Hyperthermia and reirradiation for locoregional recurrences in preirradiated breast cancers: a single institutional experience
QUESTIONS UNDER STUDY: The aim of this retrospective analysis was to evaluate the safety and efficacy of local hyperthermia (HT) and reirradiation (ReRT) in the management of preirradiated locoregional recurrent breast cancers at Kantonsspital Aarau, Switzerland.
METHODS: Twenty-four previously irradiated patients who had developed locoregional recurrences in the chest wall or breast, with or without regional lymph node involvement, were reirradiated to a mean dose of 36.8 Gy (range 20–50 Gy) delivered at a mean dose per fraction of 2.33 Gy (range 1.8–4.0 Gy). All patients received local HT at 41 to 43 °C, once or twice a week prior to radiotherapy. Online thermometry was carried out during the hyperthermia sessions.
RESULTS: An overall objective response rate of 91.7% (22/24) with a complete response in 66.7% (16/24) of patients and partial response in 25% (6/24) of patients was observed. Post-thermoradiotherapy follow-up ranged from 1 to 38 months (median 10 months). The 3-year actuarial local control rate was 59.7%. More patients who attained complete response had sustained locoregional control until their death or last follow-up when compared with those who were partial or non-responders (median local disease-free survival for complete responders not reached; for partial and non-responders 4 months; p <0.001). Post-retreatment median overall survival for all 24 patients was 10 months. Grade III/IV acute toxicity was seen in only one patient and no patient had any significant late morbidity.
CONCLUSIONS: ReRT and HT is an effective and a safe modality to treat locoregional recurrences in previously irradiated breast cancers. The approach can lead to sustainable long-term palliation with minimal morbidity.
- Siglin J, Champ CE, Vakhnenko Y, Anne PR, Simone NL. Radiation therapy for locally recurrent breast cancer. Int J Breast Cancer. 2012;2012:571946.doi: 10.1155/2012/571946.
- Cheng L, Swartz MD, Zhao H, Kapadia AS, Lai D, Rowan PJ, et al. Hazard of recurrence among women after primary breast cancer treatment – a 10–year follow-up using data from SEER-Medicare. Cancer Epidemiol Biomarkers Prevent. 2012;21(5): 800–9.
- Philippson C, Simon S, Vandekerkhove C, Hertens D, Veys I, Noterman D, et al. Early invasive cancer and partial intraoperative electron radiation therapy of the breast: experience of the Jules Bordet Institute, Int J Breast Cancer. 2014;2014:627352.doi: 10.1155/2014/627352.
- Bethke KP. Breast conservation: predictors and treatment of local recurrence. Semin Surg Oncol. 1996;12(5):332–8.
- Plasswilm L, Seegenschmiedt MH, Ganssauge F, Sauer R. Simultaneous radiochemotherapy for recurrent and metastatic breast carcinoma: evaluation of two treatment concepts. Am J Clin Oncol. 1996;19(4):403–7.
- Rauschecker H, Clarke M, Gatzemeier W, Recht A. Systemic therapy for treating locoregional recurrence in women with breast cancer. Cochrane Database Syst Rev. 2001;(4):CD002195.
- Schwaibold F, Fowble BL, Solin LJ, Schultz DJ, Goodman RL. The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys. 1991;21(2):299–310.
- Wahl AO, Rademaker A, Kiel KD, Jones EL, Marks LB, Croog V, et al. Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer, Int J Radiat Oncol Biol Phys. 2008;70(2):477–84.
- Kuerer HM, Arthur DW, Haffty BG. Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence: the potential role of partial breast irradiation, Cancer. 2004;100(11):2269–80.
- Dahlstrøm KK, Andersson AP, Andersen M, Krag C. Wide local excision of recurrent breast cancer in the thoracic wall. Cancer. 1993;72(3):774–7.
- Overgaard J. The current and potential role of hyperthermia in radiotherapy, Int J Radiat Oncol Biol Phys. 1989;16(3):535–49.
- Overgaard J. The heat is (still) on – the past and future of hyperthermic radiation oncology. Radiother Oncol. 2013;109(2):185–7.
- Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002;3(8):487–97.
- Vernon CC, Hand JW, Field SB, Machin D, Whaley JB, van der Zee J, et al. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group. Int J Radiat Oncol Biol Phys. 1996;35(4):731–44.
- Lee HK, Antell AG, Perez CA, Straube WL, Ramachandran G, Myerson RJ, et al. Superficial hyperthermia and irradiation for recurrent breast carcinoma of the chest wall: prognostic factors in 196 tumors, Int J Radiat Oncol Biol Phys. 1998;40(2):365–75.
- Hehr T, Lamprecht U, Glocker S, Classen J, Paulsen F, Budach W, et al. Thermoradiotherapy for locally recurrent breast cancer with skin involvement, Int J Hyperthermia. 2001;17(4):291–301.
- Ben-Yosef R, Vigler N, Inbar M, Vexler A. Hyperthermia combined with radiation therapy in the treatment of local recurrent breast cancer. Isr Med Assoc. 2004:6(7):392–5.
- Jones EL, Oleson JR, Prosnitz LR, Samulski TV, Vujaskovic Z, Yu D, et al. Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol. 2005;23(13):3079–85.
