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Quality of life for head and neck cancer patients treated by combined modality therapy: the therapeutic benefit of technological advances in radiotherapy

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Quality of life for head and neck cancer patients treated

by combined modality therapy: the therapeutic benefit

of technological advances in radiotherapy

Tai-Lin Huang•Wen-Ling TsaiChih-Yen Chien

Tsair-Fwu Lee•Fu-Min Fang

Accepted: 1 June 2010 / Published online: 11 June 2010 Ó Springer Science+Business Media B.V. 2010

Abstract

Purpose To evaluate quality of life (QoL) in patients with head and neck squamous cell carcinoma (HNSCC) treated by combined modality therapy, with a focus on the thera-peutic benefits of QoL that result from technological advances in radiotherapy (RT).

Methods A cross-sectional survey of QoL using the EO-RTC QLQ-C30 and QLQ-H&N35 questionnaires was performed for 307 HNSCC survivors. One hundred and thirty-five patients were treated by two-dimensional RT (2DRT), 90 by three-dimensional conformal RT (3DCRT),

and 82 by intensity-modulated RT (IMRT). The effect size between groups was calculated using Cohen’s D coefficient.

Results Those who had a higher annual family income or were treated by more advanced RT techniques had better QoL outcomes. Compared with 2DRT, the impact of 3DCRT was small (Cohen’s D: 0.02–0.40) on all QoL scales. For IMRT, the impact was small on most scales and moderate (Cohen’s D: 0.55–0.60) on opening mouth, dry mouth, and sticky saliva. Compared with 3DCRT, the impact of IMRT was small (Cohen’s D: 0.03–0.29) on all scales.

Conclusion Advances in RT provided a positive effect on QoL outcome, especially on swallowing-related QoL scales, for patients with HNSCC treated by combined modality therapy.

Keywords Head and neck squamous cell carcinoma Quality of life EORTC QLQ-C30 

EORTC QLQ-H&N35 Intensity-modulated radiotherapy

Abbreviations

EORTC European Organization of Research and Treatment of Cancer

3DCRT Three-dimensional conformal radiotherapy IMRT Intensity-modulated radiotherapy

Introduction

Head and neck squamous cell carcinoma (HNSCC) is a one of the leading causes of cancer mortality in Taiwan. More than 4,000 HNSCCs are diagnosed annually here, most of T.-L. Huang

Department of Hematology Oncology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

W.-L. Tsai T.-F. Lee  F.-M. Fang (&)

Department of Radiation Oncology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, No. 123 Ta-Pei Rd., Kaohsiung, Taiwan e-mail: fang2569@adm.cgmh.org.tw

C.-Y. Chien

Department of Otolaryngology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

T.-L. Huang C.-Y. Chien  F.-M. Fang

Department of Cancer Center, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

W.-L. Tsai

Department of Biotechnical Cosmetology, Cheng Shiu University, Kaohsiung, Taiwan

T.-F. Lee

National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan

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which are locally advanced at presentation [1]. Combined treatment modality including surgery, radiotherapy (RT), and/or chemotherapy (C/T) for advanced but potentially curative cases is well recognized. The 3-year actuarial survival rate for patients with locally advanced HNSCC after combined modality treatment ranged from 42 to 74% [2, 3]. However, composite resection of HNSCC usually has a detrimental effect on facial features, and mouth opening, swallowing or speech functions, and RT with or without C/T induces irreversible fibrosis of the organs irradiated, which leads to taste impairment, permanent xerostomia, and/or dysphagia.

