Accepted Manuscript Trismus and impact on quality of life in head and neck cancer patients post-radiation Li-Yun Lee, Shu-Ching Chen, Wen-Cheng Chen, Bing-Shen Huang, Chien-Yu Lin PII:
S2212-4403(14)01309-1
DOI:
10.1016/j.oooo.2014.10.003
Reference:
OOOO 1039
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received Date: 9 July 2014 Revised Date:
17 September 2014
Accepted Date: 6 October 2014
Please cite this article as: Lee L-Y, Chen S-C, Chen W-C, Huang B-S, Lin C-Y, Trismus and impact on quality of life in head and neck cancer patients post-radiation, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2014), doi: 10.1016/j.oooo.2014.10.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Trismus and impact on quality of life in head and neck cancer patients post-radiation Running title: HNC cancer patients’ trismus and impact on QOL Li-Yun Leea, Shu-Ching Chenb,c , Wen-Cheng Chend,e, Bing-Shen Huangc,f, Chien-Yu Linc,f, a
M AN U
SC
RI PT
Department of Nursing, China Medical University Beigang Hospital, Yunlin, Taiwan; and School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan b Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan c Head and Neck Oncology Group, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at LinKou, Taoyuan, Taiwan d Department of Radiation Oncology, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at Chiayi; and College of Medicine, Chang Gung University, Chiayi, Taiwan e Head and Neck Oncology Group, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at Chaiyi, Chaiyi, Taiwan f Department of Radiation Oncology, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at LinKou; and Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
TE D
Corresponding author: Shu-Ching Chen, PhD, Associate Professor Department of Nursing, Chang Gung University of Science and Technology, 261, Wen-Hua 1st Road, Kweishan, Taoyuan, 333, Taiwan. Tel: +886-3-2118999 Ext. 3422 Fax: +886-3-2118866 E-mail address: [email protected]
AC C
EP
Total pages: 30 Tables: 5 Illustrations: 0 ACKNOWLEDGEMENTS This study was supported grants CMUBH R100-006 and CMUBH R102-001 from the China Medical University Hospital and were supported in part by grants to Dr. Shu-Ching Chen from National Science Council Research Program (NSC101-2314-B-255-001-MY2) and Chang Gung Memorial Hospital (NMRPF3C0101) in Taiwan. The authors gratefully acknowledge the patients who participated in the study. The authors also thank Sarah Smith for English editing.
Conflicts of Interest Statement None declared.
1
ACCEPTED MANUSCRIPT ABSTRACT Objective: The aims of this study were to investigate in head and neck cancer patients: (1)
RI PT
factors related to trismus and that predict the development of trismus, (2) factors affecting quality of life and measurements of these factors, and (3) comparison of these findings in patients with and without trismus to evaluate the effects of trismus on quality of life.
SC
Methods: This cross-sectional study included questionnaires on: Hospital Anxiety and
M AN U
Depression Scale – Depression Subscale, Chewing Function Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module. A scaled ruler was used to measure MIO.
