Pretreatment Quality of Life As a Predictor of Distant Metastasis and Survival for Patients With Nasopharyngeal Carcinoma

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Pretreatment Quality of Life As a Predictor of

Distant Metastasis and Survival for Patients With

Nasopharyngeal Carcinoma

Fu-Min Fang, Wen-Ling Tsai, Chih-Yen Chien, Hui-Chun Chen, Hsuan-Chih Hsu, Tai-Lin Huang,

Tsair-Fwu Lee, Hsuan-Ying Huang, and Chien-Hung Lee

From the Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan; and the Kaohsiung Medical University, Kaohsiung, Taiwan. Submitted February 17, 2010; accepted July 2, 2010; published online ahead of print at www.jco.org on August 16, 2010.

Supported by Grant No. NSC 90- 2320-B-182A-006- from the National Science Council, Taiwan; and Grants No. CMRPG860501 and CMRPG860502 from the Chang Gung Memorial Hospi-tal, Taiwan.

Presented in part at the first Congress of Asian Society of Head and Neck Oncology, September 18-19, 2009, Taipei, Taiwan.

Authors’ disclosures of potential con-flicts of interest and author contribu-tions are found at the end of this article.

Corresponding author: Fu-Min Fang, MD, PhD, Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, 123 Ta-Pei Rd, Niao Sung Hsian, Kaohsiung Hsien, Taiwan; e-mail: fang2569@adm .cgmh.org.tw.

0732-183X/10/2828-4384/$20.00 DOI: 10.1200/JCO.2010.28.8324

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Purpose

The purpose of this study was to examine the prognostic value of pretreatment quality of life (QoL)

data on locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival

(OS) in patients with nasopharyngeal carcinoma (NPC).

Patients and Methods

A total of 347 new patients with NPC, who were curatively treated by conformal radiotherapy from

March 2003 to December 2007, were recruited. The Taiwan Chinese version of the European

Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 was

completed before treatment. Multivariate Cox’s proportional hazards models were used to analyze

the impact of clinical and QoL variables on the treatment results.

Results

The 5-year LRC, DMFS, and OS rates were 72.9%, 79.1%, and 68.4%, respectively. After

adjusting the clinical variables, 10 QoL variables were observed to be significantly (P

⬍ .05) related

to OS, and four QoL variables were related to DMFS. No QoL variable was predictive of LRC.

Among the QoL variables that significantly predicted OS and DMFS, physical functioning was the

most powerful predictor. A 10-point increase in the physical functioning score was associated with

a 23% (95% CI, 12% to 34%) reduction in the likelihood of death and a 22% (95% CI, 9% to 36%)

reduction in the likelihood of distant metastasis.

Conclusion

Our findings indicate that pretreatment QoL variables, especially physical functioning, provide

easily available prognostic value for distant metastasis and survival in patients with NPC.

J Clin Oncol 28:4384-4389. © 2010 by American Society of Clinical Oncology

INTRODUCTION

Nasopharyngeal carcinoma (NPC) is an endemic

head and neck epithelial malignancy.

Approxi-mately 70% of patients with NPC present with stage

III or IV disease at the initial diagnosis.

1

_Although

advances in diagnostic imaging, radiotherapeutic

techniques, and chemotherapy regimens have

achieved improved locoregional control (LRC),

19% to 29% of patients will have distant metastasis

with controlled locoregional disease.

2-4

_{A variety of}

strategies adopting a combination of chemotherapy

and radiotherapy (RT) have been investigated in

patients with advanced disease, but most trials failed

to observe an effect of reducing the incidence of distant

metastases.

4,5

_{To date, distant metastasis is still the}

major cause of mortality in patients with NPC.

Patient self-assessment of quality of life (QoL)

has been acknowledged as an important treatment

end point and has been used in clinical oncology

trials to compare different treatment strategies.

Evi-dence is now accumulating to indicate that QoL may

also have prognostic significance for survival of

pa-tients with cancer. Pretreatment QoL has been

shown to be predictive of treatment outcome in

terms of LRC and/or overall survival (OS) in

pa-tients with advanced lung cancer,

6,7

breast cancer,

8,9

esophageal cancer,

10

_{and head and neck cancer}

(HNC)

11-16

beyond the established factors such as

stage, grade, or performance status. Nevertheless,

thus far, no systematic study has specifically

ad-dressed the prognostic role of pretreatment QoL in

NPC patients with special attention not only to

sur-vival but also to distant metastases.

If pretreatment QoL is predictive of survival or

distant metastasis among patients with NPC, the

QoL instrument may become a practical and

nonin-vasive means of identifying those patients at high

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risk who need tailored medical support before treatment or those who

must be observed more closely after treatment. We have used the

Taiwan Chinese version of the European Organization for Research

and Treatment of Cancer Quality of Life Questionnaire-Core 30

(EORTC QLQ-C30) questionnaire as an effective tool to assess the

outcomes of patients with NPC.

17,18

Hence, the purpose of this study

was to examine the relationships between pretreatment EORTC

QLQ-C30 data and LRC, distant metastasis-free survival (DMFS), and OS

among patients with NPC after controlling for the clinical variables.

