Abstract
Background/Aim: Radiotherapy (RT) is a standard treatment for head-and-neck cancer, which can be associated with patient distress. This study provides data investigating distress during head-and-neck RT. Patients and Methods: Fifty-six patients completed the Distress Thermometer before and on the last day of their RT-course. Mean changes of distress scores and increase of distress were evaluated. Age, sex, Karnofsky performance score (KPS), tumor type, intent of RT, and previous RT were analyzed for associations with course of distress. Results: Mean pre-RT and post-RT distress scores were 5.1 (±2.6) and 5.0 (±2.7) points, respectively (mean change: ±0.0 points). Mean change of distress scores was significantly associated with age (p=0.042) and KPS (p<0.001). On multivariable analysis, increased distress (by ≥2 points) was associated with KPS 90-100 (p=0.011) and palliative intent of RT (p=0.036). Conclusion: Mean pre-RT and post-RT distress scores were almost identical. Patients with risk factors for increased distress during their RT-course should be offered immediate psychological support.
Radiotherapy (RT) is a standard treatment for head-and-neck cancer. Since it is generally associated with adverse events, particularly if concurrent chemotherapy is added, patients may have significant distress (1-5). In our preceding study, 61.5% of the patients reported one or more emotional problems when completing the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT) prior to the start of RT (6, 7). The prevalence of specific emotional problems such as worry, fears, sadness, depression, nervousness, and loss of interest in usual activities ranged between 10% (depression) and 44% (fears) when assessed prior to RT (6). In another study from our group, 43% of patients irradiated for head-and-neck cancer reported sleep disorders that were significantly correlated with emotional problems (8). Additionally, up to 58% of patients experienced depression and up to 40% anxiety prior to RT of head-and-neck cancer in studies of other groups (9-13). A cross-sectional study of 600 head-and-neck cancer patients undergoing RT indicated that 56.7% of them experienced distress (score ≥4 points) (14).
These figures demonstrate that distress prior to RT of head-and-neck cancer is a common problem that can be quite burdensome for the patients and can impair the patients’ quality of life (15). Therefore, more data are required to identify patients at risk of experiencing significant distress. Several studies have addressed this issue and found that depression, as indicator of psychological distress, was more pronounced at the end of RT when compared to pre-RT levels (9-13, 16). In the present study, we used the NCCN-DT, which accounts for many aspects of distress in addition to depression and anxiety, including physical, practical, and other emotional problems (7). This approach was also used in our pilot study of patients irradiated for different types of malignancy (17). In that study, the type of primary tumor was a significant predictor of the change of distress during RT. Therefore, separate analyses for single tumor types appear reasonable to obtain diagnosis-specific data and determine specific risk factors for increased distress. These factors may help identify high-risk patients who would benefit from immediate psychological assistance.
Patients and Methods
This study was approved by the responsible Ethics Committee at the University of Lübeck (file 2022-486). Fifty-six patients irradiated for head-and-neck cancer between 11/21 and 11/22 completed the NCCN-DT prior to the start (pre-RT) and on the last day (post-RT) of their RT-course (7). Possible distress scores ranged between 0 (no distress) and 10 (maximum distress) points. Changes of distress scores were retrospectively evaluated and obtained by deducting the pre-RT from the post-RT score. Mean values plus standard deviations of these changes were calculated. In addition, we determined the rates of improvement (decreased distress score by ≥2 points), no change (change ranging between −1 point and +1 point), and deterioration (increase by ≥2 points) of distress. Deterioration (increase) of distress was additionally evaluated using the binary variable “increase vs. no increase” of distress.
Moreover, age at start of RT [≤64 years (younger patients) vs. 65-79 years (elderly) vs. ≥80 years (very elderly)], sex (female vs. male), Karnofsky performance score (≤80 vs. 90-100), intent of RT (curative vs. palliative), and history of previous RT (no vs. yes) were analyzed for potential associations with the course of distress during RT as indicated above. The distribution of these five characteristics is given in Table I.
Patient characteristics.
Statistical analyses. The Wilcoxon two-sample test (when comparing 2 subgroups) and the Kruskal–Wallis test (when comparing 3 or more subgroups) were used for evaluation of associations between the five characteristics and mean changes of distress scores. Both tests were also applied for evaluation of the characteristics with respect to improvement, no change, or deterioration of distress. The multivariable analysis regarding the binary variable “increase vs. no increase” of distress scores was performed using a logistic regression model. We always considered p-values of <0.05 significant and p-values <0.10 showing a trend.
Results
In the entire cohort, mean pre-RT and post-RT distress scores were 5.1 (standard deviation ±2.6) and 5.0 (±2.7) points, respectively. The mean change of the distress score was 0.0 (±3.2) points (Table II). Mean change of distress scores was significantly associated with age (p=0.042) and KPS (p<0.001). Patients aged ≤64 years and patients with a KPS of 90-100 had the worst outcomes with a mean increase of 1.2 points and 1.5 points, respectively.
Mean changes of distress scores during the RT-course. p-Values were obtained using the Wilcoxon two-sample test (2 subgroups) or the Kruskal–Wallis test (≥3 subgroups).
