CLINICAL INVESTIGATION Head and Neck
PHYSICAL DISTRESS, EMOTIONAL STATUS, AND QUALITY OF LIFE IN
PATIENTS WITH NASOPHARYNGEAL CANCER COMPLICATED BY
POST-RADIOTHERAPY ENDOCRINOPATHY
B
EE-H
ORNGL
UE, M.D.,*
yxT
IEN-S
HANGH
UANG, M.D.,
yzkANDH
SIU-J
UNGC
HEN, P
H.D.
{ Departments of *Family Medicine,ySocial Medicine, andzInternal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Departments ofxFamily Medicine andkInternal Medicine, National Taiwan University Hospital, Taipei, Taiwan; and{
Department of Educational Psychology and Counseling, National Taiwan Normal University, Taipei, Taiwan Purpose: To explore factors affecting quality of life (QOL) among patients with nasopharyngeal cancer (NPC) complicated by post-radiotherapy endocrinopathy.
Methods and Materials: This cross-sectional study was conducted in a tertiary medical center and involved a total of 43 post-radiotherapy, recurrence-free NPC patients with endocrinopathy. They performed self-assessment of their emotional status using the Beck Anxiety Inventory and Beck Depression Inventory–II, and their QoL with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire and the H&N35 cancer module.
Results: Emotional and cognitive functioning of EORTC QLQ-C30 were the most affected. Fatigue, insomnia, and pain were the main concerns. Of the patients, 22 (51.2%) had anxiety and 19 (44.2%) had depression. Both depres-sion and anxiety were negatively correlated with functional scales and global QoL but positively correlated with symptom scales. Multiple linear regression analysis revealed that physical distress symptoms of QLQ-C30 and physical functioning were the significant predictors of global QoL. Emotional and social functioning could predict depression, whereas emotional and physical functioning were significant predictors of anxiety.
Conclusions: NPC patients with post-radiotherapy endocrinopathy exhibit impaired cognitive function and neg-ative emotions. Symptoms of physical distress play an important role in QoL perception. Measurement of EORTC QLQ-C30 can be a useful instrument for the early detection of patients’ impaired cognitive function and psycho-logical morbidity. The high psychopsycho-logical distress related to the endocrine disturbances or the impact of NPC itself needs further study. Ó 2008 Elsevier Inc.
Nasopharyngeal cancer, Psychological distress, Symptom distress, Quality of life, Endocrinopathy.
INTRODUCTION
Nasopharyngeal cancer (NPC) is highly prevalent in South-east Asia(1). Its annual incidence rate in Taiwan is approxi-mately 5.96 cases per 100,000 persons, making NPC the 9th most prevalent cancer in the country(2). It has been one of the 10 leading causes of cancer death up to 1996, but ranked 14th in the 2 years preceding 2005(2). However, complica-tions such as mucositis and sequelae such as dry mouth re-sulting from the main treatment modality of radiotherapy, continue to significantly impact NPC patients(3–6). Because the effectiveness of radiotherapy has been realized in clinical practice, NPC patients have had a better chance at cancer-free
life for an extended period. However late complications, including dry mouth and primary hypothyroidism, are usu-ally chronic, progressive, and irreversible(7, 8).
Hypothalamic–pituitary dysfunctions after radiotherapy for NPC are well documented in several studies(9–11), in-cluding ours(8, 12–14). Although brain injuries are irrevers-ible, endocrine disturbances are amenable to therapy. Over the past decades, subjective well-being has become recognized as important as biomedical outcome parameters, ushering a growing body of literature concerning health-related quality of life (QoL). However, research focusing on NPC patients’ psychological well-being remains sparse, and there has been no study exploring the mental health of NPC patients
Reprint requests to: Hsiu-Jung Chen, Ph.D., Department of Educational Psychology and Counseling, National Taiwan Normal University, No. 162, Sec. 1, Heping E. Road, Da-an District, Taipei City 10610, Taiwan (R.O.C.). Tel: (+886) 2-23511263, ext. 502; Fax: (+886) 2-23118674; E-mail:hsiujung@ntnu.edu.tw
Conflict of interest: none.
