A Comparative Analysis of Hypofractionated and Conventional Radiotherapy for Breast Cancer Patients: A Retrospective Cohort Study

Main Article Content

Abba Mallum Maureen Bilinga Tendwa Onyinye Balogun John M. Akudugu Wilfred Ngwa Mariza Vorster

Abstract

Breast cancer presents a substantial health challenge in Africa and marked by a continuous rise in its incidence and prevalence. The complexities of managing breast cancer on the continent are exacerbated by limited access to healthcare resources and high rates of late-stage disease at initial diagnosis. Recent studies comparing hypofractionated radiotherapy (HFRT), considered cost-effective and non-inferior to conventional fractionated radiotherapy (CFRT), have shown no significant differences in outcomes. This underscores the potential significance of HFRT in breast cancer treatment. Despite encouraging findings from researchers in developing countries, there is a noticeable lack of data on HFRT outcomes, particularly in Sub-Saharan Africa. This retrospective study analyzed individuals diagnosed with early, locally advanced or oligometastatic cancer, and who underwent treatment between January 2010 and December 2020 at Inkosi Albert Luthuli Central Hospital in the KwaZulu Natal Province of South Africa. Relevant clinical treatment details and follow-up information were retrieved from the patients' medical electronic records. This retrospective study included 645 breast cancer patients, categorized into early (37.7%), locally advanced (59.9%), and oligometastatic (2.4%) stages. Treatment modalities included surgery (100%), chemotherapy (77.8%), endocrine therapy (38.8%), and targeted therapy (4.8%). All patients received radiotherapy, with a predominant utilization of HFRT (83.7%) over CFRT (16.3%). Notably, there was no statistically significant difference (p=0.91) observed in survival probability between patients who received HFRT and CFRT. The findings of this study suggest that, in a low-income setting, HFRT does not exhibit a significant variance in survival outcomes compared to CFRT for breast cancer patients. However, to validate this conclusion, additional large-scale randomized clinical trials are imperative.

Keywords: Breast cancer; conventional radiotherapy; hypofractionation; survival outcome, Sub-Saharan Africa

Article Details

How to Cite
MALLUM, Abba et al. A Comparative Analysis of Hypofractionated and Conventional Radiotherapy for Breast Cancer Patients: A Retrospective Cohort Study. Medical Research Archives, [S.l.], v. 12, n. 8, aug. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5585>. Date accessed: 04 dec. 2024. doi: https://doi.org/10.18103/mra.v12i8.5585.
Section
Research Articles

References

1. Moodley J, Constant D, Mwaka A, Scott S, Walter F. Mapping awareness of breast and cervical cancer risk factors, symptoms and lay beliefs in Uganda and South Africa. PloS one. 2020;15(10): e0240788. Doi.org/10.1371/journal.pone.0240788.

2. Jedy-Agba E, McCormack V, Adebamowo C, dos-Santos-Silva I. Stage at diagnosis of breast cancer in sub-Saharan Africa: a systematic review and meta-analysis. The Lancet Global Health. 2016 ;4(12):e923-e935.
DOI: 10.1016/S2214-109X(16)30259-5.

3. Ngwa W, Addai BW, Adewole I, et al. Cancer in sub-Saharan Africa: a lancet oncology commission. The Lancet Oncology. 2022;23(6): e251-e312. DOI: 10.1016/S1470-2045(21)00720-8.

4. Singh D, Vignat J, Lorenzoni V, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. The lancet global health. 2023;11(2):e197-e206. Doi: 10.1016/S1470-2045(21)00720-8.

5. Patel S, Olatunji E, Mallum A, et al. Expanding radiotherapy access in Sub-Saharan Africa: an analysis of travel burdens and patient-related benefits of hypofractionation. Frontiers in Oncology. 2023;13:1136357.
Doi.org/10.3389/fonc.2023.1136357.

6. Anderson KN, Schwab RB, Martinez ME. Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast cancer research and treatment. 2014;144:1-10. DOI: 10.1007/s10549-014-2852-7.

