Pulmonary Comorbidities in HNSCC

Recently, an increased focus on competing causes of mortality among patients with HNSCC has been observed, with respiratory causes of particular interest.6,7,24 As advances in treatment modalities improve disease control and survival, the estimated number of HNSCC survivors is expected to increase.25 As a result, clinicians will be required to consider longer-term treatment effects and identify patients at highest risk for noncancer-related morbidity and mortality. Multiple studies have shown increases in adverse pulmonary outcomes among HNSCC patients compared to the general population.3,6,8,26-30 The prevalence of respiratory comorbidities in HNSCC patients approximates 10 to 15%, nearly twice as common as healthy controls.29,30 Moreover, a significant percentage (21%) of head and neck cancer patients have moderate to severe comorbidities, second only to patients with lung (40%) and colorectal (25%) cancer, with a significant relationship between comorbidity severity and overall survival (p < 0.0013).31
An analysis by Rose et al. of 34,568 patients with nonmetastatic squamous cell carcinoma identified through the Surveillance Epidemiology and End Results (SEER) registry found that the most frequent causes of noncancer mortality included cardiovascular disease (28.2%), chronic obstructive pulmonary disease (COPD, 8.5%), and cerebrovascular disease (5.6%); lung cancer was the most common cause of second primary cancer mortality (45.8%) (Table 1).7 On multivariable analysis, increased risk of noncancer mortality was associated with higher age, black race, unmarried status, localized disease, and nonsurgical treatment.7 Comparable results have been reported through other analyses of competing mortality, examining noncancer/comorbidity mortality and second primary cancer mortality.8,26,27 In a population-based review of 23,494 patients, Shen et al. also found cardiovascular diseases, lung cancer, COPD, and cerebrovascular disease to be the most frequent causes of competing death with rates of 28.3%, 10.4%, 8.5%, and 5.7%, respectively.8 These data demonstrate a disproportionate impact on the pulmonary system and increasing mortality that respiratory comorbidities may confer. Prior series have demonstrated that a large proportion of patients continue to smoke both during and after therapy. As expected, smokers have lower rates of treatment response and poorer survival compared to non-smoking counterparts, particularly if smoking continues during and after treatment.32-38