TANCA

Background

For locally advanced head and neck squamous cell carcinoma (LAHNSCC), standard of care is chemoradiotherapy using cisplatin. Local regional recurrence occurs often, mostly in the radiotherapy (RT) high dose region, resulting in poor prognosis. For patients over 70 years, cisplatin shows decreased efficacy and increased toxicity, making it contraindicated in The Netherlands. Specifically, this group of patients needs another radiosensitizer. Hyperthermia (HT) has been proven to be a radiosensitizer in many tumor sites. For head and neck (HN) cancers, HT plus RT also showed evidence of a beneficial effect over RT alone, only these studies used superficial devices. Within the Erasmus MC, we developed the HyperCollar3D, containing 20 antennas to deliver HT to superficial and deep HN tumors. Our phase I trial will evaluate the tolerability and safety of our novel technique.

Objectives

The primary outcome is the recommended phase II dose (RP2D), defined as the highest feasible dose without increased acute or late toxicity compared to RT alone. The RP2D will be the starting point of a phase II trial determining the effect of HT with RT versus RT alone.

Study population and inclusion

The patient population includes those with proven LAHNSCC in the oral cavity, oropharynx, larynx or hypopharynx, indicated for primary RT without systemic radiosensitizing therapy with curative intent. A maximum of 30 patients will be included. In this dose-escalation cohort study we use a Time-to-Event Bayesian Optimal Interval (TiTE-BOIn) design to accelerate the inclusion time, including escalation and de-escalation rules.

Treatment

The patients are treated with radiotherapy in combination with hyperthermia. The hyperthermia dose is defined as the SAR (Specific Absorption Rate, W/kg) in healthy tissue, since healthy tissue can show toxicity. Five dose levels are defined according to previous clinical data with the HyperCollar3D (40, 75, 100, 125, and 150). The HT treatment is given once a week within 2 hours after the radiotherapy fraction during the radiotherapy period (5-7 weeks). During the 6-month follow-up, trismus is closely evaluated as an expected toxicity.

• Sensius B.V.
• KWF

Internal collaborations:

• Department of Otorhinolaryngology head and neck surgery
• Department of Oral and Maxillofacial surgery
• Department of Internal Medicine/Geriatrics
• Department of Medical Oncology

External collaborations:

• Department Electrical Engineering
• Eindhoven University of Technology & Department of Radiotherapy
• Sensius BV

• Kroesen, M., et al., Feasibility, SAR Distribution, and Clinical Outcome upon Reirradiation and Deep Hyperthermia Using the Hypercollar3D in Head and Neck Cancer Patients. Cancers (Basel), 2021. 13(23).
• Verduijn, G.M., et al., Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma - a feasibility study. Int J
• Kroesen, M., et al., Confirmation of thermal dose as a predictor of local control in cervical carcinoma patients treated with state-of-the-art radiation therapy and hyperthermia. Radiother Oncol, 2019. 140: p. 150-158.