Acknowledgments—This study was supported by Research Grant NSC94-2314-B-002-189 from the National Science Council
of Taiwan. The authors are indebted to Dr. Jeng-Yuh Ko, Otolar-yngologist, for his case referral and cooperative patient care; Dr. Lai-Lei Ting, Radiation Oncologist, for reviewing this manu-script; and Chang-Wei Wang for data processing and statistical analysis.
Received Sept 28, 2006, and in revised form June 7, 2007. Accepted for publication June 7, 2007.
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complicated by endocrinopathy, even though patient-cen-tered medical care has already drawn much attention(15).
This study aimed to assess the emotional status, subjec-tive and functional outcome, and their relationship among recurrence-free NPC patients with post-radiotherapy endo-crinopathy. It also aimed to investigate predictive factors of QoL.
METHODS AND MATERIALS Participants
This study was conducted from February 2004 to February 2005 at the outpatient Endocrinology Clinic of the National Taiwan Uni-versity Hospital. From our previous research, we noted that post-radiotherapy NPC patients could develop hypothalamic–pituitary dysfunction from cranial irradiation(8). Thus patients with compli-cated physical discomfort such as malaise, constipation, decreased libido, and muscle cramps were referred from the Department of Otolaryngology to the Endocrinology Clinic for further evaluation and management.
Eligible participants were post-radiotherapy, recurrence-free NPC patients who were referred to the Endocrinology Clinic. A total of 43 patients were recruited into this study, including 8 new patients referred during the study period and 35 previous patients before the study was conducted. All of the patients received a total of 7,000 cGy on the primary lesion and an estimated total dose to the hypo-thalamic-pituitary area of 4,600 to 5,600 cGy. Written informed consent and approval from the Institutional Review Board were obtained before data collection began.
Patients were seen individually at the outpatient clinic and were asked to complete four self-reported questionnaires: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0 (EORTC QLQ-C30 v. 3), the EORTC Head and Neck Cancer Module (EORTC QLQ-H&N35), the Beck Depression Inventory–II (BDI- II), and the Beck Anxiety Inventory (BAI).
A well-trained research assistant recorded the demographic and clinical data, and assisted participants in completing the question-naires if needed.
Measures
The EORTC QLQ-C30 core questionnaire(16, 17)is a validated and broadly used instrument for a self-assessment of different di-mensions of health-related QoL and symptom scores relevant to cancer patients. It is a 30-item questionnaire scored on a four-point scale (1 = not at all, 4 = very much). All scales (five functioning, three symptom, and one global health status/QoL) and single-item measures (five additional symptoms) ranged in a transformed score of 0 to 100. A high score for the functional scale represented a high/ healthy level of functioning. A high score for the global health sta-tus/QoL represented a high QoL. A high score for the symptom scale/item represented a high level of symptomatology/problems.
The EORTC QLQ-H&N35 is a site-specific module for head-and-neck cancer as a supplement to the EORTC QLQ-C30. Both were translated into Chinese and validated in Taiwan (18). The internal consistency for scales of QLQ-C30 and QLQ-H&N35 as Cronbach’s a coefficient ranged from 0.75 to 0.92, except for cognitive functioning (0.51).
Emotional status was measured using the Chinese version of BDI-II(19) and BAI(20, 21). BDI-II is a 21-item, four-point Likert-scored scale (0 = not at all, 3 = always) that assess the presence
and severity of affective, cognitive, motivational, vegetative, and psychomotor components of depression in the last 2 weeks. Items in BDI-II include questions on changes in sleep patterns, changes in appetite, tiredness or fatigue, degrees of sadness, feelings of guilt and pessimism, and others. Higher scores indicate more severe depression. The BDI-II has produced reliable and valid results (22–24). The Cronbach’s a coefficient was 0.93 in this study.
The BAI is a valid and reliable self-report checklist for anxiety symptoms(25, 26). It consists of 21 items that assess the presence and severity of their anxiety symptoms, both psychological (e.g., feelings of nervousness and fear) and physical (e.g., heart pounding, hands trembling), in the previous week on a four-point scale (0 = not at all, 3 = severely, I can barely stand it). Higher scores indicate more severe anxiety. The Cronbach’s a coefficient was 0.91 in this study.
