Patterns of failure after definitive treatment for T4a larynx cancer in the Veterans Affairs Health System.
Authors: Voora Rohith S. , Panuganti Bharat , Flagg Mitchell , Kumar Abhishek , Kotha Nikhil V. , Qiao Edmund M. , Qian Alexander S. , Nelson Tyler J. , Weissbrod Philip A. , Stewart Tyler F. , Rose Brent S. , Mell Loren K. , Califano Joseph A. , Orosco Ryan K. 
Published: June 2021

e18006

Background: Both chemoradiotherapy (CRT) and total laryngectomy (TL) with adjuvant therapy are curative-intent treatment options for patients with T4a larynx cancer. Disease recurrence is a known negative prognosicator, but differences in recurrence patterns and the subsequent survival associations are not well characterized. To address this knowledge gap, we present long-term recurrence and survival outcomes from a novel longitudinal data source. Methods: Retrospective study of non-metastatic T4a larynx cancer patients diagnosed between 2000-2017 who underwent curative-intent treatment (TL with adjuvant therapy or primary CRT) from the VA Informatics and Computing Infrastructure database. Adjuvant therapy consisted of either postoperative radiotherapy (RT) or CRT. Fine-Gray and Cox models were used to evaluate primary outcomes – time to locoregional recurrence and distant recurrence. Secondary outcomes included overall survival (OS), cancer-specific survival (CSS), non-cancer specific survival (NCSS), and disease-free survival (DFS). These multivariable models accounted for age, race, alcohol history, smoking status, education and income, Charlson-Deyo score, N-classification, and tumor subsite. Results: The study included 1,114 patients with a median follow-up time of 63.3 months among those alive at last follow up. In the TL group, adjuvant RT was used in 69% and adjuvant CRT was used in 31%. Median time to first recurrence was 24.4 months with overall incidence of 28.5% locoregional and 9.5% distant recurrence. Primary CRT patients had higher rates of locoregional (37.2 vs. 22.9%) and distant recurrence (13.3 vs. 7.0%) (p < 0.0001). Median OS was 27.3 months for CRT (95% CI: 23.6-32.4 months) and 47.5 months (95% CI: 39.6-52.1 months) for TL. Median DFS was 14.1 months for CRT (95% CI:12.5-17.2 months) and 37.9 months (95% CI 31.2-47.5 months) for TL. On multivariable analysis compared to CRT, TL was associated with longer time to locoregional (HR 0.50, 95% CI:0.40-0.61) and distant recurrence (HR 0.50, 95% CI:0.34-0.73). Having N+ disease increased risk of distant recurrence (HR 2.20, 95% CI:1.42-3.41). TL was associated with improved OS (HR 0.78, 95% CI:0.67 – 0.91), CSS (HR 0.73, 95% CI:0.59 – 0.89), and DFS (HR 0.58, 95% CI 0.49-0.69) compared to CRT; NCSS was equivalent between groups (HR 1.09, 95% CI:0.88-1.35). Of the CRT patients with locoregional failures, 67/163 (41.1%) were salvaged with surgery. Conclusions: In this cohort of T4a larynx cancer patients, surgical management demonstrated favorable recurrence and survival results. TL with adjuvant therapy was associated with significantly lower incidence of both locoregional and distant recurrence and increased OS, CSS and DFS compared to CRT. Lower probability of disease recurrence, in addition to a survival advantage, should be considered as an important advantage to up-front surgery.