Vartanian JG, Carvalho AL, Yueh B, Priante AVM, de Melo RL, Correia LM, Köhler HF, Toyota J, Kowalski ISG, Kowalski LP. Long-term Quality-of-Life Evaluation After Head and Neck Cancer Treatment in a Developing Country. Arch Otolaryngol Head Neck Surg. 2004;130(10):1209-1213. doi:10.1001/archotol.130.10.1209
To evaluate the long-term quality of life of patients treated for head and neck cancer at a single institution in a developing country.
Cross-sectional analysis of a consecutive series of patients.
Tertiary cancer center hospital in Brazil.
Eligible subjects included patients treated between 1974 and 1999 for head and neck carcinoma who had a minimum disease-free survival of 2 years and who completed a Portuguese version of the University of Washington Quality of Life (UW-QOL) questionnaire.
Main Outcome Measures
Descriptive analyses of the results and comparisons of the scores for each UW-QOL domain, stratified by tumor site, were performed using nonparametric tests.
Findings from 344 patients were analyzed. Of the study population, 140 (41%) had survived 2 to 5 years, 125 (36%) had survived 5 to 10 years, and 79 (23%) had survived more than 10 years since treatment. Primary tumor sites were in the oral cavity in 43.3% of cases, the oropharynx in 20.9%, the larynx in 32.0%, and the hypopharynx in 3.8%. In terms of treatment, 33.1% underwent surgery alone; 16.9%, radiotherapy alone; and 50% underwent combined treatment. Overall, 78.5% of the patients classified their own health as good or excellent. Stratified analysis showed that impairment in chewing and swallowing was more common in patients with oral and oropharyngeal tumors than in those with larynx and hypopharynx tumors, and speech impairment was more frequently related to patients with larynx and hypopharynx tumors than to those with oral and oropharynx tumors. In all tumor sites, the composite scores were significantly worse in advanced tumors than early stage tumors, but the use of combined treatment had the greatest negative impact on quality-of-life scores, after we adjusted for T and N stage with multivariable analyses (P<.001).
The Portuguese version of the UW-QOL questionnaire was an effective tool to evaluate quality of life in a Brazilian population. Although many patients reported some limitations, most reported a good to excellent long-term quality of life.
The main outcome measure in oncologic patients has long been survival, based on tumor control, but recently, treatment implications for the patient's global quality of life (QOL) has been emphasized as a very important issue. In the last 20 years, an increasing number of studies have measured QOL as an end point in the evaluation of the impact of the disease and its treatment on the patient's daily life.1- 3
Head and neck cancer is a worldwide public health problem. It is especially troubling in developing countries where most patients are diagnosed at advanced clinical stages and need more aggressive treatment, which is usually associated with poor survival.4 Due to the anatomic characteristics of the head and neck, treatment of head and neck cancer can result in deficits to cosmetic appearance and varying degrees of dysfunction in speech, swallowing, and respiration. These factors could have a negative impact in the functional outcomes and psychosocial adjustments of patients and their families as well as socioeconomic consequences with regard to the health system.3,5- 7
Several instruments have been developed to assess QOL in patients with head and neck cancer.8- 10 Among them, the University of Washington Quality of Life (UW-QOL) questionnaire is a validated, accurate, and internationally accepted survey instrument.3,5,8 The use of such questionnaires allows evaluation of functional outcomes and health-related QOL and leads to better understanding of patient expectations.3,5,7- 10 The results of this type of evaluation could better define treatment strategies.
However, the UW-QOL has been used almost exclusively in populations living in developed countries. The objective of the present study is to use the UW-QOL questionnaire to evaluate long-term QOL in a large series of patients treated for head and neck cancer at a single tertiary cancer hospital in a developing country, Brazil.
We performed a cross-sectional study of a consecutive series of patients treated for head and neck cancer. All patients had a diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx and a minimum disease-free survival period of 2 years. All charts were reviewed, and the tumors were staged according to the TNM categories of the American Joint Committee on Cancer 1997 criteria.11 All patients signed a consent form, and the study was approved by the institutional ethics committee.
