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Journal of Clinical Oncology, Vol 25, No 16 (June 1), 2007: pp. 2191-2197 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.08.8005 Quality of Life in Head and Neck Cancer Patients After Treatment With High-Dose Radiotherapy Alone or in Combination With Cetuximab
From Omega Research, Dublin, Ireland; Radiation Oncology Service and Department of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Human Oncology, University of Wisconsin, Madison, WI; Department of Radiation Oncology and Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Medicine, University of Virginia, Charlottesville, VA; Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland; ImClone Systems, Branchburg, NJ; Merck KGaA, Darmstadt, Germany; and Department of Medicine, University of Alabama, Birmingham, AL Address reprint requests to Desmond Curran, Omega Research, 189 Shanliss Rd, Santry, Dublin 9, Ireland; e-mail: descurran{at}omega-research.eu.com
Purpose: In this randomized, phase III study, quality of life (QoL) was assessed in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) after high-dose radiotherapy alone or in combination with cetuximab. Patients and Methods: Patients with stage III or IV nonmetastatic and measurable squamous cell carcinoma of the oropharynx, hypopharynx, or larynx were eligible. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC QLQ Head and Neck Cancer–Specific Module at baseline, week 4, and at months 4, 8, and 12 postbaseline. Results: In this study, one of the largest conducted in a population of patients with locoregionally advanced SCCHN, 424 patients received radiotherapy alone (213 patients) or radiotherapy plus cetuximab (211 patients). Radiotherapy/cetuximab significantly improved locoregional control (P = .005) and overall survival (P = .03) compared with radiotherapy alone, without significantly increasing radiotherapy-associated adverse events. The current analysis focused on the impact of cetuximab on the QoL. Compliance with completion of QoL questionnaires was high in both arms. QoL worsened during treatment and improved after cessation of treatment, reaching baseline levels at 12 months. There were no significant differences in QoL scores between the treatment arms. This was particularly notable for global health status/QoL, social functioning, social eating, and social contact. Pretreatment global health status/QoL was identified as a significant prognostic variable in these patients. Conclusion: The addition of cetuximab to radiotherapy significantly improved locoregional control and increased overall survival without adversely affecting QoL.
Cancer of the head and neck can have profound effects on quality of life (QoL).1 The proximity of head and neck cancers to many anatomic structures involved in important aspects of physiological and social functions and the collateral damage often associated with the treatment of the disease can have profound deleterious effects on QoL. These may not be readily appreciated or quantified in the routine care of head and neck cancer patients or taken into account when evaluating therapeutic options.2,3 Most patients with squamous cell carcinoma of the head and neck (SCCHN) present with stage III or IV disease.4 Conventional therapy for these patients commonly involves radiotherapy alone or in combination with chemotherapy (chemoradiotherapy [CRT]); surgery is reserved for salvage treatment.5 Radiotherapy-associated toxicities, such as xerostomia,6 are well documented and can have a significant impact on QoL.7 The use of CRT has improved both locoregional control and survival beyond that achieved with radiotherapy alone, but is also associated with significant increases in toxicity.8-10 The main factors affecting the QoL of patients with locoregionally advanced SCCHN who undergo CRT are xerostomia, taste disturbances, dietary restrictions, dysphagia, and pain.11 Problems with social interactions and depression have also been reported.12,13 Cetuximab (Erbitux; ImClone Systems Inc, Branchburg, NJ, licensed to Merck KGaA, Darmstadt, Germany) is an immunoglobulin G1 monoclonal antibody that specifically targets the epidermal growth factor receptor and competitively inhibits endogenous ligand binding.14 Tumor epidermal growth factor receptor expression is commonly associated with more aggressive disease and decreased survival.15,16 Strong synergistic antitumor effects of cetuximab and radiation observed in preclinical studies prompted the investigation of cetuximab in combination with radiotherapy in the clinical setting.17,18 Cetuximab has a favorable safety profile; the most common adverse effects are skin reactions, typically an acne-like rash.19,20 Nail disorders, commonly occurring on the great toes and thumbs, are observed less frequently.18 Infusion-related reactions, which occur most