QJM Advance Access published May 5, 2015 QJM: An International Journal of Medicine, 2015, 1–7 doi: 10.1093/qjmed/hcv079 Advance Access Publication Date: 10 April 2015 Original paper
ORIGINAL PAPER
The use of adjunctive traditional Chinese medicine therapy and survival outcome in patients with head and neck cancer: a nationwide population-based cohort study
From the 1Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 2Office for Health Data, China Medical University Hospital, Taichung, Taiwan, 3College of Medicine, China Medical University, Taichung, Taiwan, 4Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 5Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 6Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan, 7Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 8Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan and 9Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan Address correspondence to Dr C.-H. Kao, Graduate Institute of Clinical Medical Science and School of Medicine, China Medical University, Taichung, Taiwan. No. 2, Yuh-Der Road, Taichung 404, Taiwan. email: [email protected]
Summary Background: Traditional Chinese medicine (TCM) is widely used in the treatment of patients with several types of cancer. However, no large-scale clinical studies have evaluated whether TCM is associated with better survival in patients with head and neck cancer (HNC). Methods: The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort study of patients with HNC between 2001 and 2011. The patients with HNC were separated into TCM users and non-users, and Cox regression models were applied to determine the association between the use of TCM and survival outcome. Results: The TCM and comparison cohorts comprised data for 2966 and 2670 patients, respectively. The mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison cohort. Multivariate analysis demonstrated that the use of TCM was significantly associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio, 0.68; 95% confidence interval, 0.62–0.75). Patients with longer TCM use had a lower mortality rate (P for trend < 0.001).
Received: 22 February 2015; Revised (in revised form): 21 March 2015 C The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. V
All rights reserved. For Permissions, please email: [email protected]
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Hung-Che Lin1, Cheng-Li Lin2,3, Wen-Yen Huang4, Wei-Chuan Shangkuan5, Bor-Hwang Kang1, Yueng-Hsiang Chu1, Jih-Chin Lee1,6, Hueng-Chuen Fan7 and Chia-Hung Kao8,9
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QJM: An International Journal of Medicine, 2015, Vol. 0, No. 0
Conclusions: Our study showed that adjunctive therapy with TCM is associated with higher survival outcome. However, some limitations exist, such as the lack of information of cancer stage. In addition, causality cannot be assessed with this retrospective study. A randomized controlled trial to test the effect of adjunctive TCM therapy in HNC patients is needed.
Introduction
Methods Data source The NHI program was implemented in 1995 and covers >99% of the 23.74 million Taiwan residents.14 The NHI program is a mandatory health insurance program that offers comprehensive medical care coverage, including outpatient, inpatient, emergency and TCM services as well as prescription drugs for all insurants. In the NHI program, insurants with any of the 30 categories of catastrophic illness specified by the Bureau of NHI (including cancer) can apply for catastrophic illness certificates [Registry of Catastrophic Illnesses Patient Database (RCIPD)]. If the insured has major diseases such as cancer, he or she can apply for a catastrophic illness certificate. To reduce the financial hardship associated with catastrophic illness, beneficiaries are exempted from copayments. The issuance of certificates is validated through careful review of medical records, pathological reports, and imaging studies by at least two specialists. The diseases investigated in this study were identified according to the diagnosis codes in the RCIPD, based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. All personally identifiable information in the RCIPD is scrambled to conform to the Personal Information Protection Act. This study was approved by the Institutional Review Board of China Medical University (CMU-REC-101-012).
Sampled participants Data extracted from the RCIPD were used for this retrospective cohort study. This study comprised patients aged >20 years
Outcome The study outcome was all-cause mortality during the 11-year follow-up. The identification of death events was determined according to the RCIPD. The study patients were followed from the index date until their deaths, withdrawal from the NHI program, or the end date of the database (31 December 2011).
Variables of exposure Premium-based income was categorized into three levels: 90 days were defined as TCM users, and those who used TCM for fewer than 30 days were considered TCM non-users. The date of the 90th day of TCM treatment was used as the index date. To assemble a comparison cohort, controls were randomly selected and frequency matched with patients in the TCM cohort at a ratio of 1:1, based on age group (in 10-year span); sex; comorbidities of hypertension, diabetes, congestive heart failure (CHF), stroke, chronic obstructive pulmonary disease (COPD) and liver cirrhosis; treatment for HNC; and index year, using the same exclusion criteria during the same period (Figure 1).