Conventional or so-called two-dimensional RT (2DRT) has proven effective in the treatment of HNSCC, but complications are notable and often lifelong. Over the past decade, advances in RT techniques for treating HNSCC have been made with the development of three-dimensional conformal RT (3DCRT) and, more recently, intensity-modulated RT (IMRT). The reliance of 3DCRT on computed tomography (CT)-guided 3D planning allows better delineation of the tumour target and organs at risk, with clearer radiological visualization of their spatial relations, thus providing a potentially therapeutic benefit of dose escalation to tumour tissue with reduced toxicity to normal tissues [4]. IMRT represents an advanced form of 3DCRT. It employs inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying beam intensity. Combinations of intensity-modulated fields produce cus-tom-tailored conformal dose distributions around the tumour, with steep dose gradients at the transition to adjacent normal tissues. A growing number of reports has shown that the technical and dosimetric superiority of 3DCRT and IMRT over 2DRT can translate into clinical benefits, such as reduced normal tissue toxicity (e.g. parotid gland sparing), improved local control, or even patient survival [5–8].

Little research has been conducted to specifically explore the way that locally advanced HNSCC survivors live with the threat of cancer relapse and the subsequent changes in quality of life (QoL) after aggressive combined modality treatment. Several well-validated QoL instru-ments are now available for use in patients with HNSCC. In the current study, we used the European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire, version 3.0 (EORTC QLQ-C30) together with the Head and Neck module (H&N35) to compare QoL for locally advanced HNSCC survivors treated by com-bined modality therapy. The prognostic factor of QoL was analysed by incorporating sociodemographic and clinical variables, with a focus on the therapeutic benefits of the technological advances in RT at our institute at different time periods.

Materials and methods

The study was a cross-sectional investigation that exam-ined the QoL of patients with HNSCC treated by combexam-ined modality therapies and with cancer-free survival more than 2 years after treatment. From June 1995 to July 2007, there were 1,227 newly diagnosed patients with HNSCC con-secutively treated by combined modality therapies, including surgery ? RT, surgery ? RT ? C/T, or RT ? C/ T, with curative intent at Chang Gung Memorial Hospi-tal—Kaohsiung Medical Center in Taiwan. Patients with early laryngeal cancer treated by cordectomy plus local RT (n = 62), with previous history of malignancies, RT or C/T (n = 83), or failure to complete the prescribed treatment course of RT (n = 58) were excluded. During the study period, 413 patients died of cancer, 94 died of other or unknown causes, 87 were lost to follow-up, and 31 alive with cancer, as recorded in the cancer registration database of the institute. The cancer-free status of patients was confirmed by results of clinical examinations and recent image studies. Of the remaining 399 subjects meeting the eligibility criteria, the QoL data from 307 participants were collected.

The local institutional research board approved this study, and written informed consent was obtained from each participant. After giving informed consent, each par-ticipant completed the demographic details, provided a medical history, and completed the EORTC QLQ-C30 and H&N35 module. Assistants were available to answer the questions and checked the forms for completeness. Par-ticipants who were not familiar with the Chinese characters of the questions were provided with the assistance of a trained interviewer to read them in a dialect they could understand.

Patient characteristics, including sociodemographic and cancer- and treatment-related variables, are listed in Table1. Cancers were re-staged according to the American Joint Cancer Committee (AJCC) staging system, published in 2002. Comorbidity status was recorded according to the Charlson Comorbidity Index (CCI) by review of charts and based on self-reported information [9].

With regard to sociodemographic factors, 180 (58.6%) patients, including 177 men and three women, had [6 years of education (‘‘graduated from the junior high school or more’’), 208 (67.8%) patients had an annual family income C0.6 million NTD (1 USD = 33 NTD), and 251 (81.8%) patients had spouses. Two hundred and sixty-seven (87.0%) patients had AJCC stage III or IV disease, and 133 (43.3%) had at least one kind of comor-bidity. One hundred and twenty-five (40.7%) patients were treated by surgery ? RT, 124 (40.4%) by surgery ? RT ? C/T, and 58 (18.9%) by RT ? C/T. With regard to the RT techniques, 135 (44.0%) patients were treated by 2DRT, 90

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(29.3%) by 3DCRT, and 82 (26.7%) by IMRT. The median (range) length of follow-up after treatment when QoL data were collected was 6.1 (2.2–13.2) years; specifically, it was 7.3 (3.8–13.2), 4.8 (2.7–7.5), and 3.9 (2.2–6.4) years in the 2DRT, 3DCRT, and IMRT groups, respectively.

