Health-Related Quality of Life, Psychosocial Distress and Unmet Needs in Older Patients With Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer involving the mucosal surfaces of the head and neck and is associated with a number of etiological factors, including cigarette smoking, alcohol and betel nut consumption and exposure to high-risk human papillomavirus. The risk of HNSCC increases with age, peaking in the seventh and eighth decade, but this varies by anatomical and histological subtype. While several advancements have been made in the treatment of head and neck cancer (HNC) in recent decades, undertaking curative treatment still subjects the majority of HNSCC patients to substantial treatment-related toxicity requiring patients to tolerate a gamut of physical, psychological, and emotional demands on their reserves. In conjunction with other patient-related factors, clinicians involved in treating patients with HNSCC may incorporate advancing chronological age into their decision-making process when determining treatment recommendations. While advancing chronological age may be associated with increased concerns regarding physical treatment tolerability, clinicians may also be concerned about heightened vulnerability in various health and wellbeing outcomes. The available literature, however, does not provide evidence of this vulnerability in patients with advancing age, and, in many instances, older patients self-report greater resilience compared to their younger counterparts. While this data is reassuring it is limited by selection bias and heterogeneity in trial and study design and the absence of a consistent definition of the elderly patient with HNSCC. This narrative review article also includes a review of the measures used to assess HRQL, psychosocial outcomes and unmet needs in elderly or older patients with HNSCC.

Introduction

Worldwide, head and neck cancer (HNC) accounts for more than 650,000 cases and 330,000 deaths annually and the majority of these are squamous cell carcinomas (HNSCC) (1). Treatment recommendations depend on many factors, including tumor subsite, stage, and pathologic findings, but typically involves surgery and radiation therapy (with or without systemic therapy) either alone or in combination (2). Proceeding along a curative course of treatment for any HNC exposes survivors to the possibility of permanent impairment, including those required for basic human functioning such as chewing, swallowing, tasting and communicating, and loss in these and other domains may also impose significant psychological and emotional challenges (3). It is therefore incumbent upon the HNC physician to weigh the benefits and risks of all therapeutic options, balancing the chance of cure and cost of suboptimal locoregional treatment against the potential toxicity and negative health and wellbeing impacts of curative-intent treatment. Numerous factors weigh into this decision, including performance status, perceived frailty, social supports, individual preferences for pursuing curative treatment and the individual’s physical and mental reserve, among others. Age, whether chronological or the individuals’ perceived biological age, is but one of a host of factors that clinicians may consider during this process.

There is no readily accepted or reliable threshold for defining an “older” HNC patient to incorporate into clinical decision-making, an observation reflecting the degree of variation in ability, functioning and capacity in older adults. As a consequence, tailored treatment recommendations for older patients have been lacking due to an underrepresentation in clinical trials (4). Defining the optimal treatment strategies for these patients, if they differ at all, should be considered a priority for our specialty given the advancing age of the average HNC patient. In the United States for example, the proportion of HNC patients over the age of 65 years is expected to increase from 54% in 2010 to 66% in 2030 (5). In addition, while much attention has been placed on an epidemic of younger patients presenting with human papillomavirus-associated oropharyngeal cancer (HPV+ OPC) the projected increased number of HPV+ OPC cases in the United States from 2016 to 2029 will be driven almost exclusively by patients over 65 years of age (6, 7). Aggressive treatment is definitely feasible for selected older patients with HNC, but reliance on chronological age in isolation may result in over- or under-treatment, and while functional measures may provide superior discrimination in predicting survival and the tolerability of therapy (8–14), they are time intensive and require considerable multidisciplinary expertise (15).

But what other factors do we need to consider for the older HNC patient? And where is the patient’s voice within this complex decision-making process? Do preferences for pursuing radical treatment and cure change with age? Do priorities and preferences for different oncological and functional outcomes change with increasing age? Do older patients demonstrate increased vulnerability to adverse health and wellbeing outcomes when aggressive treatment strategies are employed? Do older HNC patients have more unmet needs following completion of treatment? This narrative review will draw on published research incorporating patient-reported outcomes to examine these questions. Where possible, we have narrowed the scope to focus on studies reporting outcomes in HNSCC; however, many of the studies were very broad in their selection criteria (tumour subsite and histology) and treatment received including any treatment modifications that may have been made to improve treatment tolerance in older patients. Out of necessity, where suitable data was otherwise lacking, some mixed studies have been included in this review. It should also be acknowledged that specific details about patients’ baseline functional performance were lacking, and the presented studies largely included older patients considered fit for a radical course of treatment, introducing a degree of selection bias. Hence, these results cannot be extrapolated to poorly performing older patients.

Defining “Elderly” Head and Neck Cancer Patients

There is no strict chronological boundary for defining “elderly” patients with cancer. The United Nations and World Health Organization have defined elderly patients as those above 60 (16), while in many developed countries, the designation is tied to retirement, which varies between jurisdictions from 55 to 70 years of age (17). Further refinement of old, including young old (65–74), older old (75–84) and oldest old (≥85) have been proposed and adopted by the National Institute on Aging (18). The European Organization for Research and Treatment of Cancer (EORTC) recommended a cut-off of 70 years of age for their elderly HRQL module, the EORTC QLQ-ELD14 (19). Specifically in HNC, 70 years of age would be considered the most common clinically utilized threshold for decision-making available (4) based on the reported reduction in efficacy of concurrent chemotherapy observed in patients above this threshold (20). However, older patients have typically been underrepresented in HNC and HNSCC clinical trials (4), and caution should be observed in drawing too firm a conclusion given the significant improvement yielded in younger cohorts and the catastrophic complications of treatment failure. While the additional benefit of chemotherapy to locoregional treatment in the elderly remains an unresolved issue, it remains a fertile area of research, one where future studies, in particular, secondary analyses from phase II and III studies, could address questions of efficacy while also providing prospective and high quality data on patient-reported toxicity, HRQL and distress. Such data may provide clinically useful information to aid shared-decision making in older patients with HNSCC.

