1. INTRODUCTION

Lung cancer (LC) remains the world’s leading cause of cancer-related mortality. According to the Lung Cancer Statistics Report, there were 228 150 new cases of LC and 142 670 LC-related deaths in the United States in 2019.1 In Taiwan, LC ranks the second highest incidence in all cancers, with 39.8 cases of newly diagnosed LC per 100 000 persons in 2018.2 In addition to the high incidence rate, LC was also the most common cancer-related deaths in Taiwan, with a mortality rate of 40.8 per 100 000 persons in 2020.2

Patients diagnosed with LC experience various discomforting symptoms. Many of these symptoms begin before diagnosis and continue throughout the illness and its treatment, negatively affecting patients’ health-related quality of life (HRQOL).3 HRQOL is generally accepted as a multidimensional concept that assesses how diseases and treatments affect a patient’s sense of overall well-being. It includes domains related to physical, mental, emotional, social functioning, and supportive environments.4,5 In addition, HRQOL has been considered one of the most important prognostic factors for LC survivors.6–11

The HRQOL of newly diagnosed LC patients was reported to be lower than that of other cancer patients.12 In recent years, some studies indicated that multiple factors were associated with HRQOL among patients with LC.13 These factors include demographic factors (age, gender, educational level, and smoking status), disease factors (cancer stage, treatment, and performance status),14–16 symptom burden (SB; symptom severity and interference),17–20 psychological distress (depression and anxiety),21,22 physical activity,23,24 and sleep quality.25,26 Compared to the quantity of available literature on the HRQOL of patients diagnosed with other major cancers, few studies have explored the HRQOL and its related factors among newly diagnosed LC patients before treatment. Hence, this study aimed to examine the relationships between the SB, physical activity (PA), sleep quality (SQ), and HRQOL among newly diagnosed LC patients.

2. METHODS 2. 1. Study participants

This study is a cross-sectional design using convenience sampling. A total of 250 newly diagnosed LC patients were included between June 2015 and May 2017 at a medical center in northern Taiwan. The inclusion criteria were (1) ≥ 20 years of age; (2) diagnosed with LC for the first time (International Classification Diseases, 10th revision code, ICD-10: C34.0); and (3) has alert consciousness, can communicate, and is willing to participate. Patients diagnosed with secondary LC were excluded. All participants provided informed consent before participating in the study and were assessed on their diagnoses before receiving therapy. Further, this study was approved by the Institutional Review Board (IRB) of Taipei Veterans General Hospital (IRB no. 2015-05-005AC).

2. 2. Measures

Participants were asked to complete a structured questionnaire comprised of demographics and disease characteristics, SB, PA, SQ, and HRQOL. The demographic and disease data included age, gender, educational level, body mass index (BMI), family income, smoking status, comorbidity, and cancer type, stage, and treatment. The Eastern Cooperative Oncology Group performance status (ECOG PS) scale assessed patients’ self-care function with 5 points score (0–4).16 The data were recorded in the medical chart by the patients’ oncologists. ECOG PS was classified as either good (scores of 0–1) or poor (scores of 2–4) performance; a higher score indicates poorer functioning level.27

SB was measured using the symptom severity and symptom interference subscales with the Taiwanese version of the MD Anderson symptom inventory (MDASI-T).28 The symptom severity subscale covers the 13 cancer-related symptom items: pain, fatigue, sleep disturbance, distress, shortness of breath, difficulty remembering, drowsiness, dry mouth, sadness, poor appetite, nausea, vomiting, and numbness. The symptom interference subscale consists of 6 items that address the level of interference from symptoms, including general activity, walking, normal work, mood, relationships with others, and enjoyment of life.29,30 Each item is rated on an 11-point Likert scale from 0 (not present) to 10 (as bad as you can imagine). MDASI-T was validated among 556 patients with multiple cancer diagnoses in Taiwan, with a Cronbach’s α of 0.89 and 0.94 for symptom severity and interference items, respectively.28 Meanwhile, the Cronbach’s α of this study was 0.87 and 0.91 for symptom severity and interference items, respectively. The content validity index (CVI) scores judged by 3 experts were 1.0.

