Abstract
[Purpose] Rehabilitation can improve physical function and quality of life in patients with advanced cancer. However, relevant studies on advanced lung cancers are limited. Differences in physical function and symptoms based on the treatment phase should be considered. This study investigated the relationship between physical function and quality of life during the treatment phase in patients with advanced lung cancer. [Participants and Methods] Patients with stage IV non-small-cell lung cancer and postoperative recurrence who were hospitalized between May 2018 and October 2021 were selected. Data, including age, histological type of lung cancer, treatment details, functional independence measures, and European Organization for Research and Treatment of Cancer QLQ-C30, were collected from medical records. Patients were categorized into groups based on the treatment phase: the initial, subsequent, and best supportive care (BSC) groups comprised patients admitted for initial treatment, receiving second or subsequent treatments, and receiving best supportive care, respectively. The relationship between physical function and quality of life during each treatment phase was examined. [Results] Physical function in the subsequent group was associated with physical functioning, role functioning, cognitive functioning, social functioning, and fatigue. Meanwhile, the BSC group had fewer associated items than the other groups. [Conclusion] Rehabilitation during the ongoing treatment phase improves physical function and quality of life.
Keywords: Physical function, Quality of life, Advanced lung cancer
INTRODUCTION
In recent years, the proportion of cancer-related deaths has increased owing to rapid medical advancements and changes in social conditions. Among various types of cancer, lung cancer has caused the highest number of cancer-related deaths in Japan1). Lung cancer is difficult to detect at an early stage and is often already at an advanced stage at diagnosis, making it ineligible for surgical resection. The 5 year relative survival rate for stage IV lung cancer is 7.4%, indicating a prognosis poorer than that of other types of cancer2).
Meanwhile, medical technologies for cancer treatment, including lung cancer, have remarkably advanced. In particular, in chemotherapy for advanced lung cancer, in addition to conventional cytotoxic agents, molecular-targeted therapies and immune checkpoint inhibitors have been added to treatment regimens, leading to the development of more effective treatment options with improved survival rates. With the progress in chemotherapy, the survival period has been extended, and treatments and care focused on improving quality of life (QOL) of patients have attracted increasing interest.
Lung cancer has been reported to negatively affect QOL owing to both the effects of the cancer itself and the adverse events associated with treatment. In advanced cases, cancer-related symptoms such as dyspnea, fatigue, loss of appetite, and pain contribute to decreased QOL3, 4). Additionally, treatment-related decreases in skeletal muscle mass, strength, and endurance have been reported5, 6). The reduction in physical activity not only affects activities of daily living (ADL) but also strongly impacts QOL7). In advanced lung cancer cases, multiple complications often occur, including chronic respiratory diseases and metastases to the brain and bone. Therefore, reducing the factors that decrease the QOL in these patients is challenging.
Guidelines published in 2019 state that rehabilitation for patients with advanced cancer can improve physical function and ADL; reduce fatigue, anxiety, and depression; and improve QOL8). However, most studies have focused on breast cancer, prostate cancer, and hematological malignancies, with only a few specifically targeting advanced lung cancers. Moreover, no consensus on the effectiveness of rehabilitation for advanced lung cancer has been reported in previous studies9), and differences in physical function and symptoms depending on the timing of treatment, such as initial- or subsequent treatment, need to be considered. No studies have investigated the relationship between evaluation indicators used by physical therapists, such as muscle strength, walking ability, exercise tolerance, and QOL. Clarifying this relationship is necessary to demonstrate the effectiveness of rehabilitation in patients with advanced lung cancer.
Therefore, this study aimed to investigate the relationship between physical function and QOL in patients with advanced lung cancer according to the timing of treatment, and to contribute to future rehabilitation efforts.