frequently during the first administration of cetuximab, are also reported, and are severe in some patients.21 Recently reported results from a randomized phase III study described the combination of cetuximab and radiotherapy to be significantly more effective than radiotherapy alone in the treatment of locoregionally advanced SCCHN.18 Importantly, cetuximab did not significantly increase radiotherapy-associated adverse effects. The impact of cetuximab on QoL is largely unknown, and this article reports the findings of a QoL assessment carried out as a secondary end point in this study. The universally accepted definition of QoL is that it is multidimensional (ie, comprises elements of emotional, social, and physical well-being), a process (ie, subject to change over a patient's lifetime), and subjective (relies primarily on the patient's own judgement). These three points will be taken into account in this report. First, two validated, multidimensional QoL instruments, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer–Specific Module (H&N35), were used to assess QoL.22,23 The QLQ-H&N35 assesses symptoms specifically associated with head and neck cancer and its treatments, whereas the QLQ-C30 assesses functioning and symptoms common to most cancer patients. In this study, particular attention was paid to the impact of cetuximab on social functioning and global health status/QoL assessed using the QLQ-C30, and to the effects of local treatment on QoL parameters related to swallowing and speech assessed using the QLQ-H&N35. Second, longitudinal data analyses techniques were used, to allow change over time to be explored and to allow for individual patient variability. To our knowledge, this is the first report of the effects of cetuximab in combination with radiotherapy on the QoL of patients with SCCHN.
Study Design This was a multicenter, open-label, stratified, randomized, phase III study in patients with stage III or IV nonmetastatic and measurable squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. The primary end point was the duration of locoregional control, and secondary end points included overall survival and QoL. The study was conducted in accordance with the Declaration of Helsinki and was approved by national or local ethics committees, as appropriate. All patients provided written informed consent. Full details of the study and its results have been reported previously.18
Study Treatments
QoL Assessments QoL was evaluated in a longitudinal design in all randomly assigned patients who had at least one assessable questionnaire. Questionnaires were considered assessable if they were self-administered and had a date of assessment (within the visit window).
Statistical Methods QoL compliance was calculated as the ratio of the total number of patients with at least one assessable questionnaire to the total number of expected questionnaires (all patients alive at that time point) per time window.24 The patterns of completion of questionnaires were explored to investigate the magnitude of missing data and the extent of intermittent missing data and monotone (ie, provision of a complete series of questionnaires before dropout) missing data. Summary measures of QoL scores were generated.25 Patients' actual scores and the changes relative to baseline were calculated for each functioning and global health status/QoL scale (best and worst scores) and each symptom scale (worst scores), and were compared between the treatment arms using the Wilcoxon nonparametric test.
A logistic regression model was used to test if the dropout process was missing completely at random.26 The model included terms for clinical variables (T stage, T1-3 v T4; N stage, N0-1 v N2-3; tumor site, larynx v hypopharynx/oropharynx; KPS, A repeated-measures multivariate analysis of variance model, which is valid under missing completely at random and missing at random dropout mechanisms, was used to generate the least squares mean estimates for the visit by treatment interaction, and the difference in least squares means and their associated SEs, included terms for clinical variables (see previous paragraph) and a treatment by visit interaction.27,28 The variance-covariance structure was assumed to be autoregressive order 1. A pattern-mixture model, including the terms treatment, visit, and dropout pattern; an interaction between treatment and dropout pattern; and baseline clinical variables, was fitted for both the social functioning and global health status\QoL scales.29 If insufficient numbers of patients existed in a dropout pattern, consecutive patterns were to be combined to ensure convergence of the model. If the treatment effect in the final model was pattern dependent, the delta method was used to obtain the marginal treatment effect.30 The null hypothesis of no treatment effect was tested using a Wald statistic.
