Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

Harijati Versmessen, Vincent Vinh-Hung, Hilde Van Parijs, Geertje Miedema, Mia Voordeckers, Nele Adriaenssens, Guy Storme, Mark De Ridder, Harijati Versmessen, Vincent Vinh-Hung, Hilde Van Parijs, Geertje Miedema, Mia Voordeckers, Nele Adriaenssens, Guy Storme, Mark De Ridder

Abstract

Background: Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy.

Methods: A total of 121 stage I-II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle.

Results: On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA with the Bonferroni correction did not show any significant differences between groups in HRQOL scores.

Conclusions: TT patients had a better improvement in global health status and role- and cognitive-functioning, and a faster recovery from fatigue, than CR patients. These results suggest that a shorter fractionation schedule may reduce the adverse effects of treatment.

Trial registration: ClinicalTrials.gov NCT00459628.

Figures

Figure 1
Figure 1
Participant flow.
Figure 2
Figure 2
EORTC QLQ-C30.
Figure 3
Figure 3
EORTC QLQ-C30.
Figure 4
Figure 4
EORTC QLQ-BR23.
Figure 5
Figure 5
EORTC QLQ-BR23.

References

    1. Kamangar F, Dores GM, Anderson WE. Patterns of cancer incidence, mortality, and prevalance across five continents: Defining priorities to reduce caner disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–2150. doi: 10.1200/JCO.2005.05.2308.
    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.
    1. Munshi A, Budrukkar A. Hypofractionated Radiation Therapy in Breast Cancer: A revolutionary Breakthrough or a Long Way to Go? J Clin Oncol. 2007;25(4):458–459. doi: 10.1200/JCO.2006.09.1736.
    1. Cuzick J. Radiotherapy for breast cancer. J Natl Cancer Inst. 2005;97:406–407. doi: 10.1093/jnci/dji086.
    1. Nielsen HM, Overgaard M, Grau C, Jensen AR, Overgaard J. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol. 2006;24:2268–2275. doi: 10.1200/JCO.2005.02.8738.
    1. Van de Steene J, Soete G, Storme G. Adjuvant radiotherapy for breast cancer significantly improves overall survival: the missing link. Radiother Oncol. 2000;55:263–272. doi: 10.1016/S0167-8140(00)00204-8.
    1. Vinh-Hung V, Verschraegen C. The Breast Conserving Surgery Project. Breast conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst. 2004;96:115–121. doi: 10.1093/jnci/djh013. Available at: . Accessed September 18, 2007.
    1. Taylor ME, Haffty BG, Rabinovitch R, Arthur DW, Halberg FE, Strom EA, White JR, Cobleigh MA, Edge SB. ACR appropriateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast. Int J Radiat Oncol Biol Phys. 2009;73:997–1002. doi: 10.1016/j.ijrobp.2008.10.080.
    1. Buchholz TA. Radiation therapy for early-stage breast cancer after breast-conserving surgery. N Engl J Med. 2009;360:63–70. doi: 10.1056/NEJMct0803525.
    1. Gebski V, Lagleva M, Keech A, Simes J, Langlands AO. Survival effects of postmastectomy adjuvant radiation therapy using biologically equivalent doses: a clinical perspective. J Natl Cancer Inst. 2006;98:26–38. doi: 10.1093/jnci/djj002.
    1. Sautter-Bihl ML, Budach W, Dunst J, Feyer P, Haase W, Harms W, Sedlmayer F, Haase W, Dunst J, Wenz F, Sauer R. DEGRO practical guidelines for radiotherapy of breast cancer I: breast-conserving therapy. Strahlenther Onkol. 2007;183:661–666. doi: 10.1007/s00066-007-1811-1.
    1. Kaufmann M, Morrow M, Von MG, Harris JR. Locoregional treatment of primary breast cancer: consensus recommendations from an International Expert Panel. Cancer. 2010;116:1184–1191. doi: 10.1002/cncr.24874.
    1. Thames HD, Bentzen SM, Turesson I, Overgaard M, Van den Bogaert W. Time-dose factors in radiotherapy: A review of the human data. Radiother Oncol. 1990;19:219–235. doi: 10.1016/0167-8140(90)90149-Q.
    1. Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomized trials. Lancet. 2000;355:1757–1770.
    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. doi: 10.1093/jnci/94.15.1143.
    1. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513–520. doi: 10.1056/NEJMoa0906260.
    1. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008;9:331–341.
    1. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008;371:1098–1107.
    1. Hopwood P, Haviland JS, Sumo G, Mills J, Bliss JM, Yarnold JR. Comparison of patient-reported breast, arm, and shoulder symptoms and body image after radiotherapy for early breast cancer: 5-year follow-up in the randomised Standardisation of Breast Radiotherapy (START) trials. Lancet Oncol. 2010;11:231–240. doi: 10.1016/S1470-2045(09)70382-1.
    1. Taher AN, El-Baradie MM, Essa H, Zaki O, Ezzat S. Hypofractionation versus conventional fractionation radiotherapy after conservative treatment of breast cancer: early skin reactions and cosmetic results. J Egypt Natl Canc Inst. 2004;16:178–187.
    1. FAST Trialists group. First results of the randomised UK FAST trial of radiotherapy hypofractionation for treatment of early breast cancer. Radiotherapy Oncol. 2011;100(1):93–100. Jl.
    1. Baillet F, Housset M, Maylin C, Boisserie G, Bettahar R, Delanian S, Habib F. 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;19:1131–1133. doi: 10.1016/0360-3016(90)90216-7.