PARTICIPANTS AND METHODS
This study included patients with stage IV lung cancer and postoperative recurrence who were admitted to the Respiratory Medicine Department of Asahikawa Medical University Hospital between May 2018 and October 2021, received a treatment plan, and were prescribed rehabilitation. Patients with severe cognitive impairment, consciousness disorders, or communication difficulties were excluded. This study was conducted in accordance with the tenets of the Declaration of Helsinki. This study was approved by the Ethics Committee of Asahikawa Medical University (approval no. 19073). The research content and ability to withdraw consent at any time without disadvantage are clearly stated on the Asahikawa Medical University Hospital website.
The survey items included age; gender; body mass index; serum albumin; Geriatric Nutritional Risk Index; smoking history; presence of cohabiting family members; disease stage (stage IV or recurrence); histological type of lung cancer (adenocarcinoma, squamous cell carcinoma, or other); presence of metastasis (bone, brain, liver, other, unknown); medical history (cardiovascular disease, chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes, and cancer); and treatment details (chemotherapy, chemo-immunotherapy, immunotherapy, molecular targeted therapy, chemo-immuno-molecular targeted therapy, chemo-molecular targeted therapy, and best supportive care [BSC]). Patients were grouped according to the timing of treatment, with those hospitalized for initial treatment categorized as the “initial group”, patients undergoing second or subsequent treatments categorized as the “subsequent group”, and patients receiving BSC categorized as the “BSC group”. Data on length of hospital stay, number of days until the start of physical therapy, number of days of physical therapy, and outcomes (discharge, transfer to another hospital, and death) were collected from medical records. Physical function and ADL were evaluated by physical therapists, and QOL was assessed using a questionnaire completed by the patients. The evaluations were conducted in 2 days, starting from the day of initiation of physical therapy.
Grip strength was measured using a Takei Digital Grip D dynamometer. Two measurements were obtained for each hand, and the maximum value was used. Comfortable walking speed at 10 m was measured. Exercise tolerance was measured according to the procedure in the 6-minute walking distance (6-MWD) test manual10). Participants were fully informed of the purpose and procedures of the test. They walked along a corridor in the hospital, with distance markers placed every 5 m, and the maximum walking distance in 6 min was measured. The modified Borg scale was used to assess breathlessness and leg fatigue, and the pulse rate and peripheral oxygen saturation were measured using a pulse oximeter before and after walking. During the test, the remaining time was reported, and verbal encouragement was provided every minute. We used the Japanese version of the Functional Independence Measure (FIM[TM]) version 3.011, 12). The FIM consists of 13 motor items and 5 cognitive items that serve as indicators of ADL. Each item was evaluated on a 7-point scale. In this study, the sum of the scores for the motor and cognitive items and the total score (FIM-total) were calculated. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QLQ-C30) (version 3) was used. QLQ-C30 is a widely used 30-item questionnaire. The Japanese version of the QLQ-C30, which has demonstrated reliability and validity, was used in this study13). The 30 items were reclassified into the following scales: global health status (QL), physical functioning (PF), role functioning (RF), emotional functioning, cognitive functioning (CF), and social functioning (SF). Scales for symptom assessment include fatigue (FA), nausea and vomiting, pain (PA), dyspnea (DY), insomnia, appetite loss, constipation (CO), diarrhea (DI), and an economic impact scale (FI). Higher scores on the QL and functioning scales indicate better QOL, whereas higher scores on the symptom scales and FI indicate greater impairment in QOL. The Cancer Fatigue Scale (CFS) was used to assess fatigue. The CFS comprises physical, mental, and cognitive subscales. Higher scores indicate higher levels of fatigue. The maximum physical, mental, cognitive, and fatigue scores were 28, 16, 16, and 60, respectively. The cut-off value was 1914). The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression symptoms. The HADS consists of 7 items each for depression (HADS-D) and anxiety (HADS-A), resulting in a total of 14 items (HADS-T). Higher scores indicate more severe anxiety and depression symptoms. The cut-off scores were set at 11 for the total score and 8 for the anxiety and depression subscales15).
