Abstract
Background/Aim: Quality of life of patients with lung cancer can be impaired by psychological distress. This study evaluated prevalence of and risk factors for emotional distress in patients undergoing radiotherapy or chemoradiotherapy. Patients and Methods: Fourteen potential risk factors were retrospectively investigated in 144 patients. Emotional distress was evaluated with the National Comprehensive Cancer Network Distress Thermometer. Values of p<0.0036 (Bonferroni correction) were considered significant. Results: At least one emotional problem (worry, fear, sadness, depression, nervousness, loss of interest) was reported by the majority of patients (N=93, 65%). Prevalence of these problems was 37%, 38%, 31%, 15%, 32% and 23%, respectively. Physical problems were significantly associated with worry (p=0.0029), fear (p=0.0030), sadness (p<0.0001), depression (p=0.0008), nervousness (p<0.0001), and loss of interest (p<0.0001). Age ≤69 years was associated with worry (p=0.0003), and female sex with fear (p=0.0002) and sadness (p=0.0026). Trends were found for associations of age with sadness (p=0.045), female sex with nervousness (p=0.034), and chemoradiotherapy with worry (p=0.027). Conclusion: Many patients with lung cancer experience emotional distress. Early psycho-oncological assistance may be important, particularly for high-risk patients.
Lung cancer is the second most common type of cancer worldwide with more than two million new cases per year (1). Many of these patients receive radiotherapy or chemoradiotherapy, either following surgery or as definitive treatment. The latter group mainly includes patients with small-cell lung cancer (SCLC) or unresectable non-small cell lung cancer (NSCLC) and patients not suitable for surgery due to poor performance score or advanced age. For patients with early-stage NSCLC who are not eligible for or do not wish surgical resection, stereotactic body radiation therapy (SBRT) is a standard of care (2).
Radiotherapy and chemoradiotherapy can be associated with significant acute and late toxicities, which may lead to emotional distress for patients recommended to receive one of these treatments (3-7). The prevalence of emotional distress, namely anxiety and depression, prior to radiotherapy for lung cancer ranges between 4% and 21% (8-10). In another study, anxiety (which generally includes worry and fear) and depression were reported by 53.6% and 65.5%, respectively, of those patients who received radiotherapy (11). Because of the inconsistency of the data in the literature, additional studies investigating the prevalence of emotional distress in patients with lung cancer are required. Moreover, the other aspects of emotional distress included in the National Comprehensive Cancer Network Distress Thermometer, i.e. sadness, nervousness, and loss of interest in usual activities, should be addressed (12). The current study evaluated the prevalence of all six aspects of emotional distress of the Distress Thermometer in a cohort of patients selected for radiotherapy or chemoradiotherapy for lung cancer (12). Moreover, it aimed to determine risk factors of emotional distress that will help identify patients who already need psycho-oncological assistance, prior to the start of their treatment.
Patients and Methods
In a cohort of 144 patients with lung cancer selected for radiotherapy or chemoradiotherapy between January 2018 and March 2022, the prevalence of the six aspects of emotional distress included in the National Comprehensive Cancer Network Distress Thermometer, i.e. worry, fear, sadness, depression, nervousness, and loss of interest in usual activities, were determined (12). Moreover, 14 potential risk factors were retrospectively investigated for associations with these aspects. These factors included Coronavirus Disease 2019 (prior to vs. during the COVID-19 pandemic), number of physical problems stated by the patients when completing the Distress Thermometer (0-4 vs. ≥5 problems), age at radiotherapy (≤69 vs. ≥70 years, median=69 years); sex (female vs. male); Karnofsky performance score (≤80 vs. ≥90), primary tumor category (T1-T2 vs. T3-T4); nodal category (N0-N1 vs. N2-N3), distant metastasis (no vs. yes), histology (NSCLC vs. SCLC), surgery prior to radiotherapy (no vs. yes); chemoradiotherapy (no vs. yes), SBRT (no vs. yes), patient’s own history of another malignancy (no vs. yes), and family history of another malignancy (no vs. yes). The study received approval from the Ethics Committee (University of Lübeck, reference number 2022-412).