The prognostic values of the baseline global health status/QoL, fatigue, and physical functioning scale scores were investigated. The three QoL variables were dichotomized at the median to yield good and poor scores, respectively. Survival curves and probabilities were estimated using the Kaplan-Meier technique.31 The Cox proportional hazards regression model with stratification for treatment arm was used for both univariate and multivariate analyses. The multivariate model was used without a model selection procedure and included the baseline clinical variables and sex as covariates along with the three QoL scales of interest. The importance of a prognostic variable was assessed using the Wald
Summary of Clinical Results Between April 1999 and March 2002, 424 patients were randomly assigned to treatment with radiotherapy alone (213 patients) or radiotherapy plus cetuximab (211 patients). The median duration of locoregional control was 24.4 months for the combined-therapy arm and 14.9 months for radiotherapy alone (P = .005). The corresponding median survival times were 49.0 and 29.3 months (P = .03). Five and eight patients discontinued treatment with cetuximab due to hypersensitivity reactions and skin toxicity, respectively. Less than 5% of patients required dose reduction and 15% of patients required treatment delays of at least 4 days. With the exception of acne-like rash and infusion-related events, the incidence of adverse events was comparable between the treatment arms. Importantly, the addition of cetuximab to radiotherapy did not seem to increase the incidence of common radiotherapy-associated toxicities significantly, including mucositis, xerostomia, dysphagia, pain, weight loss, and performance status deterioration.
QoL Compliance
Summary Measures There were no statistically significant between-arm differences in the best and worst postbaseline QoL scores for the functioning and global health status/QoL scales, except for the best postbaseline physical functioning scale, which demonstrated a better score in the radiotherapy plus cetuximab arm (Table 2). However, the significance of this result was not supported by the repeated-measures multivariate analysis of variance, suggesting that it occurred by chance due to multiple testing. Large differences between baseline and worst postbaseline scores for the QLQ-C30 and QLQ-H&N35 multi-item symptom scales were noted for all scales, particularly for the swallowing, sensory problems, and social eating scales (Table 3). However, statistically significant differences between treatment groups were not apparent.
All single items showed a worsening of symptoms from baseline (data not shown). The two items that showed the largest change from baseline in both arms were sticky saliva and dry mouth.
Change of QoL As a Function of Time
Analysis of Missing Data Twenty-three patients completed the baseline questionnaire only and 33 completed both the baseline and week 4 questionnaires. One hundred sixty-four patients completed a questionnaire at all visits up to and including month 12. Monotone dropout patterns were observed in 343 patients. Intermittent missing questionnaires were also prominent. The dropout probability was higher in patients with a poor baseline KPS (P = .014), those receiving radiotherapy alone (P = .021), and those with a low global health status/QoL score (P < .001). Figure 2 presents the mean global health status/QoL scores by visit and dropout pattern for each treatment arm. Four dropout patterns, based on the visit at which the last questionnaire was completed, were defined as pattern 1, dropout at baseline or week 4 (60 patients); pattern 2, dropout at month 4 (72 patients); pattern 3, dropout at month 8 (71 patients); or pattern 4, dropout at or after month 12 (216 patients). Figure 2 illustrates that the mean global health status/QoL score decreased initially during radiotherapy in all dropout patterns. In both treatment arms there was a clear indication of differences between patterns with respect to mean global health status/QoL score. These findings were consistent with the logistic regression analysis. The plot indicates that the patterns are similar across treatment arms, in particular pattern 4, which represents the majority of patients. Analysis using pattern-mixture models for both the global health status/QoL and social functioning scales indicated no significant treatment differences between the two treatment arms (P = .103, and P = .855, respectively).
Prognostic Value of QoL Scales Kaplan-Meier estimates of survival stratified by the baseline global health status/QoL scores are shown in Figure 3. Patients with a higher global health status/QoL score at baseline survived significantly longer than patients with a lower global health status/QoL score at baseline (median survival, not reached v 18 months; P < .001). The univariate analysis results were similar for the physical functioning (median survival, 50.4 v 20.6 months, P < .001) and fatigue scales (median survival: 24.4 v 56.7 months; P = .002). Significant variables identified in the multivariate model were age (HR, 1.01; P = .045), T stage (HR, 1.64; P = .001), KPS (HR, 2.27; P < .001), and global health status/QoL (HR, 1.66; P = .005).