RT techniques

RT for HNSCC treated by combined modality was rou-tinely delivered by 2DRT in our hospital before the intro-duction of 3DCRT in April 1996. From April 1996 to Table 1 Patient characteristics (n = 307)

Variables Total (n = 307) 2DRT (n = 135) 3DCRT (n = 90) IMRT (n = 82) P value Age, median (range) years 53 (32–83) 53 (33–83) 52 (37–76) 52 (32–79) 0.54

32–48 102 (33.2%) 41 (30.4%) 34 (37.8%) 27 (32.9%) 49–56 103 (33.6%) 43 (31.9%) 32 (35.6%) 28 (34.2%) 57–83 102 (33.2%) 51 (37.7%) 24 (26.6%) 27 (32.9%) Gender 0.31 Male 296 (96.4%) 128 (94.8%) 87 (96.7%) 81 (98.8%) Female 11 (3.6%) 7 (5.2%) 3 (3.3%) 1 (1.2%) Marital status 0.35 With spouse 251 (81.8%) 115 (85.2%) 70 (77.8%) 66 (80.5%) Without spouse 56 (18.2%) 20 (14.8%) 20 (22.2%) 16 (19.5%) Education years 0.22 B6 127 (41.4%) 66 (55.8%) 32 (35.6%) 29 (35.4%) 6–12 168 (54.7%) 65 (48.1%) 54 (60.0%) 49 (59.8%) [12 12 (3.9%) 4 (3.0%) 4 (4.4%) 4 (4.9%)

Annual family income, per million NTD 0.32

\0.6 99 (32.2%) 33 (24.4%) 28 (31.1%) 29 (35.4%)

0.6–1.2 118 (38.4%) 56 (41.5%) 30 (33.3%) 32 (39.0%)

C1.2 90 (29.4%) 46 (34.1%) 32 (35.6%) 21 (25.6%)

CCI, median (range) 0 (0–4) 0 (0–3) 0 (0–3) 0 (0–4) 0.40

0 174 (56.7%) 78 (57.8%) 46 (51.1%) 50 (61.0%) C1 133 (43.3%) 57 (42.2%) 44 (48.9%) 32 (39.0%) Tumour site 0.62 Oral cavity 129 (42.0%) 56 (41.5%) 37 (41.1%) 36 (42.7%) Oropharynx 74 (24.1%) 36 (26.6%) 22 (24.5%) 16 (20.7%) Hypopharynx/Larynx 104 (33.9%) 43 (31.9%) 31 (34.4%) 30 (36.6%) AJCC stage 0.89 II 40 (13.0%) 18 (13.3%) 13 (11.7%) 9 (11.0%) III 64 (20.8%) 27 (20.0%) 21 (23.3%) 16 (19.5%) IV 203 (66.2%) 90 (66.7%) 56 (62.2%) 57 (69.5%) Treatment methods 0.17 S ? RT 125 (40.7%) 52 (38.6%) 40 (44.4%) 33 (40.2%) S ? RT ? C/T 124 (40.4%) 55 (40.7%) 34 (37.8%) 35 (42.7%) RT ? C/T 58 (18.9%) 28 (20.7%) 16 (17.8%) 14 (17.1%)

RT dose, median (range), Gy 63.0 (50.4–81.0) 63.0 (50.4–81.0) 63.0 (54.0–78.0) 63.0 (50.4–80.0) 0.52

\70 Gy 244 (79.5%) 104 (77.0%) 75 (83.3%) 65 (79.3%)

C70 Gy 63 (20.5%) 31 (23.0%) 15 (16.7%) 17 (20.7%)

Length of follow-up, median (range) years 6.1 (2.2–13.2) 7.3 (3.8–13.2) 4.8 (2.7–7.5) 3.9 (2.2–6.4) 0.001