While there is conjecture and variation surrounding an exact age-related definition of elderly, it is somewhat arbitrary; instead, clarifying core variables such as biological age, medical co-morbidity and frailty lie at the heart of what the clinician is trying to ascertain – whether the patient has sufficient reserve to tolerate the physiological insults of radical treatment. While there has been some tantalizing preliminary work focusing on methods to determine an individuals’ epigenetic clock in HNC patients, it is currently difficult, if not impossible, to measure biological age reliably. This will be discussed in more detail in a subsequent section (21, 22). We acknowledge the limitations of chronological age as a predictor for treatment tolerance, particularly when used in isolation; however, it is a parameter that is commonly used both in clinical and research settings and the purpose of this review was to address variations in health and wellbeing outcomes based on chronological age, rather than other variables, which may provide useful additional data.

Treatment and Outcome Preferences in Older Patients With HNC and HNSCC

Do older patients with HNC prioritize oncologic outcomes, such as cure, survival and functional outcomes like preserving swallow and communicating, differently than younger patients with HNC? The Chicago Priority Scale is one of the most frequently used instruments in the HNC cancer literature to characterize treatment outcome priorities (23, 24). Patients (or controls) are asked to rank their disease and functional outcome goals in order from first to last for 12 different outcomes; these are listed in Table 1. In the first of these studies, which included newly diagnosed HNC patients (n=131) from nine institutions, older patients less frequently prioritized oncological outcomes, such as cure and survival (“living as long as possible) in the top three items. The median age in this study was 59 years (range 29-87 years). In those patients aged <55 years, 55-64 years and >65 years, the frequency of ranking the cure item in the highest three priorities was 98%, 96% and 84%, respectively. While this difference was statistically significant (p<0.05), it is clear that the vast majority of older patients place a high value on being cured of their cancer. Interestingly, the older patients did less frequently prioritize length of life or survival, with the “living as long as possible” outcome showing a more notable drop off in the top three ranked items across the same three age groups (73%, 48% and 43%, respectively, p=0.01).

TABLE 1

Table 1 Chicago priorities scale.

List et al. subsequently reported results for a larger sample of recently diagnosed, but untreated HNC patients (n=247) in parallel to a control sample (n=131) of non-cancer patients with no personal experience of HNC in close friends or relatives. Similar findings were observed, with most of the “older” group of patients in this series (older was defined by the median split at >58 years) placing the cure outcome in the top three outcomes (≤58: 93% vs >58: 87%). However, older patients also prioritized the “keeping appearances unchanged” item in the top three items more frequently than younger patients (13% vs 5%). Similar observations for both cure, length of life and appearances were observed in the control group.

The Chicago Priority Scale was also used to assess preferences in a more contemporary cohort of patients from John Hopkins, which importantly included many patients with HPV+ OPC (88/150, 59%) (25). Investigators conducted a one-time interview of patients with a mix of HNSCC tumor sites and treatments (surgery ± adjuvant therapy 70%, primary CRT/RT 30%), and the time since treatment completion also varied (median 7 months, IQR 1.5-23.5 months). The median age in this study was lower than in both prior studies (median 54, IQR 54-67, range 26-90). Cure was considered the highest priority at all ages with no differences reported with increasing decade of life. Like both studies by List and colleagues, survival (“living as long as possible”) was less important with increasing age, a finding unchanged after adjustment for HPV status, disease stage and HRQL scores. In the full cohort, the survival outcome was ranked the second most important outcome after cure (median rank 2.5, IQR 2-9), in those aged 75 or over the median rank of the survival outcome was only 6 (IQR 2-11). Nonetheless, there was wider variability in the ranking of the survival item in older patients. In this study, treatment regret using the Ottawa Decision Regret Scale also did not vary by age. In a smaller series of 37 HPV+ OPC patients also from John Hopkins which included patients aged <60 years (23/37,62%), 60-69 years (7/37, 19%) and ≥70 years (7/37, 19%), Windon et al. noted few changes in treatment priorities from baseline (median 1 month after diagnosis, IQR 1-2 months) to post-treatment (median 8 months after treatment, IQR 7-10 months) with the exception that the chewing normally item was increasingly prioritized with older age in the post-treatment setting compared to its initial ranking.

Patient preferences have been appraised in other settings, for instance, where survival may be traded for reduced toxicity or organ preservation. In a Canadian study, Brotherston et al. reported that 51 previously-treated (≥3 months earlier) oropharyngeal cancer patients were willing to accept very little reduction in survival for a reduction in toxicity (which, in this case, was omitting chemotherapy), and when analyzed by age (median age 58 years; 60-69 years: 19/51, 37%, ≥70 years 4/51, 8%) there were no differences in cure sacrifice thresholds (26). In patients treated for advanced laryngeal cancers, at least one study has shown that age was not significantly associated with variations in the willingness to trade laryngeal preservation for survival (27).

In the studies reviewed, cure remains a high priority for HNC patients irrespective of age. Treatment outcome priorities and preferences studies provide some useful broad concepts to guide clinicians but are not a surrogate for eliciting preferences from patients at an individual level, which must remain first and foremost in any shared decision-making model.

Health-Related Quality of Life

A large number of studies have examined age-related variations in health-related quality of life (HRQL) outcomes; however, these reports vary in design (longitudinal or cross-sectional) and how age has been included as a variable (categorical or continuous) in the analysis. Relevant studies have been tabulated for ease of reference, including longitudinal (Table 2) and cross-sectional studies (Table 3) that have modeled age as a categorical variable, single-arm studies enrolling only elderly patients (Table 4) and those that have modeled age as a continuous variable (Table 5). Yet another strategy in the literature has been to compare the outcomes of elderly patients to age-matched population controls, allowing the authors to account for changes expected with normal aging.

