International Guidelines for Intratumoral and Intranodal Injection of NTBXR3 Nanoparticles in Head and Neck Cancers

Abstract

<h3>Purpose/Objective(s)</h3> NBTXR3, a first-in-class radio enhancer, composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral injection and activated by radiotherapy (RT). NBTXR3 is designed to locally amplify the tumor-killing effect of radiotherapy without additional toxicity to surrounding healthy tissue. NBTXR3 has been shown to prime the adaptive immune response in cancer models. NBTXR3 obtained EU marketing approval in preoperative treatment of locally advanced soft tissue sarcomas and is under investigation in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), with a phase 3 trial recruiting. However, there is currently no guidance on how to treat oropharyngeal and oral cavity SCC and cervical lymph nodes with NBTXR3. We therefore sought to develop expert consensus guidelines that facilitate injection of NBTXR3 in oropharyngeal and oral cavity SCC and cervical lymph nodes. <h3>Materials/Methods</h3> A multidisciplinary team of experts aimed to provide consensus guidelines using the Delphi method with two rounds of voting to support the injection of NBTXR3 in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to address safety, feasibility, and procedure of administration. A steering committee composed of 4 experts and a monitoring committee composed of 10 experts wrote and revised the guidelines on intratumoral and intranodal injection. An independent multidisciplinary reading committee composed of 3 members reviewed the entirety of the recommendations. <h3>Results</h3> After 2 rounds of voting a strong consensus was obtained on all of the recommendations. The reading committee recommended simplifying and clarifying the elements not commented on by the monitoring committee. Intratumoral and intranodal injection is feasible. The NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection and post treatment follow-up are described in detail in these guidelines. Here we present the most important recommendations. <h3>Conclusion</h3> The recommendations on injection of NBTXR3 hafnium oxide nanoparticles have been defined by a multidisciplinary international panel of experts, thus allowing an international standardization of injection practice.