Categorical variables are reported as frequencies and percentages. For quantitative variables, normality was tested using the Shapiro–Wilk test, and they are described as means and standard deviations or medians and interquartile ranges accordingly. Physical function was compared to that reported in previous studies and standard values. Grip strength and 6-MWD were compared with the average values for individuals aged 65–69 years from the 2022 Report on Physical Fitness and Exercise Capacity16). The 10-meter comfortable walking speed was compared with the criteria set by the Asian Working Group for Sarcopenia (AWGS)17). To evaluate the CFS and HADS scores, the number of participants with scores above the cut-off values was counted.
Groups were compared using a one-way analysis of variance for normally distributed variables and the Kruskal–Wallis test for non-normally distributed variables, with post-hoc multiple comparisons to examine differences between groups. The relationship between physical function and QOL for each treatment period was examined using Pearson’s or Spearman’s rank correlation analyses. Statistical analysis was performed using IBM SPSS Statistics 22, with a significance level set at 5%.
RESULTS
Table 1 shows the characteristics of the patients and their treatment. In this study, the initial treatment, subsequent treatment, and BSC groups included 45 (mean age 67.0 ± 8.4 years), 21 (mean age 65.8 ± 6.9 years), and 15 (mean age 70.8 ± 9.4 years) patients, respectively. Adenocarcinomas account for the most common histological type of lung cancer. The types of treatment vary, with a combination of chemotherapy and immunotherapy being the most common, along with molecular-targeted therapies.
Table 1. Characteristics of patients and treatments.
| Initial group | Subsequent group | BSC group | |
| (n=45) | (n=21) | (n=15) | |
| Age, years | 67.0 ± 8.4 | 65.8 ± 6.9 | 70.8 ± 9.4 |
| Sex, Male | 27 (60.0) | 13 (61.9) | 13 (86.7) |
| Body Mass Index, kg/m2 | 23.1 ± 2.8 | 21.4 ± 4.8 | 19.3 ± 3.7 |
| Alb, g/dL | 3.6 [1.8–4.7] | 3.0 [1.6–4.1] | 2.8 [1.9–3.5] |
| Geriatric Nutritional Risk Index | 96.3 ± 11.7 | 84.3 ± 14.6 | 74.8 ± 16.2 |
| Smoking history, yes | 16.0 (35.6) | 12.0 (57.1) | 7.0 (46.7) |
| Presence of cohabiting family members, yes | 39.0 (86.7) | 20.0 (95.2) | 14.0 (93.3) |
| Stage | |||
| Ⅳ | 38 (84.4) | 17 (81.0) | 11 (73.3) |
| Recurrence | 7 (15.6) | 4 (19.0) | 4 (26.7) |
| Histological type | |||
| Adenocarcinoma | 30 (66.7) | 15 (71.4) | 9 (60.0) |
| Squamous cell carcinoma | 11 (24.4) | 3 (14.3) | 3 (20.0) |
| Other | 4 (8.9) | 3 (14.3) | 3 (20.0) |
| Presence of metastasis | |||
| Bone | 22 (48.9) | 15 (71.4) | 8 (53.3) |
| Brain | 12 (26.7) | 8 (38.1) | 6 (40.0) |
| Liver | 2 (4.4) | 3 (14.3) | 1 (6.7) |
| Other | 8 (17.8) | 4 (19.0) | 2 (13.3) |
| Unknown | 10 (22.2) | 2 (9.5) | 3 (20.0) |
| Medical history | |||
| Cardiovascular disease | 8 (17.8) | 3 (14.3) | 4 (26.7) |
| Chronic obstructive pulmonary disease | 8 (17.8) | 5 (23.8) | 6 (40.0) |
| Hypertension | 11 (24.4) | 6 (28.6) | 2 (13.3) |
| Dyslipidemia | 3 (6.7) | 1 (4.8) | 2 (13.3) |
| Diabetes melitus | 9 (20.0) | 4 (19.0) | 4 (26.7) |
| Cancer | 4 (8.9) | 5 (23.8) | 3 (20.0) |
| Treatment details | |||
| Chemotherapy | 15 (33.3) | 8 (38.1) | 0 (0.0) |
| Chemo-immunotherapy | 17 (37.8) | 2 (9.5) | 0 (0.0) |
| Immunotherapy | 3 (6.7) | 1 (4.8) | 0 (0.0) |
| Molecular targeted therapy | 7 (15.6) | 6 (28.6) | 0 (0.0) |
| Chemo-immuno-molecular targeted therapy | 1 (2.2) | 0 (0.0) | 0 (0.0) |
| Chemo-molecular targeted therapy | 2 (4.4) | 4 (19.0) | 0 (0.0) |
| BSC | 0 (0.0) | 0 (0.0) | 15 (100.0) |
( ): %.
