The relationship between hospital spending intensity and survival in nasopharyngeal

carcinoma patients

Ching-Chih Lee, MD, PhD a,b,c; Yu-Chieh Su, MD d; Po-Chun Chen, MD e ; Chung-

I Huang, MD f; Ching-Chieh Yang, MD, MS g,h,i*

a Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

b School of Medicine, National Defense Medical Center, Taipei, Taiwan c Department of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, Taipei, Taiwan

d Department of Hematology and Oncology, E-Da hospital, Kaohsiung, Taiwan e Department of Radiation Oncology, Pingtung Christian Hospital, Pingtung, Taiwanf Department of Radiation Oncology, E-Da hospital, Kaohsiung, Taiwang Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwanh Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

i Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan

*Corresponding author:Ching-Chieh Yang B2, No.901, Zhonghua Rd., Yongkang Dist., Tainan City 710, Taiwan.Telephone: +886 6 2812811 - 53501, Fax: +886 6 2820049e-mail: cleanclear0905@gmail.com

Short title: HSI and NPC outcomes

Keywords: Nasopharyngeal carcinoma; Hospital spending index; Survival; Comorbid

Conflicts of Interest and Source of Funding: Nothing to disclose

Word count for the abstract : 219

Word count for the manuscript :2280

Number of tables: 3

Number of figures: 1

Number of supplementary elements: 0

ABSTRACT

Background.

Although hospital spending intensity (HSI) is clearly related to prognosis with many cancers,

the effect of the HSI on patients with nasopharyngeal cancer (NPC) has not been determined.

The purpose of this study was to determine the association between HSI and survival outcome of

NPC patients in Taiwan.

Methods.

Using the Taiwan National Health Insurance Research Database (NHIRD), we identified

3464 newly diagnosed NPC patients treated by radiotherapy with or without chemotherapy

between 2008 and 2011. The relationship between HSI and survival was assessed using the Cox

proportional hazards models with adjustment for patient characteristics and confounding factors.

Results.

NPC patients treated in low-spending hospitals had a poor 3-year survival rate compared to

intermediate- and high-spending hospitals (p=0.024). After adjusting for patient characteristics,

hospital factors, and co-morbidities, NPC patients treated in low-spending hospitals incurred an

additional 45% risk for mortality (adjusted hazard ratio [HR], 1.45; 95% confidence interval

[CI], 1.06-1.98). A lower HSI was associated with higher 3-year mortality rate in patients with

liver disease (14.2% vs. 13.5%) and chronic obstructive pulmonary disease (10.9% vs. 10%).

Conclusion.

HSI significnatly influenced the outcomes of NPC patients. Specifically, NPC patients treated

in low-spending hospitals had poor survival. Efforts to manage co-morbidities and the quality of

radiotherapy are likely reasons for the poor outcomes and should be improved in low-spending

hospitals.

Introduction

Nasopharyngeal carcinoma (NPC) is rare in the United States and other Western countries,

but endemic in southeast Asia and north Africa [1]. In Taiwan, the annual incidence of NPC is

6.17 per 100,000 and is increasing year-by-year [2]. Radiotherapy with or without chemotherapy

is first-line management and has demonstrated high tumor control and patient survival [3] With

great advances in the diagnostic work-up, quality of care, and treatment techniques, costs

associated with care of patients with NPC have increased dramatically in this decade.

Management for patients with NPC is an important issue for socioeconomic and public health

planning. In addition to improvement in radiotherapy techniques and healthcare, we should

explore other factors related to NPC outcomes.

Several studies have reported that higher health care spending produces better patient

outcomes and higher quality of care [4, 5]; however, some studies have failed to demonstrate a

positive relationship [6-8]. Hospital spending intensity (HSI) refers to the value of health care

delivery in the hospital [9]. Stukel et al. reported that patients with acute myocardial infarctions,

congestive heart failure, hip fractures, and colon cancer have a lower mortality and readmission

rates in hospitals with higher HSI. Subsequently, there have few studies which have discussed

the relationship between HSI and outcome in cancer patients. Our previous research confirmed

that patients with colorectal cancer, lung cancer, hepatomas, breast cancer, or prostate cancer

who received treatment at low-spending hospitals had a higher risk of mortality. The effect of

HSI on NPC outcomes is unknown especially in endemic area.