TABLE 2

Table 2 Prospective studies reporting health-reported quality of life in elderly patients^a.

TABLE 3

Table 3 Cross-sectional studies reporting health-reported quality of life in elderly HNSCC cohorts. .

TABLE 4

Table 4 Studies reporting health-related quality of life outcomes enrolling only elderly patients with HNSCC.

TABLE 5

Table 5 Studies reporting age-related differences in health-related quality age in HNSCC (age analyzed as a continuous variable).

For this narrative report, we have focused and drawn attention to studies which have measured HRQL outcomes longitudinally with pretreatment assessments as their baseline, as of the numerous available studies, they are best placed to assess and report treatment-related differences across the age continuum. We have also drawn specific attention to those studies demonstrating significant age-based differences in HRQL, whether these differences have favored either the older or younger patients. However, it should be noted that these studies have also varied in study design from small underpowered studies to studies with very large numbers of patients while also using a variety of approaches to model age, including different age-based thresholds, hampering direct comparison. There is also variation in the instruments used and their assessment times. While the European Organization for Research and Treatment of Cancer (EORTC) modules, discussed below, have been the most frequently used measures in these studies, other instruments have been used, and cross-study comparisons are difficult given differences in their content, response options and the time frame with which individual instruments ask patients to consider how they have performed for a given item (i.e., “during the last week” or “during the past 4 weeks”). These are important differences to consider when comparing studies.

Health-Related Quality of Life Instruments

A variety of instruments are available to assess HRQL in HNC populations (Table 6). These include: (1) generic measures, which may also be used in non-cancer populations, such as the Short Form Health Surveys (SF-36, SF-12) (41, 42) or the EuroQoL modules (40); (2) generic cancer measures, such as the EORTC quality of life core questionnaire (QLQ-C30) (43) and the FACT-General (FACT-G) instrument (45); (3) head and neck cancer-specific instruments including the University of Washington Quality of Life Questionnaire (UW-QOL) (53), the EORTC Quality of Life Questionnaire Head and Neck Module (EORTC-QLQ-H&N35/43) (47, 48), and the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), which includes the FACT-G and an additional HNC concerns module (49). Many of these HRQL tools are recommended and available for use in elderly HNC patients, but development and validation studies have not always included sufficient numbers of elderly patients (54). Many authors have recognized this problem, and while steps have been taken to develop psychometrically sound tools to measure HRQL in elderly cancer patients, such as the QLQ-ELD14/15 module developed by the EORTC (19, 55), often these tools do not address cancer-specific challenges faced by older HNC patients. For instance, HNC patients were not represented in the development phase of the QLQ-ELD14 (55). Thus, in selecting instruments for any given study investigating HRQL in elderly HNC patients, choices will largely depend on the clinical context and no single instrument is likely to assess all issues relevant to elderly HNC patients.

TABLE 6

Table 6 Health-related quality of life instruments often used in HNC studies.

Global Quality of Life

Despite their limitations (56, 57), global measures of HRQL (referred to hereafter as global QoL) provide a straightforward means of assessing the overall impact of cancer and its treatment (56–59). Most prospective studies including measures of global QoL have found no significant differences between younger and older HNC patients (Table 2) (63, 64, 66–80) or have found significantly better self-reported global QoL in older patients (60–62). Findings from cross-sectional studies are similar (Table 3).

Berg et al. recently investigated longitudinal HRQL trajectories in 311 Swedish HNC patients. The sample included patients with various tumor sites, stages of disease and treatment; 37% had surgery and 85% received RT or CRT, either as definitive (63%) or adjuvant (22%) treatment (60). HRQL measures (EORTC QLQ-C30, QLQ-H&N35, QLQ-ELD14) were completed at diagnosis, then at three, six and 12 months from the commencement of treatment. The authors undertook two sets of analyses to compare younger and older patients. The first compared younger and older patients (<70 vs ≥ 70 years), the second compared younger and oldest patients (<80 vs ≥80 years). Despite similar global QoL at baseline, older patients reported better global QoL (<70 vs ≥70 years: 52 vs 61, p=0.006) three months after treatment, a difference of borderline clinical significance (96, 97); the oldest group (<80 vs ≥80 years: 54 vs 67, p=0.024) also fared better on global QoL at three months. Differences at three months were no longer evident at subsequent follow-ups. Citak et al. reported a prospective study of 54 Turkish patients, all of whom underwent radiotherapy (adjuvant treatment in 69%) (61). HRQL was captured with the EORTC QLQ-C30 and QLQ-H&N35 at baseline, at the end of RT, and one and three months after treatment. Global QoL was better in the older cohort (<60 vs ≥60 years: 53 vs 41, p=0.021) at the end of RT. While clinically relevant (96, 97), score differences at baseline were not described, so these results should be interpreted with caution.

Conversely, in a study reporting HRQL in elderly Japanese patients with oral cancer, Aoki et al. reported lower global QoL in older patients six months after treatment (62). In this study, 172 patients (≥75 years, n=43) completed the FACT-H&N at baseline, at treatment completion and one, three- and six-months post-treatment. While differences were small at the earlier time points, older patients reported worse global QoL scores at six months post-treatment (graphical interpretation, 106 vs 97, p=0.009), which falls into the range of a clinically meaningful difference (98). Interestingly, younger patients showed continued improvement from completion of treatment, whereas older patients plateaued at 1-month post-treatment.

Other Health-Related Quality of Life Outcomes

While considerable attention has been given to global QoL outcomes, other HRQL outcomes are highly relevant to older HNC patients and worth exploring in more detail. As with global QoL, most prospective studies fail to demonstrate consistent age-related differences in other self-reported HRQL outcomes (73–80), with some differences attributable to normal aging, irrespective of whether the patient has cancer.

