INTRODUCTION — Head and neck cancer (HNC) includes those cancers originating in the oral cavity, pharynx (nasopharynx, oropharynx, or hypopharynx), nasal cavity, paranasal sinuses, salivary glands, and larynx.
Combined multimodality treatment including surgery, chemotherapy, and radiation has increased disease control for locally advanced HNC. These improvements have come at the expense of increased acute and late effects, which may have a more profound effect on function and quality of life (QOL) than has been previously recognized [1,2]. HNC arises in structurally complex and functionally important areas. Impairment of these areas from both disease and therapy can interfere with basic functions, including eating and speech, and can have a profound effect on social interactions and psychological state [3]. In patients with early-stage human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma, treatment deintensification is being investigated to improve functional outcomes and reduce toxicity. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Is there a role for treatment deintensification?'.)
It is critical for clinicians to have an aggressive systematic approach to prevention and treatment of acute and late treatment effects. In addition, clinicians must be aware of the social, financial, and caregiver issues that may impact long-term QOL. (See "Overview of treatment for head and neck cancer" and "Management and prevention of complications during initial treatment of head and neck cancer" and "Management of late complications of head and neck cancer and its treatment".)
DEFINITION — QOL is a broad concept, a subjective, multidimensional, global construct that seeks to provide a comprehensive picture of the patient's perception of himself or herself in the world [4]. The World Health Organization (WHO) defines QOL as an "individual's perception of his or her position in life in the context of the culture and value systems in which the patient lives and in relation to his or her goals, expectations, standards, and concerns" [5]. A fitting description defined QOL as the "perceived discrepancy between the reality of what a person has and the concept of what the person wants, needs, or expects" [6]. In judging the efficacy of treatment, extending survival does not always correlate with improvements in QOL. Conversely, specific treatments may not necessarily prolong life but may enhance its quality. The importance of QOL has been increasingly recognized and is reflected in its use as an outcome measure in cancer research, on par with response rate and survival [4,7]. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness", section on 'Measuring HRQL'.)
Health-related QOL (HRQOL) focuses upon the patient's perception of the impact of illness before, during, and after treatment. The fundamental premise of HRQOL includes:
●Multidimensionality – QOL encompasses a broad range of domains [5]. These include:
•Physical health (eg, pain, fatigue, sleep)
•Psychological (eg, body image, mood, memory, concentration)
•Level of independence/function (eg, mobility, activities of daily living, work capacity)
•Social (eg, work, personal relationships, sexuality)
•Environment (eg, financial resources, transportation resources)
•Spirituality/religion/personal beliefs
●Subjectivity – Different people may have substantially different reactions to a similar illness or disability.
•QOL must be evaluated from the patient's perspective rather than the clinician or caregiver's perspective. The use of a proxy or surrogate may reflect perceptions at odds with those held by the patient [8].
•Patient ratings are more sensitive and reliable than those of their clinicians [6].
QOL and HRQOL are often used interchangeably in the literature. However, the broad nature of QOL can make it difficult to measure. It is preferable to use HRQOL when discussing the effects of cancer, as HRQOL focuses on the impact of treatment or disease status on QOL. It should also be recognized that QOL is often mistakenly used to indicate symptom burden. While symptom burden may affect QOL, they are not synonymous.
RELATIONSHIP BETWEEN SYMPTOMS, FUNCTION IMPAIRMENT, AND QOL — A "symptom" is a perceived alteration in sensation or function. Function loss may be clinically apparent or subclinical. Subclinical function loss may be relevant but may elude capture on patient-reported outcomes. For example, a patient with HNC may have severe silent aspiration that leads to chronic fibrotic lung damage. The impact of symptoms and functional deficits is captured on the physical, functional, and emotional domains of QOL tools. However, symptoms and functional deficits may or may not adversely impact QOL. Thus, symptom burden and functional deficits are not equivalent to QOL. Tools that assess symptom burden and functional deficits cannot be used in place of QOL as a measure of global wellbeing.
There are several possible relationships between symptoms or functional deficits and QOL [1,9].
●No correlation between symptom or functional deficits and QOL, regardless of severity or duration.
●Symptom intensity or functional deficits increase and QOL decreases with equal inverse proportion.
●Only intense/severe symptoms or functional deficits affect QOL, while low-intensity symptoms have no impact.
●Low-intensity/severity symptoms and functional deficits have a notable effect on QOL, but there is a ceiling effect.
