Quality of Life of Nasopharyngeal Carcinoma Patients

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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 Med-

ical Center, Tel Hashomer and the Tel Aviv Uni-

versity Sackler School of Medicine, Tel Aviv, Israel.

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.

BACKGROUND. Quality of life (QOL) issues in patients with head and neck carci-

noma 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.

In recent years there has been an increasing awareness of quality of life (QOL) issues in clinical care. A MEDLINE search revealed only 6articles 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

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© 2002 American Cancer Society


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annual incidence rate of 0.6 per 100,000 was reported

in the U.S. and NPC was reported in another publica-

tion 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) demon-

strated a mean annual incidence rate of 1.0 per100,000 in males and 0.4 per 100,000 in females.3

Numerous studies of QOL in patients with carci-

noma of the head and neck have been reported but to

our knowledge none of these, including two large re-

cent studies,4,5 focused on NPC. NPC has unique fea-

tures among head and neck malignancies that in-

crease the significance of QOL issues. NPC affects a

younger group of patients compared with other carci-

nomas of the head and neck and it usually is not

associated with smoking or alcohol abuse. Conse-

quently, NPC patients have a lower incidence of asso-

ciated comorbidity and many are gainfully employedat the time of presentation of their disease. NPC usu-

ally is not treated with surgery and the majority of

patients are treated with radiotherapy or chemoradia-

tion.1 QOL assessment is a critical tool in the devel-

opment and evaluation of novel techniques of chemo-

therapy and radiotherapy such as intensity-modulated

radiation therapy (IMRT) that may significantly re-

duce the morbidity associated with treatment.6

We have undertaken a retrospective, cross-sec-

tional study of NPC survivors to determine their dis-

ease-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 modal-

ities, 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 re-

vised validated University of Washington (UW)-QOL

questionnaire7 was mailed to the patients. The ques-

tionnaire included an exact verified version using a

double-back translation method between indepen-

dent translators. Two extra questions pertaining to

NPC were added but were not validated. These incor-

porated information regarding dryness of the mouth

and ear problems. Although the patients did not un-

dergo surgery, the question regarding shoulder func-

tion was not deleted to ensure maximal uniformity of

the questionnaire. Scoring varied from a scale of 1–5

or 1– 6 in some questions and from 0 –100 on others.7

The questionnaire was sent to patients who under-

went recent follow-up in any of our medical center

clinics. If patient status could not be verified, no ques-

tionnaire was sent.

Data analysis included global QOL scores accord-

ing to the standard questionnaire. A breakdown of

results comparing patients receiving chemoradiation

and radiotherapy only, patients age 45 years with

those age 45 years, and patients with T1-2 tumors

with those whose tumors were classified as T3-4 wasperformed 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 Otolaryngology-

Head 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 radiother-

apy only and 18 patients were treated with chemother-

apy and radiotherapy comprised of 2–3 cycles of cis-

platin and continuous infusion 5-fluorouracil prior to

radiotherapy and weekly cisplatin during radiother-

TABLE 1Patient Data (n 28)

Age < 45 yrs Age > 45 yrs

Age range (yrs) 21–43 45–74

Mean age (yrs) 32.8 55.8M:F ratio 8:2 12:6

Chemotherapy 9 (90%) 9 (50%)

T1 1 5T2 4 3

T3 3 5

T4 3 4

N0 2 13

N1 2 0

N2 2 2N3 4 3

M 0 0

M: male; F: female.

Quality of Life of Nasopharyngeal Carcinoma Patients/Talmi et al. 1013


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apy. None of the patients included in the current study

underwent neck dissection or other surgical proce-

dures 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 pa-

tients 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/entertain-

ment, 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 ques-

tionnaire.

Patients age 45 years demonstrated a statisti-

cally significant reduction in swallowing compared

with those age 45 years. Patients age 45 years

tended to assign less importance to the activity and

employment scores. Patients treated with chemora-

diation had statistically significantly reduced swallow-

ing scores and assigned less importance to xerosto-

mia. 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.