TE D
Results: For the 104 subjects, 8.7% had clinical depression. The average MIO was 35.81 mm and 47.1% of subjects had trismus. Moderate levels of chewing dysfunction were noted by
EP
different types of food. Lower body mass index, chemoradiotherapy treatment, longer time since treatment completion, and higher radiation dose were significantly associated with
AC C
trismus. Such patients had significantly lower head and neck-specific quality of life in terms of social contact, sexuality, teeth, opening mouth, dry mouth, feeling ill, nutritional supplement, and weight loss. Conclusions: Patients with trismus should have mouth opening exercises after treatment and programs to improve trismus and quality of life. KEYWORDS 2
ACCEPTED MANUSCRIPT Head and neck cancer, radiation therapy, trismus, quality of life INTRODUCTION
RI PT
Cancer is a leading cause of death worldwide, with an estimated 550,000 new cases of head and neck cancer (HNC) occurring per year.1 The mortality of HNC is rising in Taiwan and the incidence rate has continuously increased since the late 1990s.2 Betel nut use is a
SC
major carcinogen contributing to head and neck cancer.3 Tobacco use, alcohol use, betel nut
M AN U
use, and human papillomavirus infection are risk factors for HNC, with chewing betel nut as the single most important etiological factor for developing oral submucosa fibrosis.4-5 Betel nut products can induce fibroblast proliferation and collagen synthesis and may penetrate the
TE D
oral mucosa to cause progressive cross linking of collagen fibers.6-7 Curative radiation therapy (RT) and concurrent chemoradiation therapy (CCRT) are the
EP
primary modalities for treatment of unresectable HNC.8 Radiation fibrosis causes shortening of the muscle fibers, degeneration, inflammation, pain, and atrophy, and may lead to
AC C
trismus.9-10 Trismus, or hypomobility of the mouth, results in restricted and limited normal range-of-motion of the mouth.11 Trismus is defined as mouth opening ≤35 mm (either the interincisal distance or the distance between the upper and lower alveolus),12 a definition supported by the findings of Scott et al.13 Although treatment prolongs survival, many HNC patients continue to experience complications related to trismus that interfere with the movement of the mandible.14-15 3
ACCEPTED MANUSCRIPT Approximately 5% to 38% of HNC patients experience trismus post-radiation.16-17 Radiation-induced trismus may occur in the initial three months after radiation, or up to
RI PT
12-48 months post therapy.18-20 Trismus significantly impacts both activities of daily living and vital oral function; it is associated with speech problems, difficulty eating or drinking, malnutrition, dehydration, difficulty with oral hygiene,11 and lower quality of life.21-24
SC
The characteristics of trismus may be associated with disease- and treatment-related
M AN U
factors. Significant risk factors for trismus include large tumors,25 high radiation dose radiotherapy,25-26 CCRT treatment,26 a longer time since treatment completion,24 chewing deficit,13 and greater levels of depression.27 Several studies22-25 have identified the impact of
TE D
trismus on oral function-related quality of life, including pain, eating, chewing, taste, saliva production, social functioning, social contact, and dry mouth,25 as well as a greater incidence
EP
of jaw-related problems23 and eating limitations.13, 23, 28 Based on empirical findings, the following characteristics of trismus in HNC patients
AC C
during the post-radiation period were selected for investigation: nutrition status, type of treatment, time since RT completion, radiation dose, chewing function, and depression. Given that HNC patients report different levels of quality of life that vary with levels of trismus,13, 23-24 chewing function, depression, and head and neck-specific quality of life were compared. Because atrophy and fibrosis progression occur during radiation and post-radiation, problems are not recognized without a comprehensive evaluation of patients with HNC. The 4
ACCEPTED MANUSCRIPT aims of this study were (1) factors related to trismus and that predict the development of trismus [including demographic factors (age, gender, education level, employment status,
RI PT
marital status, religion, betel nut use, smoking and alcohol history), disease-related factors (BMI, cancer site, and cancer stage), and treatment-related factors (type of treatment, RT dose, and time since RT)]; (2) factors affecting quality of life and measurement of these
SC
factors [include maximal intercisal opening (MIO), chewing function, performance status,
M AN U
depression, and head and neck-specific quality of life]; (3) comparison of these findings in patients with and without trismus to evaluate the effects of trismus on the quality of life. Results of this study may enable healthcare providers in Taiwan to better understand trismus
TE D
based on MIO and encourage prevention and rehabilitation programs (e.g., heat therapy, soft diet, muscle relaxants, and mouth opening exercises) for HNC patients.
EP
METHODS Subjects and design
AC C
The study was designed as a cross-sectional descriptive correlational study. A convenience sample was recruited from a radiation therapy clinic in a teaching hospital in southern Taiwan between August 2011 and September 2013. Patients were included if they met the following inclusion criteria: (1) diagnosis with head and neck squamous cell carcinoma and patient aware of the diagnosis, (2) treatment with curative RT or CCRT, (3) treatment completed and current post-radiation status of 3 months to 3 years, (4) age greater 5
ACCEPTED MANUSCRIPT than 18 years, (5) ability to communicate orally or in writing, and (6) agreement to participate in the study after explanation of its purposes and procedures. Because operation type may
RI PT
cause anatomical defects and different levels of trismus, patients who received surgery were excluded. Of the 112 patients invited to participate in the study, 8 (13.3%) refused. A total of 104 cases (92.9% response rate) were used for final data analysis.