7. Kanadys W, Barańska A, Malm M, Błaszczuk A, Polz-Dacewicz M, Janiszewska M, Jędrych M. Use of oral contraceptives as a potential risk factor for breast cancer: A systematic review and meta-analysis of case-control studies up to 2010. International journal of environmental research and public health. 2021;18(9):4638.
Doi: 10.3390/ijerph18094638.

8. Beltrán Ponce SE, Abunike SA, Bikomeye JC, et al. Access to radiation therapy and related clinical outcomes in patients with cervical and breast cancer across sub-saharan africa: A systematic review. JCO Global Oncology. 2023;9:e2200218. Doi: 10.1200/GO.22.00218.

9. Sanft T, Day A, Peterson L, et al. NCCN Guidelines® insights: survivorship, version 1.2022: featured updates to the NCCN guidelines. Journal of the National Comprehensive Cancer Network. 2022;20(10):1080-1090.
Doi: 10.6004/jnccn.2022.0052.

10. Gradishar WJ, Anderson BO, Abraham J, et al. Breast cancer, version 3.2020, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network. 2020; 18(4):452-478. Doi: 10.6004/jnccn.2020.0016.

11. Bhuiyan M, Maele M, Mavhungu R, Ooko F. Breast cancer: Factors influencing late-stage presentation at the Mankweng Hospital breast cancer clinic, Polokwane, Limpopo Province, South Africa. South African Medical Journal. 2022;112 (11):906-910. Doi.org/10.7196/SAMJ.2022.v112i11b.16834.

12. Joffe M, Ayeni O, Norris SA, et al. Barriers to early presentation of breast cancer among women in Soweto, South Africa. PloS one. 2018; 13(2):e0192071. Doi.org/10.1371/journal.pone.0192071.

13. Agodirin O, Aremu I, Rahman G, Olatoke S, Olaogun J, Akande H, Romanoff A. Determinants of delayed presentation and advanced-stage diagnosis of breast cancer in Africa: a systematic review and meta-analysis. Asian Pacific journal of cancer prevention: APJCP. 2021;22(4):1007. Doi: 10.31557/APJCP.2021.22.4.1007.

14. Kraus RD, Weil CR, Abdel-Wahab M. Benefits of adopting hypofractionated radiotherapy as a standard of care in low-and middle-income countries. JCO global oncology. 2022;8. DOI: 10.1200/GO.22.00215.

15. Elmore SN, Polo A, Bourque J-M, et al. Radiotherapy resources in Africa: an International Atomic Energy Agency update and analysis of projected needs. The Lancet Oncology. 2021;22 (9):e391-e399.
Doi: 10.1016/S1470-2045(21)00351-X.

16. Ndlovu N. Radiotherapy treatment in cancer control and its important role in Africa. Ecancermedicalscience. 2019;13. Doi: 10.3332/ecancer.2019.942.

17. IAEA. Directory of radiotherapy centers. 2022. Https://dirac.iaea.org/Query/Countries.

18. Gradishar WJ, Moran MS, Abraham J, et al. Breast cancer, version 3.2022, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network. 2022; 20(6):691-722. Doi: 10.6004/jnccn.2022.0030.

19. Liu L, Yang Y, Guo Q, et al. Comparing hypofractionated to conventional fractionated radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review. Radiation Oncology. 2020;15:1-15. (2020) 15:17. Doi.org/10.1186/s13014-020-1463-1.

20. Akl FM, Khater A. Hypofractionated versus conventionally fractionated radiotherapy in post-mastectomy breast cancer patients. Journal of Cancer Therapy. 2018;9(11):941-954. DOI: 10.4236/jct.2018.911078.

21. Irabor OC, Swanson W, Shaukat F, et al. Can the adoption of hypofractionation guidelines expand global radiotherapy access? An analysis for breast and prostate radiotherapy. JCO global oncology. 2020;6:667-678.
Doi: 10.1200/JGO.19.00261.

22. Swanson W, Kamwa F, Samba R, et al. Hypofractionated radiotherapy in African cancer centers. Frontiers in Oncology. 2021;10:618641. Doi.org/10.3389/fonc.2020.618641.

23. Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. Journal of the National Cancer Institute. 2002;94(15):1143-1150. DOI: 10.1093/jnci/94.15.1143.

