The results of this study confirm previous reports indicating that QOL declines as a result of CCR; however, by twelve months post-treatment, QOL returned towards normal. QOL did not differ among those proceeding to CCR versus those who required salvage surgery, although this is probably related to the relatively small number of individuals receiving surgery (n=13) compared to CCR alone (n=95). Our results add to a growing literature that demonstrates the ability of QOL scores to predict overall survival.
Using both patient report and objective measures of swallow function, patients treated on E2399 demonstrated a marked decline in swallow function 3 months after completion of chemoradiation. Swallow function returned toward baseline by 12 months post treatment. Less than 10% of patients had severe dysphagia at 12 months as scored using either the FCM or the DOSS, and very few patients were gastrostomy-tube dependent at 12 months. This compares favorably to the incidence of 12 month gastrostomy-tube dependence reported in other CCR studies (NRG RTOG 0522 17.2-21.2%; NRG RTOG 0129 18.9 -26.1%). The improvement in post-treatment swallow function may be attributed to several factors. First, this group of patients had relatively early stage disease; by definition, patients were deemed resectable at the time of study entry. Second, patients were seen by SLP periodically throughout the course of their therapy. This allowed the SLPs to have early and constant contact with patients, potentially improving overall outcomes. Third, the concurrent regimen used in this study was mild and may have resulted in less late-effect fibrosis with associated pharyngeal dysfunction.
The DOSS scores were consistently lower than the FCM scores, an expected finding given that DOSS measures function irrespective of the need for compensatory mechanisms, while the FCM measures actual disability. The FCM demonstrated consistently higher correlations with both the PSS and FACT-HN swallow items compared to the DOSS. The correlations between the FCM and self-report swallow items on the PSS and FACT-HN appear to be sufficiently strong to justify their use as a surrogate marker for swallowing function in large therapeutic trials.
Decreased swallowing function post treatment was also associated with increased mortality. It is unclear whether this is a causal relationship. It may be reasonably hypothesized, however, that dysphagia and its complications (such as aspiration) may directly impact on survival.
Our paper has several limitations. Firstly, as a trial that was initiated in a cooperative group setting in 1999, the majority of centers did not employ intensity-modulated radiation therapy (IMRT), and radiation doses to salivary glands and pharyngeal constrictors was higher than it would be in contemporary practice. However, a recent examination of two-year dysphagia rates and related outcomes in the Surveillance, Epidemiology, and End Results-Medicare database for 2002-2011 demonstrated that rates of dysphagia (45.3%), stricture (10.2%), and pneumonia (26.3%) remain high, and that indeed the rate of dysphagia had increased in the IMRT era [PMID: 30536748]. Second, this was a small study including two distinct subsites and including both patients with HPV-associated and non-HPV-associated oropharynx cancer, with their differing age of onset, co-morbidity burdens, and natural history. Finally, we collected patient-reported and functional data for only 2 years following completion of CCR. It is now recognized that a subset of head and neck cancer patients develop late dysfunction, which may be progressive even after 7 years from the completion of radiation. 17, 18