SC
Procedures
M AN U
Before data collection, the research plan was verified and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Subjects’ signed consent forms were obtained before data collection. To calculate BMI, a research nurse measured each patient’s
TE D
body weight and body height before a physician visit. Data was collected through an interview using structured questionnaires followed by a physical examination of the MIO
Sample size
EP
width and measurement by a research nurse, taking an average of 15-20 minutes.
AC C
Sample size was estimated based on a previous study of quality of life of patients with HNC.23 To attain a power of 0.08 with the level of significance (α) at 0.05 (two-sided), 102 subjects were considered to be adequate to measure the differences in quality of life and head and neck-related quality of life and to test a maximum of seven independent variables in a multiple regression analysis.29 Measures 6
ACCEPTED MANUSCRIPT The instruments used to assess patients are described below. (1) Demographic and disease/treatment information form
RI PT
Demographic information collected by means of chart review and research nurse interviews included age, gender, education level, employment status, marital status, and
religion. Disease and treatment-related characteristics included cancer stage, cancer site, type
SC
of treatment, radiation dose, time since RT completion (in months), BMI (nutrition status),
M AN U
history of betel nut chewing, smoking, alcohol use, and performance status. Performance status was measured using the Karnofsky’s Performance Status Index (KPS).30 The KPS was designed to measure the general well-being and activities of daily life
TE D
of cancer patients and may indicate whether patients follow their medical care regimen. The score ranges from 100% to 0%, with 100% indicating normal function and 0% indicating
EP
death. Patients were assessed based on their level of physical performance.30 The KPS has been widely used in clinical cancer studies37-38 and has been found to be reliable in
AC C
cancer-related studies in Taiwan.33-35 (2) Plastic scale ruler (PSR) The plastic scale ruler (PSR) is an instrument used to measure MIO.12 Patients’ heads were supported in a neutral position (e.g., sitting supported with seat backs or supine) during the assessment process. Patients were asked to open their mouths as wide as possible, while avoiding excessive pain. In this study, patients were measured three times and the average 7
ACCEPTED MANUSCRIPT maximal mouth opening width was calculated. Patients with a mean MIO of 65 64-40
S2212-4403(14)01309-1
DOI:
10.1016/j.oooo.2014.10.003
Reference:
OOOO 1039
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received Date: 9 July 2014 Revised Date:
17 September 2014
Accepted Date: 6 October 2014
Please cite this article as: Lee L-Y, Chen S-C, Chen W-C, Huang B-S, Lin C-Y, Trismus and impact on quality of life in head and neck cancer patients post-radiation, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2014), doi: 10.1016/j.oooo.2014.10.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Trismus and impact on quality of life in head and neck cancer patients post-radiation Running title: HNC cancer patients’ trismus and impact on QOL Li-Yun Leea, Shu-Ching Chenb,c , Wen-Cheng Chend,e, Bing-Shen Huangc,f, Chien-Yu Linc,f, a
M AN U
SC
RI PT
Department of Nursing, China Medical University Beigang Hospital, Yunlin, Taiwan; and School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan b Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan c Head and Neck Oncology Group, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at LinKou, Taoyuan, Taiwan d Department of Radiation Oncology, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at Chiayi; and College of Medicine, Chang Gung University, Chiayi, Taiwan e Head and Neck Oncology Group, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at Chaiyi, Chaiyi, Taiwan f Department of Radiation Oncology, Chang Gung Medical Foundation, Chang Gung Memorial Hospital at LinKou; and Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
TE D
Corresponding author: Shu-Ching Chen, PhD, Associate Professor Department of Nursing, Chang Gung University of Science and Technology, 261, Wen-Hua 1st Road, Kweishan, Taoyuan, 333, Taiwan. Tel: +886-3-2118999 Ext. 3422 Fax: +886-3-2118866 E-mail address: [email protected]
AC C
EP
Total pages: 30 Tables: 5 Illustrations: 0 ACKNOWLEDGEMENTS This study was supported grants CMUBH R100-006 and CMUBH R102-001 from the China Medical University Hospital and were supported in part by grants to Dr. Shu-Ching Chen from National Science Council Research Program (NSC101-2314-B-255-001-MY2) and Chang Gung Memorial Hospital (NMRPF3C0101) in Taiwan. The authors gratefully acknowledge the patients who participated in the study. The authors also thank Sarah Smith for English editing.