SQ was measured by the Taiwanese version of the Pittsburgh Sleep Quality Index (PSQI-T).31 The instrument comprises 19 items with 7 component scores. The component scores yield a PSQI global score (0–21); a higher PSQI global score indicates poorer sleep quality, and the global score >5 is used to differentiate poor from good sleepers.32 The PSQI-T was well validated among 205 patients with various cancer diagnoses in Taiwan, with a Cronbach’s α of 0.79.33 On the other hand, the Cronbach’s α for the PSQI-T of this study was 0.80. The CVI scores judged by 3 experts were 1.0.

The PA level was determined by the Taiwan version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF).34 The tool has been validated as an efficient method for assessing PA among Taiwanese LC patients.35–37 IPAQ-SF assesses 3 types of activity, including walking, moderate, and vigorous intensity activities, at least 7 d/wk. The 3 types of activity were computed by their energy requirements (walking = 3.3 METs, moderate PA = 4.0 METs, and vigorous PA = 8.0 METs) to yield a total PA score in metabolic equivalent of task-minutes per week (MET-min/wk). Three PA groups proposed to classify participants: low PA (LPA; total PA <600 MET-min/wk), moderate PA (MPA) (total PA ≥600 MET-min/wk), and high PA (HPA) (total PA ≥3000 MET-min/wk).38

The HRQOL in this study was measured using the Taiwan version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. Among the 28 items, the first 2 general facet items evaluated the overall QOL (G1) and general health status (G2) based on a 1–5 scale, with higher scores indicating better G1 and G2. In addition to the 2 general items, the other 26 items were distributed into 4 domains: physical, psychological, social, and environmental. Two scorings (4–20 and 0–100; a higher score indicates better QOL) can be transformed into each domain score; the 0–100 scoring was used in this study. The Cronbach’s α ranged from 0.70 to 0.77 for the 4 domains,39 and the content validity coefficients were between 0.53 and 0.78 for item-domain correlations and 0.51 and 0.64 for inter-domain correlations.39,40 Lin et al41 showed that the WHOQOL-BREF has good construct validity, allowing clinicians to evaluate how LC survivors assess their sense of well-being. The analysis of the newly diagnosed LC patients in this study reported that Cronbach’s α was 0.87, 0.81, 0.74, and 0.83 in the physical, psychological, social, and environmental domains, respectively.

The validity of IPAQ-SF and WHOQOL-BREF was not assessed in this study because the copyright holders did not allow any change to the instrument. Nevertheless, all questionnaires were approved for use in this study.

2. 3. Data analysis

The SPSS v24.0 (IBM Co., Armonk, NY) software was used for the statistical analysis in this study. Categorical and continuous variables were demonstrated by numbers with percentages and means with standard deviation, respectively. A univariate analysis was performed for each QOL domain, with G1 and G2 scores as the dependent variables and demographics, disease characteristics, SB (severity and interference composite score), groups of PA, and the PSQI global score as independent variables. Further, a multivariate stepwise linear regression analysis was used to assess the association among the significant factors in the univariate analysis and each dependent variable under adjustment for potentially confounding variables. The variance inflation factor (VIF) was used to detect multicollinearity in regression analysis, in which a p value of less than 0.05 was considered statistically significant.

3. RESULTS

A total of 250 patients (aged 35–88 years, 51.2% male, 94.0% non–small-cell LC, 56.4% stage IIIB–IV) were included in this study. The demographics and disease characteristics are listed in Table 1.

Table 1 - Distributions of demographics and disease characteristics of the participants (N = 250) Variable n (%) Mean (SD) Age (y) 61.04 (10.63) Gender  Female 122 (48.8)  Male 128 (51.2) Educational level  Below high school 49 (19.6)  Bachelor degree 110 (44.0)  Above master 91 (63.4) Religious beliefs  No 69 (27.6)  Yes 181 (72.4) Married  No 56 (22.4)  Yes 194 (77.6) Family income (NTD)  <20 000 39 (15.6)  20 000–49 999 78 (31.2)  50 000–99 999 74 (29.6)  ≥100 000 59 (23.6) BMI (kg/m2)  <18.5 11 (4.4)  18.5–23.9 128 (51.2)  24–26.9 69 (27.6)  ≥27 42 (16.8) Smoking status  Never 132 (52.8)  Past 62 (24.8)  Current 56 (22.4) Comorbidity  No 113 (45.2)  Yes 137 (54.8) Lung cancer type  SCLC 15 (6.0)  NSCLC 235 (94.0) Lung cancer stages  Stage I–IIIA 109 (43.6)  Stage IIIB–IV 141 (56.4) First-line treatment  Surgery 96 (38.4)  Medical 154 (61.6) ECOG PS scores  0–1 214 (85.6)  2–4 36 (14.4)

Comorbidity indicated CCI score >1.