In addition, the relationship between QOL and any given level of a specific symptom or functional deficit may assume one of the following trajectories:
●Remain stable over time so that for any given level of a symptom or functional deficit, the impact on QOL is unchanged.
●The patient adapts/accommodates to the symptom or functional deficit, and thus, QOL improves despite the fact that the symptom persists unabated.
●The distress of any given level of a symptom or functional deficit becomes more prominent over time, resulting in decreased QOL.
SIGNIFICANCE OF QOL MEASURES IN HEAD AND NECK CANCER — QOL measures have several potential applications [1,8]. QOL measurements can:
●Guide clinical decision-making by identifying patient preferences and treatment goals.
●Help monitor changes in response to treatment.
●Help monitor responses to treatment.
●Facilitate communication between the clinician and the patient. Patients may find a QOL scale less intimidating than a face-to-face discussion with the provider, which can save time by directing attention to important issues.
●Identify problems that have a significant impact on QOL.
●Help clinicians prioritize treatment of problems most worrisome to the patient.
●Help train staff to be more responsive to patients' needs and concerns, including patient education services and rehabilitative services.
●Help in the development of patient liaison services.
●Shape public policy and health care decisions made by the government and private institutions.
●Guide the research agendas of pharmaceutical companies and cooperative groups.
As an example, in the randomized controlled Dutch study (CONDOR) of patients with locally advanced HNC treated with induction chemotherapy, both cisplatin-containing chemoradiation (CRT) schedules investigated were not feasible due to poor health-related QOL as well as high symptom scores and toxicity rates [10,11].
Further details on the treatment approach to induction chemotherapy followed by concurrent CRT in these patients are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Induction chemotherapy'.)
PITFALLS AND LIMITATIONS OF QOL RESEARCH — There is no "gold standard" for measuring QOL [1]. The interpretation of studies of QOL in patients with HNC requires caution, as different instruments measure different symptoms and aspects of QOL. The instrument should be selected carefully for a defined clinical application [12,13].
●Different studies often employ diverse methodologies and varying assessment instruments, and include patients with different sites and stages of HNC. These issues make comparisons of results between studies difficult or impossible.
●Baseline data are necessary to attribute a decline in the level of functioning to disease or treatment-related effects. Patients with HNC often have difficulties that are unrelated to their cancer or its treatment but rather are related to comorbidities, including alcohol, tobacco, or other substance abuse.
●HNC is relatively uncommon, and many studies, thus, have analyzed a relatively heterogeneous patient population with regard to site of cancer within the head and neck region. These differences may influence different domains of QOL, independent of specific treatment effects. Many study samples are too small to provide adequate statistical power for comparisons or analysis by disease site [14-20].
●Historically, treatment approaches have varied considerably both with respect to modality of treatment (surgery, radiation therapy, and/or chemotherapy) and within modality (eg, type of resection or reconstruction, chemotherapy regimen, or radiation therapy technique). These differences must be taken into consideration when analyzing the impact of treatment on QOL.
●Patients with more medical needs (eg, advanced tumor stage, recurrent disease, or comorbid disease) might be disproportionately represented as participants in QOL studies, while patients without insurance might be underrepresented [21].
Tools should take into account the following practical considerations [1,8]:
●Validity (measure what they say they do)
●Reliability (reproducible if repeated in the same group)
●Sensitivity (respond to changes in the patient's condition)
●Ease of administration (amount of time, manpower, and resources required to collect and analyze data)
●Patient comprehension
●Ease of scoring and interpretation
●Clinical relevance (ie, changes in score are clinically significant, or meaningful benchmarks exist at which a treatment could be considered to have improved QOL)
Methodological considerations for QOL research study design include:
●No selection bias
●No floor effect (able to detect worsening of QOL in patients with existing poor QOL)
●No ceiling effect (able to detect improvement of QOL in patients with existing good QOL)
●Appropriateness across multicultural/multiracial populations
●Ease of clinical applicability
●Has an overall global score and domain scores
●Multidimensional (see 'Definition' above)
●Self-administered
The choice of tool depends on the study objective, target population, and psychometric properties of the scale [4].
PATIENT-REPORTED OUTCOME MEASURES: WHERE DO QOL INSTRUMENTS FIT IN?
Available QOL tools — A multitude of patient-reported outcome (PRO) instruments (tools) exist. Such tools are developed for specific purposes and may vary in content and length. QOL measures have been developed largely for use within research environments with the goal of capturing the patient perspective [8].
