WS-3-2 - Induction chemotherapy for organ preservation strategy (Pros)

Abstract

Based on the results of the Veterans Affairs' (VA) and EORTC studies, induction chemotherapy (ICT) followed by radiation (RT) with surgery reserved for salvage came to be considered a new standard treatment for patients with locally advanced cancer of the larynx. In the RTOG 91-11 trial for patients with resectable advanced laryngeal cancer requiring total laryngectomy, concurrent chemoradiotherapy (CRT) was superior to ICT followed by RT or RT alone for laryngeal preservation (LP) and locoregional control, leading to CRT being considered standard treatment for organ preservation in this population. However, CRT also resulted in increased significant long-term toxicities, including gastrostomy tube dependence, aspiration, and pharyngoesophageal stricture requiring dilation, leading to failure of the stated goal of organ preservation. Furthermore, these severe complications make salvage surgery after CRT a challenge. In the long-term results of RTOG91-11, although there was no significant difference in overall survival, the survival curves did separate after 4.5 years, favoring ICT. It is possible that unrecognized or under-reported late toxicity affecting swallowing function contributed to some of the non-cancer-related deaths that emerged with longer follow-up. Also, no difference between the ICT and CRT arms was seen in laryngectomy-free survival (LFS), which is now considered a more appropriate endpoint for organ preservation than LP. Using response to ICT as a surrogate predictive biomarker for successful organ preservation is an appealing concept (Pfister JCO 2006, Urba S, JCO 2006). Namely, ICT provides the opportunity for patient selection, leading to the avoidance of significant CRT toxicities and surgical complications. Treatment planning for patients with resectable locally advanced SCCHN who desire organ preservation should take account of the goal of treatment, which is good quality of survival.