both groups (P=0.2). Skin toxicity during and after treatment was acceptable in both groups. Breast size change in the conventional and the hypofractionated WBRT groups was 14.3% and 7.1%, respectively (P=0.6). Excellent or good cosmetic outcome was similar in both groups.The results of our study support the use of accelerated hypofractionated WBRT in women with invasive breast cancer less than five cm and node-negative after breast-conserving surgery, which provides a more convenient shorter course of radiotherapy with a comparable cosmetic outcome and cutaneous, cardiac, and pulmonary toxicity profile.
1. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. 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 (London, England). 2005;366(9503):2087-106. 10.1016/s0140-6736(05)67887-7P.
2. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. The New England journal of medicine. 2010;362(6):513-20. doi: 10.1056/NEJMoa0906260P.
3. Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast (Edinburgh, Scotland). 2010;19(3):192-7. 10.1016/j.breast.2010.03.003P.
4. Salek R, Shahidsales S, Mozafari V. Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran. Breast (Edinburgh, Scotland). 2016;28:95-9. 10.1016/j.breast.2016.05.003P.
5. Pinnarò P, Soriani A, Landoni V, Giordano C, Papale M, Marsella A, et al. 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. Journal of Experimental & Clinical Cancer Research : CR. 2010;29(1):9-. doi: 10.1186/1756-9966-29-9P.
6. Ciammella P, Podgornii A, Galeandro M, Micera R, Ramundo D, Palmieri T, et al. Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors. Radiation Oncology. 2014;9(1):97. 10.1186/1748-717x-9-97P.
7. Smith BD, Bentzen SM, Correa CR, Hahn CA, Hardenbergh PH, Ibbott GS, et al. Fractionation for Whole Breast Irradiation: An American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline. International Journal of Radiation Oncology*Biology*Physics. 2011;81(1):59-68. http://doi.org/10.1016/j.ijrobp.2010.04.042P.
8. Van Parijs H, Miedema G, Vinh-Hung V, Verbanck S, Adriaenssens N, Kerkhove D, et al. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial. Radiation Oncology. 2012;7(1):80. 10.1186/1748-717x-7-80P.
9. Cante D, Rosa La Porta M, Casanova-Borca V, Sciacero P, Girelli G, Pasquino M, et al. Accelerated hypofractionated adjuvant whole breast radiotherapy with concomitant photon boost after conserving surgery for early stage breast cancer: a prospective evaluation on 463 patients. The breast journal. 2011;17(6):586-93. doi: 10.1111/j.1524-4741.2011.01159.xP.
10. Hijal T, Al Hamad AA, Niazi T, Sultanem K, Bahoric B, Vuong T, et al. Hypofractionated radiotherapy and adjuvant chemotherapy do not increase radiation-induced dermatitis in breast cancer patients. Current oncology (Toronto, Ont). 2010;17(5):22-7. PMC2949365.
11. Zygogianni A, Kouloulias V, Kyrgias G, Armpilia C, Antypas C, Theodorou K, et al. Comparison of two radiotherapeutic hypofractionated schedules in the application of tumor bed boost. Clinical breast cancer. 2013;13(4):292-8. doi: 10.1016/j.clbc.2013.02.007P.
12. Amouzegar Hashemi F, Kalaghchi B, Sebzari AR, Haddad P, Shahabi Z. Comparing the effects of conventional and hypofractionated radiotherapies on early skin toxicity and cosmetic outcomes after breast cancer conserving surgery. Tehran University Medical Journal. 2012;70(9):540-7.
13. Erven K, Jurcut R, Weltens C, Giusca S, Ector J, Wildiers H, et al. Acute radiation effects on cardiac function detected by strain rate imaging in breast cancer patients. International journal of radiation oncology, biology, physics. 2011;79(5):1444-51. 10.1016/j.ijrobp.2010.01.004P.
14. Erven K, Florian A, Slagmolen P, Sweldens C, Jurcut R, Wildiers H, et al. Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy. International journal of radiation oncology, biology, physics. 2013;85(5):1172-8. 10.1016/j.ijrobp.2012.09.022P.
15. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. The Lancet Oncology. 2013;14(11):1086-94. 10.1016/S1470-2045(13)70386-3P.
16. Appelt AL, Vogelius IR, Bentzen SM. Modern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heart. Clinical oncology (Royal College of Radiologists (Great Britain)). 2013;25(3):147-52. 10.1016/j.clon.2012.07.012P.
17. Morrow M, Burstein HJ, Harris JR. Malignant Tumors of Breast. In: DeVita VT, Lawrence TS, Rosenberg SA, DePinho RA, Weinberg RA, editors. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology 10th ed. Philadelphia Wolters Kluwer; 2015. p. 1117-56.
18. Fragkandrea I, Kouloulias V, Mavridis P, Zettos A, Betsou S, Georgolopoulou P, et al. Radiation induced pneumonitis following whole breast radiotherapy treatment in early breast cancer patients treated with breast conserving surgery: a single institution study. Hippokratia. 2013;17(3):233-8.
19. Choi YW, Munden RF, Erasmus JJ, Park KJ, Chung WK, Jeon SC, et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics : a review publication of the Radiological Society of North America, Inc. 2004;24(4):985-97; discussion 98. 10.1148/rg.244035160P.
20. Beal K, Hudis C, Norton L, Wagman R, McCormick B. Radiation pneumonitis in breast cancer patients treated with taxanes: does sequential radiation therapy lower the risk? The breast journal. 2005;11(5):317-20. 10.1111/j.1075-122X.2005.21696.xP.
21. Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J. Radiotherapy-related lung fibrosis enhanced by tamoxifen. Journal of the National Cancer Institute. 1996;88(13):918-22.
2. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. The New England journal of medicine. 2010;362(6):513-20. doi: 10.1056/NEJMoa0906260P.
3. Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast (Edinburgh, Scotland). 2010;19(3):192-7. 10.1016/j.breast.2010.03.003P.
4. Salek R, Shahidsales S, Mozafari V. Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran. Breast (Edinburgh, Scotland). 2016;28:95-9. 10.1016/j.breast.2016.05.003P.
5. Pinnarò P, Soriani A, Landoni V, Giordano C, Papale M, Marsella A, et al. 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. Journal of Experimental & Clinical Cancer Research : CR. 2010;29(1):9-. doi: 10.1186/1756-9966-29-9P.
6. Ciammella P, Podgornii A, Galeandro M, Micera R, Ramundo D, Palmieri T, et al. Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors. Radiation Oncology. 2014;9(1):97. 10.1186/1748-717x-9-97P.
7. Smith BD, Bentzen SM, Correa CR, Hahn CA, Hardenbergh PH, Ibbott GS, et al. Fractionation for Whole Breast Irradiation: An American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline. International Journal of Radiation Oncology*Biology*Physics. 2011;81(1):59-68. http://doi.org/10.1016/j.ijrobp.2010.04.042P.
8. Van Parijs H, Miedema G, Vinh-Hung V, Verbanck S, Adriaenssens N, Kerkhove D, et al. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial. Radiation Oncology. 2012;7(1):80. 10.1186/1748-717x-7-80P.
9. Cante D, Rosa La Porta M, Casanova-Borca V, Sciacero P, Girelli G, Pasquino M, et al. Accelerated hypofractionated adjuvant whole breast radiotherapy with concomitant photon boost after conserving surgery for early stage breast cancer: a prospective evaluation on 463 patients. The breast journal. 2011;17(6):586-93. doi: 10.1111/j.1524-4741.2011.01159.xP.
10. Hijal T, Al Hamad AA, Niazi T, Sultanem K, Bahoric B, Vuong T, et al. Hypofractionated radiotherapy and adjuvant chemotherapy do not increase radiation-induced dermatitis in breast cancer patients. Current oncology (Toronto, Ont). 2010;17(5):22-7. PMC2949365.
11. Zygogianni A, Kouloulias V, Kyrgias G, Armpilia C, Antypas C, Theodorou K, et al. Comparison of two radiotherapeutic hypofractionated schedules in the application of tumor bed boost. Clinical breast cancer. 2013;13(4):292-8. doi: 10.1016/j.clbc.2013.02.007P.
12. Amouzegar Hashemi F, Kalaghchi B, Sebzari AR, Haddad P, Shahabi Z. Comparing the effects of conventional and hypofractionated radiotherapies on early skin toxicity and cosmetic outcomes after breast cancer conserving surgery. Tehran University Medical Journal. 2012;70(9):540-7.
13. Erven K, Jurcut R, Weltens C, Giusca S, Ector J, Wildiers H, et al. Acute radiation effects on cardiac function detected by strain rate imaging in breast cancer patients. International journal of radiation oncology, biology, physics. 2011;79(5):1444-51. 10.1016/j.ijrobp.2010.01.004P.
14. Erven K, Florian A, Slagmolen P, Sweldens C, Jurcut R, Wildiers H, et al. Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy. International journal of radiation oncology, biology, physics. 2013;85(5):1172-8. 10.1016/j.ijrobp.2012.09.022P.
15. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. The Lancet Oncology. 2013;14(11):1086-94. 10.1016/S1470-2045(13)70386-3P.
16. Appelt AL, Vogelius IR, Bentzen SM. Modern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heart. Clinical oncology (Royal College of Radiologists (Great Britain)). 2013;25(3):147-52. 10.1016/j.clon.2012.07.012P.
17. Morrow M, Burstein HJ, Harris JR. Malignant Tumors of Breast. In: DeVita VT, Lawrence TS, Rosenberg SA, DePinho RA, Weinberg RA, editors. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology 10th ed. Philadelphia Wolters Kluwer; 2015. p. 1117-56.
18. Fragkandrea I, Kouloulias V, Mavridis P, Zettos A, Betsou S, Georgolopoulou P, et al. Radiation induced pneumonitis following whole breast radiotherapy treatment in early breast cancer patients treated with breast conserving surgery: a single institution study. Hippokratia. 2013;17(3):233-8.
19. Choi YW, Munden RF, Erasmus JJ, Park KJ, Chung WK, Jeon SC, et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics : a review publication of the Radiological Society of North America, Inc. 2004;24(4):985-97; discussion 98. 10.1148/rg.244035160P.
20. Beal K, Hudis C, Norton L, Wagman R, McCormick B. Radiation pneumonitis in breast cancer patients treated with taxanes: does sequential radiation therapy lower the risk? The breast journal. 2005;11(5):317-20. 10.1111/j.1075-122X.2005.21696.xP.
21. Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J. Radiotherapy-related lung fibrosis enhanced by tamoxifen. Journal of the National Cancer Institute. 1996;88(13):918-22.
| Files | ||
| Issue | Vol 57, No 11 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v57i11.3262 | |
| Keywords | ||
| Radiotherapy Dose hypofractionation Breast cancer Clinical trials | ||
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How to Cite
1.
Hosseini S, Shahabadi M, Salek R, Fanipakdel A, Ghofraniha L, Ghaderi F, Javadinia SA. Accelerated Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer; A Randomized Phase III Clinical Trial. Acta Med Iran. 2020;57(11):645-652.