Tool selection should be governed by the research question and by the burden to the patient. Lengthy tools have the advantage of providing rich and detailed information regarding the factors contributing to adverse health and QOL-related issues. Conversely, they are associated with increased patient burden. Global single items such as "How is your QOL compared with a year ago?", although general and superficial, offer a quick and easy assessment of QOL and are often used as single items when brief assessments are desired [8]. As an example, in a randomized trial of 110 patients with HNC, nurse-guided screening using the National Comprehensive Cancer Network Distress Thermometer allowed patients the opportunity to discuss problems and challenges, but did not affect patient outcomes such as health-related QOL [22].
There are six major categories of tools that are available to assess QOL. Examples of questionnaires for each category are included below (table 1) [1,8,23]:
●General health, which can be used across a range of disease states:
•EuroQOL five dimensions questionnaire (EQ-5D, formally EuroQOL) [24]; Medical Outcomes Study (MOS) short form 36 (SF-36) [25]; Sickness Impact Profile (SIP) [26,27].
●Disease specific, which have been developed specifically for patients with cancer:
•The Cancer Rehabilitation Evaluation System (CARES) [28]; European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 [29]; Functional Assessment of Cancer Therapy-General (FACT-G) version 4 [30].
●Site specific for HNC patients:
•University of Washington QOL Questionnaire (UWQOL) [31]; EORTC-Head and Neck Quality of Life Questionnaire [32]; FACT-Head and Neck [33]; Performance Status Scale for Head and Neck Cancer Patients; MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) [34]; Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 [35].
●Domain specific:
•Voice-related QOL (V-RQOL) [36]; MD Anderson Dysphagia Inventory (MDADI) [37]; Xerostomia Questionnaire (XQ and XQOL) [38]; Shoulder Pain and Disability Index (SPADI) [39].
●Treatment specific:
•UWQOL for surgical patients [40]; Head and Neck Radiotherapy Questionnaire (HNRQ) [41]; Quality of Life Radiation Therapy Instrument Head and Neck Module (QOL-RTI/H&N) [42]; Liverpool Oral Rehabilitation Questionnaire [43].
●Symptom specific:
•Brief Fatigue Inventory (BFI) [44]; Brief Pain Inventory-Short Form (BPI-sf) [45].
Are QOL tools effective for screening? — There has been an increased interest in screening for symptoms or functional deficits. Studies have demonstrated improved outcomes in the advanced cancer population when screening tools are used to identify such symptoms and functional deficits. In general, screening tools are brief, capture relevant clinical concerns that are actionable, and can be reviewed and interpreted by the clinician at the time of the medical encounter. Screening tools should be tested in the clinic for the ability to improve pertinent clinical outcomes. However, QOL measures are not designed to screen for clinical issues and are not necessarily good screening tools.
QOL AND SURVIVAL — For cancer in general, health-related QOL (HRQOL) scores were associated with survival in a systematic review of all English language biomedical journals between 1982 and 2008 [46]. Global QOL, functioning domains, and symptoms scores (including appetite loss, pain, and fatigue) were important indicators, both individually and combined, for predicting survival in cancer patients. This held true after adjusting for demographic factors and known clinical prognostic variables. (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)
Pretreatment (baseline) QOL data also appeared to be useful in establishing prognostic criteria for treating cancer patients [46]. For example, pretreatment QOL in patients with HNC predicted for survival independent of prognostic factors in a study of 106 patients using both the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the EORTC Head and Neck Cancer Module [47].
Results from an additional prospective study using Short Form-36 (SF-36) physical and mental component scores and the Head and Neck QOL scores in 495 HNC patients within two years of their initial diagnosis of HNC at any head and neck site showed [48]:
●Outcomes associated with survival:
•SF-36 physical component scores.
•Head and Neck QOL scales for pain, eating, and speech domains.
•Level of distress as measured by the General Health Questionnaire (GHQ) sum scores predicted survival [49].
●Outcomes not associated with survival:
•SF-36 mental component score.
•Head and Neck QOL scale for emotional domain.
There are several possible explanations for why QOL predicts survival:
●Poor QOL may be a surrogate for advanced disease.
●Patients with poor QOL due to high symptom burden and poor functionality may tolerate treatment poorly and receive less than optimal dosing and scheduling of therapy.
