Organ Function Preservation Failure after (Chemo)Radiotherapy in Head and Neck Cancer: A Retrospective Cohort Analysis

Abstract

Objective The aim of the current study was to determine the incidence of organ function preservation failure (OFPF) in patients with head and neck squamous cell carcinoma (HNSCC) treated by (chemo)radiotherapy and to identify its risk factors. Study Design Retrospective cohort analysis. Setting Tertiary cancer care center. Subjects and Methods A single-center retrospective cohort analysis was done (n = 703) in which OFPF after (chemo)radiotherapy was assessed. OFPF was defined as local failure or pure functional failure in the absence of local failure because of major surgical intervention (total laryngectomy, commando resection, permanent tracheostomy) or feeding tube dependence >2 years. Results OFPF occurred in 153 patients (21.8%). Reasons for OFPF were local failure in 103 patients (14.6%) and functional failure in 50 patients (7.2%). Evidence of functional failure included need for total laryngectomy (n = 9, 1.3%), commando resection (n = 2, 0.3%), permanent tracheostomy (n = 16, 2.3%), and/or long-term feeding tube for functional reasons (n = 23, 3.3%). In a Cox proportional hazards model, OFPF was worse for patients with T4 tumors (hazard ratio [HR] <0.5 and P < .001 for all other stages), for laryngeal vs oropharyngeal cancer (HR, 1.83; 95% confidence interval [CI], 1.20-2.79, P = .005, hypopharyngeal not significant), and for smokers (HR, 1.68; 95% CI, 1.10-2.56, P = .015). Exploratory multivariate analysis by tumor site showed that T4 tumor and pretreatment tracheostomy were the strongest predictive factors for OFPF in laryngeal and hypopharyngeal carcinoma while T4 tumor and smoking were predictive for poor OFPF in oropharyngeal carcinoma. Conclusion This work shows a detrimental effect of smoking on functional outcomes after (chemo-)radiotherapy for HNSCC. Moreover, T4 tumor, laryngeal subsite, and pretreatment tracheostomy are strong predictors of OFPF.

Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR‐targeting agents to treat head and neck squamous cell carcinoma

“…[14][15][16] This is due to the limited response rates (RRs) with the current treatment options, which are often associated with serious side effects. [17][18][19] Therefore, it is becoming more important to further unravel the molecular carcinogenesis of HNSCC. This can elucidate the genetic and biological heterogeneity of the disease as well as the importance of interindividual variation in the human genome for therapy selection.…”

“…Despite this increasing knowledge of the molecular characteristics of HNSCC, the 5‐year survival remains relatively low, especially in the HPV‐negative cohort (48% in HPV‐negative and 80% in HPV‐positive HNSCC) 14–16 . This is due to the limited response rates (RRs) with the current treatment options, which are often associated with serious side effects 17–19 . Therefore, it is becoming more important to further unravel the molecular carcinogenesis of HNSCC.…”

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment

“…Of interest, almost all the patients wearing tracheostomy had T3/T4-stage lesions, reflecting the tracheostomy as a surrogate for locally advanced tumors with airway comprises. Later, in a single-institution study investigating the factor predicting organ preservation failure after CCRT, Heukelom et al 37 also identified T4 lesion and pretreatment tracheostomy as independent prognostic factors in laryngeal and hypopharyngeal cancers. Our results are consistent with these findings that the tracheostomy prior to, or during, the radiotherapy may be a surrogate for an advanced T stage.…”

Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas

“…Moreover, their results showed that patients who underwent pretreatment tracheotomy had a statistically significant decrease in both OS (HR 1.55, 95% CI=1.03−2.34, P =0.03) and DFS (HR 1.54, 95% CI = 2.07−2.22, P =0.02) ( 15 ). Some studies have also revealed that pretreatment tracheotomy was a strong predictor for long-term tracheostomy after organ-preservation strategy in laryngeal and hypopharyngeal cancers ( 16 , 17 ). In our study, which focused on HPSCC patients with pretreatment cord dysfunction, pretreatment tracheotomy was associated with OS only in the univariate analysis, but the difference was not statistically significant in the multivariate analysis.…”