Presentation by Dr Barbara Murphy, Vanderbilt Ingram Cancer Center
Written By Bailey Mars, NP | Saint Luke's Health System
At the 2023 West Oncology conference, Dr Barbara Murphy, a supportive oncologist from the Vanderbilt Ingram Cancer Center, discussed strategies for maintaining quality of life in patients with head and neck cancers. As a supportive oncologist, Dr Murphy noted that care of her patients is centered around survivorship, and the theory that “survivorship is a state of increased risk.” She noted that head and neck cancer (HNC) survivors, who are cured of their cancer, nonetheless die at an increased rate of 18%, when compared to their comorbid, age-matched controls, and most often these patients are dying of non-cancer related causes. Dr Murphy noted that the most concerning, but likely explanation is that treatments given to these patients have significant physiologic effects that can impact their long-term survival and quality of life. In addition, she noted HNC patients may also have decreased survival related to secondary cancers, increased frailty, and an overall increased symptom burden. Dr Murphy’s presentation was focused on three distinct topics related to the care of this at-risk population of HNC survivors: Pharmacologic prevention of late effects of treatment, chronic systemic symptomatology, and management of late soft tissue complications.
Pharmacologic Prevention of Late Effects
Dr Murphy reported on a trial examining the use of prophylactic gabapentin in patients with biopsy proven cancer of the larynx, pharynx, oral cavity, paranasal sinuses, or salivary glands. She noted retrospective reports and clinical observations which have suggested that gabapentin may possibly decrease the frequency and severity of pain. Gabapentin is known to have anti-inflammatory as well as neuromodulatory properties and was used in this study not only for treatment, but also for prevention of pain and associated systemic symptoms. Arm 1 was provided standard of care supportive measures, exclusive of gabapentin until after radiation. Arm 2 was provided with standard of care supportive measures, plus prophylactic gabapentin, starting on day one of radiation with dosage escalations as tolerated, up to 900 mg PO TID by Week four. The pain outcome was measured using the Vanderbilt head and neck symptom survey and the general symptom survey. Outcomes were assessed weekly. The primary aim of the study was to determine whether prophylactic gabapentin would decrease pain and its severity, while secondary aims included a decrease on severity of systemic symptoms (fatigue, sleep, neurocognitive changes, anxiety, depression) and decreased incidence and/or severity of local symptoms (swallow function, mucosal burning/sensitivity, taste, and smell). Data collected from the 79 enrolled patients revealed statistically significant improvements in xerostomia (p=0.010), pain (p<0.05), chemosensory (p=0.029) and mucosal sensitivity (p=0.007). The study also noted that the benefit of gabapentin was noted in patients regardless of their severity of pain.
Chronic Systemic Symptoms
Dr Murphy described cancer and their treatments as an “assault” on the system and noted that all patients vary in terms of their recovery trajectories. She also noted a subset of patients who experience a rapidly declining health trajectory, and in this population, an increased rate of chronic systemic symptoms is observed. One such chronic symptom is sarcopenia, a peripheral inflammatory manifestation characterized by severe skeletal muscle loss and disability. She noted that sarcopenia may be a manifestation of the cancer itself as well as the cancer treatments administered. These and other symptoms were noted within the first 4 to 5 weeks following radiation initiation. A pre-post testing study of locally advanced HNC patients undergoing concurrent chemotherapy and radiation revealed the average amount of lean muscle mass lost was 6.8 kilograms in just seven weeks. There was also a statistically significant decrease in activities of daily living (ADLs) (p= 0.02) as well as increased time for performance testing (p=0.004). Interestingly, F2 isoprostane, a marker of oxidative stress, was noted at increased levels post treatment and was associated with loss of fat and fat-free mass at a statistically significant increased rate (p=0.03). Dr Murphy stressed that the muscles wasting in these patients are not just the “biceps” or visible muscles, but also the muscles of deglutition (swallowing), and other internal muscles such as the diaphragm. As an example, in her pilot study evaluating patients receiving chemoradiation, it was noted that almost 30% of patients had some level of cardiopulmonary dysfunction. Data from this study and others suggest a profound physiologic impact of treatment on patients, which can contribute to decreased physical functioning and poor disease outcomes. Dr Murphy emphasized the need to monitor these patients closely and carefully over the long term, as their recovery can be both difficult and prolonged.