Continuous variable: mean ± SD.
Discrete variable: median [interquartile range].
BSC: best supportive care.
Table 2 presents the length of hospital stay, number of days until the start of physical therapy, and outcomes.
Table 2. Clinical course.
| Initial group | Subsequent group | BSC group | |
| (n=45) | (n=21) | (n=15) | |
| Length of hospital stay, day | 28.6 ± 15.7 | 30.2 ± 16.0 | 28.1 ± 17.0 |
| Physical therapy progress | |||
| Number of days until the start of physical therapy, day | 6.6 ± 6.2 | 8.2 ± 7.7 | 7.8 ± 4.1 |
| Number of days of physical therapy, day | 20.7 ± 13.9 | 20.4 ± 13.1 | 18.9 ± 17.1 |
| Outcomes | |||
| Discharge to home | 35 (77.8) | 17 (81.0) | 3 (20.0) |
| Transfer to another hospital | 8 (17.8) | 3 (14.3) | 11 (73.3) |
| Death | 2 (4.4) | 1 (4.8) | 1 (6.7) |
( ): %.
Continuous variable: mean ± SD.
Discrete variable: median [interquartile range].
BSC: best supportive care.
The average length of hospital stay was 30 days for all the three groups, and the average number of days of physical therapy was approximately 20. Approximately 80% of the patients in the initial treatment and subsequent treatment groups were discharged, whereas >70% of the patients in the BSC group were transferred to another hospital.
Table 3 shows the results of physical function, FIM, EORTC QLQ-C30, CFS, and HADS scores. Regarding the 6MWD of physical function, it was difficult to assess in 9 patients in the initial treatment group (5 men, 4 women), 6 patients in the subsequent treatment group (5 men, 1 woman), and 8 patients in the BSC group (6 men, 2 women).
Table 3. Physical function, EORTC QLQ-C30, CFS, HADS, FIM.
| Initial group | Subsequent group | BSC group | p-value | |
| (n=45) | (n=21) | (n=15) | ||
| Physical function | ||||
| Grip strength, kg | 28.4 ± 8.4 | 25.4 ± 7.1 | 24.5 ± 9.1 | |
| (male/female) | (33.0 ± 6.4/21.3 ± 5.6) | (28.5 ± 6.0/19.8 ± 5.5) | (27.3 ± 6.5/9.2 ± 4.0) | |
| 10-m walking speed, sec | 9.0 (7.5–13.1) | 11.2 (9.8–13.7) | 19.0 (15.9–21.6) | b**, c** |
| 6-MWD, m | 343.9 ± 153.6 | 258.6 ± 110.3 | 125.4 ± 75.3 | b** |
| (male/female) | (349.9 ± 164.0/334.6 ± 141.0) | (274.3 ± 91.8/240.7 ± 133.7) | (125.4 ± 75.3/NR) | |
| FIM | ||||
| Motor | 69.0 (55.0–73.0) | 61.0 (56.0–71.0) | 49.0 (33.5–61.0) | b** |
| Cognitive | 35.0 (35.0–35.0) | 35.0 (35.0–35.0) | 35.0 (34.5–35.0) | |
| Total | 104.0 (90.0–108.0) | 96.0 (91.0–106.0) | 84.0 (65.5–96.0) | |
| EORTC QLQ-C30 | ||||
| Global health status | 50.0 (33.3–58.3) | 33.3 (25.0–50.0) | 33.3 (16.7–45.8) | |
| Physical functioning | 73.3 (60.0–86.7) | 60.0 (40.0–73.3) | 33.3 (16.7–53.3) | b** |
| Role functioning | 83.3 (66.7–100.0) | 66.7 (33.3–83.3) | 33.3 (8.3–66.7) | b** |
| Emotional functioning | 75.0 (66.7–83.3) | 75.0 (66.7–91.7) | 58.3 (41.7–83.3) | |