●Poor QOL may relate to systemic physiologic alterations associated with cancer burden (eg, activation of inflammatory or neuroendocrine systems) [50-52].
●QOL questionnaires identify symptoms (eg, pain, dysphagia, weight loss) that may reflect persistent or recurrent disease [48].
PREDICTORS OF QOL — Potential predictors of QOL during and after treatment include:
●Pretreatment QOL [53,54].
●Patient characteristics (eg, age, race, sex, socioeconomic status) [55,56].
●Tumor-related characteristics (eg, primary site, stage) [56,57].
●Treatment-related characteristics (eg, treatment modality and extent of surgery, adjuvant chemotherapy, radiation therapy) [56,58].
●Health behaviors (eg, smoking, alcohol use) [59]. Smoking cessation may modify declining QOL [60].
●Symptom burden [61].
●Comorbidities, notably depression [1,56,57,59,61-63].
Data regarding the impact of these factors on QOL are often mixed. This may be due to methodological differences, including sample size, patient population, tool selection, and time point in treatment trajectory. Alternatively, this may be due to a weak or negligible association between these parameters and QOL. (See 'Pitfalls and limitations of QOL research' above.)
SPECIFIC SYMPTOMS AND THEIR EFFECT ON QOL
Disfigurement — HNC or its treatment may result in changes in appearance or disfigurement, with a resultant decline in QOL [64]. This is particularly important with regards to facial features. The face is a highly visible and socially significant body structure in terms of body image as well as for its role in social eating and speech. Cancers involving structures of the face, including the cheeks, lips, eyes, ears, and nose, are particularly susceptible to impaired body image and psychosocial functioning. There appears to be an additive effect of functional impairments that contribute to poorer body image [65]. Conversely, some studies have not found a link between extensive disfiguration and QOL, perhaps as a result of patient adaptation or a perceived trade-off between life/death and disfigurement [66-68]. In one study, even loss of speech and permanent stoma were found to not significantly determine QOL [68]. Psychoeducational intervention programs, including peer counseling and support groups, can help patients better cope with their disease and improve QOL [69].
In one study of patients with HNC treated with radiation that used the "Shame and Stigma Scale" (SSS) to evaluate factors that challenged patients' QOL perception, the feeling of regret had the highest impact (39 percent). Social and speech concerns related to HNC were also reported by 17 percent of patients [70].
Dysphagia — Dysphagia that is present at diagnosis is typically caused by the tumor. Treatment with surgery or radiation may also cause or acutely worsen dysphagia. The degree of dysphagia is dependent on numerous factors, including stage, primary site, and treatment parameters. Unfortunately, dysphagia persists in a significant subset of patients. On average, 50 percent of patients treated with multimodal therapy will suffer from some degree of dysphagia at 6 and 12 months after treatment, with 15 percent having moderate to severe dysphagia [71]. Concomitant administration of chemotherapy with radiation increases the incidence and severity of dysphagia. Regardless of the cause, posttreatment dysphagia influences global QOL and appetite. (See "Management of late complications of head and neck cancer and its treatment", section on 'Dysphagia'.)
Lymphedema — Lymphedema is the accumulation of lymphatic fluid in interstitial spaces. Lymphedema secondary to treatment is a common late effect in patients with HNC [72]. External lymphedema commonly involves the neck and submental areas, while internal lymphedema can involve structures such as the larynx and pharynx. Lymphedema is associated with increased symptom burden, decreased functionality, and worse QOL. (See "Management of late complications of head and neck cancer and its treatment", section on 'Lymphedema and fibrosis'.)
Voice — Numerous studies have shown that contrary to common assumption, long-term QOL is not decreased after total laryngectomy [73-75]. (See "Alaryngeal speech rehabilitation".)
Xerostomia — Xerostomia is one of the most frequent adverse effects experienced by patients who receive radiation therapy. An inverse relationship between xerostomia and QOL has been observed. Xerostomia, the subjective complaint of dry mouth, more strongly affects QOL than does hyposalivation, the objective finding of decreased salivary flow. This may be explained by the weak correlation between xerostomia and salivary flow. [76,77]. (See "Management of late complications of head and neck cancer and its treatment", section on 'Salivary gland damage and xerostomia'.)
Systemic symptoms — Acute illnesses such as infections, trauma, or cancer may result in the production of cytokines, chemokines, and growth factors that serve to modify and coordinate the healing process. In patients who experience an intense or protracted physical insult, these mediators and others yet to be clearly defined may result in harm to the host [78].
