Chronic Systemic Symptoms in Head and Neck Cancer Patients
Barbara A. Murphy, Elizabeth Wulff-Burchfield, Michael Ghiam, Stewart M. Bond, Jie Deng. J Natl Cancer Inst Monogr (2019)
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Chronic Systemic Symptoms in Head and Neck Cancer Patients
Barbara A. Murphy, Elizabeth Wulff-Burchfield, Michael Ghiam, Stewart M. Bond, Jie Deng. J Natl Cancer Inst Monogr (2019)
The systemic effects and manifestations of disease and treatment have been of interest for millennium. Until recently, basic and clinical research is just now reaching a watershed. Systemic symptoms usually do not occur in isolation but rather in clusters; however, much of the cutting-edge research pertaining to the etiology, mechanism, manifestations, and moderators of systemic symptoms in humans has been directed at individual symptoms, thus creating silos of knowledge. Breaching these silos and bridging the knowledge from disparate arenas of investigation to build a comprehensive depiction of acute and chronic systemic symptoms has been a challenge. In addition, much of the recent work in systemic symptoms has been conducted in the setting of nonmalignant disease. The degree to which the findings from other chronic disease processes can be translated into the oncologic realm is unknown. This article will explore inflammation as a major contributing factor to systemic symptoms and sicknessbehavior, discuss the most common manifestations in cancer survivors, and, where available, discuss specific data pertaining to head and neck cancer survivors.
Main findings
- Both HNC and its treatment have been associated with elevated levels of pro-inflammatory cytokines, putting patients at high risk for adverse systemic effects.Preclinical models with HNC cell lines demonstrate elevated levels of inflammatory mediators such as chemokines, cytokines, and growth factors that play a critical role in tumorigenesis, metastasis, and angiogenesis.
- Pain is a ubiquitous problem in the HNC population: up to 57% (95% confidence interval ¼ 43% to 70%) of patients have tumor-related pain at the time of presentation, effectively all patients have treatment-related pain, and up to 42% (95% confidence interval ¼ 33% to 50%) have chronic post treatment pain.
- HNC survivors describe distinct pain syndromes including neck and shoulder pain due to musculoskeletal impairment, chronic oral mucosal sensitivity due to RT, and chemotherapy-associated peripheral neuropathy. In addition, a subset of HNC survivors develops widespread joint and muscle pain due to alterations in pain and sensory processing.
- Central pain is characterized by widespread pain in the muscles and joints with no identifiable nociceptive cause.
- A substantial proportion of patients present with measurable neurocognitive deficits at diagnosis, thus highlighting the potential impact of cancer itself on neurocognitive function.
- Clinically, fatigue is one of the most pervasive symptoms experienced by HNC patients across the trajectory of treatment, recovery, and survivorship. Although fatigue is common in patients postoperatively and when undergoing chemotherapy, RT-associated fatigue has garnered particular attention due to its severity, duration, and impact.
- HNC patients are at high risk for developing mood disorders such as depression and anxiety. Depression is common in HNC patients across the cancer trajectory. In a recent systematic review, the prevalence of depression ranged from 13% to 40% at
- diagnosis, to 25% to 54% during treatment, and 11% to 45% at 6 months post treatment.
- HNC patients commonly experience profound weight loss. This has traditionally been attributed to decreased oral intake secondary to cancer-related obstruction and treatment-related toxicity. However, accumulating data support the contributory role of cachexia in this population.
- Skeletal muscle depletion was found in 35% of patients before and 65.8% at the completion of treatment. Both pre- and post treatment skeletal muscle depletion was associated with decreased overall survival. Weight loss without skeletal muscle depletion did not correlate with survival.