| Cognitive functioning | 83.3 (66.7–100.0) | 66.7 (50.0–83.3) | 50.0 (41.7–66.7) | b* |
| Social functioning | 83.3 (50.0–100.0) | 66.7 (50.0–83.3) | 66.7 (50.0–100.0) | |
| Fatigue | 44.4 (22.2–55.6) | 66.7 (33.3–66.7) | 66.7 (50.0–77.8) | a**, b** |
| Nausea and vomiting | 0.0 (0.0–16.7) | 16.7 (0.0–33.3) | 16.7 (0.0–41.7) | |
| Pain | 33.3 (0.0–50.0) | 33.3 (0.0–50.0) | 50.0 (25.0–58.3) | |
| Dyspnea | 33.3 (0.0–33.3) | 33.3 (33.3–66.7) | 66.7 (33.3–83.3) | a**, b** |
| Insomnia | 33.3 (0.0–33.3) | 33.3 (33.3–66.7) | 66.7 (33.3–66.7) | |
| Appetite loss | 33.3 (0.0–66.7) | 33.3 (33.3–66.7) | 33.3 (33.3–66.7) | |
| Constipation | 33.3 (33.3–33.3) | 33.3 (33.3–66.7) | 33.3 (0.0–66.7) | |
| Diarrhoea | 0.0 (0.0–33.3) | 0.0 (0.0–33.3) | 33.3 (0.0–33.3) | |
| Financial difficulties | 33.3 (0.0–33.3) | 33.3 (33.3–33.3) | 33.3 (0.0–33.3) | |
| CFS | ||||
| Physical fatigue | 6.7 ± 4.5 | 8.9 ± 4.1 | 14.0 ± 5.7 | b** |
| Mental fatigue | 8.9 ± 3.0 | 9.4 ± 2.6 | 8.9 ± 2.7 | |
| Cognitive fatigue | 3.7 ± 2.9 | 5.0 ± 3.0 | 6.4 ± 4.0 | b* |
| Overall fatigue | 18.9 ± 7.6 | 23.2 ± 6.6 | 29.3 ± 7.7 | b** |
| HADS | ||||
| Anxiety | 6.4 ± 3.3 | 5.6 ± 2.3 | 7.6 ± 4.7 | |
| Depression | 6.5 ± 3.5 | 7.7 ± 4.3 | 9.2 ± 4.0 | |
| Total | 12.8 ± 5.9 | 13.3 ± 5.2 | 16.9 ± 7.9 | |
( ): %.
Continuous variable: mean ± SD.
Discrete variable: median [interquartile range].
*p<0.05, **p<0.001.
a: initial group vs. subsequent group, b: initial group vs. BSC group, c: subsequent group vs. BSC group.
BSC: best supportive care; NR: not reported; 6-MWD: 6-minute walking distance; FIM: functional independence measure; CFS: cancer fatigue scale; HADS: hospital anxiety and sepression scale.
According to the 2022 Report on Physical Fitness and Exercise Capacity16), the average grip strength for individuals aged 65–69 years was 39.32 kg for men and 25.25 kg for women. In this study, the grip strength values for both sexes in all the treatment groups were lower than the reference values. However, no significant differences were observed among the three groups.
The 10-meter comfortable walking speed criterion set by the AWGS was 0.8 m/s (12.5 s for 10 m). The walking speed of the study participants was lower than the criterion, with only the BSC group showing significantly lower values than the initial treatment group (p<0.001).
According to the 2022 Report on Physical Fitness and Exercise Capacity16), the average 6-MWD for individuals aged 65–69 years was 623.64 m for men and 588.08 m for women. In this study, the 6-MWD values for both sexes in all the treatment groups were lower than the reference values. Additionally, the BSC group showed significantly lower values than the initial treatment group (p<0.001).