Statistical analysis
The mean scores of the five dimensions of functional scales, symptom scales, and global health/QoL in the QLQ-C30 and symp-tom scales in QLQ-H&N35 were calculated according to the EORTC Scoring Manual(27). Patients with a BAI score >7 were defined as having anxiety(20). Depression was defined as a BDI-II score >13 (19). The Student t test was used for comparison between groups (mean scores).
Pearson’s correlation was performed to examine the relationship between the scales, while stepwise multiple linear regression was used to explore predictors of the global QoL and their relationship between emotional status and QoL. All tests were two-tailed, and a 5% significance level was used for statistical significance. The SPSS for Windows, version 12.0 software package (SPSS Inc., Chicago, IL) was used for data processing.
RESULTS
Basic background information of the patients is shown in Table 1. The mean age was 52.0 8.7 years (median, 52.0 years; range, 33–68 years). Of the patients, 17 (39.5%) pa-tients were male. A total of 24 papa-tients (55.8%) were unem-ployed. The postradiation time varied: <5 years in 15 patients (34.9%), 5–10 and 10–15 years in 9 patients (20.9%), and >15 years in 10 patients (23.2%). The mean time after radio-therapy was 114.4 94.4 months (median, 104.0 months; range, 4–411 months).
Of the 43 patients, 41 (95.4%) had growth hormone defi-ciency, 27 (62.8%) had hypothyroidism, 12 (27.9%) had ad-renal insufficiency, 11 (25.6%) had hypogonadism, and 9 (20.9%) had hyperprolactinemia.Table 2presents the mean scores for each scale of EORTC C30 and QLQ-H&N35. The mean of the total scores of the five functional scales of the EORTC QLQ-C30 was 75.9 20.2, whereas the mean score of the nine symptom scales was 20.6 16.2. The mean score for the global health status/QoL was 52.7 24.2 and the score of symptom distress specific to NPC was 37.1 20.9.
Emotional and cognitive functionings (69.0 28.0 and 70.5 26.2, respectively) were affected significantly, and fa-tigue (39.0 26.6), insomnia (34.9 33.3), and pain (26.0 28.2) were the main complaints. The mean score of global QoL was low (52.7 24.2). The most distressful symptoms specific to NPC patients were dry mouth (72.1 29.9), sticky saliva (59.7 36.8), and dental problems (48.1 32.8).
In all, 22 (51.2%) patients had anxiety, 19 (44.2%) had de-pression, and 13 (30.2%) had both, whereas 14 (32.6%) had neither. Both depression and anxiety were significantly and negatively correlated with functional scales and global health
status/QoL (Pearson’s correlation coefficientr =0.388 to 0.702), but were significantly and positively correlated with symptom scales (r = 0.321–0.690), except for dyspnea and constipation.
A comparison of total function and symptoms, and global health status/QoL scores between patients with and those without anxiety/depression revealed significant differences. The detailed mean scores for each scale are shown inTable 3. Patients with anxiety demonstrated significantly poor tioning and global health status/QoL except for social func-tioning. Fatigue, pain, dyspnea, and insomnia were more serious and significantly different as compared with those of nonanxious patients. Depressed patients reported signifi-cantly poor functioning in all dimensions and in perceived global health status/QoL. They also presented with symp-toms of fatigue, nausea/vomiting, insomnia, and appetite loss, which were statistically different from patients without depression.
There were significantly different scores of total symptom scales between patients with and those without anxiety or de-pression in terms of detailed mean scores for the H&N35 symptom scales (Table 4). Almost every symptom was scored higher among patients with anxiety, although not statistically significant, except for swallowing problems. However, many problems, including those related to swal-lowing, speech, social eating, social contact, sexuality, teeth, and feeling ill were scored significantly higher among pa-tients with depression.
Univariate analysis did not reveal any significant relation-ship in demographic variables (age, sex, marital status, level of education), emotional status (anxiety, depression), and global health status/QoL. However, postradiation time was a relevant variable to QoL(28). Variables used for evaluating their contribution to QoL were the five functioning dimen-sions: symptom scales, H&N35 symptom scales, postradia-tion time, BDI-II, and BAI.
