Health-related Quality of life in 640 head and neck cancer survivors after radiotherapy using EORTC QLQ-C30 and QLQ-H&N35 questionnaires

This study is a cross sectional investigation, analyzing HR-QoL data of HNC patients who were cancer free when their HR-QoL was assessed during the period from January 2005 to December 2008. Eligibility criteria of patients included 1) pathologically proven HNC at nasopharynx, oral cavity, oropharynx, hypopharynx, or larynx, 2) receiving RT and regular follow-up at the department of radiation oncology at Chang Gung Memorial Hospital - Kaohsiung Medical Center, 3) cancer free survival more than two years after RT, and 4) completion of the self-reported questionnaire. Six hundred and forty HNC patients, treated with definite or postoperative RT, were collected and informed consent was obtained from all of them. They included 371 patients treated by 2DRT and 269 patients by conformal RT (3DCRT: 127 patients, IMRT: 142 patients). Concerning the existence of selection bias, we compared the distributions of sociodemographic characteristics (including age, gender, marital status, and education level) between HNC survivors in the study and all other surviving HNC patients (n = 221) found in the cancer registry database in the department. No statistically significant differences were found between them (data not shown).

Patient characteristics including sociodemographic variables and cancer- or treatment- related variables are listed in Table 1. The cancer stages were according to the staging system of the American Joint Committee on Cancer (AJCC 6^th edition) published in 2002. The comorbidity status was recorded according to the Charlson comorbidity index by review of chart and on the basis of self-report [17]. A summary of the primary cancer site included 316 cases (49%) of nasopharyx, 129 (20%) of oral cavity, 75 (12%) of oropharynx, 75 (12%) of hypopharynx, and 45 (7%) of larynx. As regards the sociodemographic information, 86% of them were educated ≦12 years, 53% with an annual family income ≦1.2 million NTD (1USD = 33NTD), 65% not employed, and 19% without a spouse (unmarried or divorced). Four hundred and thirty patients (67%) had AJCC stage III or IV disease and 267 (42%) patients had at least one kind of comorbidity. The major treatment was surgery in 249 (39%) patients and RT alone or plus C/T in 391 (61%) patients. Uneven distribution existed between the 2DRT and 3DCRT/IMRT group. The 3DCRT/IMRT group had a higher distribution in patients with lower annual family income, non-nasopharyngeal cancer site, stage III-IV, surgery, chemotherapy, or shorter survival years. The median (range) follow-up years of patients after treatment when their HR-QoL data were collected were 5.2 (2.8-14.1), 3.9 (2.1-10.3), and 3.1 (2.0-6.5) years in the 2DRT, 3DCRT, and IMRT group, respectively. This study was approved by the appropriate institutional review boards (IRB) of the hospital.

The Taiwan Chinese versions of the EORTC QLQ-C30 and QLQ-H&N35 questionnaires were obtained from the Quality of Life Unit, EORTC Data Center in Brussels, Belgium [4, 6, 22]. The EORTC questionnaires were chosen for this research because it is one of the most widely implemented questionnaires, with over 10 years of research invested to develop an integrated, modular approach, as well as utilization of the instrument in international clinical trials, and the Taiwan Chinese version is available and easily completed by our patients [23]. The EORTC QLQ-C30 incorporates a range of HR-QoL issues relevant to a broad range of cancer patients. It has been translated into many languages and validated for many types of cancer, including head-and-neck cancer. It contains five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain, and nausea/vomiting), a global QoL scale, and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-H&N35 is a module used for assessing the HR-QoL for head-and-neck cancer patients. It incorporates seven multiple-item scales that assess the symptoms of pain, swallowing ability, senses (taste/smell), speech, social eating, social contact, and sexuality. Also included are six single-item scales, which survey the presence of symptomatic problems associated with teeth, mouth-opening, dry mouth (xerostomia), sticky saliva, coughing, and feeling ill. All scales pertaining to the EORTC QLQ-C30 and QLQ-H&N35 range from zero to 100. A high score for a functional or global HR-QoL scale represents a relatively high/healthy level of functioning or global quality of life, whereas a high score for a symptom scale represents the presence of a symptom or problem(s).