One of the commonly reported but understudied acute and late effects of cancer and its therapy on systemic symptoms [79,80]. These symptoms were originally described in animal models and were characterized as "sickness behavior" [81]. Systemic symptoms may include fatigue, widespread pain, anxiety, depression, neuropsychiatric symptoms and neurocognitive dysfunction, temperature-related distress and dysregulation, disordered sleep, and gastrointestinal dysfunction. Systemic symptoms often occur in clusters rather than in isolation. In particular, fatigue increases during radiation therapy and is present in 50 to 90 percent of patients with HNC [82].
As expected, patients with HNC undergoing active therapy experience profound and severe systemic symptomatology. Of concern, 50 percent of survivors (at least 12 months posttreatment) report at least one systemic symptom. Most patients with systemic symptoms experience multiple symptoms, and in a substantial percentage of affected patients, the symptoms are moderate to severe in intensity. Systemic symptoms are associated with decreased QOL [83].
FUNCTIONAL PERFORMANCE AND QOL — The majority of data from longitudinal studies have shown that impairments in speech, swallowing, and eating do not impair QOL [1]. In spite of residual functional deficits, many patients adapt to their deficits and recover to pretreatment QOL levels. While there are subgroups of patients who continue to experience considerable emotional distress and depression, these symptoms are not clearly related to functional outcome.
Non-cancer health events can impact mortality and QOL. For example, lifestyle habits, such as tobacco, marijuana, and alcohol use, have been shown to impact treatment adherence [84]. Body mass index (BMI) <20 kg/m2, Charlson comorbidity index (CCI) ≥1, and second primary cancers have been shown to impact mortality in advanced HNC [85].
The Veterans Affairs larynx study was a landmark study in which induction chemotherapy plus radiation therapy was found to have equivalent survival rates to total laryngectomy plus postoperative radiation. This study also demonstrated better QOL scores in the induction chemotherapy plus radiation group as opposed to the surgery plus postoperative radiation therapy group. However, regardless of surgical or nonsurgical intervention, the improvement in QOL appeared to be more closely related to freedom from pain, better emotional wellbeing, and lower levels of depression compared with preservation of speech function [86,87]. In fact, numerous studies have shown that long-term QOL is not decreased after total laryngectomy, contrary to common assumption [73-75].
TRAJECTORY OF QOL AND ITS RELATIONSHIP TO TUMOR AND TUMOR-RELATED FACTORS — Patients with HNC often have a compromised overall QOL at diagnosis that decreases further during treatment. Typically, overall QOL improves slowly over time such that QOL returns towards baseline by 12 months posttreatment [1,88,89]. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer".)
However, there is a subset of patients, often those with more advanced disease or poor performance status at baseline, whose QOL fails to return to baseline.
It is important to note that most QOL tools are composed of subscales, each of which may have multiple items. A substantial percentage of patients may identify problems captured by single items or subscales. These complaints, although substantial, may not be powerful enough to impact overall QOL scores.
●In a systematic review [7]:
•Global QOL deteriorated from the period before treatment to the period one to six months after therapy and then gradually improved until the one-year mark.
•The greatest improvements during the first year were in emotional functioning.
•The greatest deterioration was in physical functioning at one year.
•Most studies in the systematic review showed full recovery of social, cognitive, and role functioning by one year.
●Most prospective studies have not followed survivors beyond a few years. Data on long-term survivors are limited. Clinical observation and scattered reports support a bimodal impact of treatment on QOL: Patients experience an initial decline in QOL immediately after therapy, followed by a return toward baseline. Years later, patients may experience a decline in QOL associated with late toxicities.
●A prospective study using the Auckland QOL questionnaire in patients with HNC at 10 years following diagnosis found that QOL decreased by an average of 11 percent from QOL prior to treatment; compared with years 1 and 2, QOL decreased by 15 percent [53].
●In another study, 80 patients with oral or oropharyngeal cancer were followed prospectively. Of these, 26 were evaluated with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ Head and Neck 35 at baseline, 6 months, 12 months, and 8 to 11 years. QOL domains significantly worsened (p<0.01) in the long-term included emotional and social functioning, swallowing, speech, taste, smell, dry mouth, sticky saliva, and coughing [88].