Table 1. Demographic variables and clinical data of the study subjects (n = 43) Variable No. (%) Age (y) Mean SD 52.0 8.7 Median 52.0 Range 3368 Gender Male 17 (39.5) Female 26 (60.5)
Education level (yr)
#6 13 (30.2) 712 14 (32.6) $13 16 (37.2) Occupational status Full-time work 16 (37.2) Part-time work 3 (7.0) Unemployed 24 (55.8)
Time after radiotherapy (mo)
Mean SD 114.4 94.4
Median 104.0
Range 4411
Endocrinopathy
Growth hormone deficiency 41 (95.4%)
Hypothyroidism 27 (62.8%) Adrenal insufficiency 12 (27.9%) Hypogonadism 11 (25.6%) Hyperprolactinemia 9 (20.9%) Marital status Unmarried 5 (11.6) Married 34 (79.1) Separated 1 (2.3) Divorced 1 (2.3) Widower/widow 2 (4.7)
Abbrevation: SD = standard deviation.
Table 2. Mean scores and standard deviation for different scales of EORTC QLQ-C30 and EORTC QLQ-H&N35
EORTC QLQ-C30 Mean SD Median EORTC QLQ-H&N35 Mean S.D. median
Functional scales 75.9 20.2 79.7 Symptom scales 37.1 20.9 38.2
Physical 81.4 19.2 86.7 Pain 12.6 19.8 8.3
Role 79.1 28.9 83.3 Swallowing 33.1 27.3 25.0
Emotional 69.0 28.0 75.0 Senses problems 26.7 27.5 16.7
Cognitive 70.5 26.2 83.3 Speech problems 33.6 30.3 22.2
Social 77.0 28.0 91.7 Trouble with social eating 30.6 30.2 16.7
Symptom scales 20.6 16.2 16.0 Trouble with social contact 19.8 23.9 6.7
Fatigue 39.0 26.6 33.3 Less sexuality 37.5 37.3 33.3
Nausea/vomiting 4.3 11.0 0 Teeth 48.1 32.8 33.3
Pain 26.0 28.2 16.7 Opening mouth 42.6 39.4 33.3
Dyspnea 17.1 22.3 0 Dry mouth 72.1 29.9 66.7
Insomnia 34.9 33.3 33.3 Sticky saliva 59.7 36.8 66.7
Appetite loss 19.4 31.1 0 Coughing 35.7 35.2 33.3
Constipation 20.2 26.4 0 Felt ill 42.6 29.4 33.3
Diarrhea 9.3 18.3 0
Financial 15.5 31.2 0
Global health status/QoL 52.7 24.2 50.0
Abbreviations: EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ-H&N35 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer Ques-tionnaire Module; Financial = financial difficulty; QoL = quality of life.
A series of stepwise linear regression analyses was per-formed, which demonstrated that physical distress symptoms of QLQ-C30 and physical functioning were the significant predictors of QoL (Table 5). Physical distress symptoms ac-counted for 52% of the variance in the final model, and phys-ical functioning explained an additional 10.7% (F = 31.31, p < 0.001).
To predict depression, the five functioning dimensions and global health status/QoL variables were entered into the re-gression analysis. We found that the model explained 53.7% of the variance (F = 23.59, p < 0.001). Emotional functioning (p = 0.001) and social functioning (p = 0.003)
were the significant predictors. For predicting anxiety, the model explained 58.1% of the variance (F = 35.64, p < 0.001). Emotional functioning and physical functioning were the significant predictors of anxiety (Table 6).