DISCUSSIONThere are dif ficulties 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 Re-

search and Treatment of Cancer (EORTC) QLQ-H&N35

module is more comprehensive and has been used

TABLE 2Results 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) 3.1 (2–4)

2. Compared to 1 year prior to diagnosis your health is now (range: much worse–much better, 1–5) 3.3 (1–5)Importance of each following item to overall QOL:

1 Not important

2 A little bit important3 Somewhat important

4 Quite a bit important

5 Extremely important

3. Pain (range: no pain–severe, not controlled pain; 100–0) 89 (50–100) [4.13]

4. Appearance (range: no change–cannot be with people; 100–0) 78 (25–100) [4.26]

5. Activity (range: as active as ever–usually in bed or chair, does not leave home; 100–0) 74 (0–100) [4.56]6. Recreation/entertainment (range: no limitations–I can’t do anything enjoyable; 100–0) 77 (0–100) [4.52]

7. Employment (range: work full time–unemployed due to cancer treatment; 100–0) 73 (20–100) [4.43]

8. Chewing (range: as well as ever–cannot chew even soft solids; 100–0) 61 (0–100) [4.52]

9. Swallowing (range: as well as ever–cannot swallow; 100–0) 73 (30–100) [4.60]

10. Speech (range: same as always–cannot be understood; 100–0) 92 (70–100) [4.95]

11. Shoulder disability (range: no problem–cannot work due to shoulder problems; 100–0) 90 (0–100) [4.69]12. Dry mouth 41 (0–100) [4.61]

No dryness 100

Mouth dry but does not constitute a problem 70

Mouth very dry and needs constant drinking 30

Severe dryness not alleviated by any measures 0

13. Ear problems 65 (0–100) [4.65]No ear problems 100

Ear/s fullness 70

Ear/s fullness with need for ventilation tubes 30

Chronic ear infection 0

Rate your overall QOL in the past week (range: very poor –excellent; 1–6) 4.2 (2–6)

QOL: quality of life.

Questions 12 and 13, which were specifically added to the standard questionnaire, are portrayed fully.

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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 problem-

atic, 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 mod-

ification 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 diag-

nosis in head and neck carcinoma patients, Hammer-

lid 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 sur-

prisingly, 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 find-

ing 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 com-

bination of chemotherapy and radiotherapy or radio-

therapy only.

Huguenin et al.12 examined the importance of the

TABLE 3Results of the Revised University of Washington (UW)-QOL Questionnaire Comparing Patient Groups

Questionno.

Patient age (yrs)

Statistics

Treatment

Statistics

Staging

Statistics

< 45 > 45 XRT Cx T1-2 T3-4

Scores Scores Scores

1 3.33 2.94 NS 3.2 3 NS 3.14 3 NS2 3.33 3.17 NS 3.5 3.06 NS 2.92 3.58 NS

3 94.44 85.29 NS 90 87.5 NS 91.07 85.41 NS

Significance 4 4.29 NS 4.5 4 NS 4.07 4.33 NS

4 80.55 76.47 NS 85 73.43 NS 82.14 72.91 NS

Significance 4.66 4 NS 3.7 4.56 P 0.05 4.28 4.16 NS

5 72.22 73.52 NS 80 68.75 NS 75 70.83 NSSignificance 4.88 4.35 P 0.055 4.2 4.75 P 0.05 4.42 4.66 NS

6 77.77 73.52 NS 80 71.87 NS 80.35 68.75 NS

Significance 4.11 4.47 NS 4.3 4.37 NS 4.5 4.16 NS

7 80 70.58 NS 72 74.66 NS 77.14 69.09 NS

Significance 4.87 4.05 P 0.060 4.1 4.46 NS 4.57 4 NS

8 55.55 64.70 NS 65 59.37 NS 64.28 58.33 NSSignificance 4.44 4.29 NS 4.1 4.5 NS 4.57 4.08 NS