BMI = body mass index (<18.5: underweight; 18.5–23.9: normal weight; 24–26.9: overweight; ≥27: obesity); CCI = Charlson Comorbidity Index; ECOG PS = Eastern Cooperative Oncology Group performance status; NSCLC = non–small-cell lung cancer; SCLC = small cell lung cancer; SD = standard deviation.

The top three prevalent symptoms among newly diagnosed LC patients were disturbed sleep, fatigue, and dry months; the mean severity scores of the three symptoms ranged from 2.14 to 3.24. In addition, the top three prevalent interferences from symptoms were mood, enjoyment of life, and working; the mean scores of the three interferences ranged from 2.63 to 2.72. The details of the prevalence are presented in Figure 1. The mean symptom severity and interference scores were 1.72 ± 1.47 and 2.26 ± 2.43, respectively. Approximately half of the patients were classified as the LPA group. The mean PSQI global score (7.85 ± 4.67; 62.4%) of the newly diagnosed lung cancer patients showed poorer sleep quality (PSQI global score >5). On average, the newly diagnosed LC patients reported moderate levels of HRQOL. Among the four QOL domains of the newly diagnosed LC patients, the social domain scored the highest, with a mean score of 68.26 ± 15.14, while the psychological domain scored the lowest, with a mean score of 59.14 ± 16.19. The mean G1 and G2 scores were 3.10 ± 0.93 and 2.58 ± 0.98, respectively. The distributions of SB scores, physical activity groups, PSQI global scores, and HRQOL scores are presented in Table 2.

Fig. 1:

The prevalence of symptoms and their interference in patients with newly diagnosed lung cancer.

Table 2 - Distributions of symptom burden scores, physical activity groups, PSQI global scores, and HRQOL scores (N = 250) Variable n (%) Mean (SD) Symptom burden scores  Symptom severity 1.72 (1.47)  Symptom interference 2.26 (2.43) PA groups  LPA 121 (48.4)  MPA 98 (39.2)  HPA 31 (12.4) PSQI global scores 7.85 (4.67) HRQOL scores  Physical domain 59.40 (18.92)  Psychological domain 59.14 (16.19)  Social domain 68.26 (15.41)  Environmental domain 62.72 (14.59)  Overall QOL (G1) 3.10 (0.93)  General health status (G2) 2.58 (0.98)

HPA = high physical activity; HRQOL = health-related quality of life; LPA = low physical activity; MPA = moderate physical activity; PA = physical activity; PSQI = Pittsburgh sleep quality index; QOL = quality of life.

The detailed univariate analysis is presented in Table 3. Notably, there was a positive correlation between age and the environmental QOL score (β = 0.224, p = 0.01), and women had significantly better QOL than men in the social domain (p < 0.001). Significant differences between educational levels (p < 0.05) were reported in physical, psychological, and environmental QOL and G1 and G2. The physical QOL of underweight patients (BMI < 18.5 kg/m2) was worse than others (p < 0.05). Low family income and advanced-stage cancer were significantly associated with a lower QOL score in the four domains (p < 0.05). Smoking status was significantly associated with physical, social, and environmental QOL and G1 and G2. Higher ECOG PS scores were significantly correlated with lower QOL in the physical, psychological, and environmental domains (p < 0.01). However, married status, religion, and comorbidity did not significantly correlate with any QOL domains (p > 0.05). The scores of symptom burden (including symptom severity and interference) and global PSQI had significantly negative correlations with the two general facet items (G1 and G2) and the four QOL domains (all p < 0.001). The scores of G1, G2, and the four QOL domains in both HPA and MPA groups were significantly higher than in the LPA group (p < 0.01).