In a prospective study of HNC patients from Sweden and Norway, Hammerlid et al. reported worse baseline (at the time of diagnosis) scores for older patients (≥75 years) on multiple scales/items of the QLQ-C30 and H&N35; however, these differences were only clinically relevant (≥10) for physical functioning, constipation, dyspnea and coughing. Older patients, however, reported better emotional functioning (99). At the 12-month follow-up, older patients (≥65 years) reported better role (difference = 11) and emotional functioning (difference = 10) but more significant problems with sexuality (difference = 18) and sticky saliva (difference = 15) than younger patients (69). Further, older patients reported less significant changes from baseline in role functioning and dryness of mouth. Nonetheless, changes from baseline in the senses (16 vs 10), sexuality (17 vs 4) and nutritional supplements (10 vs 5) were more severe.

In the previously mentioned Swedish study by Berg et al., the authors reported similar or better scores in the older cohorts with the exception of physical functioning, which was uniformly better in younger patients across the study. One exception was at the 3-month assessment. Here, differences in physical functioning were neither clinically nor statistically significant. This is largely explained by more significant declines in younger patients between baseline and 3 months. With further follow-up and recovery, however, the younger group regained its initial advantage. Older patients also reported less appetite loss and financial difficulties at various time points in this study (60). Notably, the oldest patients (≥80 years) reported worse fatigue, role functioning, and feeling ill at 12 months compared to those under 80 years. The Turkish study, which reported better global QoL at the end of RT, also found that older patients fared better with regards to senses problems and reported less weight loss, but scores were similar in other domains (61). Aoki et al., on the other hand, reported significantly worse social wellbeing and more HNC concerns in older patients (>75 years) at 6 months, as assessed by the FACT-H&N. Again, this appeared to be explained by younger patients showing better and ongoing recovery with further follow-up compared to the older patients.

Longitudinal HRQL outcomes for 785 HNC patients were collected in a North Carolina study using the FACT-H&N, with questionnaires administered to newly diagnosed HNC patients who were then assessed again at two subsequent follow-ups (median 22- and 42-months post-treatment, respectively) (70). Like most prospective studies reviewed, this series contained patients with various HNC subsites and disease stages, and they were treated with any combination of surgery (57%) and/or radiation (77%), with many also receiving concurrent chemotherapy (41%). A linear mixed model incorporating time since follow-up was used on each of the wellbeing domains, but not the total score. Age was divided into four categories, <50 years (19%), 50-64 years (49%), 65-74 years (25%) and ≥75 years (7%). Older patients generally fared better, with superior scores across the physical, emotional and functional wellbeing domains and the HNC additional concerns subscale. No significant differences were observed on the social wellbeing domain.

Physical functioning has also been reported as worse in older patients in other series, sometimes as an isolated finding among all available items/scales/domains (63), or in conjunction with limited other differences (76). While many of these studies suggest that older patients are not more adversely affected, some studies, such as that by Van Der Schroeff et al. have shown worse outcomes (72). In this longitudinal study, 118 older (≥70 years) and 148 younger (45-60 years) patients were followed for three to six years. The QoL component of the study was limited to those who completed all HRQL questionnaires (n=24 and n=33 patients, respectively). Again, the study sample was quite heterogenous in terms of tumor site, disease stage and treatment received. In the QoL cohort, about half the patients had oral cavity cancers. Patients were enrolled at diagnosis and there were no differences in the baseline EORTC QLQ-C30 and H&N35 scores. A more significant decline in physical functioning was seen in the older patients by 12 months post-treatment and this difference persisted at follow-up (i.e. three to six years post-treatment). The older patients also tended to report worse HNC symptoms, including statistically and clinically significant worse social eating (43 vs 23), swallowing (32 v 19) and speech (30 vs 19) at 12 months. Score differences on the swallowing and speech measures remained statistically significantly and clinically worse in the older patients with longer follow-up.

Laryngectomy Patients

Singer et al. conducted a prospective study of patients undergoing laryngectomy in eight German centers (34). HRQL data was collected at prior to undergoing a laryngectomy, just before hospital discharge, during inpatient rehabilitation, and 12 months later (EORTC QLQ-C30 and QLQ-H&N35). In this study, 101/175 (58%) patients were aged <60 years, 51/174 (29%) were aged 60-69 years, and 22/174 (13%) were ≥70 years. A multivariable regression analysis was undertaken to explore variations in HRQL changes from baseline to 12 months. While several outcomes, such as physical, role and social functioning, and some of the symptom items from both the QLQ-C30 and H&N35 were significantly worse one year after laryngectomy, age (analyzed as a continuous variable) was not a significant ‘predictor of scale/item scores’. On the other hand, Woodard et al. conducted a cross-sectional study in laryngectomy survivors using the Head and Neck Cancer Inventory (HNCI). Analysis of HNCI scores was limited to 33/58 survivors at median follow-up of 37 months post laryngectomy. The study included patients who had received primary surgical treatment and those who had received salvage surgery, however, the final patient contributions to the HRQL data was not reported. Younger patients (<65 years, 15/33) fared far worse across all the functional and attitude domains, as well as the global QoL score (54 vs 75). Those patients needing a laryngectomy as a component of their cancer treatment represent a distinct survivorship cohort amongst HNC patients, one resulting in many HRQL challenges, including loss of communication, body image changes and, potentially, loss of functional employment. While all patients will no doubt struggle with the physical and psychological impacts of a laryngectomy, younger patients in the prime of their adult lives may be especially vulnerable to the consequence of this life changing event.

