The impact of trismus on health-related quality of life and mental health
Joakim Johnson, M.D. Ph.D.1, Mia Johansson M.D. Ph.D.2, Anna Rydén Ph.D. 3, Erik Houltz M.D. Ph.D.4, Caterina Finizia M.D. Professor1
1
Dept. of Otorhinolaryngology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg,
2
Sahlgrenska University Hospital, Gothenburg, Sweden
Dept. of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska
University Hospital, Gothenburg, Sweden AstraZeneca, R&D, Mölndal, Sweden 4 Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital/Mölndal 3
Keywords: Trismus, Gothenburg Trismus Questionnaire, Health-Related Quality of Life, H&N cancer, Temporomandibular disorders, mental health Corresponding author: Mia Johansson M.D. Ph.D Department of Oncology Blå stråket 2 Sahlgrenska University Hospital, SU/S SE-413 45 Gothenburg, Sweden Tel +46-31-3421000 Fax +46-31-827843 E-Mail: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.23816
Abstract Background: Trismus is a common symptom often related to the treatment of head and neck (H&N) cancer and to temporomandibular disorders (TMD). The aim of the present study was to measure the impact of trismus on health related quality of life (HRQL) and mental health in patients with H&N cancer and TMD. Materials and Methods: We used the criteria for trismus of maximum interincisal opening (MIO) ≤35 mm and the study subjects responded to the following instruments; The Gothenburg Trismus Questionnaire (GTQ), the Short-Form 36 Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). The study also comprised an age- and gender-matched control group without trismus. Results: Trismus patients reported significantly more dysfunction in all GTQ domains and more facial pain compared to the control group. The patients with H&N cancer and trismus scored significantly lower on all SF-36 domains except General Health compared to the control group, and the TMD patients with trismus scored significantly lower in three of the eight domains in SF-36. According to the HADS, a greater proportion of H&N cancer patients with trismus displayed more depression compared to the control group. Conclusion: The results showed that trismus is associated with a significant impact on HRQL and that patients with trismus should be approached in a holistic way with respect for the underlying cause, treating not only the physical aspects of trismus but also addressing the patients’ mental health.
2
Introduction Trismus is the limited ability to open the mouth and can be measured objectively by Maximal Interincisal Opening (MIO) ≤ 35 mm (1, 2). It can be caused by jaw related conditions often referred to as temporomandibular disorders (TMD), which are a collection of medical and dental conditions affecting the temporomandibular joint (TMJ) and ⁄or the muscles of mastication as well as contiguous tissue components (3, 4). Trismus can also result from surgery in the TMJ area, local or metastatic tumor growth of head and neck (H&N) tumors damaging critical structures necessary for chewing, including the masseter and pterygoid muscles, nerve supply and innervation, supportive tissue and the TMJ (5). Moreover, trismus can also occur as a debilitating side effect of H&N oncology treatment, especially radiotherapy (6, 7) with a steep dose-effect relationship with increased probability of trismus with increasing radiation doses (8). Magnetic resonance imaging after radiotherapy demonstrates abnormalities in multiple structures involved in the chewing apparatus, which implies multifactorial mechanisms behind this condition (9).
In Sweden, approximately 1,200 men and women are diagnosed with H&N cancer annually. Of these, a vast majority receive radiotherapy and/or chemotherapy whilst the remaining undergo surgery and/or additional radiotherapy (10). A recent prospective study from our research group including 75 H&N cancer patients showed that the incidence of trismus was 9% pre-treatment and as high as 38% 6 months post-treatment (14). Trismus impacts heavily on many aspects of daily life, such as chewing ability, diet, eating difficulties, inability to practice effective oral hygiene, visiting the dentist, pain, speech and therefore might impair health related quality of life (HRQL) (4, 11).
3
Patient reported outcome (PRO) instruments are becoming increasingly important and reliable measures of how patients experience their symptoms and is an important part of modern cancer research. Due to the scarcity of trismus-specific PRO instruments, our research group developed and validated a comprehensive disease-specific self-administered instrument, the Gothenburg Trismus Questionnaire (GTQ). The GTQ measures symptoms and impact of trismus and is currently available in Swedish and English (12). In current literature several articles have studied trismus and its causes but few, if any, have specifically explored its effect on HRQL or mental health, both important factors in modern patient care. Therefore, the aim of this study was to evaluate how trismus symptomatology is related to HRQL and mental health among patients treated for H&N cancer and patients with TMD.