When evaluating improvement, no change, or deterioration of distress during RT, the change of distress was significantly associated with KPS (p=0.001), and age showed a trend for an association (p=0.067) (Table III). On multivariable analysis regarding “increase vs. no increase” of distress, increased distress was associated with KPS 90-100 (p=0.011) and palliative intent of RT (p=0.036) (Table IV).
Improvement, no change, and deterioration of distress scores during the course of RT. p-Values were obtained using the Wilcoxon two-sample test (2 subgroups) or the Kruskal–Wallis test (≥3 subgroups).
Results of the multivariable analysis regarding the binary variable “increase vs. no increase” of distress scores.
Discussion
RT for head-and-neck cancer is often associated with significant acute toxicities including dermatitis, mucositis with or without dysphagia, and dysgeusia (1-5). These toxicities are generally more severe when concurrent chemotherapy is added to RT (18-21). Moreover, chemotherapy itself can cause acute adverse events such as nausea, vomiting, and renal insufficiency (18-21). Therefore, many patients may have psychological distress regarding anticipated RT. In previous studies, the prevalence of specific emotional problems ranged between 8% and 58% (6, 9-13). In our preceding study, 61.5% of the patients stated at least one emotional problem (6). Lewis et al. reported approximately 57% of head-and-neck cancer patients scheduled for RT felt distressed (14). Given the prevalence of distress, this can significantly impair the patients’ quality of life (15). Several studies have investigated distress during RT for head-and-neck cancer. These studies found that distress increased during RT. In 2009, Chen et al. presented a prospective study of 40 head-and-neck cancer patients undergoing RT (12). They evaluated anxiety and depression at different time points including pre-RT and post-RT and found that the level of depression on the Hospital Anxiety and Depression Scale (HADS)-D increased in 34 patients (85%) during the RT course (12). Neilson et al. performed two prospective observational studies in head-and-neck cancer patients (9, 13). In the first study, 75 patients completed the HADS before and after RT. The rate of mild to severe depression significantly increased during RT (from 15% to 31%, whereas the rate of mild to severe anxiety decreased (from 30% to 17%) (9). In the second study of 101 patients, the prevalence of depression was 15% before RT vs. 29% at 3 weeks following RT, and the prevalence of anxiety was 20% vs. 17% (13). Moreover, in the prospective study of Gosak et al., significantly more patients had anxiety before RT than at the end of their treatment (p=0.037), and the prevalence of depression was non-significantly higher at the end of RT (11). In contrast to these data, a more recent study, which was presented by Wang et al. in 2022, found that the rates of both depression and anxiety increased during RT for cancer of the nasopharynx (10). The prevalence of depression was 25% before RT vs. 56% at the end of RT (p<0.001), and the prevalence of anxiety was 34% vs. 64% (p<0.001), respectively. All these studies focused only on two emotional problems, namely anxiety and depression.
In the present study, distress was assessed with NCCN-DT that includes additional aspects of distress including physical and practical problems, as well as more specific emotional problems (7). According to our results, the mean pre-RT and post-RT distress scores were almost identical (5.1 and 5.0 points, respectively), and the mean change of the distress score was ±0.0 points. These findings suggest that although the prevalence of specific emotional problems may undergo changes during an RT course, the overall distress level remains unchanged. However, we found that certain patients are at risk of increased distress during RT, including patients aged ≤64 years, patients with a KPS of 90-100, and patients receiving palliative RT (Table II, Table III, and Table IV). Younger age was also identified as a risk factor in two previous studies (12, 13). In contrast, patients aged >40 years were found to experience higher levels of anxiety and depression than patients ≤40 years of age in the study of Wang et al. investigating patients with nasopharynx cancer (10), This discrepancy when compared to other studies including our present one may be explained by the different tumor types investigated (nasopharynx cancer vs. any or other types of head-and-neck cancer) and the low cut-off value of 40 years. The association of KPS of 90-100 with increase of distress may be a consequence of lower pre-RT scores when compared to KPS ≤80 (mean scores of 4.2 vs. 5.9). Moreover, in our preceding study of patients with different types of primary cancer, decrease of distress was more pronounced with KPS 60-80 compared to KPS 90-100 (17). Finally, since patients receiving palliative RT have more advanced disease stages and considerably worse prognoses than patients assigned to curative RT, they may be less confident regarding the outcomes of their treatment. In these patients, decreased quality of life due to acute RT-related toxicity likely dominates over the hope of improved prognoses, which leads to increased distress. However, one should be aware of the retrospective study design during the interpretation of our results.
In conclusion, although the mean pre-RT and post-RT distress scores were almost identical in the entire cohort, risk factors for increased distress during a course of RT for head-and-neck cancer were found. These factors can be used for identification of patients who would particularly benefit from psychological support before and during RT or chemoradiation for head-and-neck cancer.
Acknowledgements
The study was funded by the European Regional Development Fund through the Interreg Deutschland-Danmark program within the TreaT project (file 148-1.1-21).
Footnotes
Authors’ Contributions
D.R., C.D., N.Y.Y. and S.J. participated in the design of the study. The data were collected by C.D., and analyzed by a professional statistician supported by D.R. All Authors reviewed and approved the article, which was drafted by D.R. and N.Y.Y.
Conflicts of Interest
On behalf of all Authors, the corresponding Author indicates no conflicts of interest related to this study.
- Received July 3, 2023.
- Revision received July 24, 2023.
- Accepted July 25, 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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