●The course of health-related QOL (HRQOL) is different for survivors of HNC versus nonsurvivors, those who will eventually die of their disease. In the first two years after treatment, survivors experienced improvement in HRQOL, while nonsurvivors had no change or deterioration. The exception was emotional functioning, which initially improved after treatment but deteriorated in the long-term for both groups [57].
TUMOR-RELATED FACTORS AND THEIR EFFECT ON QOL — Data pertaining to the impact of tumor-related factors fail to show a consistent and meaningful impact on QOL. Some general findings are worth noting.
Disease site
●Oral cavity cancers – Oral cavity cancers tend to have worse scores for a variety of domains (physical or cognitive functioning, fatigue, appetite, pain, nausea/vomiting, dyspnea, social eating, social contact, mouth opening, and coughing) compared with the other sites [57,90,91].
●Hypopharyngeal cancers – Patients with hypopharyngeal tumors were found to have suicide rates 12-fold higher than the average population in the United States. Poor emotional support and lack of coping strategies are thought to impact QOL more than functional outcomes [92]. (See "Suicidal ideation and behavior in adults".)
●Oropharyngeal cancers – Oropharyngeal tumors are recognized as a distinct biological and prognostic subset of HNC. Interest in the effects of treatment on patients with oropharyngeal primaries has increased with the epidemic of human papillomavirus (HPV) associated/p16 positive tumors, although data are limited. (See "Treatment of human papillomavirus associated oropharyngeal cancer".)
Tumor stage — Some studies have found that tumor stage is not significantly associated with any QOL scales [56,93], while other studies reported stage III and IV advanced disease stages were associated with reduced QOL [7].
●Patients with early stage disease at diagnosis have better QOL at one year with regards to eating, appetite, supplement use, role and social functioning, pain, trismus, dry mouth, and financial difficulties [94,95].
●Importantly, higher stage disease (T3, T4, N2, or N3) is an indication for more aggressive combined modality treatment, which may result in increased acute and late effects, potentially resulting in reduced QOL. (See "Overview of the diagnosis and staging of head and neck cancer" and 'Impact of treatment' below.)
HPV status — The epidemic of HPV associated oropharyngeal cancers (OPC) has led to a significant paradigm shift in the diagnosis, staging, and treatment of HNC. HPV associated OPC often occurs in patients without a history of smoking or alcohol use. Thus, these patients are less likely to have substantial comorbid disease. Although the average age at diagnosis is only slightly younger than smoking-associated cancers, there is an increased incidence in younger patients. Finally, patients with HPV associated OPC typically have a much better prognosis than those with non-HPV associated OPC. This is reflected in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system, which has delineated separate staging systems for HPV associated and non-HPV associated OPC. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer".)
●QOL in HPV associated HNC – Compared with patients with non-HPV associated HNC, patients with HPV associated OPC demonstrate similar QOL trajectories but better overall QOL [96]. Data also indicate that, similar to the general HNC population, patients treated for HPV associated OPC experience an immediate decline in QOL that gradually improves to pretreatment levels after approximately one year [96,97]. In a retrospective study of 177 patients with HNC treated with either surgery or primary radiation therapy, those with non-HPV associated HNC had worse overall QOL at baseline, 6 months posttreatment, and >1 year posttreatment compared with those with HPV associated HNC [96]. Among those with HPV associated OPC, treatment modality did not impact QOL, symptom, or functional outcomes. Given the increased comorbidities in the non-HPV associated HNC population, these findings are not unexpected.
●Treatment deintensification and QOL – Data suggest that treatment deintensification is associated with improved QOL in patients with HPV associated HNC [98,99]. In these studies, QOL, symptom burden, and functional outcome assessment are critical components of trial design [98]. Treatment deintensification in patients with HPV associated HNC remains an investigational approach and is discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Is there a role for treatment deintensification?'.)
INABILITY TO WORK AND FINANCIAL DISTRESS — Treatment for HNC may have a prolonged debilitating effect on a patient's functional status, thus limiting his/her ability to work during and after treatment. In a cross-sectional study examining work-related disability among patients with HNC, 52 percent of those who were employed at the time of diagnosis were unable to return to work after treatment was completed [100]. Those who were unable to return to work had worse global adaptation in the domains of work and psychological distress [68].
CAREGIVERS — Caregivers of patients with head and neck cancer often view the patients' QOL more negatively than the patients themselves, which can increase caregiver psychosocial distress [101]. Patients who needed a caregiver also reported lower QOL than those who did not need a caregiver. In addition, patients with increased functional and physical impairments can result in overload of the caregiver, which can in turn negatively impact patients' QOL [70].