2.2–3.5 102 (33.2%) 47 (34.8%) 31 (34.4%) 24 (29.3%)

3.5–4.7 103 (33.6%) 31 (23.0%) 31 (34.4%) 41 (50.0%)

4.7–13.2 102 (33.2%) 57 (42.2%) 28 (31.2%) 17 (20.7%)

NTD New Taiwan Dollar (1 USD = 33 NTD), CCI Charlson comorbidity index, AJCC American Joint of Cancer Committee published in 2002, S surgery, RT radiotherapy, C/T chemotherapy, 2DRT two-dimensional RT, 3DCRT three-dimensional conformal RT, IMRT intensity-modulated RT

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March 2002, 3DCRT was gradually used to replace 2DRT in the boost phase for curable HNSCC cases or in salvage treatment of recurrent disease. After becoming familiar with the techniques of 3DCRT and implementation of the IMRT system by March 2002, the physicians and physi-cists in our institute began to use the two techniques as a standard strategy in treating HNSCC for the whole course.

2DRT

One hundred and thirty-five patients were treated by 2DRT in the study. The detailed portal arrangement and dosing of conventional 2DRT in HNSCC treated by combined modality have been described previously [10]. Briefly, 2DRT was given in two phases, before and after the spinal cord tolerance dose of 44–46.8 Gy. In the first phase, patients were irradiated by a 6-MV photon beam with a daily fraction of 1.8 or 2.0 Gy (5–6 fractions per week) via bilateral opposing faciocervical fields and one lower ante-rior cervical field. For those treated by RT ? C/T, the target covers the primary tumour with surrounding ana-tomic area and regional neck lymphatics. For postoperative cases, the surgical tumour and nodal bed as well as the prophylactic nodal area at risk were included. In the second phase, the gross tumour dose was boosted to 64.8–78.0 Gy for definite RT and the tumour bed dose to 50.4–64.8 Gy in postoperative cases via bilateral opposing photon beams to shield the spinal cord. Residual neck lymph nodes or nodal bed areas at risk were simultaneously boosted by a 9- or 12-MeV electron beam to 56.0–81.0 Gy, depending on the nodal situation.

3DCRT

The procedure of 3DCRT for HNSCC treated by combined modality in our institute was as follows: (1) immobilization of patients in a supine position by a thermoplastic facial cast; (2) CT scans obtained using 3–5-mm-thick slices from the vertex of the skull to the low-neck area; (3) transfer of CT scan data to the 3D treatment planning system (ADAC Laboratories, Milpitas, CA, USA); (4) contouring of the treatment targets, including gross tumour volume (GTV) and clinical target volume (CTV), and critical organs into the treatment planning system; (5) design of beam arrangements and blocks via beam–eye view displays; (6) evaluation of dose distribution by examining isodose lines superimposed on CT slices, 3D surface dose displays, and dose–volume histograms of the contoured structures; and (7) delivery of treatment plans in a linear accelerator equipped with multi-leaf collimators. For those treated by RT ? C/T, the GTV included the gross primary tumour and neck nodal mass, and the CTV covered the GTV with *1–1.5-cm expansion and locoregional

anatomy at risk. For postoperative cases, the CTV covered the surgical tumour and nodal bed and locoregional anat-omy at risk. Shrinkage of the CTV was usually performed after the tumouricidal dose of 45.0–50.4 Gy was reached for the microscopic lesions. Additional uniform 3-mm expansions were made to yield the planning target volume (PTV), which accounted for inaccuracies in immobilisation of patients and beam placement. The numbers and direc-tions of beams depended on the extent of individual tumours. For each patient, five or seven coplanar portals were usually designed. The 90–95% isodose volume to cover the PTV with the spinal cord strictly limited below the 60% isodose line was applied. The dose/fractionation prescription of 3DCRT primarily followed the guidelines for 2DRT. For 90 patients treated by 3DCRT, the pre-scribed total dose ranged from 54.0 to 78.0 Gy (median: 63 Gy).