PATIENTS AND METHODS

Patients

This was a longitudinal investigation. From March 2003 to December

2007, 441 newly diagnosed patients with NPC were treated at Chang Gung

Memorial Hospital–Kaohsiung Medical Center. There were 347 patients

re-cruited in the study. Exclusion criteria included distant metastasis at the initial

diagnosis (n

⫽21),inabilitytocompletetheprescribedtreatmentcourseofRT

(n

⫽ 18), lost to follow-up after treatment (n ⫽ 22), with previous or

synchro-nous malignancies (n

⫽ 9), and unable to understand (n ⫽ 10) or unwilling to

complete (n

⫽ 14) the Taiwan Chinese version of the EORTC QLQ-C30. The

local institutional research board approved this study, and written

in-formed consent was obtained from each participant. The pretreatment

evaluation included a complete history, physical examination, and

com-prehensive imaging studies, including chest x-ray, computed tomography,

or magnetic resonance image scans of the head and neck, a bone scan, and

an abdominal sonogram.

The patient clinical characteristics are presented in Table 1. The median

age was 49 years (range, 13 to 84 years). Most patients were male (77.2%),

married (80.4%), and educated for fewer than 12 years (80.4%).

Approxi-mately one half of the patients had a habit of smoking (53.9%) or self-reported

one or more comorbid conditions (47.6%) based on the Charlson

Comorbid-ity Index.

19

_{The distributions of the clinical stages according to the American}

Joint of Cancer Committee (AJCC) staging system published in 2002 were I, 25

(7.2%); II, 100 (28.8%); III, 121 (34.9%); and IV, 101 (29.1%). All patients

were irradiated for the entire treatment course using a conformal technique; 93

patients (26.8%) received three-dimensional conformal RT, and 254 (73.2%)

patients received intensity-modulated RT. The technical details of the NPC

three-dimensional conformal RT/intensity-modulated RT have been

de-scribed previously.

17,18

_{The prescribed dose ranged from 68.4 to 81.0 Gy}

depending on the tumor stage, with a daily fraction of 1.8 Gy and 5

fractions per week. Two hundred forty-six patients (70.9%) received

com-bination chemotherapy because of their advanced stage. The prescribed

chemotherapy regimen was 80 to 100 mg/m

2

_{cisplatin intravenous bolus}

on day 1 and 800 to 1,000 mg/m

2

_{/24 hours continuous intravenous}

infu-sion of fluorouracil on days 1 to 4 of each cycle. One hundred sixty patients

(65.0%) received at least three cycles of chemotherapy before, during,

and/or after the RT course.

Instruments

A variety of QoL instruments have been used as an outcome predictor,

including the EORTC QLQ-C30,

6-8,10-13

_{Short-Form 36 (SF-36),}

14,16

Func-tional Assessment of Cancer Therapy–Head and Neck,

15

_{or Physical}

Self-Efficacy Scale.

20

_{The EORTC QLQ-C30 was chosen for this study because it is}

one of the most widely implemented questionnaires, with more than 15 years

of research invested to develop an integrated, modular approach, as well as

utilization in international clinical trials, and the Taiwan Chinese version,

which was obtained from the Quality of Life Unit, EORTC Data Center in

Brussels, Belgium,

21,22

_{was available and easily completed by our patients.}

Moreover, it is one of the most common QoL instruments used to predict

survival in patients with cancer. Patients completed the questionnaire at their

first visit to the oncology clinic. The EORTC QLQ-C30 questionnaire

incor-porates a range of QoL issues relevant to a broad range of patients with cancer.

It has been validated for many types of cancer including NPC.

23

_{It contains five}

functional scales (physical, role, cognitive, emotional, and social), three

symp-tom scales (fatigue, pain, and nausea/vomiting), a global QoL scale, and six

single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and

financial difficulties). All scales and items range in score from 0 to 100. A high

score for a functional or global QoL scale represents a relatively high/healthy

level of functional or global QoL, whereas a high score for a symptom scale or

item represents a high level of symptoms or problems.

Table 1. Patient Characteristics (n⫽ 347)

Variable No %

Median age, years 49

Range 13-84 ⱕ 40 73 21.0 41 to approximately 65 242 69.8 ⬎ 65 32 9.2 Sex Male 268 77.2 Female 79 22.8 Marital status With spouse 279 80.4 Without spouse 68 19.6 Education years ⱕ 6 109 31.4 6 to approximately 12 170 49.0 ⬎ 12 68 19.6 Smoking habit Ever 187 53.9 Never 160 46.1

Median Karnofsky performance status 90

Range 70-100

⬎ 80 335 96.5

ⱕ 80 12 3.5

Median Charlson comorbidity index 0

Range 0-3 0 182 52.4 ⱖ 1 165 47.6 AJCC stage I 25 7.2 II 100 28.8 III 121 34.9 IV 101 29.1 T stage T1-2a 125 36.0 T2b 104 30.0 T3 49 14.1 T4 69 19.9 N stage N0 73 21.0 N1 106 30.5 N2 131 37.8 N3 37 10.7 Chemotherapy No 101 29.1 Yes 246 70.9 RT technique 3DCRT 93 26.8 IMRT 254 73.2 Median RT dose, Gy 70.2 Range 68.4-81.0 ⱕ 70.2 218 62.8 ⬎ 70.2 129 37.2

Abbreviations: AJCC, American Joint of Cancer Committee; RT, radiotherapy; 3DCRT, three-dimensional conformal RT; IMRT, intensity-modulated RT.

QoL Predict Distant Metastasis and Survival in NPC

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QoL Predict Distant Metastasis and Survival in NPC