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Quality of Life of Nasopharyngeal Carcinoma Patients Yoav P. Talmi, M.D.1 Zeev Horowitz, M.D.1 Lev Bedrin, M.D.1 Michael Wolf, M.D.1 Gavriel Chaushu, D.M.D.2 Jona Kronenberg, M.D.1 M. Raphael Pfeffer, M.D.2,3 1
Department of Otolaryngology-Head and Neck Surgery, the Chaim Sheba Medical Center, Tel Hashomer and the Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
2
Department of Oral and Maxillofacial Surgery, the Chaim Sheba Medical Center, Tel Hashomer and the Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
3
Department of Oncology, the Chaim Sheba Medical Center, Tel Hashomer and the Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
BACKGROUND. Quality of life (QOL) issues in patients with head and neck carcinoma are of importance beyond the incidence of these tumors because of the impact of the disease and its treatment on external appearance and function of the upper aerodigestive tract. Nasopharyngeal carcinoma (NPC) patients comprise a unique subgroup in whom, to our knowledge, QOL has not been studied directly. METHODS. Adult patients with NPC treated during the past 15 years at the Chaim Sheba Medical Center with a minimum follow-up of 6 months were included in the current study. Patients were mailed the revised University of Washington quality of life (UW-QOL) questionnaire and data pertaining to their disease were recorded. Patients with recurrent disease or another malignancy or those whose present status could not be ascertained were excluded from the study. QOL scores were analyzed based on treatment, disease stage, and patient age. RESULTS. Twenty-eight patients of 35 disease-free patients (80%) responded to the questionnaire sent to patients meeting the study criteria. The mean score for general health was 3.1 (range, 1–5). Pain was not a significant factor. Other domains without noteworthy problems were speech and shoulder disability. The majority of patients described their appearance as normal or with minor changes, and questions concerning activity, recreation/entertainment, employment, and swallowing all scored ⬎ 70 (range, 0 –100). Dry mouth, chewing, and ear problems were of major concern with the majority of patients and affected the QOL indices. Nevertheless, the overall mean QOL score of these patients was rated as “good” (4.2 on a scale of 1– 6). CONCLUSIONS. In the current study, patients with NPC reported ear problems, difficulties in chewing, and dry mouth but their overall QOL appeared to be good. Ear problems such as secretory otitis media should be recognized at the time of presentation and treated. Conformal radiotherapy techniques sparing the salivary glands and temporal bone most likely will be useful in reducing the morbidity associated with treatment. Cancer 2002;94:1012–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10342
KEYWORDS: nasopharynx, carcinoma, quality of life (QOL), xerostomia, ear.
I Address for correspondence: Yoav P. Talmi, M.D., Head and Neck Service, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel; Fax: (011) 972-3-5368020; E-mail:
[email protected] Received June 26, 2001; revision received October 9, 2001; accepted October 15, 2001. © 2002 American Cancer Society
n recent years there has been an increasing awareness of quality of life (QOL) issues in clinical care. A MEDLINE search revealed only 6 articles with QOL as a key word in 1970, 234 articles in 1980, and 1384 articles in 1990, whereas 4532 articles were found in the year 2000. Beginning with scattered publications in the late 1970s and early 1980s, reports regarding QOL issues in otolaryngology-head and neck surgery have increased nearly threefold in the past decade. Although carcinoma of the nasopharynx constitutes 0.3– 4.0% of all malignant tumors in the Western world, it ranks among the most common tumors in Southeast Asia. A total of 7557 new cases of NPC were found in the U.S. National Cancer Data Base report in the years 1985–1994,1 comprising 2.6% of all reported head and neck malignancies. An
Quality of Life of Nasopharyngeal Carcinoma Patients/Talmi et al.