The patients were interviewed by 1 of 2 trained registered nurses using a Portuguese version of the UW-QOL, version 3. Although the UW-QOL scale was designed as a self-reported scale, the high real and functional illiteracy rates in our population did not allow for effective use of self-reported questionnaires. Therefore, 2 trained registered nurses completed the UW-QOL by directly reading the questions to the patients and recording their verbal responses. To avoid interviewer bias, neither nurse was involved in the patient's care. The questionnaires were administered to patients before or after their routine consultations at the Department of Otolaryngology–Head and Neck Surgery at our institution. The nurses made clear to the patients that their responses would remain confidential, that their physician would not see the individual data, and that the questionnaire would not interfere with their health care.
Statistical analyses were performed using version 10.0 of the SPSS statistical program (SPSS Inc, Chicago, Ill) for Windows. A descriptive analysis of the results was performed. The QOL scores were compared for each domain using the nonparametric Mann-Whitney and Kruskal-Wallis tests. We scored the individual domains according to the UW-QOL guidelines.12 Composite UW-QOL scores were calculated as the mean of the domain scores. Unpublished data from the University of Washington (B.Y., 2003) based on change of scores and differences in baseline T stage suggest that a 7-point difference in the composite score is the minimum clinically important difference (not all statistically significant changes are clinically meaningful). Because the site of the tumor was expected to strongly influence different domains of the questionnaire, a stratified analysis by tumor site was performed. In stratified analyses by anatomic site, multiple linear regression was used to determine the impact of combined treatment, T stage, and N stage on UW-QOL scores.
A total of 344 outpatients were enrolled in this study between 1999 and 2002. The UW-QOL questionnaires were administered by the registered nurses at the routine consultations in the outpatient clinic, which improved adherence by most patients in this study. There were 251 men (73%) aged 18 to 88 years (median age, 55 years). The primary tumor sites were oral cavity in 149 cases (43.3%), oropharynx in 72 cases (20.9%), larynx in 110 cases (32.0%), and hypopharynx in 13 cases (3.8%). The tumors were TNM clinical stage I in 61 patients (17.7%), stage II in 80 (23.3%), stage III in 115 (33.4%), and stage IV in 88 (25.6%). One hundred fourteen patients (33.1%) underwent surgery alone; 58 (16.9%), radiotherapy alone; and 172 (50.0%), combined treatment (surgery and radiotherapy). All patients survived for at least 2 years (range, 2-26 years; median survival, 6.2 years), with 140 (41%) surviving between 2 and 5 years, 125 (36%) surviving 5 to 10 years, and 79 (23%) surviving more than 10 years after treatment.
In answering the UW-QOL global questions on overall health, 78.5% of patients reported good general health, and 78.8% thought that their health was the same or better than it was prior to treatment. A summary of the level of importance assigned to each domain by the patients is provided in Table 1. Almost all of the domains were rated as important by the patients. However, the pain and appearance domains were selected relatively less often than the functional domains, which suggests that functional status was of higher priority to this series of patients (Table 1).
Oral cavity and oropharyngeal tumors behave differently biologically and require different treatment approaches than laryngeal and hypopharyngeal tumors, mainly with regard to the surgical approach. Such differences might impact differently individual domains and consequently affect composite scores. For this reason, we performed a stratified analysis by tumor site.