The mean scores and standard deviations of the HR-QoL scales were calculated according to the EORTC QLQ scoring manual [24]. To analyze the correlations between the factors and the HR-QoL scales, general linear model (GLM) multivariate analysis of variance (MANOVA) was used [25]. The GLM-MANOVA approach is used to test the hypothesis of a significant association between a set of interrelated dependent variables (HR-QoL scales) and independent variables. The independent variables analyzed in the present study consisted of five sociodemographic variables: age (<40 v. 40~60 v. ≥ 60 years), sex (male v. female), years of education years (≤6 v. 6~12 v. >12 years), marital status (with v. without spouse), and annual family income (<0.6 v. 0.6~1.2 v. ≥1.2 million NTD), and six clinical factors: CCI score (0 v. ≥1), tumour site (Oral cavity v. Oropharynx v. Hypopharynx/Larynx v. Nasopharynx), AJCC stage (stage I-II v. III-IV), treatment methods (surgery + RT v. surgery + RT + C/T v. RT ± C/T), RT technique (2DRT v. 3DCRT v. IMRT), and follow-up years (2~3 v. 3~5 v. > 5).

Being the most concerned scales of HR-QoL in the study, the global QoL and xerostomia were further analyzed by multiple linear regression models to explore their associated prognosticators, respectively. All the data processing was performed using the statistic software SPSS for Windows (version 15.0; SPSS Inc., Chicago, IL).

The mean score for global QoL was 54.6. The value of the five scales of functioning ranged from 75.1 (social functioning) to 86.4 (role functioning). The highest symptom score on QLQ-C30 was for fatigue, followed by financial problems and insomnia. In the H&N35 module, dry mouth, sticky saliva, and tooth problems ranked as the three worst symptoms. (Table 2)

In the first step of the GLM-MANOVA, the association between the independent variables (five sociodemographic and six clinical variables) and the dependent variables (15 scales of QLQ-C30) was investigated (one-factor model, Table 3). This analysis showed that 10 of the 11 variables (except the length of follow-up) (p < 0.05) were associated with the overall outcome on QLQ-C30. The 11 variables were then entered into the multifactor model analysis, which indicated that the variables of gender, annual family income, tumor site, AJCC stage, treatment methods, and RT technique remained significant. The same statistical procedures were repeated for the analysis of the association between the 11 independent variables and the scales of H&N35. In a one-factor model, four of the five sociodemographic variables and four of the six clinical variables (except CCI and the length of follow-up) were significantly (p < 0.05) associated with the overall outcome on H&N35. In the multifactor model, only tumor site and RT technique remained significant (Table 3).

The variables specifically associated with global QoL and xerostomia were further analyzed. As demonstrated by linear regression model in Table 4 we observed a significant trend that survivors with CCI ≥ 1 (β = 5.2, p = 0.034), tumor sits at nasopharynx (β=-9.1, p = 0.034), or treated by 2DRT (β=-12.2, p < 0.01) had a higher probability to report a high level of xerostomia. Meanwhile, survivors with family annual income ≧1.2 million NTD (β = 5.2, p < 0.01), CCI = 0 (β=-6.1, p < 0.01), or treated by 3DCRTor IMRT (β = 7.7, p < 0.01) had a higher probability of reporting a better global QoL.

Significant difference (p < 0.05) of HR-QoL outcome at different tumor sites was observed at 11 of the 15 scales in QLQ-C30 and 10 of the 13 scales in H&N35 (Table 5). Compared with nasopharyngeal cancer survivors, three worse scales (social eating, social contact, and opening mouth) were significantly observed on oral cancer survivors, so were six scales (appetite loss, pain, swallowing, speech, social eating, and social contact) on oropharyngeal cancer survivors and eight scales (physical functioning, role functioning, dyspnea, constipation, swallowing, speech, social contact, coughing) on hypopharyneal/laryngeal cancer survivors. Meanwhile, compared with oral cavity survivors, five worse scales (cognitive functioning, fatigue, nausea/vomiting, appetite loss, and pain) were observed in oropharyngeal cancer survivors, and five worse scales (physical functioning, nausea/vomiting, dyspnea, speech, and coughing) in hypopharyneal/laryngeal cancer survivors. On the contrast, better results in opening mouth and dry mouth were observed in hypopharyneal/laryngeal cancer survivors compared with the other survivors.

Significant difference (p < 0.05) of HR-QoL outcome by different RT techniques was observed at 2 of the 15 scales in QLQ-C30 and 10 of the 13 scales in H&N35 (Table 6). Compared with 2DRT, IMRT had significant better outcome in the scales of global QoL, physical functioning, swallowing, senses (taste/smell), speech, social eating, social contact, teeth, opening mouth, dry mouth, sticky saliva, and feeling ill. Only three scales (teeth, dry mouth, and sticky saliva) with better results were observed in 3DCRT compared with 2DRT. IMRT had better scores in most scales compared with 3DCRT, but without reaching statistically significant difference.