assessment of quality of life of nasopharyngeal carcinoma patients ...

Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 5, pp. 1347–1353, 2005 Copyright © 2005 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/05/$–see front matter

doi:10.1016/j.ijrobp.2005.05.057

CLINICAL INVESTIGATION

Head and Neck

ASSESSMENT OF QUALITY OF LIFE OF NASOPHARYNGEAL CARCINOMA PATIENTS WITH EORTC QLQ-C30 AND H&N-35 MODULES MUSTAFA CENGIZ, M.D.,* ENIS ÖZYAR, M.D.,* MUSTAFA ESASSOLAK, M.D.,* MUSA ALTUN, M.D.,* MÜGE AKMANSU, M.D.,* MEHMET S¸EN, M.D.,* ÖMER UZEL, M.D.,* AYDıN YAVUZ, M.D.,* GAMZE DALMAZ, M.D.,* CEM UZAL, M.D.,* AYS¸E HIÇSÖNMEZ, M.D.,* SÜREYYA SARIHAN, M.D.,* BÜNYAMIN KAPLAN, M.D.,* BESTE MELEK ATASOY, M.D.,* CÜNEYT ULUTIN, M.D.,* UFUK ABACIOG˘ LU, M.D.,* AYS¸E NUR DEMIRAL, M.D.,* AND MUTLU HAYRAN, M.D.† *Turkish Oncology Group (TOG)–Head and Neck Cancer Working Party, and †Department of Preventive Oncology, Hacettepe University, Ankara, Turkey Purpose: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. Patients and Methods: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient’s 33 QoL scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. Results: One hundred eighty-seven patients with median age of 46 years (range, 16 –79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months–24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n ⴝ 85 [45.4%]; Stage IV, n ⴝ 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on QoL, whereas concomitant chemotherapy adversely affected 5 symptom scores. Conclusion: Quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined therapies. The factors that adversely affect quality of life are advanced tumor stage, female gender, and long-term follow-up. Further controlled studies to evaluate both preradiotherapy and postradiotherapy status are necessary to clarify the contribution of each treatment modality to QoL. © 2005 Elsevier Inc. Nasopharyngeal cancer, Radiotherapy, Quality of life, EORTC questionnaire, Chemotherapy.

INTRODUCTION

like other head-and-neck carcinomas, it is seen in a young age group and is not associated with smoking or alcohol abuse. The primary treatment of NPC is radiotherapy alone or chemoradiotherapy, depending on stage of the disease, and surgery is generally not an initial option. The tumor is located in close proximity to base of the skull and important vital structures, such as optic nerves, optic chiasma, brain, ears, and major salivary glands. Most of these structures are

Whereas the incidence of nasopharyngeal carcinoma (NPC) is greater than 20 of 100,000 in Southern China, it is less than 1 of 100,000 in most of the United States and Western Europe. However, an intermediate incidence rate is observed among the peoples of the Mediterranean region where Turkey is located (1). NPC has several unique features compared with other head-and-neck carcinomas. UnReprint requests to: Mustafa Cengiz, M.D., Department of Radiation Oncology, Hacettepe University, Sihhiye, Ankara 06100, Turkey. Tel: (⫹90) 312-305-2903; Fax: (⫹90) 312-309-2914; E-mail: [email protected] Presented at the 46th Annual Meeting of the American Society

for Therapeutic Radiology and Oncology (ASTRO), October 3–7, 2004, Atlanta, GA. Received April 22, 2005 and in revised form May 31, 2005. Accepted for publication May 31, 2005. 1347