In this randomized phase III study, QoL was assessed in patients with locoregionally advanced SCCHN after treatment with either high-dose radiotherapy alone or high-dose radiotherapy plus cetuximab. Compliance with completion of QoL questionnaires was high in both treatment arms, particularly in the combination-treatment arm. The results indicated an inverse relationship between QoL scores and the probability of dropout. These findings suggest that simplified analyses such as worst score summary measures are potentially biased in favor of the radiotherapy-alone arm, given that patients with a lower QoL tended to dropout early and the dropout rate was higher in the radiotherapy-alone treatment arm. Although a few statistically significant differences in QoL between the treatment arms were demonstrated, these differences were small, inconsistent, and likely due to chance. Any negative impact of cetuximab-associated acne-like rash and infusion-related reactions should have been detected by the EORTC QLQ-C30 social functioning scale. However, no significant differences in this scale between the treatment arms were observed. The lack of significant differences between the treatment arms also was observed after application of the pattern-mixture model, which takes missing data and dropout pattern into account. This confirms the robustness of the results and also supports the findings of no treatment differences obtained using the best and worst score for both the global health status/QoL and social functioning scales. Taken in conjunction with a significant improvement in locoregional control and overall survival compared with radiotherapy alone, the apparent lack of a negative impact on QoL of cetuximab combined with radiotherapy is noteworthy. Although CRT has also demonstrated improved locoregional control and survival compared with radiotherapy, the effects are achieved at the cost of increased toxicity, including dysphagia and mucosal and hematologic toxicities.7,8,10,32 Moreover, CRT regimens can be difficult to implement in community practice.32 In this study, radiotherapy plus cetuximab was well tolerated and cetuximab did not significantly increase common radiotherapy-associated toxicities, including mucositis, xerostomia, dysphagia, pain, weight loss, and performance status deterioration. More than 95% of all patients were able to receive the full dose of cetuximab in combination with radiotherapy. Both the EORTC QLQ-C30 and QLQ-H&N35 modules were sufficiently sensitive to detect changes in QoL over time. The majority of scales demonstrated a worsening of QoL during treatment, with a corresponding increase in QoL post-treatment in both treatment arms. During treatment, the most significant impact of radiotherapy was seen on role functioning, fatigue, appetite loss (all assessed using the EORTC QLQ-C30), swallowing, sensory problems, and trouble with eating (all assessed using the QLQ-H&N35). This reduction in QoL was expected and can be attributed to the adverse effects of the radiotherapy. The subsequent relatively good scores at months 8 and 12 indicate that most symptoms are transient and resolve after treatment cessation. This phenomenon of a return to baseline QoL scores after treatment in patients still on study at 12 months has been observed elsewhere.25,33 Global health status/QoL was the only scale that was identified on multivariate analysis, after adjusting for other clinical variables, as a significant prognostic variable. Other studies have also suggested that baseline QoL is a prognostic variable for survival in patients with head and neck cancer.34,35 In summary, the addition of cetuximab to radiotherapy significantly improved locoregional control and survival compared with radiotherapy alone in patients with locoregionally advanced SCCHN, without apparently adversely affecting social functioning or global health status/QoL. These findings provide additional support that adding cetuximab to radiotherapy is an attractive therapeutic option for patients with locoregionally advanced SCCHN.
Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment: Eric K. Rowinsky, ImClone Systems Inc; Nadia Amellal, Merck KGaA; Sylvie Comte, Merck KGaA Leadership: N/A Consultant: Desmond Curran, Merck KGaA; Paul M. Harari, Bristol-Myers Squibb Co, ImClone Systems Inc; K. Kian Ang, Bristol-Myers Squibb Co, ImClone Systems Inc; Roger B. Cohen, Bristol-Myers Squibb Co, ImClone Systems Inc; Merrill S. Kies, ImClone Systems Inc; José Baselga, Roche, Amgen, AstraZeneca, Bristol-Myers Squibb Co, Merck KGaA Stock: Eric K. Rowinsky, ImClone Systems Inc Honoraria: Paul M. Harari, Bristol-Myers Squibb Co, ImClone Systems Inc; Roger B. Cohen, Bristol-Myers Squibb Co, ImClone Systems Inc; Merrill S. Kies, ImClone Systems Inc, Bristol-Myers Squibb Co; José Baselga, Roche, Merck KGaA, Glaxo; James A. Bonner, ImCone Systems Inc, Bristol-Myers Squibb Co Research Funds: Merrill S. Kies, ImClone Systems Inc, Bristol-Myers Squibb Co; Jacek Jassem, Merck KGaA; José Baselga, Bristol-Myers Squibb Co Testimony: N/A Other: N/A
Conception and design: Paul M. Harari, K. Kian Ang, José Baselga, Nadia Amellal, James A. Bonner Financial support: Sylvie Comte Administrative support: Eric K. Rowinsky, Nadia Amellal, Sylvie Comte Provision of study materials or patients: Jordi Giralt, Paul M. Harari, K. Kian Ang, Roger B. Cohen, Merrill S. Kies, José Baselga, James A. Bonner Collection and assembly of data: Eric K. Rowinsky, Nadia Amellal, James A. Bonner Data analysis and interpretation: Desmond Curran, Jordi Giralt, Merrill S. Kies, Eric K. Rowinsky, Nadia Amellal, James A. Bonner Manuscript writing: Desmond Curran, K. Kian Ang, Jacek Jassem, Eric K. Rowinsky, Nadia Amellal, James A. Bonner Final approval of manuscript: Desmond Curran, Jordi Giralt, Paul M. Harari, K. Kian Ang, Roger B. Cohen, Jacek Jassem, José Baselga, Eric K. Rowinsky, Sylvie Comte, James A. Bonner
We thank the patients and staff of all institutions participating in the clinical trial.
Supported by Merck KGaA. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Campbell BH, Marbella A, Layde PM: Quality of life and recurrence concern in survivors of head and neck cancer. Laryngoscope 110:895-906, 2000[CrossRef][Medline] 2. Morris J: Widening perspectives: Quality of life as a measure of outcome in the treatment of patients with cancers of the head and neck. Eu J Cancer B Oral Oncol 30B:29-31, 1994[CrossRef] 3. Vickery LE, Latchford G, Hewison J, et al: The impact of head and neck cancer and facial disfigurement on the quality of life of patients and their partners. Head Neck 25:289-296, 2003[CrossRef][Medline] 4. Vokes EE, Weichselbaum RR, Lippman SM, et al: Head and neck cancer. N Engl J Med 328:184-194, 1993 5. Garden AS, Asper JA, Morrison WH, et al: Is concurrent chemoradiation the treatment of choice for all patients with stage III or IV head and neck carcinoma? Cancer 100:1171-1178, 2004[CrossRef][Medline] 6. Hammerlid E, Mercke C, Sullivan M, et al: A prospective quality of life study of patients with oral or pharyngeal carcinoma treated with external beam irradiation with or without brachytherapy. Oral Oncol 33:189-196, 1997[Medline] 7. Nguyen NP, Sallah S, Karlsson U, et al: Combined chemotherapy and radiation therapy for head and neck malignancies: Quality of life issues. Cancer 94:1131-1141, 2002[CrossRef][Medline] 8. Brizel DM, Albers ME, Fisher SR, et al: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338:1798-1804, 1998 9. Harari PM: Promising new advances in head and neck radiotherapy. Ann Oncol 16:vi13-vi19, 2005 (suppl 6) 10. Calais G, Alfonsi M, Bardet E, et al: Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 91:2081-2086, 1999 11. List MA, Siston A, Haraf D, et al: Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: A prospective examination. J Clin Oncol 17:1020-1028, 1999 12. Huguenin P, Glanzmann C, Taussky D, et al: Hyperfractionated radiotherapy and simultaneous cisplatin for stage III and IV carcinomas of the head and neck: Long-term results including functional outcome. Strahlenther