annual incidence rate of 0.6 per 100,000 was reported in the U.S. and NPC was reported in another publication to account for 4% of head and neck tumors or 0.25% of all cancers.2 A nationwide study of NPC in Israel during a 9-year period (1960 –1968) demonstrated a mean annual incidence rate of 1.0 per 100,000 in males and 0.4 per 100,000 in females.3 Numerous studies of QOL in patients with carcinoma of the head and neck have been reported but to our knowledge none of these, including two large recent studies,4,5 focused on NPC. NPC has unique features among head and neck malignancies that increase the significance of QOL issues. NPC affects a younger group of patients compared with other carcinomas of the head and neck and it usually is not associated with smoking or alcohol abuse. Consequently, NPC patients have a lower incidence of associated comorbidity and many are gainfully employed at the time of presentation of their disease. NPC usually is not treated with surgery and the majority of patients are treated with radiotherapy or chemoradiation.1 QOL assessment is a critical tool in the development and evaluation of novel techniques of chemotherapy and radiotherapy such as intensity-modulated radiation therapy (IMRT) that may significantly reduce the morbidity associated with treatment.6 We have undertaken a retrospective, cross-sectional study of NPC survivors to determine their disease-related QOL.
MATERIALS AND METHODS Adult patients (age ⬎ 17 years) with NPC who were treated at the Chaim Sheba Medical Center between 1986 –2000 were included in the current study. Clinical data obtained from patient charts included age at diagnosis, gender, follow-up period, treatment modalities, radiotherapy fields and dose scheduling, and tumor restaging according to the 1997 American Joint Committee on Cancer staging manual. Patients with recurrent disease or a diagnosis of other malignancies were excluded. Inclusion in the current study required a minimum follow-up period of 6 months after the conclusion of treatment. A Hebrew version of the revised validated University of Washington (UW)-QOL questionnaire7 was mailed to the patients. The questionnaire included an exact verified version using a double-back translation method between independent translators. Two extra questions pertaining to NPC were added but were not validated. These incorporated information regarding dryness of the mouth and ear problems. Although the patients did not undergo surgery, the question regarding shoulder function was not deleted to ensure maximal uniformity of the questionnaire. Scoring varied from a scale of 1–5
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TABLE 1 Patient Data (n ⴝ 28)
Age range (yrs) Mean age (yrs) M:F ratio Chemotherapy T1 T2 T3 T4 N0 N1 N2 N3 M
Age < 45 yrs
Age > 45 yrs
21–43 32.8 8:2 9 (90%) 1 4 3 3 2 2 2 4 0
45–74 55.8 12:6 9 (50%) 5 3 5 4 13 0 2 3 0
M: male; F: female.
or 1– 6 in some questions and from 0 –100 on others.7 The questionnaire was sent to patients who underwent recent follow-up in any of our medical center clinics. If patient status could not be verified, no questionnaire was sent. Data analysis included global QOL scores according to the standard questionnaire. A breakdown of results comparing patients receiving chemoradiation and radiotherapy only, patients age ⬍ 45 years with those age ⱖ 45 years, and patients with T1-2 tumors with those whose tumors were classified as T3-4 was performed as well. Statistical analysis was performed using the Student t test.
RESULTS A computerized database search found 99 adult NPC patients who were diagnosed and/or treated over the past 15 years in the Departments of OtolaryngologyHead and Neck Surgery and Oncology at the Chaim Sheba Medical Center. Of this group, 21 patients were known to be dead either of disease or other causes and 6 patients were known to be alive with disease. An additional 37 patients were not being followed in the hospital-based clinic. Twenty-eight of 35 disease free patients (80%) responded to the questionnaire. Twenty patients were males and 8 were females. The mean age was 47 years (range, 21–74 years). The mean follow-up was 5.4 years (range, 7 months–14 years, median, 5 years). Tumor staging is presented in Table 1. The radiotherapy dose ranged from 6800 to 7240 centigrays. Ten patients were treated with radiotherapy only and 18 patients were treated with chemotherapy and radiotherapy comprised of 2–3 cycles of cisplatin and continuous infusion 5-fluorouracil prior to radiotherapy and weekly cisplatin during radiother-