24. 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. Radiotherapy and oncology. 2005;75(1):9-17. Doi: 10.1016/j.radonc.2005.01.005.

25. Owen JR, Ashton A, Bliss JM, et al. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. The lancet oncology. 2006;7(6):467-471. Doi: 10.1016/S1470-2045(06)70699-4.

26. Yarnold J, Bentzen SM, Coles C, Haviland J. Hypofractionated whole-breast radiotherapy for women with early breast cancer: myths and realities. International journal of radiation oncology, biology, physics. 2011;79(1):1-9. DOI: 10.1016/j.ijrobp.2010.08.035.

27. Group ST. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. The Lancet. 2008;371 (9618):1098-1107.
Doi: 10.1016/S0140-6736(08)60348-7.

28. Whelan TJ, Pignol J-P, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. New England Journal of Medicine. 2010;362(6):513-520. DOI: 10.1056/NEJMoa0906260.

29. Haviland JS, Owen JR, Dewar JA, 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):1086-1094. Doi: 10.1016/S1470-2045(08)70077-9.

30. Wang S-L, Fang H, Song Y-W, et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. The Lancet Oncology. 2019;20(3):352-360. Doi: 10.1016/S1470-2045(18)30813-1.

31. Offersen B, Alsner J, Nielsen H, Jakobsen E, Nielsen M, Krause M. Danish Breast cancer Group radiation Therapy committee. hypofractionated Versus standard Fractionated radiotherapy in patients With early Breast cancer or Ductal carcinoma In situ in a randomized phase III Trial: The DBcG hYpO Trial. J clin Oncol. 2020;38(31).
Doi: 10.1200/JCO.20.01363.

32. Wang S-L, Fang H, Hu C, et al. Hypofractionated versus conventional fractionated radiotherapy after breast-conserving surgery in the modern treatment era: a multicenter, randomized controlled trial from China. Journal of Clinical Oncology. 2020;38(31):3604-3614. Doi: 10.1200/JCO.20.01024.

33. Jd C. 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: 1341-1346. Doi: 10.1016/0360-3016(95)00060-C.

34. Brunt AM, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. The Lancet. 2020;395(10237):1613-1626.
Doi:https://doi.org/10.1016/S0140-6736(20)30932-6.

35. Brunt AM, Haviland JS, Sydenham M, et al. Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer. Journal of Clinical Oncology. 2020;38(28):3261. Doi: 10.1200/JCO.19.02750.

36. Group FT. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiotherapy and Oncology. 2011;100(1):93-100. Doi:10.1200/JCO.19.02750.

37. Veluthattil AC, Sudha SP, Kandasamy S, Chakkalakkoombil SV. Effect of hypofractionated, palliative radiotherapy on quality of life in late-stage oral cavity cancer: a prospective clinical trial. Indian Journal of Palliative Care. 2019;25(3):383. Doi: 10.4103/IJPC.IJPC_115_18.

38. Zingeta GT, Worku YT, Awol M, et al. Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study. JCO Global Oncology. 2024;10:e2300253. Doi: 10.1200/GO.23.00253.

39. Shaitelman SF, Lei X, Thompson A, et al. Three-year outcomes with hypofractionated versus conventionally fractionated whole-breast irradiation: results of a randomized, noninferiority clinical trial. Journal of Clinical Oncology. 2018;36(35):3495. Doi: 10.1200/JCO.18.00`317.

40. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of surgical oncology. 2010;17(6):1471-1474. Doi: 10.1245/s10434-010-0985-4.

41. Engstrom P, Benson 3rd A, Cohen A, et al. NCCN Colorectal Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Williston Park, NY). 1996;10(11 Suppl):140-175. PMID: 8953601.

42. Green F, Page D, Fleming I, Fritz A, Balch C, Haller D, Morrow M. AJCC cancer staging manual. In: New York: Springer; 2002. https://www.facs.org/media/tauiudl3/ajcc_6thed_cancer_staging_manual_part1.pdf.

43. Team RDC. R: A language and environment for statistical computing. (No Title). 2010.
https://www.scirp.org/reference/referencespapers?referenceid=493779.

