Hyperthermia and Radiotherapy Combination for Locoregional Recurrences of Breast Cancer: A Review

Abstract

Practice pointsr Locoregional breast recurrences still occur in more or less 5-20% of patients despite receiving adjuvant radiotherapy. r Resection alone provides limited local control with approximately 33% at 5-years compared to 42% with resection plus other oncologic treatments necessitating curative intent multidisciplinary approach. r Hyperthermia (HT) is the use of elevated temperature to the degrees of 40-44 • C for 30-60 min. The addition of HT to ionizing radiation results in a synergistic effect called radiosensitization. r Toxicity related to HT includes generally second-and third-degree skin and subcutaneous burns, which are usually self-limited making this combination a favorable easy to use modality. r Data addressing the use of HT in locoregional breast recurrences (LRBR) is well-validated and includes randomized trials and meta-analysis. r Thermoradiotherapy enhances local control rates in LRBR with minimal acute, late morbidity and is even more effective in previously irradiated group. r Two trials conducted by European Society for Hyperthermic Oncology will further clarify the multimodal treatment with chemotherapy in R1/R2 resection and neoadjuvant use of thermoradiotherapy.Breast cancer is a second common form of malignancy and is one of the leading causes of mortality among cancer patients across the world. Locoregional recurrence occurs in 5-20% of patients despite upfront treatment. Local therapy (surgery plus minus re-irradiation) with or without systemic therapy is generally recommended for management. Local control rates vary; months to years, but a significant percentage lives 5 years. Therefore, treatment strategies to increase response rates are significant. Hyperthermia is one of the most potent radiosensitizers and data from meta-analysis and randomized trials support its use with radiotherapy. This study reviews the biologic rationale and clinical evidence about concomitant use of hyperthermia and radiotherapy in locally-recurrent breast cancer patients. Chest wall or whole breast irradiation with or without regional nodal sites is indicated after modified radical mastectomy and breast conserving surgery (BCS), respectively. Although adjuvant radiotherapy (RT) effectively reduces locoregional recurrences, data from randomized trials have demonstrated that this type of recurrences still occur in more or less 5-20% of patients despite receiving adjuvant RT after surgery (mastectomy or BCS) [1][2][3][4][5][6].Although locally-recurrent breast cancer (LRBC) is usually accompanied by concurrent or subsequent distant metastases [3,7,8], a significant percentage, more than 50% live 5 years [9]. In a retrospective study of 145 patients with isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases, 5-year survival rates were 42% overall but it was 100% for a highly favorable subgroup [10].

Combined wIRA-Hyperthermia and Hypofractionated Re-Irradiation in the Treatment of Locally Recurrent Breast Cancer: Evaluation of Therapeutic Outcome Based on a Novel Size Classification

“…A meta-analysis and systematic review based on randomized clinical trials, single-arm studies and retrospective analyses have proven the efficacy of sHT combined with RT in the treatment of LRBC [15]. This has been confirmed by several recent reviews [16][17][18][19][20]. Hyperthermia can also be combined with adjuvant re-RT after surgery of local recurrences in the case of "microscopic disease" upon R1 resection or high-risk situations due to close surgical margins [21][22][23].…”

Neoadjuvant Treatment Options in Soft Tissue Sarcomas

“…A particularly challenging situation is reirradiation due to STS relapse or radiation-induced STS. HT might be added to enhance tumor response to RT, whose dose is limited by previous RT [101][102][103]. In a retrospective analysis, the authors assessed the outcomes of 16 patients with radiation-induced STS in the thoracic region treated with HT+HFRT using two moderately hypofractionated regimens (3 Gy to 36 Gy, 12 fractions, three weeks, 6× HT; or 4 Gy to 32 Gy, eight fractions, two weeks, 4× HT) [6].…”

Radiation Enhancement with Polyethyleneimine-Coated Gold Nanoparticles Under MV Photons

“…a radiosensitizer (RS) are examples for enhancing intratumoral dose, and they thus improve the therapeutic ratio. [2,3,4] Nanotechnology is a rapidly developing branch of science. Its use in radiation oncology has three major aspects: 1) facilitate image-guided radiotherapy (IGRT) through mechanisms based on increased uptake of particles by cancer cells similar to positron emission tomography imaging [5]; 2) increased synergistic cytotoxic effects with hyperthermia, chemotherapy, and targeted therapy combinations [6,7,8,9]; and 3) radiation enhancement via radiosensitizing effect.…”