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● Biology ● Physics

included within or in close proximity to the radiotherapy field. After radiotherapy, late effects such as xerostomia, trismus, swallowing difficulties, neck stiffness, hearing problems, and neuroendocrine dysfunction may lead to deterioration of patients overall well-being (2). In addition to such conventional outcome parameters as survival and disease-free survival, subjective well-being of patients cured of their disease is equally important and is increasingly emphasized in the literature (3). Disturbances of the patient, singly or in combination, profoundly affect quality of life (QoL). QoL is most appropriately considered to be a construct that reflects the individual’s perception of overall well-being. The QoL concerns are a fundamental aspect of care for patients with head-and-neck cancer, and this concern is reflected by a growing interest in the investigation of QoL issues (4). In previous studies, self-assessment by patients of the complaints caused by disease and treatment side effects was found to yield worse results compared with assessment by physicians (5, 6). Self-assessment by the patients should, therefore, become an integrated component of the analysis of treatment results. This critical tool should be included in the assessment of the risks and benefits associated with different treatment options such as intensity-modulated radiotherapy (IMRT) and novel chemoradiotherapy schedules (7). Although several QoL studies in patients with head-andneck cancer have been reported in the literature, data concerning QoL in patients with NPC are only rarely reported (8 –12). These few reported series used Fact-G, Chinese SF-36, or University of Washington questionnaires for the evaluation of QoL issues. To the best of our knowledge, the current QoL study of NPC patients is the first published study that made use of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30 and the head-and-neck (H&N) 35 module. PATIENTS AND METHODS Patients with the diagnosis of nonmetastatic NPC from 14 TOG (Turkish Oncology Group) member radiation oncology centers with a minimum of 6 months follow-up were included in the current study. All centers were academic university hospitals, coordinated by the Department of Radiation Oncology at Hacettepe University. Patients were asked to complete Turkish versions of the EORTC QLQ-C30 and the H&N-35 module during their latest follow-up visit to the hospital. Inclusion criteria were history of NPC treated by radiotherapy or chemoradiotherapy without any evidence of second primary or recurrent tumor at their latest evaluation and freedom from major psychiatric disorder that might confound QoL evaluation. Each center provided clinical data that included age at diagnosis, gender, tumor stage according to the AJCC 1997, treatment modalities, and radiotherapy parameters. No limitations were imposed with regard to age or performance status.

Questionnaires A core QoL questionnaire—EORTC QLQ-C30 version 3.0 (13)—is used together with diagnosis-specific modules to increase

Volume 63, Number 5, 2005

the coverage, sensitivity, and specificity of the assessments in various patient and treatment groups. It is a cancer-specific, selfreport questionnaire validated in several studies and includes 30 questions. The cross-cultural validity and psychometric properties are considered satisfactory (14 –16). The questionnaire comprises 5 functioning scales (physical, role, emotional, cognitive, and social functioning), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status/QL scale. The EORTC QLQ H&N-35 module is designed to be used together with the core QLQ-C30 to measure symptoms and problems related to tumor location and treatment. Seven subscales have been constructed that measure pain, swallowing, sense, speech, social eating, social contact, and sexuality. Eleven items relate to teeth, mouth opening, dry mouth, sticky saliva, coughing, ill feeling, weight loss, weight gain, use of pain killer, nutritional supplements, and feeding tube. The time frame of the module is “during the past week,” and the format is similar to the core questionnaire. Thirty-five questions regarding the functions and symptoms of the patients were included in this questionnaire. Each patient’s 33 QoL scores, including function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/ problems. Statistical analyses made use of the Kruskal-Wallis test for variables with more than 2 categories and the Mann-Whitney U-test for pairwise comparisons that accounted for the nonparametric distribution of the QoL scores. A p value of 0.05 was used to flag significant determinants.

RESULTS One hundred eighty-seven patients with median age of 46 years (range, 16 –79 years) participated in this study by completing the questionnaires. The patient characteristics are summarized in Table 1. Median follow-up time is 3.4 years (range, 6 months–24 years). Most of the patients in the analysis (75%) were in advanced stage. Eighty-five patients (45.4%) and 55 patients (29%) had Stage III and Stage IV disease, respectively. All patients received external-beam radiotherapy by 6-MV linear accelerator or 60Co teletherapy machine. Median external-beam radiotherapy dose was 67.8 Gy (range, 50 –74 Gy) by use of conventional fractionation. Externalbeam radiotherapy was delivered in 2 lateral opposing portals. In addition to external-beam radiotherapy, 59 patients (32%) received adjuvant brachytherapy boost after externalbeam radiotherapy by HDR 192Ir source. Brachytherapy was delivered by use of a single-channel nasal applicator modified from a pediatric endotracheal tube. The brachytherapy dose was prescribed to a point 1 cm from the source axis, and a total dose of 12 Gy in 3 fractions was administered immediately after external-beam radiotherapy on 3 consecutive days. Median external-beam radiotherapy dose to na-