9 64.44 78.82 P 0.05 82 68.75 P 0.05 73.57 74.16 NS

Significance 4.55 4.35 NS 4.4 4.43 NS 4.64 4.16 NS

10 85.55 94.70 NS 94 90 NS 90.71 92.5 NS

Significance 4.88 4.70 NS 4.6 4.87 NS 5 4.5 P 0.060

11 96.66 87.05 NS 91 90 NS 95.71 84.16 NSSignificance 4.11 4.70 NS 4.6 4.43 NS 4.57 4.41 NS

12 35.55 44.11 NS 46 38.12 NS 34.28 49.16 P 0.060

Significance 4.44 4.70 NS 4.9 4.43 P 0.05 4.57 4.66 NS

13 55.55 70 NS 68 63.12 NS 62.85 67.5 NS

Significance 4.55 4.70 NS 4.9 4.5 P 0.05 4.57 4.75 NS14 4.22 4.17 NS 4.12 4.18 NS 4.21 4.16 NS

QOL: quality of life; XRT: radiation treatment; Cx: chemotherapy; NS: not significant.



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radiotherapy target volume on the QOL of patients

cured of head and neck carcinoma. The EORTC QLQ-

C30 core questionnaire with the head and neck carci-

noma module was used and administered by mail.

The response rate for the NPC group was 71% com-

pared with the response rate of 80% in the currentstudy. 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 radio-

therapy, 8 of whom also received chemotherapy. Ra-

diation 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 dif ficulty. Although

role function was reduced significantly in patients

with NPC compared with those with carcinoma of thelarynx (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 xe-

rostomia, 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 im-ply 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 chemo-

therapy (90%) compared with only 50% of the patients

age 45 years. In addition, patient expectations may

differ rather than actual dif ficulties. However, because

no difference appeared to be associated with the im-

portance of swallowing with regard to QOL between

the two groups, further studies are warranted to de-

termine 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 radi-

ation-induced changes such as xerostomia or de-

creased pharyngeal mobility due to fibrosis or damageto pharyngeal innervation.14

As anticipated, patients age 45 years tended to

assign less importance to the activity and employment

scores. Patients treated with chemoradiation had sta-

tistically significantly reduced swallowing scores. Al-

though xerostomia was not found to be more severe in

the patients treated with chemoradiation, it was as-

signed reduced importance. Significantly increased

scores were found with regard to the importance of

appearance and activity in patients treated with che-

moradiation. Scores for appearance and activity were

reduced in the chemoradiation group but no apparentstatistical 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 re-

sults 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 instru-

ment. Scores for different domains may vary but if the

importance of such variability to the patient is mini-mal the actual significance of this variation is ques-

tionable.

The toxicity of radiotherapy for NPC is influenced

by the tumor volume irradiated. In particular, major

salivary gland irradiation largely is responsible for dry-

ness of the mouth, the major reported toxicity of irra-

diation. With the advent of computed tomography-

based 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 radia-

tion to various tumor volumes within the treatment

field, has been introduced into clinical use.16 This

greatly simplifies the planning and delivery of parotid-

sparing radiotherapy techniques without compromis-

ing target coverage.17

It is oversimplification to link QOL with a single

cause such as salivary function. Nevertheless, mini-

mizing 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

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knowledge it is not at present low enough to preserve

salivary function completely 16 in all patients.

Defining QOL in any given patient group is im-

portant 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 patientand family to plan ahead. This has particular impor-

tance 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 quantifi-

cation of QOL using validated instruments should be

performed in NPC patients. Longitudinal studies indi-

cating 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 long-term problems defined as severe such as ear prob-

lems, xerostomia, and chewing dif ficulties.

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Quality of Life of Nasopharyngeal Carcinoma Patients