IMRT

The immobilization, target definition and delineation, and dose/fractionation prescription of IMRT for HNSCC trea-ted by combined modality were approximately the same as described previously for 3DCRT. We used the Cadplan or Pinnacle treatment planning system (ADAC Laboratories) to perform the inverse planning and dose optimization. For each patient, IMRT plans with five or seven coplanar portals were created. The delivery of the plans was per-formed in Varian machines equipped with dynamic multi-leaf collimators. The dose/fractionation prescription of IMRT primarily followed the guidelines for 3DRT. For 82 patients treated by IMRT, the prescribed total dose ranged from 54.0 to 80.0 Gy (median: 63 Gy).

C/T

A total of 182 patients (59.3%) were treated with a com-bination of systemic C/T as adjuvant or concurrent sequence of RT. The regimens used involved a combination of cisplatin and 5-fluorouracil, administered intravenously.

QoL instruments

The Taiwan Chinese versions of the EORTC QLQ-C30 and H&N35 questionnaires were obtained from the Quality of Life Unit, EORTC Data Center in Brussels, Belgium [11,

12]. The QLQ-C30 is a widely used questionnaire. It incorporates a range of QoL issues that are relevant to a broad range of patients with cancer. It has been translated into many languages and validated for many types of cancer, including head and neck. It contains five functional scales (physical, role, cognitive, emotional, and social),

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scales. However, such improvement became moderate for mouth opening, dry mouth, and sticky saliva after IMRT was used.

The advantage of 3DCRT over IMRT in terms of QoL was ambiguous and small in our study. In contrast, a recently reported, non-randomized prospective comparison between patients with HNSCC treated by 3DCRT or IMRT demonstrated that IMRT resulted in a significant reduction in patient- and observer-rated xerostomia, as well as other head and neck symptoms, compared with standard 3DCRT [24]. With locally advanced disease treated by aggressive combined surgery, RT, and/or C/T, we found that the dosimetric improvement for 3DCRT compared with IMRT might not be sufficiently large to demonstrate any signifi-cant difference in QoL.

Our results also indicated that the improvement in head and neck symptoms elicited after RT did not translate into a better outcome in global QoL or functional domains. Several other studies have also revealed discordance between reported symptoms and global QoL. For example, more than 5 years after RT, NPC survivors have reported a higher rate of symptomatic problems, including dry mouth, sticky saliva, and swallowing difficulty, but a better global QoL than other patients with HNSCC [25]. After employing the SF-36, EORTC QLQ-C30, and H&N35 questionnaires for HNSCC survivors at 3 years after treatment, Hammerlid and Taft reported that most of the treatment-related symptomatic problems appeared to be worse than in the normal Swedish population. However, such a difference was not found in most of the physical or psychosocial functional scales or in global QoL [26].

Xerostomia-related symptoms are usually cited as the most prevalent complications in patients with HNSCC after RT. However, the association between xerostomia and broad aspects of QoL is still controversial, and a direct cause–effect relationship has not been confirmed. We observed that the effect size of IMRT on xerostomia was moderate (Cohen’s D: 0.60), although the new technique was primarily focused on sparing of the parotid glands. On the other hand, some reports have shown that radiation-induced dysphagia also plays an important role in QoL domains [27,28]. Dysphagia is usually multifactorial and strongly associated with xerostomia. It has become increasingly important to identify the anatomical structures that are involved in swallowing problems after RT. A cross-sectional study of 81 patients with oropharyngeal cancer, reported by Levendag et al., showed that the probability of swallowing complaints is significantly associated with the mean total radiation dose in the supe-rior and middle pharyngeal constrictor muscle [27].