- Gabriele P, Ferrara T, Baiotto B, Garibaldi E, Marini PG, Penduzzu G, et al. Radio hyperthermia for re-treatment of superficial tumours. Int J Hyperthermia. 2009;25(3):189–98.
- Perez CA, Kuske RR, Emami B, Fineberg B. Irradiation alone or combined with hyperthermia in the treatment of recurrent carcinoma of the breast in the chest wall: a nonrandomized comparison. Int J Hyperthermia. 1986;2(2):179–87.
- van der Zee J, Treurniet-Donker AD, The SK, Helle PA, Seldenrath JJ, Meerwaldt JH, et al. Low dose reirradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer recurring in previously irradiated areas. Int J Radiat Oncol Biol Phys. 1988;15(6):1407–13.
- Lindholm CE, Kjellen E, Nilsson P, Hertzman S. Microwave-induced hyperthermia and radiotherapy in human superficial tumours: clinical results with a comparative study of combined treatment versus radiotherapy alone. Int J Hyperthermia. 1987;3(5):393–411.
- Dragovic J, Seydel HG, Sandhu T, Kolosvary A, Blough J. Local superficial hyperthermia in combination with low-dose radiation therapy for palliation of locally recurrent breast carcinoma. J Clin Oncol. 1989;7(1):30–5.
- Masunaga S, Hiraoka M, Takahashi M, Jo S, Akuta K, Nishimura Y, et al. Clinical results of thermoradiotherapy for locally advanced and/or recurrent breast cancer- comparison of results with radiotherapy alone. Int J Hyperthermia. 1990;6(3):487–97.
- Kapp DS, Barnett TA, Cox RS, Lee ER, Lohrbach A, Fessenden P. Hyperthermia and radiation therapy of local-regional recurrent breast cancer: prognostic factors for response and local control of diffuse or nodular tumors. Int J Radiat Oncol Biol Phys. 1991;20(5):1147–64.
- Perez CA, Pajak T, Emami B, Hornback NB, Tupchong L, Rubin P. Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors: final report by the Radiation Therapy Oncology Group. Am J Clin Oncol. 1991;14(2):133–41.
- Phromratanapongse P, Steeves RA, Severson SB, Paliwal BR. Hyperthermia and irradiation for locally recurrent previously irradiated breast cancer. Strahlenther Onkolol. 1991;167(2):93–7.
- Cancer Therapy Evaluation Programme, Common Terminology Criteria for Adverse Events, version 3.0, DTCD, NCI, NIH, DHHS, March 31, 2003, published date, August 9,2006. Available from: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf (Accessed on 17 July, 2014)
- US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Programme, “Common Terminology Criteria for Adverse Events”, version 4.1, published date, June 14, 2010. Available from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010–06–14_QuickReference_5x7.pdf (Accessed on 17 July, 2014)
- Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.
- Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.
- Kaplan EL, Meier P. Nonparametric estimations from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81.
- Cox DR. Regression models and life-tables. J R Stat Soc Series B Stat Methodol. 1972;34(2):187–220.
- Willner J, Kiricuta IC, Kölbl O. Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis. Int J Radiat Oncol Biol Phys. 1997;37(4):853–63.
- Perez CA, Gillespie B, Pajak T, Hornback NB, Emami B, Rubin R. Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a report by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1989;16(3):551–8.
- Zagar TM, Oleson JR, Vujaskovic Z, Dewhirst MW, Craciunescu OI, Blackwell KL, et al. Hyperthermia combined with radiation therapy for superficial breast cancer and chest wall recurrence: a review of the randomised data. Int J Hyperthermia. 2010;26(7):612–7.
- Linthorst M, van Geel AN, Baaijens M, Ameziane A, Ghidey W, van Rhoon GC, et al. Re-irradiation and hyperthermia after surgery for recurrent breast cancer. Radiother Oncol. 2013;109(2):188–193.
- Müller AC, Eckert F, Heinrich V, Bamberg M, Brucker S, Hehr T. Re-surgery and chest wall re-irradiation for recurrent breast cancer: a second curative approach. BMC Cancer. 2011;11:197. doi: 10.1186/1471–2407–11–197.
- Zoul Z, Filip S, Melichar B, Dvorák J, Odrázka K, Petera J. Weekly paclitaxel combined with local hyperthermia in the therapy of breast cancer locally recurrent after mastectomy – a pilot experience. Onkologie. 2004;27(4):385–8.
- Kouloulias VE, Dardoufas CE, Kouvaris JR, Gennatas CS, Polyzos AK, Gogas HJ, et al. Liposomal doxorubicin in conjunction with reirradiation and local hyperthermia treatment in recurrent breast cancer: a phase I/ II trial. Clin Cancer Res. 2002;8(2):374–82.
- Feyerabend T, Weidemann GJ, Jäger B, Vesely H, Mahlmann B, Richter E. Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease. Int J Radiat Oncol Biol Phys. 2001;49(5):1317–25.
- Borenstein BA, Zouranjian PS, Hansen JL, Fraser SM, Gelwan LA, Teicher BA, et al. Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma. Int J Radiat Oncol Biol Phys. 1993;25(1):79–85.
- Hurwitz M, Stauffer P. Hyperthermia, radiation and chemotherapy: the role of heat in multidisciplinary cancer care. Semin Oncol. 2014;41(6):714–29.