Quality of life of nasopharyngeal carcinoma patients

Table 1. Patient characteristics Characteristics Sex Male Female Stage I IIa IIb III IVA IVB Chemotherapy None Neoadjuvant Concomitant Adjuvant Radiotherapy dose ⬍70 Gy ⱖ70 Gy Brachytherapy Follow-up ⱕ4 years ⬎4 years

Number

%

121 66

64.7 35.3

9 13 24 86 37 18

4.8 7 12.8 46 19.8 9.6

49 70 70 25

26.2 37.4 37.4 13.4

79 108 59

57.8 42.2 31.6

111 76

59.4 40.6

sopharynx in the brachytherapy group was 66 Gy (range, 50 –72 Gy) and for the external-beam radiotherapy only group, median dose was 70 Gy (range, 50 –74 Gy). External-beam radiotherapy dose was significantly higher in the external-beam radiotherapy only group (p ⬍ 0.001). Overall, 138 patients (74%) were treated with chemotherapy beside external-beam radiotherapy. Whereas 70 patients received concomitant chemotherapy, 95 patients received adjuvant/neoadjuvant chemotherapy. Concomitant chemotherapy was solely cisplatinum and adjuvant/neoadjuvant chemotherapy was also cisplatin-based protocols. Only 3

● M. CENGIZ et al.

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patients underwent surgery in the form of neck dissection after radiotherapy. Our observation showed that completion of questionnaires took 15 to 30 minutes among the patients. Calculated scores for the QLQ-C30 and the H&N-35 module are shown in Tables 2 and 3, respectively. Mean global health status was calculated as 73. In our patient population, the highest symptom scores of EORTC QLQ-C30 were financial difficulties and fatigue. Among functional scales, emotional functioning was the worst and role functioning ranked the highest scores. In the H&N-35 module, dry mouth and sticky saliva ranked the highest scores, followed by weight gain, teeth problems, pain killers, and mouth opening. Global health status was better in patients with male gender, early-stage disease, and less than 4-year follow-up (p ⬍ 0.05) (Figs. 1 and 2). Functional parameters were better in males and in early-stage disease (p ⬍ 0.05). Factors that yielded better symptom scores were short interval after treatment (10 scores: dyspnea, pain, financial difficulties, swallowing, speech problems, trouble with social eating, coughing, feeling ill, pain killer, and weight gain), male gender (7 scores: fatigue, appetite loss, nausea-vomiting, sense problems, opening mouth, and feeling ill), and lower external-beam radiation dose (6 scores: financial difficulties, swallowing, sense problems, trouble with social eating, teeth problems, and dry mouth) (p ⬍ 0.05). Patients who received neoadjuvant or adjuvant chemotherapy did as well as patients who did not receive chemotherapy as far as QoL scores were concerned, whereas concomitant chemotherapy seem to adversely effect 5 symptom scores (insomnia, trouble with social eating, ill feeling, weight gain, and the need of nutritional supplement) when compared with radiotherapy-only patients. Because of a possible bias in which stage of the disease might determine the treatment, we ran the

Table 2. Calculated scores for QLQ-C30 Version 3.0 Scale name Global health status/QOL Global health status Functional Scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Symptom scales/items Fatigue Nausea and vomiting Pain Dyspnoea Insomnia Appetite loss Constipation Diarrhea Financial difficulties

Mean score

Median score

IQR

Range

73.0

66.7

(50.0–83.3)

(8.3–100.0)

84.8 91.3 76.7 81.2 83.0

86.7 100.0 83.3 83.3 100.0

(73.3–93.3) (83.3–100.0) (66.7–91.7) (66.7–100.0) (66.7–100.0)