Comparison to Age- and Gender-Matched Populations

Several studies have contrasted the outcomes of elderly patients to age- and gender-matched cohorts to differentiate HRQL changes attributable to treatment vulnerability and those that may be expected as a consequence of aging alone. Ferri et al. reported the outcomes of patients aged >75 years who had undergone HNC surgery with microsurgical reconstruction. This multi-site cross-sectional study used the SF-36 to assess HRQL two years after surgery. Of the eligible patients, 76/115 had died, leaving 39/115 enrollees with an average age of 81 years at the time of surgery. Most patients had also received adjuvant treatment (26/39, 67%). While the Mental Component Summary scores were similar to an age-matched Italian cohort, the average Physical Component Summary scores for the treated cohort indicated better physical health (46.5 vs 37.9) compared to the age-matched population. In a series of 50 older patients (>65 at time of treatment) who were at least one year from curative-intent radiotherapy (definitive or adjuvant), Ruhle et al. contrasted cross-sectional HRQL outcomes to an age-matched German sample (30). Using the EORTC QLQ-C30, patients reported very similar global QoL to the matched group. However, social functioning (85 vs 71), appetite loss (8 vs 19) and constipation (7 vs 20) were worse in the treated group; conversely, pain scores were lower (22 vs 33).

In a larger study also from Germany, 817 patients were enrolled to a cross-sectional study which compared HRQL, emotional distress and fatigue in HNC patients to a gender- and aged-matched population (<65 years, n=476; and ≥65 years, n=341) (100). The study sample included all HNC subtypes and a mix of primary and adjuvant treatment. Younger treated patients were more adversely affected (larger negative impacts) compared to their age- and gender-matched peers across all measured outcomes. Even so, older patients (≥65 years) did report worse HRQL compared to their matched peers. Global QoL (EORTC QLQ-C30) was worse for both the older males (65 vs 54) and females (63 vs 54). Older patients also reported worse fatigue (males 45 vs 24, females 48 vs 25) compared to the non-cancer patients.

Psychosocial Distress

The term “distress”, in the context of cancer, was chosen by the NCCN because it is felt to be less stigmatizing than descriptors like “psychiatric” and “psychosocial” concerns. It is defined by the NCCN as “a multifactorial, unpleasant, emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment (101)”. It encompasses both normal feelings such as vulnerability, sadness, and fears, as well as problems that can significantly impact a patient’s life such as depression, anxiety, panic, social isolation, and personal crisis (101).

This report has focused on multiple types of distress, including the more commonly appreciated forms anxiety, depression and suicidality, but also other measures including fear of cancer recurrence, post-traumatic stress disorder, coping strategies and body image distress. This section will also discuss what is known about pain, fatigue, and sleep in older patients with HNC. Where possible, this review has focused on longitudinal, prospective studies, but this was not always possible for some of the less frequently studied outcomes, and where cross-sectional studies have provided novel or additional information, they have been included. The variation in instrument selection in these reports is considerable, and as for the HRQL section, cross-comparison is limited by significant variations in their content and application.

Instruments Measuring Psychosocial Distress in HNC

Tools commonly used to measure distress in HNC research are listed in Table 7. While most HRQL measures include mental health and/or wellbeing scales, this section will focus on tools specifically designed to assess anxiety, depression and/or distress. These include: (1) generic measures which may also be used in a non-cancer population, such as the Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire 9 (PHQ-9); (2) generic cancer measures, such as the Distress Thermometer (DT), Mini-Mental Adjustment to Cancer (Mini-MAC), and Distress Inventory for Cancer (DIC2); and (3) head and neck cancer specific instruments, such as the Patient Concerns Inventory (PCI). Additionally, there are tools for assessing other factors that directly impact patient distress levels, such as coping style, fear of cancer recurrence, fatigue and sleep, social support, pain, and body image. These will be discussed in their respective sections.

TABLE 7

Table 7 Common Instruments used to capture distress in HNC studies.

Anxiety and Depression

Patients receiving HNC therapy self-report high levels of psychological distress, depression, and anxiety (119). Despite this awareness, psychological issues often remain unidentified or unassessed, albeit with significant effects on quality of life, functional status, and survival (8). Social isolation and lack of support have been linked to higher cancer mortality rates and poorer treatment tolerance (120). This is especially concerning in an older patient population because many elderly patients live alone (121). Literature on interventions to improve QOL and mood in patients with HNSCC have been summarized elsewhere (122).

Many studies have explored the relationship between age, and anxiety and depression in HNC patients. Due to the sheer volume of published studies, this paper will focus on results from prospective longitudinal studies (Table 8); results from cross-sectional studies are largely compatible. The overwhelming majority of prospective studies indicate that older HNC patients experience either similar rates of anxiety and depression (72, 74, 141–156), or less of one or both (123–138), than do their younger counterparts. Results from very few studies indicate worse distress among older HNC patients (139, 140).

TABLE 8

Table 8 Prospective studies reporting distress and age in elderly patients with HNSCC.

The largest prospective study to investigate the relationship between distress and age was reported by Hammerlid et al. in 1999 (127). The HADS was used to provide a measure of distress at baseline (after diagnosis but prior to initiating treatment) and one, two, three, six and 12 months after initiation of treatment in a mixed group of 357 HNC patients receiving various therapies. On average, patients <65 years reported higher levels of distress at diagnosis and at the one year follow up than did older patients. Another large prospective study evaluated a mixed group of 306 HNC patients from the US at their initial clinic appointment, and three- and twelve-months post-diagnosis, using the BDI and the Head and Neck Cancer Inventory. Younger age was associated with worse social disruption at three months (129). Prospective studies showing an association between distress and younger patient age have been reported from investigators in the UK, Japan, India, Australia, Taiwan, China, and the Netherlands (131, 133, 134, 136–138). In several studies, younger age is specifically linked to higher rates of anxiety, especially before and during treatment, which some speculate is due to increased fear of recurrence (126, 134, 135, 137).

There are only two prospective studies wherein older patients fared worse with regards to distress, and it is notable that the larger of the two reported on only nasopharyngeal cancer patients in China, with a median age of 51 years. In this study, rates of anxiety and depression in patients over the age of 40 was significantly higher than in those under 40 years at all timepoints; however, the interquartile range was 40-57, and this study is not representative of a broad elderly HNC population. The other prospective study reporting lower distress in younger patients is a very small study from the US reporting on preoperative distress in locally advanced HNC patients. Patients over 65 years were found to experience more depression than younger patients. This study did not utilize commonly utilized instruments and is far too small to draw any useful conclusions (139).

In summary, the preponderance of prospective evidence from a wide range of countries and across most head and neck disease sites and treatments suggests that elderly patients actually fare better with regards to distress as compared to their younger counterparts and that the reasoning for this is likely nuanced. Factors may include mid-life responsibilities more characteristic of younger patients, such as employment, childcare, greater perceived importance of social life, and less earned resilience. As discussed in the following sections, fear of cancer recurrence, pain, fatigue, sleep, body image issues, and post-traumatic stress may also be higher in younger patients. While most of these studies consist of self-reports based on screening tools rather than diagnostic interviews, which is a limitation, the results align with those from the general population; namely, that older people typically report lower levels of distress and anxiety than do younger people (157).

Fear of Cancer Recurrence

Fear of cancer recurrence (FCR) is a common concern reported by cancer survivors, including patients treated for HNC (Table 9). There are a number of methods used to gather information about FCR. FCR severity may be measured using standardized tools like the Fear of Cancer Recurrence Inventory (169, 170) or the Fear of Recurrence questionnaire (166). Concerns about FCR may also be gathered as part of various patient concerns inventories. Irrespective of the method used to gather information on FCR, older cancer survivors report lower levels/rates of FCR on average than younger patients (171). This observation has also been seen in HNC studies where variations in FCR have been analyzed by age (Table 9), with the majority showing an increased vulnerability to FCR in younger patients (158–164).

TABLE 9

Table 9 Head and neck cancer studies reporting variations in fear of cancer recurrence measures by age.

Concerns about cancer recurrence (perhaps fear of progression) may begin early on the cancer journey, and age-related differences may be observed even before treatment has commenced. Mirosevic et al. reported FCR outcomes in 216 newly diagnosed HNC patients using the 8-item Cancer Worry Scale (158). FCR scores were higher in younger patients, and age, along with baseline HADS anxiety scores were the strongest predictors of baseline FCR. As shown in Table 9, many studies have included substantial proportions of patients treated for oral cavity cancer with surgery alone. Irrespective of study design, younger patients appear more vulnerable, with the oldest patients (≥75 years) reporting low or lower rates of FCR (162, 164). In a cross-sectional cohort of 136 patients with HPV-associated oropharyngeal cancer treated with definitive (chemo)radiotherapy Casswell et al. measured FCR using the FCRI-short form (which assesses the severity domain of the larger FCRI version). In this study, age was analyzed as a continuous variable, and it is interesting to note that even with this favorable HNC cohort harboring a typically low risk of recurrence (given most had had a complete response to treatment and the mean time since treatment completion was 3 years) that older patients continued to report lower rates of FCR.

Body Image Distress in Older Patients With HNSCC

Body image studies in HNC have mostly been undertaken in samples of patients undergoing major surgery for their cancer, as detailed in Table 10. In summary, evidence of an association between age and body image distress is weak but limited cross-sectional and retrospective data suggest similar or less severe body image distress in older HNC patients (172–175). Further high-quality research is needed in this area.

TABLE 10

Table 10 Studies reporting on body image, pain, fatigue/sleep, and post-traumatic stress.

Fatigue and Sleep in Older Patients With HNSCC

There is a paucity of data on sleep quality in HNC patients; however, insight into sleep quality would likely help healthcare providers better support their patients. Sleep disturbance and fatigue have been shown to contribute significantly to depressive symptoms, and sleep is unique as it is an often treatable risk factor (141). Tools used to assess sleep and fatigue in HNC patients include the Pittsburgh Sleep Quality Inventory (PSQI), Fatigue Symptom Inventory, Lee Fatigue Scale, and General Sleep Disturbance Scale (GSDS).

Table 10 outlines studies reporting on fatigue and sleep in head and neck cancer patients. Hickok et al. prospectively administered a one-page symptom inventory to 372 patients weekly for five weeks during radiotherapy. Of note, this included patients with all types of cancer and only 23 had HNC. Mean age of the HNC patients was 61 years, and age was not predictive of fatigue severity at any time in this study (179). Other studies are cross-sectional in design but have the advantage of being limited to head and neck cancer and, like most of the other domains reviewed, they appear to show an association between younger age and poor sleep quality and fatigue (180, 181). As with body image distress, more high-quality research would be helpful in investigating this relationship further.

Pain in Older Patients With HNSCC

Pain is experienced as one of the most impactful sources of distress in cancer survivors and has been linked to poorer outcomes and decreased QoL (177). Most of the literature on pain and HNC indicates that younger patients experience higher levels of pain than older patients. Relevant studies are reported in Table 10. In summary, one prospective trial conducted using the PROMIS scale in a Veterans Administration Hospital population showed that at six months post-diagnosis, younger adults (64 years and younger) described significantly higher levels of pain and of pain intensity as compared to older adults (≥65). It is notable that this was a mixed population of cancer patients, with 40% having HNC (177).

Two retrospective papers show similar trends, with younger patients experiencing more pain. Interesting findings from these studies include that the incidence of pain among survivors was as high as 45.1% at a median of 6.3 years since treatment completion, and that pain was the third-most important issue identified by survivors, after swallowing and saliva. Additionally, patients with pain were significantly more likely to report issues with anxiey and mood (176). The findings also suggest that younger patinets may have more functional problems, including dysphagia and shoulder function (178).

This is an interesting observation with many possible confounders, and future research efforts may look to focus on understanding this association and strategies to help support younger patients affected by HNC.

Post-Traumatic Stress in Elderly HNC Patients

As with other factors influencing distress, the literature evaluating the relationship between PTSD and age in HNC patients is mixed, with some showing no difference in rates, and some showing higher incidence in younger patients (Table 10). There have been two similarly powered prospective studies, with contradictory findings regarding an asssociation between PTSD and age (183, 186). Cross-sectional studies, as well as one small prospective study of patient-partner dyads, have shown mixed results (182, 184, 185). In summary, the literature suggests either no association between age and PTSD, or a trend toward higher rates in younger patients.

Differences in Coping Styles

Coping refers to the ways in which people respond to and behave during stressful events, and it is likely to influence how one evaluates his or her quality of life (146). Research suggests older people adapt better to cancer because serious illness is more common and expected with increasing age and their experience of physical decline may be less dramatic. Younger people also often have more stage of life-related stressors like child-rearing and employment (146).

Pre- and post-treatment depression and anxiety have been linked to ineffective coping styles such as helplessness/hopelessness, fatalism, and avoidant coping (128). Some authors have noted that although depression and anxiety are more easily measured than coping styles, patient coping strategies may be more amenable to intervention (128). Notably, coping styles seem to vary quite predictably with age in samples of HNC patients (Table 11).

TABLE 11

Table 11 Studies reporting on coping styles.

One prospective study showed that older and younger patients use different coping and locus of control strategies, with younger patients using more active coping strategies and perceiving more internal control, and older patients tending to use religion. These differences in coping styles did not significantly impact QoL or depressive symptoms, but avoidant coping style was associated with worse depressive symptoms and QoL regardless of age group (146).

One retrospective study showed that younger age is significantly associated pretreatment anxiety and with negative coping styles such as helplessness, denial, venting, substance abuse, and behavioral disengagement (128). Another showed that older patients tended to use a “resigned” coping style (versus dependent or problem-focused). The dependent-coping pattern, which includes smoking, drinking, seeking support and engaging self-distraction, was found to be the most common style and was also the most likely to be associated with depression (189).

There are other studies, in contrast, that have shown no association between age and coping style, most notably, the Norweigan studies by Aarstad et al. (187, 188). Again, this area would benefit from further exploration.

Suicidality in Older Patients With HNSCC

At the extreme end of unrecognized or poorly managed psychosocial distress are self-inflicted injuries including suicide. Patients with any cancer diagnosis have been reported to have higher risks of suicide (191–193) or non-fatal self-injury (NFSI) compared to the general population, and patients with HNC may harbour even higher rates compared to most other types of cancer (191, 193–196). Other factors such as increasing age, social supports and a history of mental health have also been associated with an increased suicide risk (197).

Zaorsky et al. compared rates of suicide outcomes in cancer patients via the US-based SEER database from 1973 to 2014 (191). Compared to the general population, the relative risk of suicide was highest for those patients diagnosed with head and neck, lung, and testicular cancer, as well as Hodgkin lymphoma. The standardized mortality ratio (SMR) for HNC patients was highest in the first year after diagnosis and decreased with time from the initial diagnosis. Across the entire cancer cohort, elderly, white men with localized cancer who were not married were at highest risk. In a SEER study focusing primarily on patients with HNC (including thyroid), Kam et al. reported an adjusted (age, sex, race) suicide rate of 37.9 per 100 000 person-years, corresponding to a SMR of 3.21 (95% CI 2.18-4.23). Across all HNC subsites, older patients (60-79 years and >80 years) had the highest SMR. All of the HNC subsites, except for thyroid, had a higher risk of suicide than the general population, with those patients diagnosed with hypopharynx having the highest risk (SMR 13.91, 95% CI, 11.78-16.03). There was a decline in SMR over time for most of the subsites, though for all but thyroid and nasal cavity/sinuses, the risk exceeded that of the general population, while those with NPC had a persistently elevated and high risk even 15 to 30 years after their diagnosis.

In a Korean study, Choi et al. reported higher suicide risk amongst cancer patients older than 60 years of age compared to sampled population data (includes ~10% of the entire population (193). Similar to the Zaorsky et al. study, the risk of suicide was highest in the first year after any cancer diagnosis, accounting for 34.9% of all cases (median time to suicide was 1.74 years). For those patients diagnosed with a HNC, the adjusted hazard ratio was 2.28 (95% CI 1.47-3.54) which was amongst the highest risk for any cancer type.

Unmet Needs in Elderly Patients With HNSCC

Although various unmet needs tools are available for use in cancer populations, their content and structure is highly variable. Individual items and needs domains covered may range from physical and psychological needs to informational needs. Needs domains may also include, but are not limited to, nutritional, dental, financial, and sexual needs. Shunmugasundaram et al. recently conducted a systematic review comparing the content of self-reported unmet needs instruments in head and neck cancer populations, concluding that the PCI was the most comprehensive of the available tools, covering all twelve specified needs included in the conceptual framework of unmet needs developed by the research team (198). This is perhaps not surprising given it was the only unmet needs instrument which was developed specifically in a head and neck cancer population and has undergone continual refinement since its initial development. Studies of HNC patients including unmet needs tools are summarized in Table 12.

TABLE 12

Table 12 Studies reporting variations in unmet needs by age in HNC patients.

Almost all of these studies focused on patients who had emerged from the acute post-treatment period with exception of the Canadian study by Giuliani et al. which included patients from diagnosis through to survivorship and that by Chen which evaluated patients shortly after they had undergone surgery (206). The survivors included in many of these studies are quite heterogenous, as has been seen in many of the QoL and psychosocial distress reports with only the study by Chen et al. focusing on patients with oral cavity cancer (206). Despite variability in the instruments used, the available evidence suggests that older patients report fewer unmet needs than younger patients. In those studies which report a summed overall assessment of unmet needs, most have shown a lower burden in older patients (199, 202, 206) or no age-related differences at all (164, 200, 201, 205). For individual domains, older patients generally report less unmet needs, including in the sexuality domain (201, 206), or domains assessing psychological/emotional or spiritual needs (164, 203, 204, 207).

