Abstract

PurposeTo investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. MethodsIn this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010–2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4–5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into ‘low’ (n = 56) and ‘high’ TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. ResultsTD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1–107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2–60.2), lymph node involvement (HR 2.9; 95%CI 1.2–7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8–11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4–11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). ConclusionsHigh thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.

Highlights

  • To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia

  • Threeyear LRC rates for the low and high TD groups were 74.0% vs. 92.3%, respectively (p = 0.008)

  • For patient subgroups treated with 8 fractions of 4 Gy (2010–2017, n = 34) and 23 fractions of 2 Gy (2014– 2017, n = 78), three-year LRC rates for the low and high TD group were 55.6% and 81.2% (p = 0.07), and 81.6% and 97.3% (p = 0.025), respectively, see Supplementary Figs. 3 and 4A

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Summary

Introduction

To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. Conclusions: High thermal dose (best CEM43T50 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity. Higher intratarget temperatures have been shown to be associated with improved complete response rate and LRC in patients treated with RT-HT for primary locally advanced cervical cancer [16,17,18], malignant melanoma [19], head and neck tumors [20], rectal cancer [21] and unresectable locoregional recurrent breast cancer [22,23,24,25,26]. Our institutional treatment guidelines impose implantation of thermometry catheters for intratarget thermometry when possible [29] In this retrospective cohort study, we analyzed the impact of achieved intratarget temperatures on LRC, OS and toxicity in patients with resected locoregional recurrent or second ipsilateral primary breast cancer treated with postoperative re-irradiation with HT

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