Systemic Inflammation Induced Neuroinflammation and Systemic Symptoms
Disease states such as infection, burns, as well as cancer, or cancer therapy, may result in the production of soluble factors such as cytokines and chemokines. These act as peripherally to central messengers, assisting the central nervous system (CNS) to coordinate the body’s response to various disease states. One of the ways the CNS responds to disease is to alter behavioral patterns. Such behaviors may include decreased appetite, which spares energy from being directed at digestive processes, as well as slowed thinking and fatigue, which serve to limit energy-requiring activity. Commonly called “sickness behavior” or “systemic symptoms,” these behaviors can be adaptive in the short term but are also maladaptive in the long term. If the peripheral production of signaling molecules is prolonged, or particularly robust, sickness behaviors may last for protracted periods of time, and may be permanent. For example, in a cross-sectional study of cured HNC patients who were at least 12 months post treatment, pain, sleep, activation, cognition and mood/behavior were assessed. The study found a high rate of systemic symptoms in HNC survivors. Additional data demonstrated that activating behaviors are dramatically altered in a subset of survivors; this includes decreased motivation, distractibility, slowed movements, irritability, difficulty with decisions, decreased interest in activities, and mood swings. Dr Murphy noted that HNC patients often require complex and time-consuming self-care regimens in order to attain or maintain their function, and that systemic symptoms may impede their treatment compliance.
Dr Murphy noted that lymphedema and/or fibrosis will occur in 100% of HNC patients at some point along their treatment trajectory. The primary treatment for moderate to severe lymphedema starts with therapist-directed treatment, but is then followed by lifelong commitment to a program of home-based self-care. Compliance and feasibility with at-home therapy can be a struggle for many patients, but enhancing home-based self-care is critical to improve long term neuromusculoskeletal health. One study aimed at evaluating the feasibility and safety of an at home pneumatic compression device for lymphedema treatment (Flexitouch) revealed statistically significant improvement in lymphedema with the use of this device. There was also decreased heaviness, tightness, and swelling noted by patients (p=0.008) as well as digital photo evidence of decreased swelling. There was also a statistically significant increase in swallow ability (p=0.016) and mucous related symptoms (p=0.050). Dr Murphy also briefly discussed end stage neck and the negative impact this has on quality of life. She emphasized that providers should be aggressive in treating neuromuscular changes and toxicities upfront.
The NP Take Home Message
Nurse practitioners are trained in holistic care, and Dr Murphy’s review of supportive care for HNC patients highlights the need for awareness of the frailty and risks associated with this population. In this regard, NPs should consider not only the physiologic impact of their cancer, but also the toxicities of cancer treatment in HNC patients, and the various interventions available to address these adverse effects. A greater awareness among NPs of the unique burden of symptoms in HNC patients, and principles of systemic symptom management is important not only to improve patient care in this setting, but also for educating HNC patients about their disease.
Head and neck cancer (HNC) survivors, even if cured of their cancer, remain at an increased risk of death, mainly from non-cancer related causes and physiologic conditions related to their cancer treatment.
Long-term supportive care is thus especially important for HNC survivors.
Prophylactic use of gabapentin, an anticonvulsant with anti-inflammatory and neuromodulatory properties has been shown to improve pain and HNC-related events such as xerostomia and mucosal sensitivity, when compared to standard of care supportive measures without gabapentin.
HNC patients are also subject to a higher incidence of physiologic complications such as sarcopenia, a peripheral inflammatory manifestation characterized by severe skeletal muscle loss and disability. The physiologic manifestations can contribute to decreased physical functioning and poor disease outcomes.
The increased morbidity in HNC patients may also relate to neuroinflammatory changes resulting in symptoms like decreased motivation, distractibility, slowed movements, irritability, and difficulty with decisions.
Complications such as lymphedema are observed in essentially all HNC patients, and this requires long-term at-home care which can be challenging for patients.
HNC patients are subject to a range of unique and difficult to manage adverse events and physiologic changes likely related to their cancer treatment, and close monitoring of these patients is essential.
NPs are trained in holistic care and can assist in this process with patient education, as well as monitoring and symptom management over the long-term.
See more from the 2023 West Oncology Conference here.
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