Interventions that can improve QOL for caregivers include assessing for caregiver distress and facilitating communication between the caregiver, patient, and treatment team [101]. (See "Overview of psychosocial issues in the adult cancer survivor", section on 'Caregivers'.)
IMPACT OF TREATMENT
Surgery — For early stage disease, patients may be treated with curative intent using surgery alone and attain high long-term QOL [102]. However, more extensive surgery for HNC can cause symptoms or functional deficits that result in decreased QOL. Common surgery-associated adverse outcomes include lymphedema and fibrosis, disfigurement, voice loss, difficulty with chewing or swallowing, drooling, and neurologic dysfunction. Upfront neck dissection is also associated with more severe dysphagia as measured by patient and physician scores, and swallowing videofluoroscopy [103]. (See "Management and prevention of complications during initial treatment of head and neck cancer" and "Management of late complications of head and neck cancer and its treatment".)
Patients often express particular concern or fear of laryngectomy. Laryngectomy is clearly associated with increased symptom control and functional issues; however, long-term QOL is not decreased after total laryngectomy [73-75]. This is likely due to adaptation of expectations with the reality faced by the patient, as well as cognitive behaviors such as benefit finding (see 'Functional performance and QOL' above). There is no statistical difference in QOL between horizontal supraglottic laryngectomy and partial vertical surgery, although horizontal surgery has better voice quality [68].
Radiation — Intensity-modulated radiation therapy (IMRT) is standard of care for HNC due to conformal dose distribution with improved sparing of normal tissue [90,102,104,105]. One study reported over 80 percent of five-year survivors being satisfied with their QOL, highlighting the ability of IMRT to preserve long-term functioning [106]. (See "Radiation therapy techniques in cancer treatment" and "General principles of radiation therapy for head and neck cancer", section on 'Intensity-modulated RT' and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations".)
The prominent long-term adverse local effects of radiation therapy are hyposalivation and taste changes. The former may lead to adverse oral health outcomes, including radiation caries, periodontal disease, and osteoradionecrosis. Radiation may also cause lymphedema and fibrosis, which leads to long-term issues with jaw, neck, and shoulder range of motion and swallowing. The addition of concurrent chemotherapy exacerbates all of these side effects. If severe, symptoms and functional deficits may adversely impact overall QOL. The acute and long-term complications of radiation therapy are discussed separately. (See "Management of late complications of head and neck cancer and its treatment" and "Management and prevention of complications during initial treatment of head and neck cancer".)
When radiation is used in the postoperative setting, acute and late effects tend to escalate. The adverse soft tissue toxicity of combined surgery and radiation may be severe. In one study, adjuvant radiation therapy after laryngeal surgery was the most powerful correlative with adverse outcomes in a multivariate analysis [93].
The acute and late effects of radiation therapy may manifest differently based on the primary site. For example, laryngeal cancers are more likely to report issues with speech and taste compared with other sites [7,56,93]. Cancers of the larynx are less likely to experience severe pain and have a higher probability of improvement in global QOL at one year compared with oral and pharyngeal cancers [7,90,107].
Chemoradiation as primary therapy — Data comparing surgery plus adjuvant radiation with chemoradiation (CRT) as primary therapy have failed to demonstrate a major overall QOL advantage for either treatment modality. For example, studies have reported similar long-term QOL for patients with advanced carcinoma of the larynx whether they underwent total laryngectomy or received concurrent CRT for organ conservation [107,108]. A study of oral cavity squamous cell carcinoma showed no difference in overall health-related QOL (HRQOL) between primary CRT and surgery (with or without adjuvant treatment), with both groups providing acceptable HRQOL [109]. With regards to induction therapy versus concurrent CRT, the European Organisation for Research and Treatment of Cancer (EORTC) 24954 phase III randomized controlled trial comparing combined chemotherapy with sequential induction chemotherapy and RT versus alternating CRT showed a trend towards worse scores in the alternating therapy arm. HRQOL returned to baseline for the majority of patients [110]. Once again, it is important to distinguish QOL for symptoms and functional deficits; differing treatment regimens, while resulting in similar overall QOL, may cause very different acute and late toxicities.