DISCUSSION
The present study investigates the QoL of post-radiother-apy NPC patients complicated with endocrinopathy, and its relationship with emotional status. The results demonstrate that emotional and cognitive functionings are significantly affected over other measures of function. The low mean
Table 3. Comparison of scores of quality of life dimensions between patients with and those without anxiety or depression
Anxiety Depression
EORTC QLQ-C30 With Without p Value With Without p Value
Functional scales 68.5 18.8 86.5 12.4 0.001 66.2 18.8 86.0 12.3 0.001 Physical 75.2 21.4 90.3 9.6 0.005 75.4 22.8 88.1 11.2 0.036 Role 72.7 29.3 90.0 19.8 0.030 70.2 31.7 89.9 17.2 0.022 Emotional 56.4 25.6 86.3 16.3 <0.001 55.7 25.6 83.0 19.7 <0.001 Cognitive 61.4 30.2 81.7 16.1 0.010 60.5 27.3 79.7 22.5 0.017 Social 73.8 28.7 84.2 21.3 0.198 65.7 30.0 89.1 15.6 0.006 Symptom scales 27.1 15.9 11.4 8.4 <0.001 29.5 15.0 11.4 8.9 <0.001 Fatigue 46.5 26.0 27.8 20.6 0.014 51.5 26.2 26.1 17.6 0.001 Nausea/vomiting 6.1 13.2 0.8 3.7 0.086 7.9 14.0 .00 .00 0.025 Pain 36.4 28.5 10.8 14.6 0.001 32.5 26.3 17.4 24.4 0.062 Dyspnea 25.8 25.1 8.3 14.8 0.010 22.8 15.9 13.0 26.1 0.162 Insomnia 48.5 32.1 18.3 27.5 0.002 52.6 33.9 18.8 24.3 0.001 Appetite loss 21.2 28.3 13.3 29.4 0.381 29.8 33.1 7.3 20.0 0.015 Constipation 21.2 30.1 16.7 20.2 0.573 26.3 30.6 13.0 19.4 0.096 Diarrhea 13.6 22.2 5.0 12.2 0.124 15.8 23.2 4.4 11.5 0.061 Financial 24.2 35.9 1.7 7.5 0.008 26.3 37.8 2.9 9.6 0.016
Global health status/QoL 47.4 26.8 61.3 15.8 0.050 39.9 22.0 65.6 16.9 <0.001
Data presented as mean standard deviation.
Abbreviations: EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; Financial = financial difficulties; QoL = quality of life.
Table 4. Comparison of EORTC H&N-35 scores between patients with and without anxiety or depression
Anxiety Depression
EORTC H&N-35 With Without p Value With Without p Value
Symptom scales 41.18 18.70 29.10 16.17 0.041 44.66 18.80 28.77 15.18 0.007
Pain 9.85 15.57 11.25 13.59 0.759 11.84 14.52 9.42 14.72 0.596
Swallowing 39.02 24.04 23.33 25.16 0.045 42.11 28.39 22.83 19.50 0.013
Senses problems 28.03 23.22 21.67 27.63 0.422 30.70 25.62 20.29 24.60 0.188
Speech problems 34.34 28.26 29.44 30.00 0.589 42.69 32.56 23.19 22.45 0.034
Trouble with social eating 36.51 30.45 20.83 24.56 0.078 42.59 34.29 18.12 17.16 0.011
Trouble with social contact 22.86 21.35 12.67 18.59 0.112 29.63 23.46 8.70 11.62 0.002
Less sexuality 44.44 37.76 25.93 32.95 0.114 52.94 40.50 22.72 26.99 0.013 Teeth 54.55 31.78 38.33 31.11 0.103 57.89 33.04 37.68 28.96 0.041 Opening mouth 45.45 40.56 36.67 37.31 0.471 52.63 42.04 31.88 34.05 0.085 Dry mouth 77.27 27.96 65.00 31.48 0.188 75.44 29.06 68.12 30.94 0.437 Sticky saliva 63.64 35.50 53.33 38.08 0.370 66.67 40.06 52.17 33.07 0.206 Coughing 40.91 36.99 26.67 29.81 0.180 33.33 33.33 34.78 35.50 0.893 Felt ill 46.97 30.27 35.00 25.31 0.174 57.89 29.06 27.54 19.21 <0.001
Data are presented as mean standard deviation.
Abbreviations: EORTC QLQ-H&N35 = The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer Questionnaire Module.
scores of emotional functioning are similar to those of previ-ous studies(29, 30).
In this study, the median time point for the assessment of QoL after radiotherapy is 8.67 years, which was 5.9 years and 3.4 years in the studies by Huguenin and Cengiz, respec-tively(29, 30). This indicates that a lack of emotional well-being is a complication of radiotherapy that is long lasting and probably not easy to overcome.