Conflicts of Interest Statement None declared.
1
ACCEPTED MANUSCRIPT ABSTRACT Objective: The aims of this study were to investigate in head and neck cancer patients: (1)
RI PT
factors related to trismus and that predict the development of trismus, (2) factors affecting quality of life and measurements of these factors, and (3) comparison of these findings in patients with and without trismus to evaluate the effects of trismus on quality of life.
SC
Methods: This cross-sectional study included questionnaires on: Hospital Anxiety and
M AN U
Depression Scale – Depression Subscale, Chewing Function Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module. A scaled ruler was used to measure MIO.
TE D
Results: For the 104 subjects, 8.7% had clinical depression. The average MIO was 35.81 mm and 47.1% of subjects had trismus. Moderate levels of chewing dysfunction were noted by
EP
different types of food. Lower body mass index, chemoradiotherapy treatment, longer time since treatment completion, and higher radiation dose were significantly associated with
AC C
trismus. Such patients had significantly lower head and neck-specific quality of life in terms of social contact, sexuality, teeth, opening mouth, dry mouth, feeling ill, nutritional supplement, and weight loss. Conclusions: Patients with trismus should have mouth opening exercises after treatment and programs to improve trismus and quality of life. KEYWORDS 2
ACCEPTED MANUSCRIPT Head and neck cancer, radiation therapy, trismus, quality of life INTRODUCTION
RI PT
Cancer is a leading cause of death worldwide, with an estimated 550,000 new cases of head and neck cancer (HNC) occurring per year.1 The mortality of HNC is rising in Taiwan and the incidence rate has continuously increased since the late 1990s.2 Betel nut use is a
SC
major carcinogen contributing to head and neck cancer.3 Tobacco use, alcohol use, betel nut
M AN U
use, and human papillomavirus infection are risk factors for HNC, with chewing betel nut as the single most important etiological factor for developing oral submucosa fibrosis.4-5 Betel nut products can induce fibroblast proliferation and collagen synthesis and may penetrate the
TE D
oral mucosa to cause progressive cross linking of collagen fibers.6-7 Curative radiation therapy (RT) and concurrent chemoradiation therapy (CCRT) are the
EP
primary modalities for treatment of unresectable HNC.8 Radiation fibrosis causes shortening of the muscle fibers, degeneration, inflammation, pain, and atrophy, and may lead to
AC C
trismus.9-10 Trismus, or hypomobility of the mouth, results in restricted and limited normal range-of-motion of the mouth.11 Trismus is defined as mouth opening ≤35 mm (either the interincisal distance or the distance between the upper and lower alveolus),12 a definition supported by the findings of Scott et al.13 Although treatment prolongs survival, many HNC patients continue to experience complications related to trismus that interfere with the movement of the mandible.14-15 3
ACCEPTED MANUSCRIPT Approximately 5% to 38% of HNC patients experience trismus post-radiation.16-17 Radiation-induced trismus may occur in the initial three months after radiation, or up to
RI PT
12-48 months post therapy.18-20 Trismus significantly impacts both activities of daily living and vital oral function; it is associated with speech problems, difficulty eating or drinking, malnutrition, dehydration, difficulty with oral hygiene,11 and lower quality of life.21-24
SC
The characteristics of trismus may be associated with disease- and treatment-related
M AN U
factors. Significant risk factors for trismus include large tumors,25 high radiation dose radiotherapy,25-26 CCRT treatment,26 a longer time since treatment completion,24 chewing deficit,13 and greater levels of depression.27 Several studies22-25 have identified the impact of
TE D
trismus on oral function-related quality of life, including pain, eating, chewing, taste, saliva production, social functioning, social contact, and dry mouth,25 as well as a greater incidence
EP
of jaw-related problems23 and eating limitations.13, 23, 28 Based on empirical findings, the following characteristics of trismus in HNC patients
AC C
during the post-radiation period were selected for investigation: nutrition status, type of treatment, time since RT completion, radiation dose, chewing function, and depression. Given that HNC patients report different levels of quality of life that vary with levels of trismus,13, 23-24 chewing function, depression, and head and neck-specific quality of life were compared. Because atrophy and fibrosis progression occur during radiation and post-radiation, problems are not recognized without a comprehensive evaluation of patients with HNC. The 4
ACCEPTED MANUSCRIPT aims of this study were (1) factors related to trismus and that predict the development of trismus [including demographic factors (age, gender, education level, employment status,
RI PT
marital status, religion, betel nut use, smoking and alcohol history), disease-related factors (BMI, cancer site, and cancer stage), and treatment-related factors (type of treatment, RT dose, and time since RT)]; (2) factors affecting quality of life and measurement of these
SC
factors [include maximal intercisal opening (MIO), chewing function, performance status,
M AN U
depression, and head and neck-specific quality of life]; (3) comparison of these findings in patients with and without trismus to evaluate the effects of trismus on the quality of life. Results of this study may enable healthcare providers in Taiwan to better understand trismus
TE D
based on MIO and encourage prevention and rehabilitation programs (e.g., heat therapy, soft diet, muscle relaxants, and mouth opening exercises) for HNC patients.