In patients with oral cavity and oropharynx tumors, women were more likely than men to report a worse score for pain (86.1 vs 93.0; P = .004). Younger patients (<60 years) reported worse scores for appearance than older patients (76.8 vs 86.0; P = .001). Patients with advanced local disease (stage T3 or T4) reported worse scores than those with early stage lesions (stage T1 or T2) for appearance (77.0 vs 81.9, P = .01), chewing (65.7 vs 73.1; P = .03), swallowing (77.3 vs 82.4; P = .01), and speech (70.8 vs 84.3; P<.001). Patients with regional metastases reported worse scores for appearance than those without clinically evident metastatic lymph nodes in the neck (71.7 vs 83.2; P<.001), recreation (85.7 vs 90.7; P = .02), chewing (62.5 vs 72.9; P = .01), swallowing (74.6 vs 82.4; P = .001), speech (72.6 vs 80.7; P = .005), and shoulder (75.1 vs 86.1; P<.001). Treatment was the most important variable interfering with QOL for patients with oral and oropharynx tumors, and combined treatment (surgery and radiotherapy) was associated with the worst scores. These patients had worse scores than those who underwent single-modality treatment in the domains of appearance (P<.001), recreation (P = .01), chewing (P<.001), swallowing (P<.001), and speech (P<.001) (Table 2). No statistically significant differences were noted in the other domains. These results were also reflected in the composite scores, where the lowest scores were found for female sex (78.7 vs 83.4; P = .04), advanced (T3 or T4) local disease (79.6 vs 84.1; P = .002), regional metastases (77.5 vs 84.1; P<.001), and combined treatment (78.5 [combined] vs 86.5 [surgery] vs 85.7 [radiotherapy]; P<.001) (Table 2). The differences in composite scores for patients with regional metastases and combined treatment were not only statistically significant but were also clinically important (ie, worse by 7 points or more than the scores of patients with negative neck findings and those who underwent single-modality treatment).
For patients with larynx and hypopharynx cancer, sex and age were not associated with differences in scores in any of the domains. However, patients with advanced local disease (T3 or T4) reported worse scores than those with early local disease (T1 or T2) for appearance (P = .01), recreation (P = .002), and speech (P<.001). Patients with nodal metastases reported worse scores than those without for chewing (77.6 vs 92.0; P = .006), swallowing (84.1 vs 91.2, P = .02), and shoulder (78.0 vs 87.4; P = .02). Treatment was again the most important influence on QOL, and the worst score was again associated with combined treatment (surgery and radiotherapy), affecting the domains of appearance (P = .001), recreation (P = .02), chewing (P = .01), swallowing (P = .003), speech (P<.001), and shoulder (P = .001) (Table 3). Also, the results were similar to the composite scores, with the worse scores being reported for advanced (T3 or T4) local disease (82.4 vs 89.7; P<.001), regional metastases (86.8 vs 80.1; P = .01), and combined treatment (79.8 [combined] vs 85.7 [surgery] vs 95.1 [radiotherapy]; P<.001) (Table 3). All of these differences in composite scores were not just statistically significant but also clinically important.
Combined treatment was associated with worse QOL scores than single-modality treatment in both the oral cavity/oropharynx and larynx/hypopharynx groups. Because advanced tumors are more likely to receive combined treatment, it was important to adjust for advanced disease. After we controlled for T and N stage, combined treatment still had the greatest association with low UW-QOL scores (P<.001) because combined treatment was associated with a lowering of at least 7 points in UW-QOL scores (Table 4).
Even with modern advances in diagnostic and treatment methods, mainly the increasing use of chemoradiation regimens, the overall survival rates among patients with head and neck cancer have been largely unchanged. This lack of improved survival has turned attention to evaluation of the function and QOL of survivors.1- 3
Because of the unique anatomic characteristics of the affected areas, head and neck cancer and its treatments have a remarkable impact on the patient's daily life. Such tumors usually result in some degree of dysfunction of speech, swallowing, and/or respiration as well as disfigurement of appearance. Such alterations in function and appearance may have a significant impact on the patient's self-image and may affect the psychosocial areas of the patient's life.3,7,9 For these reasons, it is important to assess QOL in the head and neck cancer population.
