Key points

Introduction

Head and neck cancer contributes significantly to the global burden of cancer-related disease and is ranked fifth worldwide in overall incidence. Squamous cell carcinoma may arise in the mucous membranes of the oral cavity, oropharynx, larynx, paranasal sinuses, nasopharynx, skin, and, infrequently, in the salivary glandular tissue. Management of such malignancies involves use of surgery and irradiation, alone or in combination with chemotherapy. Each therapy has significant potential for treatment-related adverse effects. When management involves a combination of therapeutic choices, treatment-related side effects are exacerbated.

Patients who receive treatment of HNSCC often experience significant acute toxicities as well as a plethora of long-term sequelae. The unique combination of challenges posed by cosmetic disfigurement, physical and functional impairment, and psychosocial stress resulting from the disease and its treatment requires dedicated and multidisciplinary collaborative efforts for effective management.

Improved diagnostic tools, more effective and diverse therapeutic choices, and the changing demographics of the population with head and neck cancer have led to significantly improved survival rates. A longer posttreatment survival is, however, accompanied by additional long-term morbidities resulting from therapy. These complications of therapy may not become manifest for 5 or 10 years, but the younger patient population and improved survival makes these considerations all the more germane. As a result, identification of strategies aimed at minimizing treatment-related complications and optimizing their long-term management are increasingly critical.

Institutions and head and neck cancer teams devoted to the multidisciplinary care of patients with HNSCC should incorporate a robust plan for addressing survivorship. The goals for ongoing care should include not only early identification and management of locoregional or distant failure and second primary malignancies but also effective management of treatment-related complications such as xerostomia, dental disease, osteoradionecrosis (ORN), hypothyroidism, speech, and swallowing disturbances. Other areas critical to healthy survivorship that require specialized attention to diagnose and treat include nutritional deficiency, substance abuse, and behavioral health. Although an in-depth examination of available evidence for individual management strategies for these diverse but related issues is beyond the scope of this article, it outlines recommended management strategies, provides consensus guidelines, and identifies areas where controversy and knowledge gaps exist.

Introduction

Head and neck cancer contributes significantly to the global burden of cancer-related disease and is ranked fifth worldwide in overall incidence. Squamous cell carcinoma may arise in the mucous membranes of the oral cavity, oropharynx, larynx, paranasal sinuses, nasopharynx, skin, and, infrequently, in the salivary glandular tissue. Management of such malignancies involves use of surgery and irradiation, alone or in combination with chemotherapy. Each therapy has significant potential for treatment-related adverse effects. When management involves a combination of therapeutic choices, treatment-related side effects are exacerbated.

Patients who receive treatment of HNSCC often experience significant acute toxicities as well as a plethora of long-term sequelae. The unique combination of challenges posed by cosmetic disfigurement, physical and functional impairment, and psychosocial stress resulting from the disease and its treatment requires dedicated and multidisciplinary collaborative efforts for effective management.

Improved diagnostic tools, more effective and diverse therapeutic choices, and the changing demographics of the population with head and neck cancer have led to significantly improved survival rates. A longer posttreatment survival is, however, accompanied by additional long-term morbidities resulting from therapy. These complications of therapy may not become manifest for 5 or 10 years, but the younger patient population and improved survival makes these considerations all the more germane. As a result, identification of strategies aimed at minimizing treatment-related complications and optimizing their long-term management are increasingly critical.

Institutions and head and neck cancer teams devoted to the multidisciplinary care of patients with HNSCC should incorporate a robust plan for addressing survivorship. The goals for ongoing care should include not only early identification and management of locoregional or distant failure and second primary malignancies but also effective management of treatment-related complications such as xerostomia, dental disease, osteoradionecrosis (ORN), hypothyroidism, speech, and swallowing disturbances. Other areas critical to healthy survivorship that require specialized attention to diagnose and treat include nutritional deficiency, substance abuse, and behavioral health. Although an in-depth examination of available evidence for individual management strategies for these diverse but related issues is beyond the scope of this article, it outlines recommended management strategies, provides consensus guidelines, and identifies areas where controversy and knowledge gaps exist.