44. Mushonga M, Weiss J, Liu ZA, et al. Hypofractionation in breast cancer radiotherapy across World Bank income groups: Results of an international survey. JCO global oncology. 2023;9:e2200127. Doi.org/10.1200/GO.22.00127.

45. Atun R, Jaffray DA, Barton MB, et al. Expanding global access to radiotherapy. The lancet oncology. 2015;16(10):1153-1186. Doi: 10.1016/S1470-2045(15)00222-3.

46. Monten C, Lievens Y. Adjuvant breast radiotherapy: how to trade-off cost and effectiveness? Radiotherapy and Oncology. 2018;126(1):132-138. Doi: 10.1016/j.radonc.2017.11.005.

47. 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-Pacific Journal of Oncology Nursing. 2018;5(1): 107-113. Doi: 10.4103/apjon.apjon_46_17.

48. Grosche S, Bogdanova NV, Ramachandran D, et al. Effectiveness of hypofractionated and normofractionated radiotherapy in a triple‐negative breast cancer model. Frontiers in oncology. 2022;12:852694. Doi.org/10.3389/fonc.2022.852694.

49. Korreman S, Rasch C, McNair H, et al. The European Society of Therapeutic Radiology and Oncology–European Institute of Radiotherapy (ESTRO–EIR) report on 3D CT-based in-room image guidance systems: a practical and technical review and guide. Radiotherapy and Oncology. 2010;94(2):129-144.
Doi: 10.1016/j.radonc.2010.01.004.

50. Datta NR, Samiei M, Bodis S. Radiation therapy infrastructure and human resources in low-and middle-income countries: present status and projections for 2020. International Journal of Radiation Oncology* Biology* Physics. 2014;89 (3):448-457. Doi: 10.1016/j.ijrobp.2014.03.002.

51. Abdel-Wahab M, Bourque J-M, Pynda Y, Iżewska J, Van der Merwe D, Zubizarreta E, Rosenblatt E. Status of radiotherapy resources in Africa: an International Atomic Energy Agency analysis. The lancet oncology. 2013;14(4):e168-e175. Doi: 10.1016/S1470-2045(12)70532-6.

52. Mutebi M, Anderson BO, Duggan C, et al. Breast cancer treatment: A phased approach to implementation. Cancer. 2020;126:2365-2378. Doi: 10.1002/cncr.32910.

53. Langenhoven L, Barnardt P, Neugut AI, Jacobson JS. Phenotype and treatment of breast cancer in HIV-positive and-negative women in Cape Town, South Africa. Journal of global oncology. 2016;2(5):284-291. Doi.org/10.1200/JGO.2015.002451.

54. Muddather HF, Elhassan MM, Faggad A. Survival outcomes of breast cancer in sudanese women: a hospital-based study. JCO Global Oncology. 2021;7(1):324-332. Doi.org/10.1200/GO.20.00538.

55. Brandão M, Guisseve A, Bata G, et al. Breast cancer subtypes: implications for the \treatment and survival of patients in Africa—a prospective cohort study from Mozambique. ESMO open. 2020;5(5):e000829.
Doi: 10.1136/esmoopen-2020-000829.

56. Vanderpuye V, Grover S, Hammad N, PoojaPrabhakar n, Simonds H, Olopade F, Stefan D. An update on the management of breast cancer in Africa. Infectious agents and cancer. 2017;12:1-12. Doi: 10.1186/s13027-017-0124-y.

57. Cubasch H, Joffe M, Hanisch R, et al. Breast cancer characteristics and HIV among 1,092 women in Soweto, South Africa. Breast cancer research and treatment. 2013;140:177-186. Doi: 10.1007/s10549-013-2606-y.

58. Othieno-Abinya N, Nyabola L, Abwao H, Ndege P. Post-surgical management of patients with breast cancer at Kenyatta National Hospital. East African medical journal. 2002;79(3):156-162. Doi: 10.4314/eamj.v79i3.8897.

59. Adebamowo C, Adekunle O. Case‐controlled study of the epidemiological risk factors for breast cancer in Nigeria. British Journal of Surgery. 1999;86(5):665-668. Doi: 10.1046/j.1365-2168.1999.01117.x.