Several survey instruments have been designed to assess the QOL in patients with head and neck cancer.8- 10 The UW-QOL questionnaire has been proven to have psychometric validity, reliability, and responsiveness over time, which are critical requirements in a survey instrument.1- 3 It is self-completed by the patients, inexpensive, and easy to administer.3,5 In the present study we used a Portuguese version of the UW-QOL questionnaire. However, owing to the large number of illiterate patients in our population, the questionnaire was administered verbally by a health professional not involved with the patient's care so as to avoid interviewer bias. Had we asked the physician responsible for patient care to administer the questionnaire, we might have unintentionally influenced the patients to provide artificially better scores.
Regarding the global reports of health, our results showed 78.5% of the patients reported good general health, and 78.8% said that it was the same or better than 1 year prior to treatment. No clear data indicate whether cultural aspects might have influenced these results. A cross-cultural analysis comparing results from the same survey instrument could better define whether cultural factors are at play. For example, patients in developing countries with poorer access to high-quality medical care tend to be grateful to the attending physicians and so might try to not "disappoint" them, despite our assurances that the data would not be shown to their physicians.
The interpretation of composite QOL scores should be guided by an understanding of what differences are clinically important, whether or not the differences are statistically significant. One way to do this is to compare observed differences with what is considered a minimum important clinical difference. For the UW-QOL composite score, which represents the "overall picture," a 7-point difference is considered clinically significant. Therefore, our findings demonstrate that there are not only statistically significant worse long-term UW-QOL composite scores in those with advanced disease, regional metastases, and those who have received combined treatment, but also that these differences are for the most part clinically important. These findings correlate with individual domains stratified by site, as detailed in Table 2 and Table 3. Clearly, combined treatment strongly influenced the score in most of the domains in both oral and larynx/hypopharynx tumor sites. The results of multivariable analyses suggested that this effect was not due solely to the confounding influence of more advanced disease (Table 4).
The importance ascribed by patients to each UW-QOL domain (Table 1) suggests that functional status was of greater priority than pain control and appearance in our population of long-term survivors. This finding is quite different from that of a study of patients' expectations before treatment, in which the functional aspects were among the 3 major priorities in only 10% to 24% of patients.13
The present study demonstrates the value of the UW-QOL questionnaire as an important tool even for a population living in a developing country. We believe, based on comparisons of groups of patients who underwent different types of treatment and achieved the same oncologic results,1- 3,8 that QOL assessment could have a great impact on treatment strategies and could be used as a determining factor to better define those strategies. However, Weymuller et al,12 in an analysis of subsets of patients of a single institution, could not achieve statistical significance. The lack of randomization and the small number of patients after stratification (mainly in advanced tumor stages) are the most important issues that limit the results of such a study.
The present study has several limitations as well. First, the UW-QOL scale was administered by a health professional, which may bias the results. Second, cultural differences between the developed country where the survey instrument was developed (United States) and the developing country where it was applied (Brazil) are unmeasured. Finally, these data come from a single-institution study. Future efforts should address some of these limitations. The psychometric validation of the translated survey instrument is ongoing, and a cross-cultural analysis will be important to understand whether observed QOL differences are due to differences in cancer presentation, cancer treatment, or cultural expectations.
Nonetheless, the present study represents the first report on QOL assessment in the Brazilian population. These data are important for health care workers and patients living in other developing countries and may have relevance to minorities living in developed countries who have limited access to health care.
We agree that several instruments have been developed to measure QOL data, and it is not necessary to develop another tool. However, it is necessary to perform similar analyses among different populations and different institutions to better understand the results and to make possible comparisons among all head and neck cancer treatment institutions. It would also be helpful to undertake a multi-institutional study to include a statistically significant number of patients and analyze the QOL as an end point outcome measure.12 Only such an effort can result in objective data that can be universally used to change treatment guidelines.
Correspondence: Luiz Paulo Kowalski, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Hospital do Câncer A. C. Camargo, Rua Professor Antônio Prudente, 211, 01509-900 São Paulo, Brazil (firstname.lastname@example.org).
Submitted for publication December 4, 2003; final revision received April 14, 2004; accepted May 14, 2004.