Abstract
Background/Aim: Radiotherapy for head-and-neck cancer is often associated with significant toxicities, which may cause emotional distress. We evaluated prevalence and risk factors for pre-treatment emotional problems in patients irradiated for head-and-neck cancer. Patients and Methods: Twelve characteristics were retrospectively investigated in 213 patients for associations with emotional problems (worry, fear, sadness, depression, nervousness, loss of interest). After Bonferroni adjustment, p-values <0.0042 were regarded significant. Results: At least one emotional problem was reported by 131 patients (61.5%). Specific prevalence for emotional problems ranged between 10% and 44%. Physical complaints showed significant associations with all six emotional problems (p<0.0001) and female sex with sadness (p=0.0013). Trends were found for associations between female sex and fear (p=0.0097), history of another tumor and sadness (p=0.043), worse performance status and nervousness (p=0.012), and cancer site (oropharynx/oral cavity) and nervousness (p=0.063). Conclusion: More than 60% of patients reported emotional distress prior to radiotherapy for head-and-neck cancer. Patients with risk factors likely require near-term psycho-oncological assistance.
Radiotherapy with or without concurrent chemotherapy is a standard treatment for head-and-neck cancers and often associated with significant acute and late toxicities (1-9). Potential adverse events of radiotherapy include radiation dermatitis, oral mucositis, dysphagia, dysgeusia, hypothyroidism and xerostomia (1-6). Administration of concurrent chemotherapy increases radiation-related toxicities and adds chemotherapy-specific adverse events including nausea and vomiting, decreased renal function, hearing problems, polyneuropathy, and hematologic toxicity (7-11). When looking at the severity and number of potential treatment-related side effects, it becomes obvious that a considerable number of head-and-neck cancer patients assigned to radiotherapy or radiochemotherapy experience significant emotional distress. When compared to radiotherapy of other tumor sites, head-and-neck cancer patients wear a tight mask over the head and shoulders which may cause further distress (12).
In the literature, the prevalence of depression and anxiety, both aspects of emotional distress, prior to radiotherapy for head-and-neck cancer ranged between 8% and 58% and between 20% and 40%, respectively (13-17). Given the lack of data and inconsistency, particularly with respect to depression, additional studies are needed to better define the prevalence of emotional distress in head-and-neck cancer patients assigned to radiotherapy. Moreover, other aspects of emotional distress included in the National Comprehensive Cancer Network (NCCN) Distress Thermometer, namely worry, fear, sadness, nervousness, and loss of interest in usual activities, should be considered (18). In this study, all aspects of emotional distress of the NCCN Distress Thermometer are separately evaluated with respect to prevalence and potential risk factors (18). The knowledge of risk factors will contribute to identification of head-and-neck cancer patients who may require near-term psycho-oncological assistance prior to their course of radiotherapy or radio-chemotherapy.
Patients and Methods
A total of 213 head-and-neck cancer patients recommended for loco-regional radiotherapy or radio-chemotherapy according to the decision of a multidisciplinary tumor board were included in this retrospective study, which was approved by the local Ethics Committee (University of Lübeck, 2022-412).
Seventy-nine patients (37%) received definitive irradiation using volumetric modulated arc therapy (VMAT). The mean total dose was 70 Gy (5×2.0 Gy per week). Sixty-eight of these patients were scheduled for concurrent radio-chemotherapy with two courses of cisplatin (20 mg/m2/d1-5 or 25 mg/m2/d1-4), administered every 4 weeks. Chemotherapy was finally refused by one patient and not given due to decrease of the performance status until the start of treatment in another patient. Cisplatin was administered as planned in 34 patients. Due to comorbidity, reduced performance status, treatment-related toxicity, or expected complications, 32 patients received alternative systemic therapies including carboplatin alone (n=18), cisplatin followed by carboplatin (n=8), mitomycin C with or without 5-fluorouracil (n=3), cetuximab (n=2), and paclitaxel (n=1). In four patients receiving definitive treatment, external-beam radiotherapy (EBRT) was supplemented by a brachytherapy boost.
A total of 134 patients received adjuvant radio-(chemo)therapy (VMAT). The mean total dose was 66 Gy (5×2.0 Gy per week). Extent of resection was microscopically complete (R0) in 99 patients (six patients with close margins), microscopically incomplete (R1) in 20 patients, macroscopically incomplete (R2) in three patients, and unclear in 12 patients. Seventy-seven patients with risk factors were scheduled for concurrent radio-chemotherapy with cisplatin. Chemotherapy was not given in one patient due to decreased performance status. Cisplatin was administered as planned in 57 patients (in two patients combined with pembrolizumab). Due to the reasons stated above, 19 patients received other systemic therapies, i.e., carboplatin alone (n=17), cisplatin followed by carboplatin (n=1), or mitomycin C/5-fluorouracil (n=1). Four patients in an adjuvant situation were treated with brachytherapy alone (9-12 fractions of 3-4 Gy), and five patients received a brachytherapy boost in addition to EBRT.
In the entire cohort of 213 patients, we evaluated the prevalence of emotional distress, represented by six emotional problems (worry, fear, sadness, depression, nervousness, loss of interest in usual activities). These emotional problems were part of the NCCN Distress Thermometer completed by the patients prior to the informed consent discussion regarding their planned radio-(chemo)therapy (18).