For the FIM, the cognitive items had almost the maximum scores, whereas the motor items contributed to the overall scores. The FIM-motor scores were significantly lower in the BSC group than in the initial treatment group (p=0.002).
In the EORTC QLQ-C30, the BSC group had significantly lower PF (p<0.001), RF (p=0.011), and CF (p=0.016) scores than the initial treatment group. The subsequent treatment group had significantly higher FA (p=0.035) and DY (p=0.005) scores than the initial treatment group. The BSC group had significantly higher FA (p=0.006) and DY (p<0.001) scores than the initial treatment group. Overall, a trend toward worsening scores was observed across all items in the initial treatment, subsequent treatment, and BSC groups.
For the CFS, the BSC group had significantly higher scores for physical (p<0.001), cognitive (p=0.04), and overall fatigue (p<0.001) than the initial treatment group. More than half of the participants in each treatment period exceeded the cut-off values, with 51.1% in the initial treatment group, 76.2% in the subsequent treatment group, and 100% in the BSC group, all of whom reported high levels of fatigue.
No significant differences in the HADS scores were observed among the three groups. The number of participants exceeding the cut-off values was 35.6% on HADS-A and 71.1% on HADS-D in the initial treatment group, 28.6% on HADS-A and 81.0% on HADS-D in the subsequent treatment group, and 60% on HADS-A and 86.7% on HADS-D in the BSC group. More than 70% of the participants in all groups showed symptoms of depression according to HADS-D.
Table 4 shows the correlation between the EORTC QLQ-C30 and physical function. Items with a correlation coefficient (ρ) of ≥0.4 are indicated in bold. In the initial treatment group, PF, DY, and several other parameters correlated. In the subsequent treatment group, correlations were observed between PF, RF, CF, SF, and FA. The BSC group showed correlations with QL, SF, and DI, although the correlations were fewer than those in the other groups.
Table 4. Relationship between EORTC QLQ-C30 and physical function.
| Initial group (n=45) | Subsequent group (n=21) | BSC group (n=15) | ||||||||||||||||
| Grip strength | 10-m walking speed | 6-MWD | Grip strength | 10-m walking speed | 6-MWD | Grip strength | 10-m walking speed | 6-MWD | ||||||||||
| ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | ρ | p-value | |
| EORTC QLQ-C30 | ||||||||||||||||||
| Global health status | 0.09 | 0.54 | −0.28 | 0.09 | 0.32 | 0.06 | 0.22 | 0.35 | −0.45 | 0.06 | 0.24 | 0.40 | 0.08 | 0.79 | 0.24 | 0.48 | 0.90 | 0.01 |
| Physical functioning | 0.33 | 0.03 | −0.50 | 0.00 | 0.63 | 0.00 | 0.57 | 0.01 | −0.62 | 0.01 | 0.79 | 0.00 | −0.01 | 0.96 | 0.03 | 0.94 | 0.45 | 0.32 |
| Role functioning | 0.12 | 0.44 | −0.22 | 0.19 | 0.37 | 0.03 | 0.29 | 0.21 | −0.57 | 0.01 | 0.29 | 0.29 | −0.15 | 0.63 | −0.08 | 0.82 | 0.37 | 0.42 |
| Emotional functining | 0.18 | 0.23 | −0.03 | 0.87 | 0.19 | 0.27 | −0.14 | 0.57 | −0.37 | 0.13 | 0.15 | 0.60 | 0.16 | 0.59 | −0.22 | 0.52 | 0.70 | 0.08 |