Of the 144 patients (entire cohort), 100 patients had NSCLC (48 squamous cell carcinomas, 47 adeno carcinomas, five not otherwise specified) and 29 patients SCLC. In 15 patients, the histological type was not available or not specified. Of the patients with NSCLC, 79 patients received definitive radiotherapy (n=39) or chemoradiotherapy (n=40), and 21 patients received adjuvant treatment (n=19 and n=2, respectively). Eighty-eight patients were treated with volumetric-modulated arc therapy (planned total doses of 60-70 Gy with 2 Gy per fraction) and 12 patients with fractionated SBRT (42 to 64 Gy with 3 to 8 Gy per fraction). In the 42 patients with NSCLC receiving concurrent chemotherapy, systemic treatment consisted of cisplatin/vinorelbine in 18 patients, cisplatin/pemetrexed in 13 patients, nab-paclitaxel or paclitaxel in six patients, carboplatin/paclitaxel in four patients, and vinorelbine in one patient.
Of the 29 patients with SCLC, 12 patients received definitive radiotherapy and 17 patients definitive chemoradiotherapy. Twenty-eight patients were treated with volumetric modulated arc therapy (planned total doses of 56-66 Gy with 2 Gy per fraction) and one patient with fractionated SBRT (7×8 Gy). Concurrent chemotherapy consisted of cisplatin/etoposide in 11 patients, carboplatin/etoposide in five patients, and weekly paclitaxel following four neoadjuvant courses of cisplatin/etoposide in one patient. The 15 patients with unspecified histology were treated with definitive radiotherapy alone. Thirteen patients received fractionated SBRT (44 to 64 Gy with 4 to 8 Gy per fraction), and two patients volumetric-modulated arc therapy (one patient died after 6 Gy; radiotherapy was discontinued in one patient after 50 Gy).
Statistical analyses were mainly performed with chi-square test. When one or more subgroups included fewer than five patients, Fisher’s exact test was applied. To consider the phenomenon of multiple comparisons, the Bonferroni correction was appliedand a value of p<0.0036 was then regarded as significant (alpha level <0.05). In addition, p<0.05 was considered to indicate a trend.
Results
At least one of the six emotional problems worry, fear, sadness, depression, nervousness, and loss of interest was reported by 93 patients (65%) prior to the start of treatment. The prevalence rates of these problems were 37%, 38%, 31%, 15%, 32% and 23%, respectively. Five or more physical problems were significantly associated with worry (p=0.0029) (Table I), fear (p=0.0030) (Table II), sadness (p<0.0001) (Table III), depression (p=0.0008) (Table IV), nervousness (p<0.0001) (Table V), and loss of interest (p<0.0001) (Table VI). In addition, age ≤69 years was significantly associated with worry (p=0.0003) (Table I) and female sex with fear (p=0.0002) (Table II) and sadness (p=0.0026) (Table III). Moreover, trends were found for associations between age ≤69 years and sadness (p=0.045) (Table III), between female sex and nervousness (p=0.034) (Table V), and between chemoradiotherapy and worry (p=0.027) (Table I). The complete results of the six analyses regarding associations between investigated potential risk factors and emotional problems are shown in Table I, Table II, Table III, Table IV, Table V and Table VI.
Associations of the investigated characteristics and worry.
Associations of the investigated characteristics and fear.
Associations of the investigated characteristics and sadness.
Associations of the investigated characteristics and depression.
Associations of the investigated characteristics and nervousness.
Associations of the investigated characteristics and loss of interest in usual activities.