EP
METHODS Subjects and design
AC C
The study was designed as a cross-sectional descriptive correlational study. A convenience sample was recruited from a radiation therapy clinic in a teaching hospital in southern Taiwan between August 2011 and September 2013. Patients were included if they met the following inclusion criteria: (1) diagnosis with head and neck squamous cell carcinoma and patient aware of the diagnosis, (2) treatment with curative RT or CCRT, (3) treatment completed and current post-radiation status of 3 months to 3 years, (4) age greater 5
ACCEPTED MANUSCRIPT than 18 years, (5) ability to communicate orally or in writing, and (6) agreement to participate in the study after explanation of its purposes and procedures. Because operation type may
RI PT
cause anatomical defects and different levels of trismus, patients who received surgery were excluded. Of the 112 patients invited to participate in the study, 8 (13.3%) refused. A total of 104 cases (92.9% response rate) were used for final data analysis.
SC
Procedures
M AN U
Before data collection, the research plan was verified and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Subjects’ signed consent forms were obtained before data collection. To calculate BMI, a research nurse measured each patient’s
TE D
body weight and body height before a physician visit. Data was collected through an interview using structured questionnaires followed by a physical examination of the MIO
Sample size
EP
width and measurement by a research nurse, taking an average of 15-20 minutes.
AC C
Sample size was estimated based on a previous study of quality of life of patients with HNC.23 To attain a power of 0.08 with the level of significance (α) at 0.05 (two-sided), 102 subjects were considered to be adequate to measure the differences in quality of life and head and neck-related quality of life and to test a maximum of seven independent variables in a multiple regression analysis.29 Measures 6
ACCEPTED MANUSCRIPT The instruments used to assess patients are described below. (1) Demographic and disease/treatment information form
RI PT
Demographic information collected by means of chart review and research nurse interviews included age, gender, education level, employment status, marital status, and
religion. Disease and treatment-related characteristics included cancer stage, cancer site, type
SC
of treatment, radiation dose, time since RT completion (in months), BMI (nutrition status),
M AN U
history of betel nut chewing, smoking, alcohol use, and performance status. Performance status was measured using the Karnofsky’s Performance Status Index (KPS).30 The KPS was designed to measure the general well-being and activities of daily life
TE D
of cancer patients and may indicate whether patients follow their medical care regimen. The score ranges from 100% to 0%, with 100% indicating normal function and 0% indicating
EP
death. Patients were assessed based on their level of physical performance.30 The KPS has been widely used in clinical cancer studies37-38 and has been found to be reliable in
AC C
cancer-related studies in Taiwan.33-35 (2) Plastic scale ruler (PSR) The plastic scale ruler (PSR) is an instrument used to measure MIO.12 Patients’ heads were supported in a neutral position (e.g., sitting supported with seat backs or supine) during the assessment process. Patients were asked to open their mouths as wide as possible, while avoiding excessive pain. In this study, patients were measured three times and the average 7
ACCEPTED MANUSCRIPT maximal mouth opening width was calculated. Patients with a mean MIO of 65 64-40