To better understand and provide a comprehensive view of the relationship between HSI

and cancer mortality in NPC patients, we designed a population-based study using data from the

Taiwan National Health Insurance Research Database (NHIRD). This database provides basic

demographic data, as well as socioeconomic status, medical services, and hospital

characteristics. We hypothesized that a high HSI is associated with comprehensive care and

improved survival in patients with NPC.

Methods

Ethics statement

This study was approved by the Institutional Review Board of Kaohsiung Veterans General

Hospital. The requirement for written informed consent was waived because all data were de-

identified prior to analysis.

Data source and study population

The NHIRD is organized and managed by the Taiwan National Health Research Institutes,

which has been based on the Taiwan National Health Insurance Program since 1995. The

program covers up to 99% of the residents of Taiwan and 97% of the medical providers are

included in this program [10]. This database contains comprehensive information on all insured

individuals, including basic demographic data, the International Classification of Diseases (ninth

revision) clinical modification (ICD-9-CM) diagnostic codes, details of prescribed medications,

expenditures amounts, and outcome at hospital discharge. The database contained a registry of

contracted medical facilities, a registry of board-certified physicians, and monthly claims

summary for all inpatient claims. From the above-mentioned data, patients with newly-diagnosed

NPC (International Classification of Disease, ninth revision [clinical modification codes147.0–

147.9]) between 2008 and 2011 verified by heavy catastrophic disease were included. NPC

patients who were treated with a second course of radiotherapy, induction chemotherapy, or

distant metastases were excluded.

Measurement

The key dependent variable was the 3-year overall survival rate. Death-free survival for NPC

patients was determined by linking the 2008-2011 mortality database with claim data. In this

dataset, disease-specific survival rates could not be determined. Roohan et al. [7] supported the

opinion that there is no significant difference between survival models for all-cause mortality and

cancer-specific mortality.

Hospital spending intensity index

In the current study, the key independent factor of interest was the HSI. There are two

methods (retrospective and prospective) to define the HSI. We prefer the retrospective method

through end-of-life medical expenditures. The hospital end-of-life expenditure index (EOL-EI),

which was defined as the mean hospitalization spending of decedents during the last 6 months of

life as modified from Stukel et al. [9], was used as a proxy of the HSI. The HSI was estimated

using a retrospective method, and the amount of HSI was calculated from a different cohort who

died in the hospital. The retrospective method can reduce the "reverse causality effect," which

implies that patients with worse conditions may incur higher medical-care expenditures. In

agreement with Stukel et al., our previous report validated the retrospective method [11]. The

index was categorized into three subgroups of HSI, as follows: high; medium; and low.

Other variables

Basic characteristics, including gender, age of diagnosis, treatment modality, wait time, length

of radiotherapy, whole body PET, and salvage surgery, were included and analyzed in this study.

Common co-morbidities in NPC patients, such as diabetes, liver disease, peptic ulcer, chronic

obstructive pulmonary disease, and cerebrovascular disorders, were also extracted from the

NHIRD [12]. The amount of insurance payment was used as a proxy of individual

socioeconomic status (SES) and classified as high, moderate, and low. Urbanization of residence

was categorized as urban, suburban, and rural according to population density, percentage of

residents with a college level or higher education, percentage of residents who were agriculture

workers, and the number of physicians per 100,000 residents [13]. Hospital characteristics, such

as ownership, accreditation level, number of physicians, geographic regions, and caseload, were

captured.

Statistical analysis

All statistical operations were performed using SPSS (version 15; SPSS Inc., Chicago, IL,

USA). Pearson’s chi-square test was used for categorical variables. Continuous variables were

analyzed with ANOVA. The cumulative 3-year survival curves were constructed and compared

by the log-rank test. A scatter plot for 3-year survival rates and HSI amount was created. Survival

curves, stratified by HSI, were measured from the time of cancer diagnosis by using overall

mortality as the event variable.