TCM and survival in head–neck cancer
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Figure 1. The flowchart of study design and selection procedure of study participants.
proportional hazards model to identify the independent predictors of mortality. To verify the dose–response relationship between TCM use and mortality, the TCM use category was treated as a continuous variable to calculate the P value of the linear trend. The herbal prescription patterns and herbal formulae were described. The Statistical Analysis System (SAS), Version 9.3 (SAS Institute, Cary, NC) computer software program was used to perform all statistical analyses. Comparison results with a P value of
ORIGINAL PAPER
The use of adjunctive traditional Chinese medicine therapy and survival outcome in patients with head and neck cancer: a nationwide population-based cohort study
From the 1Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 2Office for Health Data, China Medical University Hospital, Taichung, Taiwan, 3College of Medicine, China Medical University, Taichung, Taiwan, 4Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 5Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 6Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan, 7Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 8Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan and 9Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan Address correspondence to Dr C.-H. Kao, Graduate Institute of Clinical Medical Science and School of Medicine, China Medical University, Taichung, Taiwan. No. 2, Yuh-Der Road, Taichung 404, Taiwan. email: [email protected]
Summary Background: Traditional Chinese medicine (TCM) is widely used in the treatment of patients with several types of cancer. However, no large-scale clinical studies have evaluated whether TCM is associated with better survival in patients with head and neck cancer (HNC). Methods: The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort study of patients with HNC between 2001 and 2011. The patients with HNC were separated into TCM users and non-users, and Cox regression models were applied to determine the association between the use of TCM and survival outcome. Results: The TCM and comparison cohorts comprised data for 2966 and 2670 patients, respectively. The mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison cohort. Multivariate analysis demonstrated that the use of TCM was significantly associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio, 0.68; 95% confidence interval, 0.62–0.75). Patients with longer TCM use had a lower mortality rate (P for trend < 0.001).
Received: 22 February 2015; Revised (in revised form): 21 March 2015 C The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. V
All rights reserved. For Permissions, please email: [email protected]
1
Downloaded from by guest on November 19, 2015
Hung-Che Lin1, Cheng-Li Lin2,3, Wen-Yen Huang4, Wei-Chuan Shangkuan5, Bor-Hwang Kang1, Yueng-Hsiang Chu1, Jih-Chin Lee1,6, Hueng-Chuen Fan7 and Chia-Hung Kao8,9
2
|
QJM: An International Journal of Medicine, 2015, Vol. 0, No. 0
Conclusions: Our study showed that adjunctive therapy with TCM is associated with higher survival outcome. However, some limitations exist, such as the lack of information of cancer stage. In addition, causality cannot be assessed with this retrospective study. A randomized controlled trial to test the effect of adjunctive TCM therapy in HNC patients is needed.
Introduction
Methods Data source The NHI program was implemented in 1995 and covers >99% of the 23.74 million Taiwan residents.14 The NHI program is a mandatory health insurance program that offers comprehensive medical care coverage, including outpatient, inpatient, emergency and TCM services as well as prescription drugs for all insurants. In the NHI program, insurants with any of the 30 categories of catastrophic illness specified by the Bureau of NHI (including cancer) can apply for catastrophic illness certificates [Registry of Catastrophic Illnesses Patient Database (RCIPD)]. If the insured has major diseases such as cancer, he or she can apply for a catastrophic illness certificate. To reduce the financial hardship associated with catastrophic illness, beneficiaries are exempted from copayments. The issuance of certificates is validated through careful review of medical records, pathological reports, and imaging studies by at least two specialists. The diseases investigated in this study were identified according to the diagnosis codes in the RCIPD, based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. All personally identifiable information in the RCIPD is scrambled to conform to the Personal Information Protection Act. This study was approved by the Institutional Review Board of China Medical University (CMU-REC-101-012).
Sampled participants Data extracted from the RCIPD were used for this retrospective cohort study. This study comprised patients aged >20 years
Outcome The study outcome was all-cause mortality during the 11-year follow-up. The identification of death events was determined according to the RCIPD. The study patients were followed from the index date until their deaths, withdrawal from the NHI program, or the end date of the database (31 December 2011).
Variables of exposure Premium-based income was categorized into three levels: 90 days were defined as TCM users, and those who used TCM for fewer than 30 days were considered TCM non-users. The date of the 90th day of TCM treatment was used as the index date. To assemble a comparison cohort, controls were randomly selected and frequency matched with patients in the TCM cohort at a ratio of 1:1, based on age group (in 10-year span); sex; comorbidities of hypertension, diabetes, congestive heart failure (CHF), stroke, chronic obstructive pulmonary disease (COPD) and liver cirrhosis; treatment for HNC; and index year, using the same exclusion criteria during the same period (Figure 1).
TCM and survival in head–neck cancer
| 3
Downloaded from by guest on November 19, 2015
Figure 1. The flowchart of study design and selection procedure of study participants.
proportional hazards model to identify the independent predictors of mortality. To verify the dose–response relationship between TCM use and mortality, the TCM use category was treated as a continuous variable to calculate the P value of the linear trend. The herbal prescription patterns and herbal formulae were described. The Statistical Analysis System (SAS), Version 9.3 (SAS Institute, Cary, NC) computer software program was used to perform all statistical analyses. Comparison results with a P value of
