Dysphagia and shortness-of-breath as markers for treatment failure and survival in oropharyngeal cancer after radiation

Abstract

Background: Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established.

Methods: This prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main outcome was overall survival (OS), and the secondary outcomes were local, regional, and distant disease control.

Results: The majority of patients (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable analysis showed significant associations between OS and all three symptoms of swallowing, choking, and shortness-of-breath. A composite variable integrating scores of all three symptoms was significantly associated with OS on multivariable Cox regression (p = 0.0018). Additionally, this composite symptom score showed the best predictive value for OS (c-index = 0.75). Multivariable analysis also revealed that the composite score was significantly associated with local (p = 0.044) and distant (p = 0.035) recurrence/progression. Notably, the same significant associations with OS were seen for HPV-positive only subset analysis (p < 0.01 for all symptoms).

Conclusions: Quantitative patient-reported measures of dysphagia and shortness-of-breath 3-to-6 months post-treatment are significant predictors of OS and disease recurrence/progression in OPC patients and in HPV-positive OPC only.

Keywords: Dysphagia; HPV; Oropharyngeal cancer; Post-treatment symptoms; Treatment failure.

Figure 1:

Kaplan-Meier analysis of overall survival (OS) based on patient reported metrics at the 3-to-6 month follow-up. Symptoms of moderate-severe swallowing (MDASI score ≥6), moderate-severe choking (MDASI score ≥6), and mild-severe shortness-of-breath (MDASI score ≥2) at 3-to-6 months post-treatment (M3–6) and a composite symptom score were assessed for association with OS. P-values determined using log-rank test.

Figure 2:

Kaplan-Meier analysis of local, regional, and distant disease-free survival based on patient reported metrics at the 3-to-6 month follow-up. Symptoms of moderate-severe swallowing (MDASI score ≥6), moderate-severe choking (MDASI score ≥6), and mild-severe shortness-of-breath (MDASI score ≥2) assessed at 3-to-6 months post-treatment (M3–6) and a composite symptom score were assessed for association with local, regional, and distant disease control. P-values determined using log-rank test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001

Figure 3:

Kaplan-Meier analysis of overall survival (OS) for p16/HPV positive patients based on patient reported metrics at the 3-to-6 month follow-up. Symptoms of moderate-severe swallowing (MDASI score ≥6), moderate-severe choking (MDASI score ≥6), and mild-severe shortness-of-breath (MDASI score ≥2) at 3-to-6 months post-treatment (M3–6) and a composite symptom score were assessed for association with OS. P-values determined using log-rank test.