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TABLE 2 Results of the Revised University of Washington (UW) QOL Questionnaire Questions
Results, mean (range) [significance]
1. In general your health is: (Range: poor–excellent; 1–5) 2. Compared to 1 year prior to diagnosis your health is now (range: much worse–much better, 1–5) Importance of each following item to overall QOL: 1 ⫽ Not important 2 ⫽ A little bit important 3 ⫽ Somewhat important 4 ⫽ Quite a bit important 5 ⫽ Extremely important 3. Pain (range: no pain–severe, not controlled pain; 100–0) 4. Appearance (range: no change–cannot be with people; 100–0) 5. Activity (range: as active as ever–usually in bed or chair, does not leave home; 100–0) 6. Recreation/entertainment (range: no limitations–I can’t do anything enjoyable; 100–0) 7. Employment (range: work full time–unemployed due to cancer treatment; 100–0) 8. Chewing (range: as well as ever–cannot chew even soft solids; 100–0) 9. Swallowing (range: as well as ever–cannot swallow; 100–0) 10. Speech (range: same as always–cannot be understood; 100–0) 11. Shoulder disability (range: no problem–cannot work due to shoulder problems; 100–0) 12. Dry mouth No dryness Mouth dry but does not constitute a problem Mouth very dry and needs constant drinking Severe dryness not alleviated by any measures 13. Ear problems No ear problems Ear/s fullness Ear/s fullness with need for ventilation tubes Chronic ear infection Rate your overall QOL in the past week (range: very poor–excellent; 1–6)
3.1 (2–4) 3.3 (1–5)
89 (50–100) [4.13] 78 (25–100) [4.26] 74 (0–100) [4.56] 77 (0–100) [4.52] 73 (20–100) [4.43] 61 (0–100) [4.52] 73 (30–100) [4.60] 92 (70–100) [4.95] 90 (0–100) [4.69] 41 (0–100) [4.61] 100 70 30 0 65 (0–100) [4.65] 100 70 30 0 4.2 (2–6)
QOL: quality of life. Questions 12 and 13, which were specifically added to the standard questionnaire, are portrayed fully.
apy. None of the patients included in the current study underwent neck dissection or other surgical procedures other than endoscopy and biopsy. The results are summarized in Tables 2 and 3. The mean score of general health was 3.1 (range, 1–5) corresponding with “good” on the scale. Pain was not a significant factor although the majority of patients ranked its presence as “quite a bit important.” Other domains without significant problems were speech (mean score of 92 of 100) and, as expected, shoulder disability (mean score of 90). The majority of patients described their appearance as either normal or with minor changes. Activity, recreation/entertainment, employment, and swallowing all scored ⬎ 70. Low scores were obtained for chewing (61) and ear problems (65). Dry mouth was a major concern with the majority of patients (mean score of 41). Overall, the mean QOL score over the previous week was 4.2, corresponding to “good” on the questionnaire. Patients age ⬍ 45 years demonstrated a statistically significant reduction in swallowing compared
with those age ⱖ 45 years. Patients age ⱖ 45 years tended to assign less importance to the activity and employment scores. Patients treated with chemoradiation had statistically significantly reduced swallowing scores and assigned less importance to xerostomia. Significantly increased scores were found for the importance of appearance and activity in patients treated with chemoradiation (Table 3). Patients with advanced tumors (T3– 4) tended to report better scores for xerostomia and to assign lower importance to speech impairment, although these results were not found to be statistically significant.
DISCUSSION There are difficulties in using a single questionnaire to evaluate QOL adequately;8,9 nevertheless, the UW-QOL questionnaire is a suitable routine measure of outcome in patients with head and neck carcinoma, being quick and simple for patients to complete and easy to process. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-H&N35 module is more comprehensive and has been used
Quality of Life of Nasopharyngeal Carcinoma Patients/Talmi et al.