    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 a randomised trial. Lancet Oncol. 2006;7:467–471. doi: 10.1016/S1470-2045(06)70699-4.
    1. Shahid A, Athar MA, Asghar S, Zubairi R, Murad S, Yunas N. Post mastectomy adjuvant radiotherapy in breast cancer: a comparision of three hypofractionated protocols. J Pak Med Assoc. 2009;59:282–287.
    1. Mandelblatt JS, Eisenburg JM. Historical and methodological perspectives on cancer outcomes research. Oncology. 1995;9:23–32.
    1. Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, Goh TT, Lindley R, Cairns J. A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial. Health Technol Assess. 2007;11(31):1–149. iii-iv.
    1. Sprangers MAG. Quality-of-life assessment in oncology – achievements and challenges. Acta Oncol. 2002;41:229–237. doi: 10.1080/02841860260088764.
    1. Schwartz CE, Sprangers MAG. Methodological approaches for assessing response shift in longitudinal health-related quality-of-life research. Soc Sci Med. 1999;48:1531–1548. doi: 10.1016/S0277-9536(99)00047-7.
    1. Sprangers MAG, Schwartz CE. Integrating response shift into health-related quality-of-life research. Soc Sci Med. 1999;48:1507–1515. doi: 10.1016/S0277-9536(99)00045-3.
    1. Efron B. Forcing a sequential experiment to be balanced. Biometrika. 1971;58:403–417. doi: 10.1093/biomet/58.3.403.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Dues NJ, Fliberti A, Fletchtner H, Fleishman SB, de Haes JC. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376. doi: 10.1093/jnci/85.5.365.
    1. Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, Franzini L, Williams A, de Haes HC, Howood P, Cull A, Aaronson NK. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: First results from a three-country field study. J Clin Oncol. 1996;14:2756–2768.
    1. Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 scoring manual. 3. Brussels: European Organisation for Research and Treatment of Cancer; 2001.
    1. 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;31:1341–1346. doi: 10.1016/0360-3016(95)00060-C.
    1. LENT SOMA tables. Radiother Oncol. 1995;35:17–60.
    1. Michelson H, Bolund C, Nilsson B, Brandberg Y. Health-related quality of life measured by the EORTC QLQ-C30—reference values from a large sample of Swedish population. Acta Oncol. 2000;39:477–484. doi: 10.1080/028418600750013384.
    1. Osoba D. Interpreting the meaningfulness of changes in health-related quality of life scores: lessons from studies in adults. Int J Cancer Suppl. 1999;12:132–137.
    1. Lee TS, Kilbreath SL, Refshauge KM, Pendlebury SC, Beith JM, Lee MJ. Quality of life of women treated with radiotherapy for breast cancer. Support Care Center. 2008;16(4):399–405. doi: 10.1007/s00520-007-0328-6.
    1. Kunkler IH. In: Cancer of the breast. Bomford CK, Kunkler IH, editor. Amsterdam: Elsevier Science: Walter and Miller’s textbook of radiotherapy; 2002. p. 451.
    1. Whelan TJ, Levine M, Julian J, Kirkbride P, Skingley P. The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomised trial. Cancer. 2000;88:2260–2266. doi: 10.1002/(SICI)1097-0142(20000515)88:10<2260::AID-CNCR9>;2-M.
    1. Graydon J. Women with breast cancer: their quality of life following a course of radiation therapy. J Adv Nurs. 1994;19:617–622. doi: 10.1111/j.1365-2648.1994.tb01131.x.
    1. Wengstrom Y, Haggmark C, Strander H, Forsberg C. Perceived symptoms and quality of life in women with breast cancer receiving radiation therapy. Eur J Oncol Nurs. 2000;4:78–88. doi: 10.1054/ejon.1999.0052.
    1. Walker BL, Nail LM, Larsen L, Magill J, Schwartz A. Concerns, affect and cognitive disruption following completion of radiation treatment for localised breast or prostate cancer. Oncol Nurs Forum. 1996;23:1181–1187.
    1. Drouin JS, Armstrong H, Krause S, Orr J, Birk TJ, Hrynicuk WM, Hryniuk LE. Effects of aerobic exercise training on peak aerobic capacity, fatigue, and psychological factors during radiation for breast cancer. Rehabil Oncol. 2005;23:11–17.
    1. Mock V, Dow KH, Meares CJ, Grimm PM, Dienemann JA, Haisfield-Wolfe ME, Quitasol W, Mitchell S, Chakravarthy A, Gage I. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum. 1997;24:991–1000.
    1. Back M, Ahern V, Delaney G, Graham P, Steigler A, Wratten C. New South Wales Breast Radiation Oncology Group. Absence of adverse early quality of life outcomes of radiation therapy in breast conservation therapy for early breast cancer. Australas Radiol. 2005;49:39–43. doi: 10.1111/j.1440-1673.2005.01392.x.
    1. Geinitz H, Zimmermann FB, Thamm R, Keller M, Busch R, Molls M. Fatigue in patients with adjuvant radiation therapy for breast cancer: longterm follow-up. J Cancer Res Clin Oncol. 2004;130:327–333. doi: 10.1007/s00432-003-0540-9.
    1. Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer. 2007;7(12):949–960. doi: 10.1038/nrc2288.
    1. Osoba D. Health-related quality of life and cancer clinical trials. Ther Adv Med Oncol. 2011;3(2):57–71. doi: 10.1177/1758834010395342.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa