Relationship between demoralization and quality of life in end‐of‐life cancer patients

To examine the relationship between demoralization and health‐related quality of life (HRQoL) in a sample of end‐of‐life cancer patients with a life expectancy of 4 months or less undergoing palliative care, controlling for sociodemographic, clinical, and psychological variables.


| BACKGROUND
Although not being formally included among the psychiatric diagnoses, years of research have proven and continue to confirm the importance of the clinical concept of demoralization, which is characterized by feelings of hopelessness and helplessness due to loss of purpose and meaning in life. 1 As a possible manifestation of psychological and existential distress, demoralization implies a persistent inability to cope with a stressful situation, usually occurring in the context of troubling situations or circumstances, such as a chronic and/or progressive illness that affects the patient's integrity, life, and well-being. 2,3 The clinical manifestation of demoralization encompasses a spectrum of severity, ranging from an initial sense of disheartenment to a deeper sense of hopelessness and failure, to a strong sense of loss of meaning and purpose. 4 Demoralization has been observed in various clinical populations, with both physical and mental illnesses. 1,5,6 Although it is considered a treatable clinical condition and several therapies have been shown to be effective in reducing it, [6][7][8][9] it is often dismissed or unrecognized as an individual's understandable reaction to the circumstances of their medical condition. 1 However, because demoralization is associated with suicidal ideation and the desire to hasten death, 5,10,11 it is important to address this syndrome and its impact on patient wellbeing and quality of life (QoL). Despite their consistent comorbidity and to properly target treatment interventions, [11][12][13] it is also important to distinguish depression from demoralization, which involves a loss of hope and meaning, with a loss of anticipatory pleasure rather than general anhedonia. 1,2 Most studies have focused on demoralization in oncology and palliative care settings. 6 A recent literature review revealed a mean pooled prevalence of 35.8% severe demoralization in cancer patients, 6 ranging from 16% to 57.6%. The wide variability in prevalence can be explained by many factors, such as worsening clinical condition and increase in physical discomfort and loss of functioning in the last weeks of life, 14 palliative treatment, 15 high level of psychological distress, 13 or desire for death. 4 Several studies have highlighted that demoralization is associated with the number and type of physical symptoms such as fatigue, limited mobility and activity, respiratory problems, constipation, memory or concentration problems, and pain. 6,10,16,17 Inconsistent associations between sociodemographic factors and demoralization have been identified, 6,10 while consistent data seem to suggest that demoralized cancer patients have low levels of QoL. 18,19 Quality of life is a central concept of palliative care, which aims not only at pain management, but also at the best possible physical, psychological, social and spiritual well-being of terminally ill patients and their families. 20 However, no studies deepen our understanding of the relationship between demoralization and QoL in cancer patients at the end-of-life, that is, patients with few weeks of life expectancy, which have unique characteristics. 14,21 Thus, the main objective of the present study was to examine the relationship between demoralization and QoL in a sample of end-oflife cancer patients with a life expectancy of 4 months or less undergoing palliative care. Following our previous work on this specific population, which investigated the prevalence of demoralization and its associations with different medical and psychosocial variables, 14 in the present study we specifically aimed to assess the independent effect of demoralization on patients' health-related quality of life (HRQoL), controlling for clinical (such as functional status, physical symptoms, or prognosis awareness) and psychological (i.e., depressive symptoms, spiritual well-being) variables.

| METHODS AND MATERIALS
Participants in this study were recruited in the Palliative Care and Medical Oncology departments of the "Cittàdella Salute e della Scienza" Hospital and the "V. Valletta" Hospice of Turin. Hospitalized patients diagnosed with cancer and meeting national criteria for access to palliative care were assessed as potential candidates. According to Piedmont regional legislative Decree n. Palliative care physicians recorded sociodemographic and clinical data and assessed whether or not the patient was aware of the diagnosis and/or prognosis during a clinical interview with patients and caregivers. A score of 0 was assigned if the patient did not know or overestimated the prognosis, whereas a score of 1 was assigned if he/she knew the prognosis. During the psychosocial assessment, which was conducted at the bedside, the psychologist reassessed the patient's prognosis awareness. Patients were asked to read and complete a test battery, and they were encouraged to ask questions if in doubt. To avoid overwhelming the patients, the assessment was based on the patients' rhythm and needs.
A total of 245 patients were identified as possible candidates: 32 patients did not want to take part in the study, due to lack of motivation or to their physical or emotional state; 8 did not meet