Survivorship care plans

Care of the patient with head and neck cancer is complex and, in addition to engagement of the patients and their families, requires involvement of multiple health care teams, including surgeons, medical and radiation oncologists, dental providers, speech and language pathology professionals, social workers, nurse managers, psychologists, and the patients’ primary care providers. Efficient and cost-effective care patterns require superior interdisciplinary coordination and safe and effective transitions of care to community physicians when considered appropriate. Survivorship care plans (SCPs) may serve as important tools in helping achieve these goals.

The Institute of Medicine (IOM) recommendations stress the importance of measures geared toward improving awareness about unique needs of a cancer survivor and the significance of a comprehensive care summary describing follow-up plans and ongoing management for patients on completion of primary therapy. The IOM recommendations are rooted in the 2 key observations that many cancer survivors are lost to follow-up and that important opportunities for intervention are missed during transitions of care.

However, adoption of SCP has been far from universal. Among the National Cancer Institute–designated cancer centers, only about half of the patients who underwent therapy for breast or colorectal malignancies received SCPs. Although SCPs may lead to increased sense of comfort for primary care providers entrusted with caring for cancer survivors and reduction in anxiety related to care transitions for the patients, several barriers continue to limit the use of such tools. These barriers include the additional demands relating to time, personnel, and resources that may be needed for generating and communicating effective SCPs to the intended audience, in a cost-sensitive health care environment, with no additional reimbursements for such efforts.

Concerns about the ability of patients and providers to integrate SCPs into ongoing clinical care exist, and the additional documentation can easily be lost within the large volume of documentation encountered through the process of cancer care. Studies indicate that a large number of patients and many physicians failed to remember if they received an SCP document, and most patients could not locate the document 3 years after therapy completion. In addition, scientifically accurate verbiage in such a document may hold little or no value to patients, and hence a single static document may not effectively serve the needs of a community physician and the patient during care transitions.

Regardless of the medium used, effective communication between health care providers and the patient is critical to reduce errors, improve efficiencies, ensure timely interventions, and avoid duplicity of efforts and investigations. Such communication should include clear summation of the disease process, administered therapy, ongoing interventions, and future plans for follow-up, investigations, and interventions. Whenever possible, the rational for future interventions and investigations should be included.

Although consensus guidelines specific to the care of HNSCC survivors are not readily available, physicians may use standardized guidelines and resources from a global cancer care perspective to help manage patients, including clinical practice guidelines from the IOM and cancer survivorship guidelines from the National Comprehensive Cancer Network (NCCN). Other guidelines addressing chemotherapy-related neuropathy, fatigue, and anxiety and depression have been made available by the American Society of Clinical Oncology.

Cancer treatment–related physical effects

Head and neck cancer therapy can be associated with debilitating physical effects. Although acute toxicity related to irradiation and chemotherapeutic or targeted agents may subside soon after therapy cessation, some, including mucositis, may persist for a significant duration. Other side effects may persist for a long time, be permanent, or may appear after a delay. These treatment sequelae contribute toward long-term toxicity and the associated compromise in quality of life, including issues such as xerostomia, hypothyroidism, radiation-related accelerated vascular disease, ORN, and associated symptoms such as dysphagia, pain, chronic aspiration, and decline in nutrition and general well-being. Other long-term sequelae, such as lymphedema, soft-tissue fibrosis, decreased range of motion, trismus, and speech and swallowing disturbances, require continued participation of physical therapists and speech and language pathology specialists in survivor care.

A variety of regimens and agents have been tried for the management of mucositis with variable benefit. Poor quality of available evidence limits interpretation of value of individual agents used in the management of oral mucositis. Recently published consensus guidelines indicate that relief of pain associated with mucositis, using 2% morphine oral rinse and tricyclic antidepressants such as doxepin may be of value. The role of antifungals and topical anesthetic agents remains unclear. Evidence suggests that routine use of oral antibiotics, chlorhexidine mouthwashes, and coating agents such as sucralfate did not improve outcomes, and use of these agents is generally not recommended. Small-scale studies and a randomized control trial investigating the role of low-level laser therapy to affected mucosa has shown some promise.