Discussion
Radiotherapy and chemoradiotherapy of lung cancer may cause various acute and late toxicities (3-7). Therefore, being assigned to such a treatment regimen can lead to significant emotional distress for patients with lung cancer. In the literature, the prevalence of pre-treatment emotional distress in patients with lung cancer varies (8-10). In a randomized controlled trial by Falk et al. comparing immediate to delayed palliative radiotherapy with 2×8.5 Gy or 1×10 Gy in 230 patients with unresectable NSCLC, baseline anxiety rates were 12% for those who underwent immediate treatment and 11% for those who underwent delayed treatment, respectively (8). Borderline anxiety was reported by additional 24% and 16% of patients, respectively, resulting in total anxiety rates of 36% and 27%, respectively. In that trial, baseline depression rates were 4% and 8%, respectively (8). Borderline depression was reported by an additional 17% and 12% of patients, respectively, resulting in total depression rates of 21% and 20%, respectively. In another randomized trial of 509 patients that compared 2×8.5 Gy to 13×3 Gy for unresectable NSCLC, psychological distress was reported by 17.8% and 17.1% of patients, respectively, prior to radiotherapy (9). In a prospective observational cohort study of 191 patients, pre-radiotherapy rates of anxiety were 21% in younger patients (aged 43-65 years) and 12% in elderly patients (aged 75-89 years), respectively. Prevalence rates of depression were 21% and 21%, respectively (10). Moreover, in a cross-sectional study in China, anxiety and depression were reported by 53.5% and 65.5%, respectively, of patients who received radiotherapy (11). The great variety of rates of emotional distress demonstrate that additional studies are required to properly define the seriousness of this complication. Therefore, the present study was performed to investigate the prevalence of the six emotional problems addressed by the National Comprehensive Cancer Network Distress Thermometer in patients assigned to radiotherapy or chemoradiotherapy for lung cancer (12). The prevalence rates ranged between 15% and 38%. These rates were similar to the total rates of anxiety and depression in the randomized trial of Falk et al. (8) and in younger patients of the prospective observational study of Turner et al. (10) that ranged between 20% and 36%. Moreover, when comparing patients aged ≥70 years of our study to the elderly patients of the study of Turner et al., the rates of emotional problems were also similar (7-21% versus 12-21%) (10). The prevalence of emotional problems in the trial of Macbeth et al. (9) was lower than in our study and the trial of Falk et al. (8). This can be explained by the fact that the trial of Macbeth et al. was limited to patients with a good performance status (9). Moreover, 65% of our patients reported at least one emotional problem. This frequency was similar to the rates of anxiety and depression observed in a previous cross-sectional study (11). The fact that the prevalence rates found in our study were similar to the findings of most previous studies indicate consistency of our results.
In addition to the prevalence of emotional distress, we investigated potential risk factors. According to our results, at least one emotional problem was significantly associated with a greater number of physical problems, younger age, and female sex. In addition, a trend was found for an association with concurrent chemoradiotherapy. The fact that physical problems and symptoms increase psychological distress in patients with lung cancer was previously described for different situations (13-16). Moreover, in our previous study, a greater number of physical problems was identified as a significant risk factor for sleep disorders that can be a consequence of emotional distress (17). Associations between emotional distress and younger age were also found in other studies. In the prospective observational study of Turner et al., younger patients reported more concerns, and the prevalence of anxiety was non-significantly higher (10). In the cross-sectional study of Yan et al., patients reporting anxiety and depression were significantly younger than patients without these problems (11). Moreover, in the study of Mazanec et al. that investigated predictors of psycho-social adjustment following radiotherapy in patients with lung, breast or prostate cancer, younger age was associated with poor adjustment (18). An impact of sex on emotional distress was also found in previous studies of patients with lung cancer. In the study of Yan et al., female patients were more likely to experience anxiety (51% vs. 40%, p=0.060) and depression (64% vs. 54%, p=0.067) (11). In a study of lung cancer survivors, women had almost two-fold odds of being distressed, and in a study of patients with SCLC, women tended to have higher distress scores, indicating higher levels of distress (13, 19). The trend for an association between emotional distress and concurrent chemotherapy can be explained by the fact that the addition of chemotherapy to radiotherapy significantly increases treatment-related acute toxicities, which has been demonstrated in several studies (20-24). Although the results of our study with respect to prevalence and identification of risk factors for emotional distress are in line with the results of previous studies or can be well explained, the retrospective nature of the data, particularly the risk of a hidden selection bias, needs to be considered during their interpretation.
In summary, many patients assigned to radiotherapy or chemoradiotherapy for lung cancer experience emotional distress. For patients with risk factors such as greater number of physical problems, younger age, female sex and concurrent chemotherapy, psycho-oncological assistance is important, ideally prior to the start of treatment.
Footnotes
Authors’ Contributions
The study was designed by all Authors. Data collection was performed by A. A.-S. and D.R.; data analysis by D.R. The article, which was drafted by D.R. and N.Y.Y., was reviewed and finally approved by all Authors.
Conflicts of Interest
The Authors state declare no conflicts of interest related to this study.
- Received February 27, 2023.
- Revision received March 8, 2023.
- Accepted March 9, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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