60. Rais G, Raissouni S, Aitelhaj M, et al. Triple negative breast cancer in Moroccan women: clinicopathological and therapeutic study at the National Institute of Oncology. BMC Women's Health. 2012;12(1):1-9. Doi: 10.1186/1472-6874-12-35.

61. Darré T, Tchandikou L, Simgban P, et al. Factors associated with late diagnosis of breast cancer in women in Togo, Sub-Saharan Africa. BMC Women's Health. 2023;23(1):1-8.

62. Omotoso O, Teibo JO, Atiba FA, et al. Addressing cancer care inequities in sub-Saharan Africa: current challenges and proposed solutions. International Journal for Equity in Health. 2023; 22(1):189. Doi.org/10.1186/s12905-023-02257-8.

63. Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA oncology. 2015;1(6): 778-784. Doi: 10.1001/jamaoncol.2015.2378.

64. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of Oncology. 2016;27(8):1386-1422. Doi: 10.1093/annonc/mdw235.

65. Roeland E, LeBlanc T. Palliative chemotherapy: oxymoron or misunderstanding? BMC palliative care. 2016;15(1):1-3. Doi: 10.1186/s12904-016-0109-4.

66. Fiorin de Vasconcellos V, RCC Bonadio R, Avanço G, Negrão MV, Pimenta Riechelmann R. Inpatient palliative chemotherapy is associated with high mortality and aggressive end-of-life care in patients with advanced solid tumors and poor performance status. BMC Palliative Care. 2019;18 (1):1-8. Doi: 10.1186/s12904-019-0427-4.

67. Bugat R, Bataillard A, Lesimple T, et al. Summary of the standards, options and recommendations for the management of patients with carcinoma of unknown primary site (2002). British journal of cancer. 2003;89(1):S59-S66. Doi: 10.1038/sj.bjc.6601085.

68. Seve P, Sawyer M, Hanson J, Broussolle C, Dumontet C, Mackey JR. The influence of comorbidities, age, and performance status on the prognosis and treatment of patients with metastatic carcinomas of unknown primary site: a population‐based study. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2006;106(9):2058-2066. Doi: 10.1002/cncr.21833.

69. Ettinger DS, Abbruzzese J, Gams R, et al. NCCN practice guidelines for occult primary tumors. Oncology. 1998;12(11 A):226-309. Doi: 10.6004/jnccn.2011.0117.

70. Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. Journal of Clinical Oncology. 2021;39 (13):1485. Doi.org/10.1200/JCO.20.03399.

71. ACSCA N. COVID-19 pandemic ongoing impact on cancer. Patients and Survivors Survey Findings Summary. 2020;2020.
https://www.fightcancer.org/policy-resources/covid-19-pandemic-ongoing-impact-cancer-community-may-2020.

72. Madigan LI, Dinh P, Graham JD. Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines. Breast Cancer Research. 2020;22(1):1-13. Doi: 10.1186/s13058-020-01314-6.

73. Coates AS, Colleoni M, Goldhirsch A. Is adjuvant chemotherapy useful for women with luminal a breast cancer. J Clin Oncol. 2012;30 (12):1260-1263. Doi: 10.1200/JCO.2011.37.7879.

74. Hayes DF. Targeting adjuvant chemotherapy: a good idea that needs to be proven! Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2012;30(12):1264-1267. Doi: 10.1200/JCO.2011.38.4529.

75. Alba E, Albanell J, de la Haba J, et al. Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial. British journal of cancer. 2014;110(5):1139-1147.
Doi: 10.1038/bjc.2013.831.

76. Tapia M, Hernando C, Martínez MT, et al. Clinical Impact of New Treatment Strategies for HER2-Positive Metastatic Breast Cancer Patients with Resistance to Classical Anti-HER Therapies. Cancers. 2023;15(18):4522.
Doi: 10.3390/cancers15184522.

77. Choong GM, Cullen GD, O’Sullivan CC. Evolving standards of care and new challenges in the management of HER2‐positive breast cancer. CA: a cancer journal for clinicians. 2020;70(5):355-374. Doi: 10.3322/caac.21634.

78. Yalaza M, İnan A, Bozer M. Male breast cancer. The journal of breast health. 2016;12(1):1. Doi: 10.5152/tjbh.2015.2711.