Where and when to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer

Abstract

AbstractThe treatment of locoregionally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) is reviewed, highlighting the milestones in systemic therapy in that setting, with focus on the role of induction chemotherapy (ICT). The road to what is now considered the standard ICT regimen, i.e. the TPF (docetaxel/cisplatin/5-FU) regimen is described, and the differences between the European and the American TPF are discussed. The article describes the respective roles of ICT for larynx preservation, for treatment intensification, its role in patients with borderline resectable or unresectable oral cavity cancer, its role as a selection tool for radiotherapy dose de-escalation in patients with oropharyngeal squamous cell cancer (OPSCC) and its potential future role in strategies aiming at synchronous oligometastatic disease.ICT has an established role for organ preservation in advanced laryngeal and hypopharyngeal cancer and the TPF regimen has been validated in that setting. This approach is presently being compared in a randomized controlled trial to concurrent chemoradiotherapy (CCRT), which in many parts of the world is considered the standard organ preservation procedure. There remains uncertainty about the benefit of the sequential approach of ICT followed by CCRT, despite the fact that ICT significantly reduces the occurrence of distant metastases. It is advised that future studies should include patients who have the highest risk to develop distant metastases, in particular patients with low neck nodes and matted nodes. Moreover, further studies in patients with HPV-associated OPSCC at risk for distant failure (T4 or N3 disease) should be considered for that also. These approaches still need to be confirmed in adequately sized randomized controlled trials. Outside clinical trials, the utility of ICT is restricted to uniquely pragmatic clinical scenarios, such as unavoidable delay in radiation or in the situation that RT is not tolerated or feasible. This can happen when there is severe pain from advanced disease or there is impending airway compromise or neurologic dysfunction that necessitates rapid initiation of treatment. In all those circumstances whether within the context of trials or outside trials, it is imperative that the present backbone of ICT, the TPF regimen, is being administered by experienced oncologists, familiar with the necessary protocols and supportive care requirements to ensure patient safety and maximize adherence throughout the treatment.Future areas of research are the role of ICT in strategies whereby ICT is combined with upfront metastases-directed treatments and the usefulness of targeted agents or immune checkpoint inhibitors in the induction setting. Studies in that direction have already started. Finally, the application of radiographic, proteomic and genomic biomarkers will get attention to further define prognostic groups and guide treatment selection with greater precision.