(13.3–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (16.7–100.0)

25.2 5.4 13.8 4.5 13.8 10.5 19.1 4.2 27.5

33.3 0.0 16.7 0.0 0.0 0.0 0.0 0.0 33.3

(11.1–33.3) (0.0–0.0) (0.0–33.3) (0.0–0.0) (0.0–33.3) (0.0–33.3) (0.0–33.3) (0.0–0.0) (0.0–33.3)

(0.0–88.9) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0)

Abbreviations: IQR ⫽ interquartile range; QOL ⫽ quality of life; QLQ ⫽ quality of life questionnaire.

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Table 3. Calculated scores for QLQ H&N-35 Scale name

Mean score

Median score

IQR

Range

Symptom scales/items Pain Swallowing Sense problems Speech problems Trouble with social eating Trouble with social eating Less sexuality Teeth Opening mouth Dry mouth Sticky saliva Coughing Feeling ill Pain killers Nutritional supplements Feeding tube Weight loss Weight gain

14.8 24.2 17.4 11.9 13.2 9.5 19.3 44.9 36.0 66.4 57.3 17.5 16.9 42.7 15.3 0.0 16.2 45.0

8.3 25.0 8.3 11.1 8.3 0.0 0.0 33.3 33.3 66.7 66.7 33.3 16.7 0.0 0.0 0.0 0.0 0.0

(0.0–25.0) (16.7–41.7) (0.0–33.3) (0.0–22.2) (0.0–25.0) (0.0–13.3) (0.0–33.3) (0.0–100.0) (0.0–66.7) (33.3–100.0) (33.3–100.0) (0.0–33.3) (0.0–33.3) (0.0–100.0) (0.0–0.0) (0.0–0.0) (0.0–0.0) (0.0–100.0)

(0.0–91.7) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–86.7) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0) (0.0–100.0)

Abbreviations: IQR ⫽ interquartile range; H&N ⫽ head and neck; QLQ ⫽ quality of life questionnaire.

statistics for correlation among selected treatment and stage of disease. The analysis showed the stages were similar between the groups who received and did not receive concomitant chemotherapy (p ⫽ 0.958). Patients who received adjuvant brachytherapy boost after external-beam radiotherapy did as well as patients who did not undergo such procedure in regard to QoL. We also analyzed the effect of centers on QoL both descriptively and analytically and concluded that the effect of centers was negligible. No differences occurred in treatment among centers in regard to field size, technique, and chemotherapy usage.

We also performed statistical analysis to see if any coincidence occurred between weight gain and mouth and teeth problems. However, our data showed that all the correlation coefficients between the weight gain and other symptom scales mentioned are statistically insignificant (all r ⬍ 0.1, all p ⬎ 0.2). DISCUSSION Radiotherapy treatment fields for NPC are usually large and include several critical structures that may adversely

Fig. 1. Median global health status and functional scale scores by gender.



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Fig. 2. Median global health status and functional scale scores by stage.

affect QoL, such as the parotid glands, neural structures, and temporomandibular joints (2). A previous QoL study in head-and-neck cancer patients performed by Huguenin et al. (17) showed that the patients with nasopharyngeal carcinoma had the highest morbidity, most probably because of large radiotherapy fields used during treatment. In our study, we used the EORTC C30 version 3.0 together with the H&N-35 module. These questionnaires are comprehensive, and their validity, internal consistency, and reliability in patients from different nations were tested in large patient groups (14 –16). The Turkish version of the questionnaires were previously tested, confirmed, and validated by EORTC. However, completion of the questionnaires takes approximately 15 to 30 minutes, and calculation of the scores requires statistical expertise. Differences of high and low means in global QoL score, symptom scales, and functional scales make the process complicated. Furthermore, EORTC C30 version 3.0, together with the H&N-35 module, is a general head-and-neck QoL scoring system and may have some limitations for evaluation of nasopharyngeal carcinoma patients, because it does not deal with deafness, otitis media, symptoms from temporal lobe injury, and hypopituitarism well enough. Our results showed that patients with early-stage disease, male gender, and shorter follow-up time had better QoL. Although higher radiation dose and concomitant chemotherapy did not have any effect on global health status, they caused significantly higher scores in some symptoms. The core questionnaire revealed that financial difficulties and fatigue ranked the highest symptom scores and emotional functioning was the worst of the functional scores among our patient population. Moreover, the H&N-35 question-

