Association of tumor volume and outcomes in T3 larynx cancer with organ preservation approach.
Authors: Malik Nauman , Hainc Nicolin , Gill Gia , Nakoneshny Steven , Kerr Paul , Matthews Wayne , Globerman Adam , Dort Joseph C. , Maralani Pejman , Yu Eugene , Lysack John , Hosni Ali , Karam Irene , Eskander Antoine 
Published: June 2021

e18044

Background: Organ preservation approaches to treatment of locally advanced larynx cancers are widely used and consist of radiotherapy (RT) with or without concurrent systemic therapy (CRT). Analyses of the National Cancer Database point to decreasing survival as CRT became widely adopted in place of total laryngectomy (TL). Tumor volume in T3 laryngeal tumors has been postulated as one variable to explain this finding, with higher volume associated with lower local control based on small sample size studies largely in pre-intensity modulated radiotherapy (IMRT) era, and low volume T3 tumors being associated with improved local control with CRT. We sought to validate these findings in a contemporary cohort of T3 larynx patients treated with IMRT. Methods: This was a national, multicentre retrospective cohort study of patients diagnosed with American Joint Committee on Cancer (AJCC) T3 N0-3 M0 glottic and supraglottic cancers who underwent curative intent IMRT with or without systemic treatment from 2002-2018. Tumor volumes were calculated using a validated standardized approach by a Neuroradiologist. Primary predictor was tumor volume, primary outcome was local control (LC), and secondary outcomes included overall survival (OS), as well as late grade 3+ toxicities. Kaplan Meier estimates and log-rank tests were used for survival analyses, with Cox proportional hazards used for univariable analyses. Results: 246 patients met inclusion criteria, 147 glottic and 99 supraglottic cancers. At baseline, glottic patients were more likely to be male (p < 0.01), have a fixed vocal cord (p < 0.01), not have pre-epiglottic space invasion ( < 0.01), be cN0 (p < 0.01), and have lower grade tumors (p < 0.01). Mean tumor volumes for glottic and supraglottic tumors were 5.0 (4.2-5.8) cc and 13.0 (10.3–15.6) cc respectively. Univariable analysis showed systemic therapy was associated with improved local failure (HR 0.49, 95%CI 0.24 – 0.99, p = 0.05). Within the glottic cohort, tumor volume was not associated with local failure (HR 1.09, 95%CI 0.71 – 1.67, p = 0.38), however having a local failure event was associated with increased feeding tube dependence (HR 2.52, 95%CI 1.05 – 6.02, p = 0.04). Median local failure free survival in the overall cohort was 28.5 months, with median OS 23.2 months. There was a trend towards improved local control in the supraglottic cohort compared to glottic patients (log-rank p = 0.08), but the supraglottic cohort had significantly worse overall survival (log-rank p = 0.02). Conclusions: In this retrospective cohort study, there were baseline and outcome differences between patients with T3 glottic and supraglottic larynx cancer, with worse overall survival in supraglottic patients. Tumor volume was not associated with local control in the glottic cohort. These findings are pending further validation in a larger cohort and will be analyzed separately for supraglottic tumors.