Based on multivariate analysis, the impact of HSI on NPC outcomes was analyzed with the

Cox proportional hazard model. Statistical models controlled for basic patient characteristics,

including age, gender, SES, treatment modalities, wait time, length of radiotherapy, salvage

surgery, individual co-morbidities at diagnosis, hospital caseload, number of physicians,

ownership, and region. In order to test the robustness of our hypothesis, we used two models to

explore the association between HSI and NPC outcomes. Model 1 included factors, except the

co-morbidities, and model 2 consisted of all factors because the coding quality of co-morbidities

among NPC patients or cancer patients may vary in different health care institutions [4]. A two-

sided p-value (p< 0.05) was considered significant.

Results

The current study consisted of 2598 men and 866 women with a mean age of 50±12 years.

Most NPC patients (82.5%) underwent concurrent chemoradiotherapy. There were no significant

differences between age, co-morbidities, and HSI. Females and residents in rural areas were

more likely to visit low-spending hospitals (Table 1). NPC patients treated in high-spending

hospitals tended to be associated with shorter wait times, a longer duration of radiotherapy, and

undergo multi-modality treatment. High-spending hospitals were more likely to be high-volume

medical centers, public institutions, have PET availability, and offer salvage surgery.

The 3-year survival rates were 81.2%, 80.2%, and 77.1% for high-, medium-, and low-

spending hospitals, respectively. Figure 1 illustrates the cumulative mortality rate for NPC

patients. NPC patients treated in low-spending hospitals incurred a higher cumulative risk of

mortality than high and medium-spending hospitals (p=0.024).

Adjusted hazard ratios for mortality between different HSI indices are shown in Table 2. After

adjusting for patient characteristics and hospital factors, except co-morbidities, NPC patients

treated in low-spending hospitals incurred an additional 44% mortality risk (adjusted hazard ratio

[HR], 1.44; 95% confidence interval [CI], 1.05-1.97). The full model results were in agreement

with model 1 (adjusted HR, 1.45; 95% CI, 1.06-1.98).

We attempted to explore the possible mechanisms underlying the NPC outcomes and HSI.

Thus, the association between HSI and co-morbidities were analyzed. Table 3 shows that a lower

HSI was associated with worse outcomes in patients with liver disease (3-year mortality rate,

14.2% vs. 13.5%) and chronic obstructive pulmonary disease (3-year mortality rate, 10.9% vs.

10%). Among patients with peptic ulcer disease, a reduced 3-year mortality was also seen (8.5%

vs. 8.7%) in low-spending hospitals.

Discussion

We explored the association between the hospital spending intensity and NPC outcomes with

a population-based study in an Asian country. In agreement with prior studies and our previous

report, lower hospital spending intensity incurred worse prognosis in NPC patients. We also

found that patients treated at high-spending hospitals were more likely to receive a

comprehensive diagnosis and treatment, better quality of co-morbid care, and less wait time of

radiotherapy to improve survival, when compared with patients treated at low-spending

hospitals.

The current study has three main strengths. This is the first study to evaluate the influence

of HSI on outcomes of NPC patients. Second, NPC is endemic in Taiwan, which permits the

collection of a large sample size to validate our estimate. Third, the current study is based on the

NHIRD, which encompasses all cancer age groups, near-complete follow-up information, and

hospitalization. Therefore, the current study provides an accurate and comprehensive record of

NPC patients, related treatments, and costs in Taiwan.

Previous studies have investigated whether or not higher health care spending produces

better patient outcomes and higher quality of care [7, 14]. Most of these studies focused on short-

term outcomes and demonstrated patients treated in higher-spending hospitals was associated

with better in-hospital or 30-day mortality [4, 15]. It would be facile to interpret this result as

indicating that higher spending and providing more money to lower spending hospitals would

improve outcomes. High-spending hospitals differ in many ways from low-spending hospitals,

such as a greater use of evidence-based care, skilled nursing and critical care staff, more

intensive inpatient specialist services, and high technology of diagnosis or treatment, all of which

are more expensive. Cancer care is complicated and the treatment is conducted by

multidisciplinary teams, including oncology surgeons, radiation oncologists, hematologic

oncologists, radiologists, specialized nurses, and nutritionists. Keating et al. [8] reported that

high-spending hospitals with more intensive inpatient specialist services are more likely to

deliver NCCN guideline-recommended care and to adopt multidisciplinary therapies. Therefore,

it may be the reason that high-spending hospitals have better outcomes than low-spending

hospitals for cancer patients [8].