| Cognitive functioning | 0.22 | 0.15 | 0.02 | 0.93 | 0.22 | 0.20 | 0.23 | 0.33 | −0.50 | 0.03 | 0.31 | 0.26 | 0.26 | 0.39 | −0.15 | 0.66 | 0.07 | 0.87 |
| Social functioning | 0.05 | 0.76 | 0.01 | 0.95 | 0.13 | 0.45 | 0.48 | 0.03 | −0.53 | 0.02 | 0.52 | 0.05 | 0.64 | 0.02 | −0.30 | 0.37 | 0.02 | 0.96 |
| Fatigue | −0.08 | 0.62 | 0.17 | 0.30 | −0.34 | 0.04 | −0.60 | 0.01 | 0.52 | 0.03 | −0.58 | 0.02 | 0.11 | 0.73 | 0.04 | 0.91 | −0.23 | 0.62 |
| Nausea and vomiting | −0.24 | 0.11 | 0.27 | 0.10 | −0.18 | 0.28 | 0.28 | 0.24 | 0.03 | 0.90 | −0.04 | 0.90 | −0.06 | 0.84 | −0.03 | 0.93 | −0.47 | 0.28 |
| Pain | −0.14 | 0.35 | 0.20 | 0.24 | −0.23 | 0.18 | −0.28 | 0.24 | 0.32 | 0.19 | −0.48 | 0.07 | 0.14 | 0.65 | 0.31 | 0.36 | 0.04 | 0.94 |
| Dyspnea | 0.05 | 0.74 | 0.48 | 0.00 | −0.27 | 0.11 | −0.22 | 0.34 | 0.03 | 0.89 | 0.11 | 0.69 | 0.19 | 0.54 | 0.13 | 0.71 | −0.31 | 0.50 |
| Insomnia | 0.10 | 0.52 | 0.09 | 0.59 | −0.38 | 0.02 | −0.37 | 0.11 | 0.06 | 0.82 | −0.32 | 0.25 | −0.06 | 0.85 | 0.29 | 0.39 | −0.17 | 0.72 |
| Appetite loss | −0.04 | 0.78 | 0.19 | 0.25 | −0.33 | 0.05 | 0.07 | 0.78 | 0.12 | 0.64 | −0.45 | 0.09 | 0.10 | 0.74 | 0.23 | 0.50 | −0.65 | 0.12 |
| Constipation | −0.19 | 0.21 | 0.24 | 0.15 | −0.32 | 0.06 | −0.33 | 0.15 | 0.14 | 0.58 | −0.25 | 0.37 | −0.18 | 0.55 | 0.58 | 0.06 | 0.16 | 0.74 |
| Diarrhoea | 0.02 | 0.89 | 0.05 | 0.78 | −0.02 | 0.89 | 0.30 | 0.20 | −0.32 | 0.19 | 0.01 | 0.97 | 0.61 | 0.03 | −0.18 | 0.60 | 0.06 | 0.90 |
| Financial difficulties | −0.15 | 0.32 | −0.01 | 0.95 | −0.11 | 0.53 | −0.35 | 0.13 | 0.46 | 0.05 | −0.64 | 0.01 | −0.34 | 0.25 | 0.51 | 0.11 | 0.09 | 0.85 |
Items with a correlation coefficient (ρ) of 0.4 or higher are indicated in bold.
BSC: best supportive care; 6-MWD: 6-minute walking distance.
DISCUSSION
Patients with cancer had low physical function at the start of treatment18). In lung cancer cases, grip strength is low, frailty is common at the start of treatment19), and 43% of individuals diagnosed with lung cancer already have sarcopenia20). In the present study, the initial treatment group showed a tendency toward lower grip strength and 6-MWD than the reference values, suggesting that physical function was already impaired at the start of the treatment, which is consistent results from with previous studies.
Furthermore, QOL (physical factors, functional factors, fatigue, and dyspnea) worsens with subsequent treatments, and fatigue and dyspnea worsen over time21). Additionally, depressive symptoms have been reported regardless of disease stage22). In the present study, physical function and QOL declined as treatment progressed, with significant differences observed in fatigue and dyspnea among the three groups. Moreover, more than half of the participants in each group exceeded the cut-off values for depressive symptoms, which is consistent with previous studies. Based on these results, we discuss the relationship between physical function and QOL according to the treatment period.
