Comparison of Functional Larynx Preservation in Patients with Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated with Induction Chemotherapy vs Concurrent Chemoradiation Alone

Abstract

Functional organ preservation is an important outcome measure in the treatment of squamous cell carcinoma (SCC) of the larynx and hypopharynx (HPX) as laryngectomy is associated with significant morbidity. Numerous studies have established the efficacy of larynx preservation with concurrent chemoradiation therapy (CRT) in the setting of locally advanced disease. However, the role of induction chemotherapy (IC) remains a topic of ongoing investigation. This study aims to compare outcomes of patients with locally advanced SCC of the larynx and HPX who received either IC plus CRT to those who received CRT alone. The primary outcome is to determine whether the addition of IC improves functional larynx-preservation survival (FLPS) in patients treated with definitive CRT for stage III-IV SCC of the larynx and HPX. Secondary outcomes are laryngectomy rate, overall survival (OS), and progression-free survival (PFS). Records of patients with clinical stage III and IV SCC of the larynx and HPX treated non-operatively between 2005 and 2019 were identified. Eligible patients were at least 18 years of age, had pathologically confirmed SCC of the larynx or HPX, and were treated definitively with IC plus CRT or CRT alone. Patients with distant metastases were excluded. FLPS was defined as the time until death, local progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, and PFS. These outcomes were compared using the stratified log-rank test and laryngectomy rates were compared using Fisher’s Exact Test, where a p-value < 0.05 was considered statistically significant. Ninety patients met inclusion criteria: 52 patients had laryngeal SCC; 19 received IC plus CRT and 33 were treated with CRT alone. Thirty-eight patients had SCC of the HPX; 19 received IC plus CRT and 19 were treated with CRT alone. The median follow-up was 24 months. There were no significant differences in T stage between the IC and CRT arms. Patients who underwent IC received a median of 3 cycles (range 1-6). There was no difference in 3-year FLPS (61% vs 67.8%; p = 0.88), OS (73.9% vs 86.2%; p = 0.42) or PFS (53.6% vs 62.6%; p = 0.44) between the IC plus CRT vs CRT, respectively, in the entire cohort. These outcomes were also not statistically different between the two groups when stratified by primary site of larynx or HPX. Laryngectomy rates were not statistically different between those receiving IC compared to CRT alone (18.4 % vs 7.7%; p = 0.19). This result was also seen on subset analysis by site. In this retrospective study of patients with locally advanced SCC of the larynx and HPX, IC did not significantly improve 3-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone for the entire cohort or on subgroup analysis by site. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.