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TABLE 3 Results of the Revised University of Washington (UW)-QOL Questionnaire Comparing Patient Groups Patient age (yrs) < 45 Question no. 1 2 3 Significance 4 Significance 5 Significance 6 Significance 7 Significance 8 Significance 9 Significance 10 Significance 11 Significance 12 Significance 13 Significance 14
> 45 Scores
3.33 3.33 94.44 4 80.55 4.66 72.22 4.88 77.77 4.11 80 4.87 55.55 4.44 64.44 4.55 85.55 4.88 96.66 4.11 35.55 4.44 55.55 4.55 4.22
Treatment
2.94 3.17 85.29 4.29 76.47 4 73.52 4.35 73.52 4.47 70.58 4.05 64.70 4.29 78.82 4.35 94.70 4.70 87.05 4.70 44.11 4.70 70 4.70 4.17
ⴙCx
XRT Statistics NS NS NS NS NS NS NS P ⫽ 0.055 NS NS NS P ⫽ 0.060 NS NS P ⬍ 0.05 NS NS NS NS NS NS NS NS NS NS
Scores 3.2 3.5 90 4.5 85 3.7 80 4.2 80 4.3 72 4.1 65 4.1 82 4.4 94 4.6 91 4.6 46 4.9 68 4.9 4.12
Staging T1-2 Statistics
3 3.06 87.5 4 73.43 4.56 68.75 4.75 71.87 4.37 74.66 4.46 59.37 4.5 68.75 4.43 90 4.87 90 4.43 38.12 4.43 63.12 4.5 4.18
NS NS NS NS NS P ⬍ 0.05 NS P ⬍ 0.05 NS NS NS NS NS NS P ⬍ 0.05 NS NS NS NS NS NS P ⬍ 0.05 NS P ⬍ 0.05 NS
T3-4 Scores
3.14 2.92 91.07 4.07 82.14 4.28 75 4.42 80.35 4.5 77.14 4.57 64.28 4.57 73.57 4.64 90.71 5 95.71 4.57 34.28 4.57 62.85 4.57 4.21
Statistics 3 3.58 85.41 4.33 72.91 4.16 70.83 4.66 68.75 4.16 69.09 4 58.33 4.08 74.16 4.16 92.5 4.5 84.16 4.41 49.16 4.66 67.5 4.75 4.16
NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS P ⫽ 0.060 NS NS P ⫽ 0.060 NS NS NS NS
QOL: quality of life; XRT: radiation treatment; Cx: chemotherapy; NS: not significant.
widely,10 and is a valuable tool in conjunction with the QLQ-C30, but has undergone limited reliability and validity testing.9 Asking patients to define their current health compared with 1 year prior to diagnosis is problematic, especially in those patients followed for long time periods. Nevertheless, routine use of the UW-QOL questionnaire in clinical practice has not led to a modification of this question (Question 2). Its value is in the current recollection of the patient of his or her status prior to diagnosis rather than the actual past condition. In a prospective study of QOL at the time of diagnosis in head and neck carcinoma patients, Hammerlid et al.11 separately described results for 11 NPC patients of their total group of 357 head and neck cancer patients. These patients scored the second worst global QOL (after patients with hypopharyngeal carcinoma) and NPC patients also had the worst social and role functioning and were the group with the highest pain score and highest use of painkillers. The three major concerns in NPC patients were trouble
enjoying meals, feeling ill, and dry mouth. Rather surprisingly, dry mouth was a significant concern in these patients at the time of presentation and scored the highest of all tumors reported. Despite the relatively small number of NPC patients in this report, this finding is intriguing. Dry mouth is an expected and major concern after treatment and scored the lowest of the domains addressed in the current study; however, we did not specifically inquire regarding the situation prior to treatment. Although pain was a foremost complaint in the patients in the study by Hammerlid et al.11 prior to treatment, our posttreatment results imply that it is not a major concern with the current study patients. Presumably, the use of chemoradiation in the patients in the current study served well to control the tumor and reduce pain associated with its presence. Treatment-related pain that is associated with surgical tumor ablation was not encountered in this group of patients, who were treated with a combination of chemotherapy and radiotherapy or radiotherapy only. Huguenin et al.12 examined the importance of the
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radiotherapy target volume on the QOL of patients cured of head and neck carcinoma. The EORTC QLQC30 core questionnaire with the head and neck carcinoma module was used and administered by mail. The response rate for the NPC group was 71% compared with the response rate of 80% in the current study. Follow-up ranged from 5.1–5.9 years compared with a mean of 5.4 years in the current study. The series in the report by Huguenin et al. included 87 patients, 12 of whom were treated for NPC. These 12 patients were treated with hyperfractionated radiotherapy, 8 of whom also received chemotherapy. Radiation fields included the temporomandibular joints and salivary glands. Increased problems reported in the NPC group were dry mouth, sticky saliva, trismus, problems with teeth, and eating difficulty. Although role function was reduced significantly in patients with NPC compared with those with carcinoma of the larynx (T1/T2), no impact was noted on their global QOL scores. These results are compatible with the findings of the current study both in the domains addressed and global QOL scores. Dry mouth and sticky saliva are recognized problems in patients with carcinoma of the head and neck, and for the most part are induced by treatment. Candidiasis frequently accompanies xerostomia, especially in terminally ill patients, leading to severely hampered