Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129.

BACKGROUND: Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters. METHODS: Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters. RESULTS: Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy. CONCLUSIONS: Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies.

Symptom clusters in patients with head and neck cancer receiving concurrent chemoradiotherapy.

OBJECTIVES: This study is to identify symptom clusters for head and neck (HNC) patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: A secondary data analysis of 684 HNC patients treated on the Radiation Therapy Oncology Group (RTOG) 0129 trial comparing different RT fractionation schedules with concurrent chemotherapy was used to examine clusters. Treatment-related symptoms were measured by clinicians at three time-points during and after chemoradiotherapy using the National Cancer Institute Common Toxicity Criteria v2.0. Exploratory factor analysis was applied to identify symptom clusters, which was further verified by confirmatory factor analysis. Coefficients of congruence and alpha coefficients were employed to examine generalizability of cluster structures over different time-points and in different subgroups. RESULTS: Two clusters were identified. The HNC specific cluster is composed of radiodermatitis, dysphagia, radiomucositis, dry mouth, pain, taste disturbance, and fatigue. The gastrointestinal (GI) cluster involves nausea, vomiting, and dehydration. With the exception of patients 65years old or older, diagnosed with larynx cancer, or with stage III cancer, the two clusters were generalizable to different subgroups defined by age, gender, race, education, marital status, history of tobacco use, treatments, primary sites, disease stages, and tube feedings, as well as to the three symptom assessment time-points. CONCLUSIONS: The data provides preliminary support for two stable clusters in patients with HNC. These findings may serve to inform the symptom management in clinical practice. Moreover, the findings necessitate future research to examine the generalizability of identified clusters in the late symptom phase or other treatment modalities, and to understand the underlying biological mechanism.