In the initial treatment group, fewer items were related to physical function and QOL, whereas the subsequent treatment group showed a greater correlation with various items. This may be due to adverse events of repeated treatments and impact of disease progression on the QOL in the subsequent treatment group. Specifically, the SF, FA, and PF of the EORTC QLQ-C30 were associated with grip strength, walking speed, and 6-MWD.
SF assesses whether the physical condition or treatment interferes with the household or social activities. Studies targeting community-dwelling older adults have reported associations between physical functions such as grip strength, walking speed, social activities, and daily life23, 24). Similarly, in surveys of patients with chronic obstructive pulmonary disease, the 6-MWD was correlated with activity level and household- or work-related activities25). Although this study did not investigate employment status or roles at home, reports have indicated that many elderly patients with cancer continue social activities even while receiving treatment26, 27). Thus, the impact of physical function on social activity is considerable, even in patients with lung cancer receiving treatment.
FA is also associated with physical function28,29,30). In patients with cancer receiving treatment, associations between the 6-MWD and self-reported fatigue have been reported31). Studies involving patients with advanced lung cancer have demonstrated a correlation between lower-limb strength and fatigue32). Studies targeting the elderly have reported a relationship between decreased speed and fatigue33,34,35); however, this relationship is less apparent in studies involving patients with cancer. Studies on patients with prostate cancer receiving treatment have shown no association between walking speed and fatigue, and similar results were observed in surveys of cancer survivors36). However, in this study involving patients with advanced lung cancer, fatigue was associated with grip strength, walking speed, and 6-MWD. This may be related to nutritional disorders.
PF represents items related to physical function, and its association with physical functions such as grip strength and walking speed became apparent, as investigated in this study. PF is an independent prognostic factor for overall survival across various cancer types and stages37). Therefore, addressing muscle strength, walking speed, and exercise tolerance may not only impact patient QOL but also their survival period. Additionally, even in the initial group, PF was correlated with walking speed and 6-MWD, indicating the need for early rehabilitation interventions.
For the BSC group, the results may differ from those of the subsequent groups owing to individual variations in function and symptoms. The complexities of issues affecting QOL in patients with advanced or terminal cancers have been noted, and QOL can be maintained despite low physical function and ADL38). To maintain QOL, rehabilitation tailored to psychological aspects, pain, respiratory difficulties, fatigue, and other symptoms is considered necessary.
Among the items related to physical function, walking speed was associated not only with SF, FA, and PF but also with RF and CF. In a study targeting elderly residents in the community without a history of cancer, “decline in walking speed” strongly correlated with items such as “physical function”, “role limitations owing to physical health”, “social functioning”, and “vitality” in the SF-36 questionnaire, which are indicators of QOL39). In this study, walking speed was associated with PF, RF, CF, SF, and FA and yielded similar results. Walking speed is a simple evaluation that can be performed in routine clinical practice and is a particularly useful indicator of QOL, during treatment.
Based on the results of this study regarding the relationship between physical function and QOL according to the treatment phase, interventions targeting physical function and symptoms during hospitalization, outpatient visits, and homecare could contribute to improving QOL. To the best of our knowledge, this study is the first to investigate the relationship between physical function and QOL according to the treatment phase and to demonstrate the associations between grip strength, walking speed, and 6-MWD in patients with advanced lung cancer and the QOL indicators SF, FA, and PF. However, the limitations of this study include its single-center design, small sample size, grouping of patients receiving treatment into subsequent groups, and inclusion of patients who selected BSC among the treatment options.
Patients with advanced lung cancer experience reduced physical function, increased fatigue, and depressive symptoms, leading to a decreased QOL even at treatment initiation. The decline in physical function and QOL worsened with subsequent treatments. Rehabilitation interventions during treatment may improve physical function and QOL. However, maintaining physical function and addressing symptoms are crucial during BSC. Therefore, a tailored approach that considers individual symptoms during the BSC period and focuses on maintaining physical function is necessary.
Funding
The authors received no funding support.
Conflicts of interest
The authors declare no conflicts of interest.
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