Another plausible mechanism by which high-spending hospitals were associated with better

outcomes in NPC patients might be due to the difference in comprehensive care for comorbid

conditions. Indeed, comorbidities are associated with worse survival due to the development of

non-cancer-associated competing mortality [12, 16]. NPC patients with other comorbid diseases

may have a substantial and direct impact on delivery of NCCN guideline therapy and subsequent

outcomes. The comorbidities may vary among people in different geographic regions or races;

the most common co-morbidities in NPC patients include diabetes, liver disease, chronic

obstructive pulmonary disease, cerebrovascular disorders, and congestive heart failure [12]. Prior

studies have shown that high-spending hospitals have better outcomes for patients with

cerebrovascular disorders and congestive heart failure [4, 9]. We further conducted a small study

to determine the association between HSI and several co-morbidities in NHIRD between 2008

and 2011. Table 3 shows that a lower HSI was associated with worse outcomes in patients with

liver disease and chronic obstructive pulmonary disease, which suggests that high-spending

hospitals may provide better multidisciplinary medical care for these comorbidities [16].

Although there was no significant difference in comorbidities between different HSI institutions,

NPC patients treated in low-spending hospitals may not be provided with adequate care for

comorbidities. A change in the multidisciplinary approach may be required to improve outcomes

in NPC patients.

There have been great advances in diagnostic and radiotherapy techniques over the last

decade. Many studies have reported that PET/CT is more accurate than MRI for determining

cervical nodal and distal metastases [17]. Compared to conventional two-dimensional RT (2D-

RT) or three-dimensional conformal RT (3DCRT), the application of intensity-modulated RT

(IMRT) has resulted in better outcomes of NPC due to a more conformal dose distribution, a

steeper dose gradient, and an ability to spare the surrounding tissue [18]; however, each of these

increasingly complex techniques has led to clinical benefits, but there is often an increase in

costs. Our study showed that high-spending hospitals were more likely to be high-volume

medical centers, public institutions, and provision of PET, modern radiation techniques, and

salvage surgery. Furthermore, the current study also showed that NPC patients treated in high-

spending hospitals tended to be associated with shorter wait times and undergo multi-modality

treatment. Based on previous studies [19, 20], the findings herein strongly confirmed that NPC

patients treated in high-spending hospitals have better outcomes.

Our research had several limitations. First, the diagnosis of NPC and comorbidities were

extracted from ICD-9 codes on the NHIRD. The coding quality varied from hospital-to-hospital;

however, the NHI program regularly reviews the charts and incorrect or sufficient coding results

in punitive actions. The accuracy of NPC diagnosis was further verified by the catastrophic

disease database. Second, the key independent variable was 3-year overall survival rates instead

of 3-year disease-specific survival rates. Cause-specific mortality was not available in the present

database; however, the literature revealed that the adjusted risk ratio did not differ between the

overall survival rates and cancer-specific survival rates [21]. Third, our study used EOL-EI as a

proxy of the HSI, which may reduce the potential "reverse causality effect" [9]. The high-

spending hospitals may provide overt aggressiveness in end-of-life care, and may not necessarily

adhere to evidence-based medicine, more well-trained nursing care and specialists, and a more

efficient approach for the patients [22]. Given the robustness of the evidence, these limitations

may not have compromised our observations.

Conclusion

This study was the first to show that HSI influences outcomes in NPC patients. Patients

treated in low-spending hospitals were associated with worse outcomes. Pubic strategies, such as

providing more financial support, increasing the number of specialists, a multi-disciplinary

approach for comorbidities, and greater use of evidence-based medicine in the low-spending

hospitals, may be initiated.

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Figure legends

Figure1. The relationship of cancer 3-year cumulative mortality rate and hospital spending

intensity catogory.