| MEASURES
The Edmonton Symptom Assessment System (ESAS) 23 is a selfadministered scale, developed to assess the presence and intensity of nine palliative care patients' symptoms (pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, lack of well-being, and shortness of breath) on an 11-point Likert scale, ranging from zero (no symptom) to 10 (worst possible symptom).
The Italian version of the Patient Health Questionnaire-9 (PHQ-9), a reliable tool with good psychometric properties, was used to assess the severity of depressive symptoms during the last 2 weeks 24 The Functional Assessment of Cancer Therapy Scale -General Measure (FACT-G) is a 27-item scale divided into four QoL domains: physical well-being, social/family well-being, emotional well-being, and functional well-being (FWB). Patients provide responses on a 5point scale ranging from 0 (not at all) to 4 (very much). The total FACT-G score is the sum of the scores for the four subscales: higher scores indicate higher HRQoL. 25 The Functional Assessment of Chronic Illness Therapy -Spiritual Well-Being (FACIT-Sp-12) is a 12-item scale that includes 3 spirituality factors (Meaning, Comfort and Faith) and is widely used in cancer setting. 26 Higher scores indicate better spiritual wellbeing.
The Demoralization Scale -Italian Version (DS-IT) is a self-report scale. 27

| Sociodemographic and clinical characteristics
The end-of-life cancer patients had an average age of approximately 69 years (Table 1). Two-thirds of the sample were male, and most patients had a middle or primary school degree. Regarding cancer-related variables, the average KPS score was around 40, 75% of patients had metastatic cancer, and the most common cancers were lung, hepaticpancreatic, colon-rectal and kidney cancer ( Table 1). The average life expectancy was about 27 days, ranging from <24 h to 120 days.
The demoralization data showed that more than 51% and 14% of the sample had severe or moderate demoralization, respectively, highlighting "Disheartenment" and "Sense of failure" as the most critical DS-IT domains ( Table 2).

| Demoralization associations with sociodemographic, clinical and psychological characteristics
t-test comparisons showed that there were no statistically significant differences in DS-IT scores between male and female (37.7 (13.8) versus 35.4 (13.9), respectively; p = 0.300); married/cohabiting patients and patients who were single, divorced, or widowed (36.3

| Regression analyses
Hierarchical multiple regression analysis was performed to investigate whether demoralization is a significant predictor of HRQoL (FACT-G) in end-of-life cancer patients. Age, gender, cancer stage, and prognosis awareness did not show a significant correlation with the FACT-G total score and were therefore not included in the regression analysis (see Table 3). The KPS, ESAS, and PHQ-9 scores were entered into the first regression block, the DS-IT subscales scores into the second block, and the FACIT-Sp12 total score into the third block. The result of the regression analysis is shown in Table 4. Demoralization and, in particular, the dimensions "Disheartenment" and "Sense of failure"

| DISCUSSION
This study aimed to assess the independent effect of demoralization on HRQoL in a sample of end-of-life cancer patients, also examining its relationship with various sociodemographic, clinical, and psychological variables. As previous studies have shown, end-of-life cancer patients, that is, patients in the very last stage of advanced cancer with a life expectancy of 4 months or less, have unique characteristics. 14,21 Recognizing the role that demoralization plays in affecting QoL of patients in their last days of life is of paramount importance to identify preventive or targeted therapeutic interventions.
Our results suggest a very high prevalence of demoralization (66.5% including moderate-to-severe demoralization), which is higher than that found among terminal cancer patients in Portugal (52.5%), 13 and in advanced-stage cancer patients in Taiwan (27.55%) 17 and Germany (39.1%), 12   Patients closer to death often face limited lifespan, increasing physical symptoms, and increasing psychological distress, which could heighten demoralization and decrease well-being. 23,34 QoL is a global measure of well-being and has been associated with the desire for a hastened death in end-of-life patients. 33,[35][36][37] Not only was demoralization associated with patients' HRQoL, but regression analysis showed that demoralization, and specifically the

| Study limitations
This study has some limitations. Because of the cross-sectional methodology, measuring variables in a single cohort period, the study is essentially descriptive in nature, allowing inferences to be drawn but not truly verifying whether terminally ill patients experience changes in the dimensions of HRQoL and demoralization as they approach death. As recently reported, 39

| Relationship between demoralization and quality of life in end-of-life cancer patientsClinical implications
The strength of this study is that it is one of the few studies to examine possible associations between demoralization and QoL in dying cancer patients, thus expanding knowledge of the mechanisms underlying the relationship between physical suffering and psychological outcome in terminal cancer patients. The findings underscore the need for the health care system to adequately assess demoralization in terminal cancer patients, not only because of its high prevalence, but especially because it independently affects multiple aspects of patients' HRQoL, including mental and physical health, even controlling for physical and psychological problems.
Physical problems could play a central role in the process of demoralization by affecting the sense of mastery and competence at the end of life. On the one hand, this result highlights the great need to adequately treat physical symptoms in terminal cancer patients, as their significant impact on psychological well-being is amplified. On the other hand, the strong association between demoralization and physical problems should encourage healthcare providers to assess the presence of demoralization in terminally ill patients who are close to death and have only a few weeks to live and who face difficult physical symptoms, to recognize their existential suffering and promote clinical approaches to optimize their QoL.

ACKNOWLEDGEMENT
Open Access Funding provided by Universita degli Studi di Torino within the CRUI-CARE Agreement.