QOL.13 The global score of NPC patients in the current study was surprisingly good and this finding may imply that other domains not addressed in the UW-QOL questionnaire have a positive, moderating effect on the global score. The addition of a question addressing ear function is important in these patients. Only six patients did not report having any ear problems whereas scores of 70 denoting chronic ear fullness were noted by 13 patients (46%). Six patients required tympanocentesis and the introduction of ventilation tubes and one patient reported a chronic state of infection with a score of 0 for this domain. Statistically significantly worse swallowing scores for patients age ⬍ 45 years compared with those age ⬎ 45 years could well be attributed to the fact that all but 1 of the patients in this group received chemotherapy (90%) compared with only 50% of the patients age ⬎ 45 years. In addition, patient expectations may differ rather than actual difficulties. However, because no difference appeared to be associated with the importance of swallowing with regard to QOL between the two groups, further studies are warranted to determine whether if an objective discrepancy exists. Hughes et al. noted the occurrence of dysphagia in treated NPC patients by both subjective reports and objective measures such as videofluoroscopy.14 A total
of 76% reported dysphagia and 97% had xerostomia. The mean follow-up time was 56 months, which is quite similar to the follow-up in the current study. Hughes et al. attributed long-term dysphagia to radiation-induced changes such as xerostomia or decreased pharyngeal mobility due to fibrosis or damage to pharyngeal innervation.14 As anticipated, patients age ⱖ 45 years tended to assign less importance to the activity and employment scores. Patients treated with chemoradiation had statistically significantly reduced swallowing scores. Although xerostomia was not found to be more severe in the patients treated with chemoradiation, it was assigned reduced importance. Significantly increased scores were found with regard to the importance of appearance and activity in patients treated with chemoradiation. Scores for appearance and activity were reduced in the chemoradiation group but no apparent statistical significance was attained (Table 3). Patients with advanced tumors (T3– 4) tended to have better scores for xerostomia and assigned lower importance to speech impairment although these results were not statistically significant. The majority of statistically significant differences between the groups compared were with regard to the importance associated with the domains addressed. This in itself is indicative of the importance of the incorporation of such questions into a QOL instrument. Scores for different domains may vary but if the importance of such variability to the patient is minimal the actual significance of this variation is questionable. The toxicity of radiotherapy for NPC is influenced by the tumor volume irradiated. In particular, major salivary gland irradiation largely is responsible for dryness of the mouth, the major reported toxicity of irradiation. With the advent of computed tomographybased conformal irradiation, it has become possible to adequately cover the tumor in the nasopharynx and high risk lymph node groups, yet reduce the dose of radiation to the parotid glands to below the threshold dose for parotid dysfunction.15 More recently, IMRT,6 which allows the delivery of different doses of radiation to various tumor volumes within the treatment field, has been introduced into clinical use.16 This greatly simplifies the planning and delivery of parotidsparing radiotherapy techniques without compromising target coverage.17 It is oversimplification to link QOL with a single cause such as salivary function. Nevertheless, minimizing radiation damage to the salivary glands could well alleviate many of the problems reported by NPC patients. Unfortunately, although the mean parotid gland radiation dose can be reduced with IMRT, to our
Quality of Life of Nasopharyngeal Carcinoma Patients/Talmi et al.
knowledge it is not at present low enough to preserve salivary function completely16 in all patients. Defining QOL in any given patient group is important for portraying the expected course of disease and treatment to the patient. In the majority of cases this serves to reduce anxiety and allows the patient and family to plan ahead. This has particular importance in the NPC patient population (mean age 47 years), and patients may be expected to resume their normal productive activities, including work, after treatment with good survival rates. To assess current and future treatment regimens, appropriate quantification of QOL using validated instruments should be performed in NPC patients. Longitudinal studies indicating QOL variability during the course of diagnosis and treatment in these patients are essential. Patients treated with curative intent for NPC should receive more focused care for reported longterm problems defined as severe such as ear problems, xerostomia, and chewing difficulties.
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