Table 3 - Univariate analysis of the HRQOL and its related factors (N = 250) Variables HRQOL scores Physical Psychological Social Environmental G1 G2 β β β β β β Age −0.014 0.056 0.072 0.224a 0.009 0.008 Gender (male/female) −3.181 −0.711 −6.936b −2.492 −0.077 −0.204 Age −0.014 0.056 0.072 0.224a 0.009 0.008 Educational level  Bachelor degree/below high school −6.948a −6.549a −3.566 −7.604c −0.327a −0.350a  Above master/below high school −4.082 −3.484 −0.077 −5.414a −0.003 −0.181 Religious beliefs (yes/no) −0.954 0.028 0.579 1.200 −0.022 −0.085 Married (yes/no) 2.213 1.441 0.795 2.271 0.014 −0.155 Family income  20 000–49 999/<20 000 1.359 5.449 3.372 2.359 −0.026 −0.179  50 000–99 999/<20 000 8.653a 7.581a 4.287 4.960 0.082 −0.009  ≥100 000/<20 000 11.953c 8.201a 8.000a 11.654b 0.246 0.190 BMI  18.5–23.9/<18.5 14.342a 6.872 5.939 4.690 0.229 0.464  24–26.9/<18.5 3.638c 8.700 8.179 4.141 0.399 0.648a  ≥27/<18.5 1.346a 7.781 2.478 6.481 0.325 0.409 Smoking status  Past/never −5.986a −0.837 −7.657c −2.124 −0.162 −0.267  Current/never −8.752c −3.641 −8.489b −7.065c −0.457a −0.413c Comorbidity (yes/no) −3.767 −1.819 −0.963 −0.391 −0.011 −0.192 Cancer type (NSCLC/SCLC) 8.152 10.428 9.567a 9.068a 0.319 0.613a Cancer stages (IIIB–IV/I–IIIA) −13.206b −4.460a −6.062c −6.492b −0.229 −0.443b ECOG PS scores (2–4/0–1) −20.225b −7.071c −5.139 −9.380b 0.636 −0.316 Symptom burden scores  Symptom severity −8.162b −5.037b −3.895b −3.795b −0.277b −0.308b  Symptom interference −5.171b −2.859b −2.450b −2.249b −0.188b −0.189b PA groups  Moderate/low PA 11.761b 6.059c 6.395c 7.727b 0.461b 0.455c  High/low PA 12.802b 11.136c 7.941c 7.271a 0.681b 0.540c PSQI global scores −2.047b −1.313b −0.853b −0.956b −0.077b −0.067b

β = unstandardized coefficients; BMI = body mass index (<18.5: underweight, 18.5–23.9: normal weight, 24–26.9: overweight, ≥ 27: obesity); ECOG PS = Eastern Cooperative Oncology Group performance status; G1 = overall quality of life; G2 = general health status; HRQOL = health-related quality of life; NSCLC = non–small-cell lung cancer; PA = physical activity; PSQI = Pittsburgh sleep quality index; SCLC = small-cell lung cancer.

ap < 0.05.

bp < 0.001.

cp < 0.01.

A multivariate stepwise linear regression was used to determine the predictors of the physical, psychological, social, and environmental domains of QOL, as well as overall QOL. The VIF for all variables was below 5, indicating the absence of a multicollinearity problem. Further, this study found that gender, age, family income, smoking status, cancer stage, ECOG PS scores, PA, symptom severity, symptom interference, and PSQI global scores predicted the HRQOL of newly diagnosed LC patients. Different combinations of the predictors accounted for 57.5%, 26.9%, 21.7%, 22.4%, and 30.7% of the physical, psychological, social, environmental, and overall QOL, respectively. The PSQI global score was a significant predictor in the overall QOL and all QOL domains, except for the environmental domain; however, it explained less variance in any regression model. SB (including symptom severity and interference) was the most robust factor for predicting HRQOL among newly diagnosed LC patients. Symptom severity was the dominant predictor affecting the psychological and environmental QOL, accounting for 23.2% and 14.6% of the variance, respectively. Symptom interference was the dominant predictor affecting the physical, social, and overall QOL, accounting for 44.4%, 15.0%, and 24.1% of the variance, respectively (Table 4).

Table 4 - Multiivariate analysis of the HRQOL and its related factors (N = 250) Variables HRQOL scores Physical Psychological Social Environmental Overall QOL (G1) R 2 = 0.575 R 2 = 0.269 R 2 = 0.217 R 2 = 0.224 R 2 = 0.307 β R 2 β R 2 β R 2 β R 2 β R 2 Age 0.242a 0.031 Gender (male/female) −7.283a 0.046 Family inc