Immunotherapy — Patient-reported outcomes (PROs) were assessed as an exploratory endpoint in the CheckMate 141 phase III trial for platinum-refractory recurrent or metastatic HNC, in which patients were randomly assigned to either nivolumab (3 mg/kg every two weeks) or a single-agent investigator's choice of therapy (methotrexate, docetaxel, or cetuximab) [111]. (See "Overview of treatment for head and neck cancer".)
Using the EORTC Quality of Life Questionnaire (QLQ)-30 and EORTC QLQ Head and Neck 35, no clinically meaningful deterioration in QOL was noted in the nivolumab treatment group as compared with the chemotherapy group, in which 8 of 15 domains showed a deterioration. The three-level European Quality of Life-5 Dimensions (EQ-5D) questionnaire showed clinically meaningful improvement using nivolumab as opposed to clinically meaningful deterioration in the chemotherapy group [111].
Feeding tubes — The majority of patients receiving CRT for locally advanced disease experience significant loss of weight and muscle mass, with resultant sarcopenia.
The role of prophylactic placement of feeding tubes is controversial and data are mixed. One randomized study showed significantly higher QOL scores (EORTC) in the group receiving prophylactic gastrostomy [112]. However, some argue that prophylactic feeding tube placement leads to disuse of swallowing muscles and, ultimately, higher rates of feeding tube dependence. The importance of these issues led to the development of a specific instrument that measures the impact of enteral feeding tubes on the QOL of these patients [113]. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Head and neck cancer'.)
REHABILITATION — Data suggest that patients with HNC benefit from referral to a variety of specialists who can assist in symptom control and function recovery. These include speech and swallow therapy, physical therapy, occupational therapy, lymphedema therapy, audiologists, ophthalmologists, pain control specialists, nutritionists, gastroenterologists, and psychologists. Further studies are required to determine the impact of many of these services on overall long-term QOL.
As examples, in a randomized controlled trial of 148 patients with HNC undergoing chemoradiation (CRT), an 11-week structured exercise program improved QOL and functional capacity and prevented worsening of fatigue compared with standard physical activity recommendations [114]. In another randomized controlled nutrition intervention trial, "Eating as Treatment" (EAT), resulted in improved QOL, less depression, and fewer treatment interruptions [115]. Rehabilitation, when used in combination in a systematic manner to maximize effect, has also been demonstrated to improve overall QOL [116].
Further details on available rehabilitation services for patients with HNC are discussed separately.
●(See "Alaryngeal speech rehabilitation".)
●(See "Speech and swallowing rehabilitation of the patient with head and neck cancer".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Throat cancer (The Basics)")
SUMMARY
●Definitions – Health-related quality of life (QOL) incorporates several dimensions (physical, functional, social, psychological) and is subjective, based upon the patient's perception of his/her illness and disability. QOL requires multiple assessments over time to judge the impact of interventions. (See 'Definition' above.)
●Significant of QOL – The importance of QOL has been increasingly recognized and is reflected in its use as an outcome measure in cancer research, on par with response rate and survival. There are, however, continued challenges in the field of head and neck cancer (HNC) QOL research. (See 'Significance of QOL measures in head and neck cancer' above and 'Pitfalls and limitations of QOL research' above.)
●Measures – Various instruments are available to assess QOL. These include some that are available for cancer patients in general, as well as a number of validated tools that were specifically designed for use in patients with HNC. Selection of the appropriate QOL instrument should be guided by the correct clinical or research question (table 1). (See 'Patient-reported outcome measures: where do QOL instruments fit in?' above.)
●Factors associated with QOL
•QOL and survival – Health-related QOL scores were shown to be associated with survival. (See 'QOL and survival' above.)
•Symptom burden – Physical and psychosocial issues affect QOL. Awareness of symptom burden can prompt early palliative intervention and/or referral to rehabilitation. (See 'Specific symptoms and their effect on QOL' above.)
•Tumor-related factors – Certain tumor related-factors (eg, disease site, tumor stage, and HPV status) may impact QOL in patients with HNC. (See 'Tumor-related factors and their effect on QOL' above.)
•Treatment – In addition to the cancer itself, the modalities used to treat disease (eg, surgery, radiation therapy, systemic therapy) are all associated with significant complications and/or toxicities that can have an important impact on QOL. A full consideration of these issues is necessary in managing patients with HNC. (See 'Impact of treatment' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jonas A de Souza, MD, and Marcy A List, PhD, who contributed to earlier versions of this topic review.