naire showed that the NPC survivors suffered mostly mouth, teeth, and swallowing problems and weight gain. Our analysis did not show any coincidence with weight gain and mouth problems. Despite absence of coincidence, weight gain in such a group of patients is still a confusing problem. We speculate that the patients dealing with such a disease eat more to feel better. We observed that our patients mostly experienced symptoms directly related to xerostomia, beside limitation of mouth opening. These side effects mainly result from irradiation of the parotid gland, temporomandibular joint, and masticatory mucles. The new treatment modalities, such as IMRT and use of stereotactic boost, may help to lower radiation dose to these structures and to improve QoL in the NPC patient group (7). Although IMRT and stereotactic techniques are present in only a few centers, the number of new facilities is increasing in Turkey. However, the contradictory issue is that the use of these expensive sophisticated techniques in radiotherapy will increase the expenses for cancer treatment and eventually increase the financial difficulties of individuals in developing countries such as Turkey and, consequently, might adversely affect QoL. The impact of financial or socioeconomical status on healthrelated QoL is also discussed by other authors. Yu et al. (9) and Fang et al. (12) reported the importance of financial problems on QoL by use of Fact-G and Chinese SF-36 questionnaires. Nevertheless, further controlled studies should be performed to test impact of new treatment modalities on QoL. Intensification of the treatment by increase of the radiation dose and use of concomitant chemotherapy have adverse effects on symptom scores but no effect on global

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health status and functional scores. Previous studies on NPC did not analyze the effect of treatment factors on QoL (8 –12). Although no change in global health status occurred, we believe that change in symptom scores is also important and should have some impact on the choice of treatment plan. Our findings point out the importance of reduction of radiation dose, especially when chemotherapeutic agents are used. To increase radiation dose to nasopharynx, brachytherapy boost might be a rational strategy in selected patients because it did not lead to any worsening in QoL scales when patient groups were compared. The strongest determinant of global health score, majority of functional scores, and symptom scales was gender in our study. We cannot explain why males did significantly better than females. Gender of the patients has not been shown to be an important determinant in previous studies by authors who used Fact-G, Chinese SF-36, and University of Washington questionnaires (9 –12). The reason might be the subjectivity of questionnaires and use of different questionnaires in previous studies or cultural differences among patient populations. Early-stage disease was another important factor that yielded better QoL in our analysis. This finding is consistent with the other findings that relatively less-intensive treatments used in early-stage disease led to decreased worsening of the QoL. However, this observation is not the case in our patient group. Therefore, in our patient population, selection of treatments is not associated with stage of the disease, and tumor burden probably is the leading factor for worsening of QoL. Yu et al. (9) also showed that early-stage disease had less effect on QoL with respect to advanced stage. In our study, the reported severity of the symptoms was higher in the patients with more than 4 years of follow-up after radiotherapy, and global health score was significantly lower in this group when compared with patients at earlier periods, which is consistent with the previous report by