Although our results provided a positive effect of the advances in RT techniques on some swallowing-related QoL scales for patients with HNSCC treated by combined

modality therapy, there are several limitations in the study. First, this is a comparison of non-randomized groups with heterogeneous patient components, which were treated in different ways in different periods. Second, the dosimetric results of the normal organs such as the parotid glands, oral cavity, or larynx were not available in the retrospective analysis; therefore, the specific therapeutic impact of technological evolutions in RT on QoL issue for patients with different tumour sites and tumour stages could not be performed in details. In light of these limitations, the clinical reality of QoL outcomes among these patients treated by different RT techniques might be much more complex than our data have provided.

Acknowledgments Supported by grant ‘‘CMRPG860501’’ and ‘‘CMRPG860502’’ from the Chang Gung Memorial Hospital, Taiwan. Conflict of interest statement No actual or potential conflict of interest exists.

References

1. Annual report of Taiwan cancer incidence and mortality rates. (1997). Department of Health, Taiwan Provincial Government, Taipei, Taiwan.

2. Amdur, R., Parsons, J., Mendenhall, W., Million, R., Stringer, S., & Cassisi, N. (1989). Postoperative irradiation for squamous cell carcinoma of the head and neck: an analysis of treatment results and complications. International Journal of Radiation Oncology, Biology, Physics, 16(1), 25–36.

3. Peters, L., Goepfert, H., Ang, K., Byers, R., Maor, M., Guilla-mondegui, O., et al. (1993). Evaluation of the dose for postop-erative radiation therapy of head and neck cancer: First report of a prospective randomized trial. International Journal of Radiation Oncology, Biology, Physics, 26(1), 3–11.

4. Teo, P., Ma, B., & Chan, A. (2004). Radiotherapy for nasopha-ryngeal carcinoma: Transition from two-dimensional to three-dimensional methods. Radiotherapy & Oncology, 73(2), 163– 172.

5. Chao, K., Majhail, N., Huang, C., Simpson, J., Perez, C., Haug-hey, B., et al. (2001). Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor con-trol in patients with oropharyngeal carcinoma: A comparison with conventional techniques. Radiotherapy & Oncology, 61(3), 275– 280.

6. Jen, Y., Shih, R., Lin, Y., Su, W., Ku, C., Chang, C., et al. (2005). Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: A dosimetric and clinical comparison with conventional radiotherapy. Radiotherapy & Oncology, 75(2), 204–209. 7. Lee, N., Xia, P., Quivey, J., Sultanem, K., Poon, I., Akazawa, C.,

et al. (2002). Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: An update of the UCSF experience. International Journal of Radiation Oncology, Biology, Physics, 53(1), 12–22.

8. Wolden, S., Chen, W., Pfister, D., Kraus, D., Berry, S., & Zelefsky, M. (2006). Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience. International Journal of Radiation Oncol-ogy, BiolOncol-ogy, Physics, 64(1), 57–62.

(6)

9. Charlson, M., Pompei, P., Ales, K., & MacKenzie, C. (1987). A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Dis-eases, 40(5), 373–383.

10. Fang, F., Leung, S., Huang, C., Liu, Y., Wang, C., Chen, H., et al. (1997). Combined-modality therapy for squamous carcinoma of the buccal mucosa: Treatment results and prognostic factors. Head and Neck, 19(6), 506–512.

11. Aaronson, N., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N., et al. (1993). The European organization for research and treatment of cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute, 85(5), 365–376. 12. Bjordal, K., Hammerlid, E., Ahlner-Elmqvist, M., de Graeff, A.,

Boysen, M., Evensen, J., et al. (1999). Quality of life in head and neck cancer patients: validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35. Journal of Clinical Oncology, 17(3), 1008–1019. 13. Fayers, P., Aaronson, K., & Bjordal, K. (2002). EORTC

QLQ-C30 scoring manual (2nd ed.). Brussels, Belgium: EORTC Data Center, 1999.

14. Langendijk, J., Doornaert, P., Verdonck-de Leeuw, I., Leemans, C., Aaronson, N., & Slotman, B. (2008). Impact of treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. Journal of Clinical Oncology, 26(22), 3770–3776.