Our subjects’ cognitive functioning scores were relatively lower than those in the studies by Hugueninet al.(29), Cen-gizet al.(30), and Chieet al.(18). The latter was conducted at the Department of Otolaryngology of the National Taiwan University Hospital, where the subjects did not have endo-crinopathy. Memory impairment, intellectual deficits, and other cognitive problems in NPC patients after radiotherapy have been documented by previous researchers (9–11). From these studies, the median time for neuropsychologic dysfunction relating to temporal lobe radio-necrosis was about 5 years, whereas that for endocrine dysfunction was 8 years. In this study, the median time after radiotherapy was 8.67 years. Therefore, profound cognitive function im-pairment was highly correlated with cranial irradiation.
As to global health status/QoL, the mean scores were also remarkably lower (52.7 24.2) as compared with previous studies that had similar irradiation dosages for NPC (18, 29, 30). Because our patients’ cases were complicated by en-docrine problems although these patients had been receiving hormonal therapy, the debilitating situation might explain their lower scores of emotional and cognitive functioning, as well as the global health status/QoL. The most severe symptoms were fatigue, insomnia, and pain, and the distress-ful symptoms specific to NPC patients were dry mouth and sticky saliva. These presentations were consistent with earlier studies(4, 5, 18, 29, 30).
From the BAI and BDI assessment, one third of patients had neither anxiety nor depression. Several studies using BDI to screen depression among cancer patients showed that the prevalence of depression was approximately 15% to 20%(24, 31–33). In the study by Fowleret al., 29% of gy-necologic cancer patients showed significant anxiety using the BAI assessment (34). Compared with these, the higher percentage of depression and anxiety in our results indicate that our subjects’ endocrinopathy probably contributed to
their emotional status. Although our subjects received appro-priate adrenal, thyroid, and gonadal hormone replacement therapy, 41 patients (95.4%) with growth hormone deficiency were reluctant to take growth hormone supplement because of the high cost of the treatment regimen and the inconve-nience in terms of daily injection.
Physiologic effects of growth hormone deficiency in adults and the benefits of growth hormone replacement are well docu-mented(35). As to the psychological impact, which includes decreased energy, increased tiredness, irritability, pain, depres-sion, social isolation, and impaired QoL, these are demonstrated from many studies(36–39). Possible mechanisms by which growth hormone may improve QoL at the neural and somatic sites are being proposed and are still under investigation(36). Moreover, there is neuropsychological evidence that growth hormone deficiency is associated with cognitive impairment in adults and treatment with growth hormone can improve cog-nitive function(40–42). Therefore, growth hormone deficiency in our subjects may play an important role in psychological morbidity, impaired QoL, and cognitive function.
Patients with the complication of endocrinopathy have to be closely followed to monitor their physical condition and to examine their endocrine parameters, aside from hormonal therapy. Whether their frequent hospital visits reinforce their sick roles and affect their psychological well-being needs more exploration. A study by Chawlaet al. regarding the tem-poral assessment of QoL in head-and-neck cancer patients receiving radiotherapy revealed that BDI scores increased during weeks 3 to 4 and were improved but not restored to pretreatment levels at 3 months post-radiotherapy (43). In this study, we did not assess our subjects at multiple time points, and the postradiation time did not contribute to the QoL as a result of the rejection by the regression model.
There was a strong association between emotional status and role functions and symptoms. Patients with anxiety or
Table 5. Multiple linear regression analysis of functioning, symptoms, and post-radiation time to global health status/
quality of life
Model b-coefficient SE p Value Adj. R2
1 (Constant) 76.748 4.182 <0.001
Symptom scales* 1.113 0.176 <0.001 0.520
2 (Constant) 27.543 15.204 0.079
Symptom scales* 0.752 0.189 <0.001
Physical functioning 0.514 0.154 0.002 0.627
Abbreviations: Adj. = adjusted; EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; SE = standard error.
* Subscale of EORTC QLQ-C30.