Onkol 174:397-402, 1998[Medline] 13. Terrell JE, Fisher SG, Wolf GT, et al: Long-term quality of life after treatment of laryngeal cancer. Arch Otolaryngol Head Neck Surg 124:964-971, 1998 14. Goldstein NI, Prewett M, Zuklys K, et al: Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1:1311-1318, 1995[Abstract] 15. Ang KK, Berkey BA, Tu X, et al: Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62:7350-7356, 2002 16. Hitt R, Ciruelos E, Amador ML, et al: Prognostic value of the epidermal growth factor receptor (EGFR) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy. Eur J Cancer 41:453-460, 2005[CrossRef][Medline] 17. Robert F, Ezekiel MP, Spencer SA, et al: Phase I study of anti–epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 19:3234-3243, 2001 18. Bonner JA, Harari PM, Giralt J, et al: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:568-578, 2006 19. Thomas M: Cetuximab: Adverse event profile and recommendations for toxicity management. Clin J Oncol Nurs 9:332-338, 2005[CrossRef][Medline] 20. Hollywood E: Clinical issues in the administration of an anti-epidermal growth factor receptor monoclonal antibody, IMC-C225. Semin Oncol Nurs 18:30-35, 2002 (suppl 2)[Medline] 21. Riddle J, Lee P, Purdom M: The epidermal growth factor receptor as a novel target for cancer therapy: Case studies and clinical implications. Semin Oncol Nurs 18:11-19, 2002 (suppl 4)[Medline] 22. Fayers PM, Aaronson NK, Bjordal K, et al: EORTC QLQ-C30 Scoring Manual (ed 9). Brussels, Belgium, EORTC, 1999 23. Bjordal K, de Graeff A, Fayers PM, et al: A 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 36:1796-1807, 2000[CrossRef][Medline] 24. Machin D, Weeden S: Suggestions for the presentation of quality of life data from clinical trials. Stat Med 17:711-724, 1998[CrossRef][Medline] 25. Curran D, Aaronson N, Standaert B, et al: Summary measures and statistics in the analysis of quality of life data: An example from an EORTC-NCIC-SAKK locally advanced breast cancer study. Eur J Cancer 36:834-844, 2000[CrossRef][Medline] 26. Curran D, Molenberghs G, Fayers PM, et al: Incomplete quality of life data in randomized trials: Missing forms. Stat Med 17:697-709, 1998[CrossRef][Medline] 27. Troxel AB, Fairclough DL, Curran D, et al: Statistical analysis of quality of life with missing data in cancer clinical trials. Stat Med 17:653-666, 1998[CrossRef][Medline] 28. Diggle PJ, Liang KY, Zeger SL: Analysis of Longitudinal Data. Oxford, United Kingdom, Clarendon Press, 1994 29. Verbeke G, Molenberghs G: Linear Mixed Models in Practice. New York, NY, Springer-Verlag, 1997 30. Curran D, Molenberghs G, Aaronson NK, et al: Analysing longitudinal continuous quality of life data with dropout. Stat Methods Med Res 11:5-23, 2002 31. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958[CrossRef] 32. Harari PM, Ritter MA, Petereit DG, et al: Chemoradiation for upper aerodigestive tract cancer: Balancing evidence from clinical trials with individual patient recommendations. Curr Probl Cancer 28:7-40, 2004[CrossRef][Medline] 33. Abdel-Wahab M, Abitbol A, Lewin A, et al: Quality-of-life assessment after hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and paclitaxel (Taxol) in inoperable and/or unresectable head and neck squamous cell carcinoma. Am J Clin Oncol 28:359-366, 2005[CrossRef][Medline] 34. Hammerlid E, Wirblad B, Sandin C, et al: Malnutrition and food intake in relation to quality of life in head and neck cancer patients. Head Neck 20:540-548, 1998[CrossRef][Medline] 35. de Graeff A, de Leeuw JR, Ros WJ, et al: Sociodemographic factors and quality of life as prognostic indicators in head and neck cancer. Eur J Cancer 37:332-339, 2001[CrossRef][Medline] Submitted August 23, 2006; accepted January 23, 2007. Related Editorial
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
80 v > 80; age, continuous; and sex), assessment visit, treatment, visit by treatment interaction, and global health status/QoL. The Wald 
2 test was used to evaluate the effect of QoL scores on dropout. 