Novel Approaches

Biological Age

Recently, Xiao et al. reported associations between epigenetic age acceleration (EAA), survival and HRQL in HNC patients (22). EAA )describes discordance between the chronological age of an individual and their “epigenetic age”; EAA’s can be both positive, where the epigenetic age is greater than the patients’ chronological age, or more simply where aging has been accelerated, and negative where the reverse is seen, indicating a slower aging process. In this sample, they identified clinical variables associated with increased EAA, which was associated with worse survival outcomes. However, they also analyzed longitudinal variations in the FACT-H&N. Using a multivariable generalized estimating equation, and controlling for covariates, patients with a negative EAA had higher FACT-H&N total score over, indicating better QoL, than those with a positive EAA. The estimated score difference was 10.6 points (p<0.001), which is in excess of a commonly cited MCID (98). These are intriguing results, but how best to utilize these measures in clinical practice and how to incorporate them into complex treatment decision-making pathways and counselling will require additional research.

Comprehensive Geriatric Assessment

Across the oncology landscape, interest is increasing in the use of comprehensive geriatric assessments (CGAs) to aid clinical decision making in older individuals with cancer. The CGA has been defined as “a multidimensional, interdisciplinary diagnostic process focusing on determining an older person’s medical, psychosocial, and functional capabilities to develop a coordinated and integrated plan for treatment and long-term follow-up” (209, 210). The International Society of Geriatric Oncology have recommended a core set of domains to assess in a CGA, including functional status, fatigue, medical comorbidities, cognitive capacity and underlying mental health issues, social status and the anticipated degree of social support, nutritional status and the presence of any geriatric syndromes, which is a term encompassing many issues of the elderly including falls, delirium and dementia, osteoporosis and polypharmacy, amongst others (210). In HNC populations, the CGA may be more adept at uncovering impairments beyond that of the multi-disciplinary team; it has also been associated with the length of post-operative inpatient stays and the rates of surgical complications and successful completion of radiotherapy (211–214). Deficits in some of the CGA domains may predict more significant declines in global QoL (215) or other HRQL domains (214) after treatment in HNC patients. The implementation and use of CGA in routine clinical practice is, however, resource intensive and while a comprehensive assessment of every older patient being considered for curative-intent HNC treatment would no doubt lead to many opportunities for pre-treatment optimization, how best to incorporate a CGA into routine practice would need considerable resource and multi-disciplinary investment at a local or institutional level.

Limitations

This narrative review provides an overview of findings from studies investigating health and wellbeing outcomes and unmet needs in older and elderly patients with HNC and HNSCC and contrasts them to outcomes reported in younger HNC patients. Of the available studies, there are several limitations hampering the ability to draw firm conclusions. Most notably the data is hindered by a lack of consensus in defining the threshold for an older HNC patient. These studies which largely included patients treated with radical treatment also represent the outcomes for a biased population of robust older patients and their outcomes are likely not generalizable to all older patients with HNC, particularly those who may be more frail. It is also worth considering that these studies did not include detailed information about the treatments received, and whether older patients may have undergone reduced intensity treatment to accommodate their age, such as alterations in surgical fields, radiation volumes or chemotherapy dosing. The available studies also vary widely in the different PROs used, the methodologies used in their application and the statistical methods with which they have been analyzed and interpreted. Future studies and high-quality research will hopefully add to our understanding and avoid some of the aforementioned limitations. Well-defined secondary analyses from prospective phase II or III studies where older patients are included would be a welcome addition to the literature. In this review, where possible we have focused on those studies including only HNSCC, however, this was not always possible particularly with the lesser-studied psychosocial distress outcomes. However, despite their histological similarities, HNSCC encompasses a diverse range of tumors, including tumors with different etiology (HPV or smoking-related), primary sites and treatment, factors which may all impart different HRQL and psychosocial challenges for individual HNC patients. Interpretation outcomes from the various studies included in this review was frequently hampered by a reliance on statistical inferences rather than focusing on differences that would be clinically relevant, a theme which echoes throughout most of the PRO literature. Future studies of age-related changes would benefit from taking into account what is already known about changes over the life course in the general population. This would further our understanding of cancer- and treatment-related issues in younger and older patients. Future research exploring variations in age-related outcomes in HNC populations will need to focus on these challenges to draw more meaningful conclusions for our patients.

Conclusions and Future Directions

While there are many limitations to the available data this review should be reassuring when considering intensive treatment in the older HNC and HNSCC population. In synthesizing the varied health and wellbeing outcomes included in this report, when undergoing curative intent protocols, older patients have tended to demonstrate more resilience in HRQL and psychosocial outcomes when compared to their younger counterparts, with the caveat the older patients included in most of these studies were considered robust enough to treat with radical treatment. While refining optimal survivorship models will remain across the continuum of patients presenting with HNC, these findings suggests that we should be in fact more aware of the support that younger HNC patients may need across multiple HRQL and psychosocial distress domains following HNC treatment, despite their perceived physical robustness. Future research efforts in reporting age-related variations in HRQL, psychosocial distress and unmet needs will need to work towards harmonizing the definition of the older HNC patient, narrow the research question in more homogenous HNC populations and investigate novel approaches to measure biological rather than chronological age.

Author Contributions

LM and CH designed the concept of the submitted manuscript, were responsible for data acquisition and wrote the first draft. All authors (LM, CH, KG, and DR) were involved in the interpretation of the data included and in drafting and revising the first draft. All authors have provided approval for publication of the included content.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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