Radiation-induced xerostomia contributes to life-long morbidity with associated symptoms that include burning sensation, pain, altered taste, poor dentition, and malnutrition. Strategies for management include maintenance of oral hygiene, salivary substitutes (including lysozyme-containing gels, lactoferrin, and peroxidase), sialogogues such as pilocarpine, xylitol chewing gums, sorbitol lozenges, hydration, fluoride-rich agents, and antimicrobials. However, data regarding individual efficacy of these agents are difficult to interpret. Early and continued involvement of an experienced dental provider may help to mitigate and manage risks related to xerostomia-related dental caries and ORN. Finally, the role of acupuncture has been investigated in a randomized controlled trial, and there seems to be increased salivary flow and symptomatic relief.

Nearly half of the patients treated for HNSCC with irradiation to the neck develop hypothyroidism months or years after completion of therapy. Symptoms of hypothyroidism can be innocuous, and diagnosis may be suspected in a patient with vague features such as fatigue, depression, and poor energy levels. A high index of suspicion and appropriate screening with serum measurements of thyroid stimulating hormone every 6 to 12 months is recommended, and thyroid hormone replacement should be instituted as appropriate when hypothyroidism is identified.

Investigators report a high incidence of accelerated atherosclerotic cardiovascular disease and related mortality risk in HNSCC survivors with advanced age. Higher incidence of carotid stenosis and cerebrovascular events in patients following radiation therapy to head and neck may contribute to a substantial number of deaths in HNSCC survivors. Although evidence-based guidelines for prevention and management of radiation-associated vasculopathy are scarce, patients should be evaluated based on individual risks, suspicious examination findings such as vascular bruits, and symptoms related to cerebral ischemia. Screening tools such as vascular duplex ultrasound imaging, may be used and lifestyle modifications may be indicated in patients, because many patients share common risk factors for vascular disease (such as tobacco and alcohol use). In these patients, risk reduction strategies such as use of statins or antiplatelet therapy should be based on their overall cardiovascular risk.

Perhaps the most significant long-term complication occurs because of fibrosis of the muscles of swallowing. The slow but relentless loss of ability to elevate the larynx, invert the epiglottis, and protect from aspiration is one of the mechanisms for all-cause survival being reduced in survivors of health and neck cancer. Coupled with cranial neuropathies that reduce the ability of the tongue and vocal cords to perform their function, chronic aspiration is a slow but relentless enemy of survival and quality of life. The combination of irradiation and chemotherapy increase this risk. Prevention and strengthening exercises may mitigate this risk to some degree and, although not definitively proven to decrease long-term swallowing and cranial neuropathies, they at least enhance awareness.

Cancer-related psychological distress

Fear of cancer recurrence, treatment-related anxiety, and depression are often underrecognized in HNSCC survivors. Although most patients experience a modest fear of cancer recurrence, such fear is more strongly felt among patients with lower education levels and lack of optimism and among patients who identify as Hispanic or white. Such fear affects quality of survivorship experience, psychosocial well-being, and risk for continued tobacco abuse. A high index of suspicion, appropriate screening, and evaluation by trained behavioral health professionals are often required, along with behavioral therapy, when indicated for management of patient symptoms. Additional sources of psychosocial stress may stem from treatment-related disfigurement, altered social interactions, loss of professional position, and perceived compromise to humanity in the setting of impaired breathing, speech, eating, and challenges with physical intimacy. One-half of HNSCC survivors report quality-of-life issues relating to food intake, whereas 1 in every 5 patients has long-term pain issues and one-third of the patients report significant long-term psychological distress.

Development of depression is common in HNSCC survivors, and 13% to 44% of patients reported symptoms of depression. These statistics are comparable with other cohorts of patients with cancer. Patients who experience depression during the treatment of HNSCC are 1.5 times more likely to inflict self-harm and commit suicide. Management strategies depend on early identification of at-risk patients, use of screening tools, involvement of social contacts and/or family, psychotherapy, counseling, and antidepressants.

There is randomized, placebo-controlled evidence to support the role of prophylactic antidepressants in patients who undergo therapy for HNSCC. In a randomized controlled trial published by the authors’ group, prophylactic use of escitalopram led to a 50% reduction in the rate of depression in patients being treated for HNSCC. In addition, prophylactic pharmacotherapy resulted in improved quality of life for up to 3 months after cessation of therapy.