Table 6. Multiple linear regression analysis of functioning dimensions and global health status/quality of life to
emotional status BDI-II
Model b-coefficient SE p Value Adj. R2
1 (Constant) 34.390 3.991 <0.001 Emotional functioning 0.290 0.053 <0.001 0.429 2 (Constant) 40.980 4.167 <0.001 Emotional functioning 0.199 0.056 0.001 Social functioning 0.168 0.054 0.003 0.537 BAI
Model b-coefficient SE p Value Adj. R2
1 (Constant) 27.775 3.399 <0.001
Emotional functioning 0.252 0.045 <0.001 0.435
2 (Constant) 41.923 4.717 <0.001
Emotional functioning 0.219 0.039 <0.001
Physical functioning 0.200 0.052 <0.001 0.581
Abbreviations: Adj. = adjusted; BAI = Beck Anxiety Inventory; BDI-II = Beck Depression InventoryII; SE = standard error.
depression demonstrated poorer functioning, especially emotional and cognitive functioning, global QoL, and more serious symptoms. As expected, depressive cases manifested more impaired social function. The significant symptoms reported also fitted the symptomatology of anxiety or depres-sion. As to the relationship between QoL and emotional sta-tus, regression analysis revealed that impaired social functioning could explain depression in addition to the con-tribution of emotional functioning measured by EORTC QLQ-C30. Poorer physical functioning also accounted for anxiety, along with emotional functioning.
These results indicate the strong predictive power of emo-tional functioning in EORTC QLQ-C30 for psychological morbidity, which is consistent with the findings of Mystaki-douet al.(44). However, our results highlight the predictive power of social functioning in depression and physical func-tioning in anxiety.
With regard to QoL, we focused on the global QoL be-cause we were more interested in the dimensions that affected the patients’ overall perception of QoL. Multiple regression analysis demonstrated stressful symptoms and physical functioning significantly predicted global QoL. This result was not compatible with a study conducted in Switzerland(29), in which NPC patients reported the high-est morbidity on the H&N module although there was no great impact on global QoL. However, that study included only 12 NPC cases, and no further analysis was performed to verify the conclusions. As compared to the general population, the study conducted in Finland indicated that global QoL judgments were likely to be based on emotional status(45).
In the current study, we found that physical distress played a much more important role in the perception of QoL. These distressful symptoms might hamper physical functioning and lead to dissatisfaction with the QoL. However, the symptoms included in the EORTC QLQ-C30, but not in the H&N35 module, were strongly associated with global QoL. Although we closely examined the salient symptoms (i.e., fatigue, insomnia, pain), we thought these actually inferred several psychological components. Therefore, careful management
of side effects after radiotherapy is important and masked depression and anxiety needs more careful attention from the clinician for early detection.
The limitation of this study is the specific recruitment of patients with endocrinologic complications. As such, our re-sults only represent the QoL in a more serious or chronic group and cannot be generalized to all post-radiotherapy NPC patients.
Based on our findings here, several issues need to be ex-plored. First, should sophisticated neuropsychological tests be used to verify the nature and magnitude of cognitive im-pairment after screening by EORTC QLQ-C30? Second, is the cognitive impairment solely due to late temporal lobe ne-crosis after irradiation or related to growth hormone defi-ciency? Third, does growth hormone replacement have beneficial effects to some or all cognitive functions and neg-ative emotions?
Furthermore, the endocrinopathies that occur after radio-therapy should be considered a potential surrogate that could be helpful in the identification of patients who might be at risk for emotional distress. Early recognition is crucial and other surrogates should be sought. Routine application of the EORTC QLQ-C30 at multiple time points is suggested to help clinicians provide timely and effective therapy. Fur-ther large scale, sequential, and prospective investigations into the interrelationship among emotions, brain functioning, and endocrine markers are also highly recommended to elucidate the impact of irradiation.
CONCLUSIONS
In conclusion, NPC patients with post-radiotherapy endo-crinopathy demonstrate impaired cognitive function and ob-vious negative emotions that are strongly associated with functional status, physical distress, and QoL. The different dimensions of EORTC QLQ-C30 seem to mirror depression or anxiety as measured by BDI or BAI, making it a potentially useful instrument for the early identification of patients at risk for difficulties and compromised QoL.
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