In addition to evaluation of the prevalence, twelve characteristics were investigated for associations with each of the six emotional problems. These characteristics were timely connection to the COVID-19 pandemic (before vs. during), number of physical complaints (≤4 vs. ≥5), age (≤65 vs. ≥66 years, median=65 years), sex (female vs. male), Karnofsky performance score (KPS ≤80 vs. ≥90), main tumor site (oropharynx/oral cavity vs. other sites), p16-status as surrogate marker for the human papilloma virus (HPV)-status (negative vs. positive) (19), upfront surgery (no vs. yes), primary tumor category (T1-T2 vs. T3-T4), nodal status (negative vs. positive), being scheduled for concurrent chemotherapy (no vs. yes), and history of another tumor (no vs. yes).
Statistical analyses were performed with the Chi-square test or (if the number of patients was <5 in at least one subgroup) the Fisher’s exact test. When using the Bonferroni adjustment to account for multiple comparisons, a p-value <0.0042 represented an alpha level of <0.05 and, therefore, was regarded as significant. Moreover, p-values <0.07 were regarded as representing a trend.
Results
At least one emotional problem was experienced by 131 patients (61.5%). The specific prevalence for the emotional problems, such as worry, fear, sadness, depression, nervousness, and loss of interest in usual activities was 37%, 44%, 29%, 10%, 32%, and 14%, respectively. A greater number of physical complaints showed significant associations with all six emotional problems (p<0.0001), and female sex was significantly associated with sadness (p=0.0013). A strong trend was found for an association between female sex and fear (p=0.0097). In addition, trends were observed for correlations between history of another tumor and sadness (p=0.043), a KPS ≤80 and nervousness (p=0.012), and between cancer site (oropharynx/oral cavity) and nervousness (p=0.063). The results of the complete analyses are presented 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
Since radiotherapy and radio-chemotherapy of head-and-neck cancer often leads to burdensome side effects, patients assigned to one of these treatments may experience considerable emotional distress (1-9). In previous studies of head-and-neck cancer patients, 8-58% had depression and 20-40% of anxiety prior to radiation treatment (13-17). Moreover, in the study of Lewis et al., 56% of patients with head-and-neck cancer who were planned for cancer-directed radiotherapy had significant general (not further specified) distress (20). Furthermore, in our previous study, 44 of 103 (43%) head-and-neck cancer patients selected for definitive or adjuvant radio-(chemo)therapy reported sleep disorders that were significantly associated with the number of emotional problems (p=0.001) (21). In our present study, the proportion of patients who experienced at least one emotional problem was higher than the rates of depression, anxiety, and general distress found in previous studies (13-17, 20). However, the specific prevalence of the six investigated emotional problems in our study was within the range previously reported for depression and anxiety (13-17). This result demonstrates consistency of our data.
In addition to the prevalence of the six emotional problems, we aimed to identify corresponding risk factors. According to the results of this study, a higher number of physical complaints and female sex showed significant associations with at least one emotional problem. In addition, trends were found for history of another tumor, worse performance status, and cancer site (oropharynx/oral cavity). The retrospective design of this study should be considered when interpreting its results. However, our findings are in line with those of previous studies. Neilson et al. found that higher depression and anxiety scores were related to the number of physical symptoms (15). In the study of Gosak et al., depression and anxiety were more frequently recorded by patients with nutritional problems and cachexia (14). Lewis et al. observed a tracheostomy tube, which likely led to physical complaints, to be predictive of general distress (20). In our previous study, sleep disorders were significantly correlated with more physical complaints (21). Moreover, in a study that investigated psychological distress over the course of radiotherapy in head-and-neck cancers and their caregivers, physical complaints, sleep problems, pain, sore mouth, eating problems, and fatigue were the most frequently stated causes of distress (22). In another study evaluating distress following radiotherapy, physical functioning was a significant predictor of anxiety (23). Associations between female sex and the incidence of depression and intensity of anxiety were found in the study of Wang et al. that investigated the psychological status of patients with nasopharynx cancer assigned to radiotherapy (13).
The impact of the history of another tumor on emotional distress was not previously described for head-and-neck cancer patients prior to radiotherapy. However, Ninu et al. found that distress was higher in patients with previous cancer in another area in their study investigating head-and-neck cancer patients during the first year following treatment (24). In addition, our previous study revealed an association between history of another malignancy and sleep disorders (p=0.012) (21). Moreover, fear of a recurrence of cancer was stated as major concern by patients with head-and-neck cancer in previous studies (25, 26). With respect to the prognostic impact of a worse performance score, an association between lower KPS and prevalence of sleep disorders was found in our previous study (21). In addition, Gunn et al. reported that a worse performance status was correlated with a higher symptom burden including distress prior to radiotherapy of head-and-neck cancer (27). Our finding that the tumor site may have an impact on the prevalence of emotional distress is supported by the study of Lewis et al. that demonstrated a significant correlation between cancer site (oral cavity) and general distress (p=0.02), and by our previous study that showed a trend for an association between cancer site (oropharynx) and sleep disorders (p=0.052) (20, 21). In contrast to the risk factors stated above, the COVID-19 pandemic was not associated with the prevalence of emotional distress. This result agrees with that of a previous cross-sectional study from Brazil that found no increase of distress levels during the pandemic in head-and-neck cancer undergoing radiotherapy (28).
In summary, more than 60% of patients reported emotional distress prior to radiotherapy for head-and-neck cancer. Patients with risk factors, i.e., greater number of physical complaints, female sex, history of another tumor, worse performance status, and cancer of the oropharynx or oral cavity, likely require near-term psycho-oncological assistance.
Footnotes
Authors’ Contributions
All Authors participated in the study design. A. A.-S. and D.R. collected the data, which were analyzed by D.R. The article drafted by A. A.-S., D.R., and N.Y.Y. was reviewed and finally approved by all Authors.
Conflicts of Interest
The Authors declare no conflicts of interest related to this study.
- Received March 10, 2023.
- Revision received March 20, 2023.
- Accepted March 21, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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