15. Cohen, J. (2007). Statistcial power analysis for the behavioral sciences (2nd ed.). NJ, Erlbaum: Hillsdale.

16. Middel, B., Stewart, R., Bouma, J., Sonderen, E., & van den Heuvel, W. (2001). How to validate clinically important change in health-related functional status. Is the magnitude of the effect size consistently related to magnitude of change as indicated by global question rating. Journal of Evaluation in Clinical Practice, 7(4), 399–410.

17. Osoba, D., Rodrigues, G., Myles, J., Zee, B., & Pater, J. (1998). Interpreting the significance of changes in health-related quality-of-life scores. Journal of Clinical Oncology, 16(1), 139–144. 18. Fang, F., Chiu, H., Kuo, W., Wang, C., Leung, S., Chen, H., et al.

(2002). Health-related quality of life for nasopharyngeal carci-noma patients with cancer-free survival after treatment. Inter-national Journal of Radiation Oncology, Biology, Physics, 53(4), 959–968.

19. Fang, F., Tsai, W., Chien, C., Chiu, H., & Wang, C. (2004). Health-related quality of life outcome for oral cancer survivors after surgery and postoperative radiotherapy. Japanese Journal of Clinical Oncology, 34(11), 641–646.

20. Chie, W., Hong, R., Lai, C., Ting, L., & Hsu, M. (2003). Quality of life in patients of nasopharyngeal carcinoma: validation of the Taiwan Chinese version of the EORTC QLQ-C30 and the EO-RTC QLQ-H&N35. Quality of Life Research, 12(1), 93–98. 21. Adler, N., Boyce, W., Chesney, M., Folkman, S., & Syme, S.

(1993). Socieconomic inequalities in health: No easy solution. The Journal of the American Medical Association, 269(24), 3140–3145.

22. Penson, D., Stoddard, M., Pasta, D., Lubeck, D., Flanders, S., & Litwin, M. (2001). The association between socioeconomic sta-tus, health insurance coverage, and quality of life in men with prostate cancer. Journal of Clinical Epidemiology, 54(4), 350– 358.

23. Dijkema, T., Terhaard, C., Roesink, J., Braam, P., van Gils, C., Moerland, M., et al. (2008). Large cohort dose-volume response analysis of parotid gland function after radiotherapy: Intensity-modulated versus conventional radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 72(4), 1101– 1109.

24. Vergeer, M., Doornaert, P., Rietveld, D., Leemans, C., Slotman, B., & Langendijk, J. (2009). Intensity-modulated radiotherapy reduces radiation-induced morbidity and improves health-related quality of life: Results of a nonrandomized prospective study using a standardized follow-up program. International Journal of Radiation Oncology, Biology, Physics, 74(1), 1–8.

25. Huguenin, P., Taussky, D., Moe, K., Meister, A., Baumert, B., Lutolf, U., et al. (1999). Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: The importance of the target volume. International Journal of Radiation Oncol-ogy, BiolOncol-ogy, Physics, 45(1), 47–52.

26. Hammerlid, E., & Taft, C. (2001). Health-related quality of life in long-term head and neck cancer survivors: A comparison with general population norms. British Journal of Cancer, 84(2), 149– 156.

27. Levendag, P., Teguh, D., Voet, P., van der Est, H., Noever, I., de Kruijf, W. J., et al. (2007). Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radia-tion therapy dose to the superior and middle constrictor muscle: A dose-effect relationship. Radiotherapy & Oncology, 85(1), 64– 73.

28. Teguh, D., Levendag, P., Noever, I., van Rooij, P., Voet, P., van der Est, H., et al. (2008). Treatment techniques and site consid-erations regarding dysphagia-related quality of life in cancer of the oropharynx and nasopharynx. International Journal of Radiation Oncology, Biology, Physics, 72(4), 1119–1127.

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