Session Item

Randomized clinical studies showed better complete response rates for patients with unresectable locoregional (LR) recurrence in previously irradiated area treated with re-irradiation and hyperthermia (reRT-HT) than with reRT alone. Single-arm studies suggested that post-operative reRT-HT is effective for patients with resected LR recurrence. However, HT dose delivered during treatment was often poorly monitored and documented. We investigated the impact of HT dose on LR control, overall survival (OS) and toxicity in patients with LR recurrent breast cancer treated with post-operative reRT-HT guided by extensive invasive thermometry in the target region.

Observational study of 112 women with LR recurrent breast cancer, stages (y)pT0-4N0-3M0-1, treated with post-operative reRT+HT. Mean age was 64±11 years, 85% had received systemic treatment, 63% had salvage mastectomy, and 37% had a local resection after previous mastectomy. ReRT was given to a total dose of 46Gy in 23 (n=78), or 32Gy in 8 fractions (n= 34), combined with 4-5 weekly HT sessions guided by invasive thermometry. Patients were divided in ‘low’ (n=56) and ‘high’ thermal dose (TD) groups (n=56) by the session with the highest invasive dose CEM43T50 (=median cumulative equivalent minutes at 43°C) <7.2 and ≥7.2minutes, respectively. LR control, OS and late toxicity incidence according to Common Terminology Criteria for Adverse Events version 5.0, were evaluated. Backward multivariable Cox regression was performed to identify outcome-associated patient and treatment characteristics.

Median follow-up period was 43 months (range 1-107). Actuarial 3-year rate LR  control and OS were 83.2% and 85.4%, respectively. Three-year LR control was 74.0% vs. 92.3% in the low and high TD group, respectively (p=0.008) (Figures 1+2). Three-year LR control was also significantly different for the low and high TD groups, 81.6% and 97.3% (p=0.013) for 46 Gy in 23 fractions, and 55.6% and 81.2% (p=0.033) for 32 Gy in 8 fractions, respectively. After 3 years, 25% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. TD was associated with LR control (p=0.0013), but not with OS (p=0.29) or late toxicity (p=0.74). Multivariable analysis showed that presence of distant metastases (HR 17.6; 95% CI 5.2 - 60.2), lymph node involvement (HR 2.9; 95% CI 1.2-7.2), site of recurrence (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 worse LR control.

Patients with resected LR recurrent breast cancer receiving post-operative reRT combined with high dose HT had a significantly higher LR control than patients receiving reRT and low dose HT, without augmenting treatment-associated toxicity. This result also indirectly suggests that HT does enhance the effectiveness of post-operative reRT after resection of LR recurrent breast cancer, and stresses the value of invasive temperature guidance during HT.