Huguenin et al. (17). The patients in his study reported most severe symptoms 5 years after radiotherapy. Therefore, close attention and care should be given to patients not only during the period of radiotherapy but also during follow-up. We believe that this finding also might result from subjectivity of the questionnaires. Cure of the tumor may lead patients to stop worrying about tumor and put treatmentrelated morbidity up front and, consequently, experience worsening of the health-related QoL as time passes by. On the other hand, these findings do not necessarily mean that the symptoms are getting worse with time. However, these problems warrant clinical attention because they were still very important issues for patients who survived long enough. The design of our study is cross-sectional, and QoL is measured only once for each of the patients. The pattern of changes in QoL with time can best be evaluated by longitudinal studies, in which QoL is measured before, during, and at specified timepoints after treatment for every patient. The scores of most of the function and symptom scales on the QLQ-C30 in our patients are comparable to previous results from studies that used different instruments in NPC patients. In all studies, regardless of the questionnaires used (9 –12), the main QoL concerns are pain, mouth, teeth, and eating problems, as is the case in our study. In conclusion, radiation therapy adversely affected QoL in NPC patients. Through the use of new radiotherapy techniques, such as IMRT, and biologic agents, such as radioprotectors, the critical structures within the radiotherapy field, especially temporomandibular joints and salivary glands, can be protected while radiotherapy is escalated to higher doses. Thus, patients might benefit in terms of tumor control without severe side effects and might have a higher QoL in the long run. Further controlled longitudinal studies are necessary to clarify the contribution of patient-related, tumor-related, and treatment-related factors to QoL.

REFERENCES 1. Hoffman HT, Karnell LH, Funk GF, et al. The national cancer database report on cancer of the head and neck. Arch Otolaryngol Head Neck Surg 1998;124:951–962. 2. Chao KSC, Perez CA. Nasopharynx. In: Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK, editors. Principles and practice of oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins: 2004. p. 918 –961. 3. Morton RP, Izzard ME. Quality of life outcomes in head and neck cancer patients. World J Surg 2003;27:884 – 889. 4. Portenoy RK, Spebner KT. Quality of life issues in patients with head and neck cancer. In: Harrison LB, Sessions RB, Hong WK, editors. Head and neck cancer. 2nd ed. Philadelphia: Lippincott Williams & Wilkins: 2004. p. 165–177. 5. Presant CA. Quality of life in cancer patients: Who measures what? Am J Clin Oncol 1984;7:571. 6. Kahn SB, Hums PS, Harding SP. Quality of life and patients with cancer: A comparative study of patients versus physicians perceptions and its implications for cancer education. J Cancer Ed 1992;7:421.

7. Cengiz M, Chao KSC, Perez CA. Intensity-modulated radiotherapy (IMRT) with concurrent cisplatin chemotherapy yields superior therapeutic outcome than conventional techniques with or without chemotherapy in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2000; 48(Suppl. 3):325. 8. Yu CL, Fielding R, Chan CL. The mediating role of optimism on post-radiation quality of life in nasopharyngeal carcinoma. Qual Life Res 2003;12:41–51. 9. Yu CL, Fielding R, Chan CL, et al. Chinese nasopharyngeal carcinoma patients treated with radiotherapy. Cancer 2001; 92:2126 –2135. 10. McMillan AS, Pow ENH, Leung WK, et al. Oral health related quality of life in southern Chinese following radiotherapy for nasopharyngeal carcinoma. J Oral Rehab 2004;31: 600 – 608. 11. Talmi YP, Horowitz Z, Bedrin L, et al. Quality of life of nasopharyngeal carcinoma patients. Cancer 2002;94:1012–1017. 12. Fang FM, Chiu HC, Kuo WR, et al. Health related quality of


life for nasopharyngeal carcinoma patients with cancer-free survival after treatment. Int J Radiat Oncol Biol Phys 2002;53:959 –968. 13. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85:365–376. 14. Bjordal K, de Graeff A, Fayers PM, et al. 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer 2000;36:1796 –1807. 15. Sherman AC, Simonton S, Adams DC, et al. Assessing quality


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of life in patients with head and neck cancer: Cross-validation of the European Organization for Research and Treatment of Cancer (EORTC) quality of life head and neck module (QLQ-H&N35). Arch Otolaryngol Head Neck Surg 2000; 126:459 – 467. 16. Bjordal K, Hammerlid E, Ahlner-Elmqvist M, et al. Quality of life in head and neck cancer patients: Validation of the European Organization Research and Treatment of Cancer quality of life questionnaire—H&N 35. J Clin Oncol 1999;17:1008 – 1019. 17. Huguenin PU, Thaussky D, Moe K, et al. Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: The importance of the target volume. Int J Radiat Oncol Biol Phys 1999;45:47–52.