Methods Study design and participants Patients with TMD or H&N cancer with trismus (MIO ≤ 35 mm) were asked to participate in the study. Patients with poor language comprehension and cognition were considered ineligible. Patients with TMD were seen by a stomatognatic physiologist and included at the Department of Orofacial Pain, Gothenburg. Patients with H&N cancer and trismus were included at the Department of Oral and Maxillofacial Surgery, Faculty of Odontology, Gothenburg University and the Department of Otorhinolaryngology at Sahlgrenska University Hospital, Gothenburg, and at the Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Patients were identified and considered eligible for the study at oncology grand rounds or at follow-up visits after termination of treatment when there were clinical signs of trismus (MIO ≤ 35 mm). The study also comprised an age- (5-year interval) and gender-matched control group of patients from the department of Otorhinolaryngology at Sahlgrenska University Hospital, Mölndal. The control patients demonstrated no subjective or
4
objective signs of trismus and answered the instruments in clinic. The study subjects responded to the following PRO instruments: the Gothenburg Trismus Questionnaire (GTQ) (12), the Short-Form 36 Health Survey (SF-36) (13, 14) and the Hospital Anxiety and Depression Scale (HADS) (15). Instruments were distributed to patients at the clinic and mailed back. Patients who had not returned their instruments within 2 weeks were reminded once by mail. The material in this paper is in part a secondary analysis of data previously published by our research group (16).
Gothenburg Trismus Questionnaire (GTQ) The GTQ is an instrument developed to serve as a screening tool and endpoint in intervention and jaw physiotherapy/rehabilitation studies in trismus patients (12). The instrument contains 21 items divided into three domains; Jaw related problems (items 1,2,3,4,5,6), Eating limitations (items 8,9,10,11) and Muscular tension (items 7,12,13). The remaining 8 items measure pain at different time points and limitations in mouth opening and its effects (Appendix A). A five-point Likert scale is used, except for certain items covering pain and limited mouth opening, for which a seven-point Likert scale is used. The questionnaire has a one-week recall period for the three domains, and the items covering pain and limitations in mouth opening refer to the situation as it is right now or with one month recall period.
Short-Form 36 Health Survey (SF-36) The SF-36 is a widely used generic instrument for measuring HRQL with a recall period of four weeks for the standard version (13, 14). The instrument contains 36 items in eight domains: Physical Functioning (PF, 10 items), Role limitations due to Physical problems (RP, four items), Bodily Pain (BP, two items), General Health (GH, five items), Vitality (VT, four items), Social Functioning (SF, two items), Role limitations due to Emotional problems (RE, three items), Mental Health (MH, five items) and one question concerning perceived health
5
during the last year. A score for each domain between 0 (worst possible) and 100 (best possible) is calculated using a standardised scoring system. The Swedish version has welldocumented reliability and validity (13).
Hospital Anxiety and Depression Scale (HADS) The HADS is an instrument used to detect mood disorders in somatically ill patients (15) and has frequently been employed in cancer studies, including H&N cancer (17, 18). The Swedish version has been documented in several studies. HADS consists of 14 items on a four-point response scale ranging from 0-3. The summary scale scores for anxiety (7 items) and depression (7 items) thus range from 0-21. Each person is also grouped according to a clinically tested classification of psychiatric morbidity. A scale score < 8 is within normal range, a score 8-10 indicates a possible mood disorder whilst a score >10 indicates a probable mood disorder.
Statistical methods Descriptive statistics were calculated according to standard procedures. The trismus and control patients were matched according to age and gender. Tests between patients and control groups were carried out with Wilcoxon signed rank test for continuous variables and The Sign Test for categorical variables. Tests between TMD and H&N cancer groups were carried out using the Mann-Whitney U test for continuous variables and Fisher’s Exact test for dichotomous variables and the Mantel–Haenszel Chi Square Exact test for ordered categorical variables. Level of significance was set at 5% throughout.
Ethical considerations The study was approved by the Regional Ethical Review Board at Gothenburg University and performed in accordance with the Declaration of Helsinki.
6
Results Patient characteristics During the study period 138 patients were eligible for inclusion, and all accepted participation. However, nine patients failed to return their instruments, resulting in a final 129 participants (response rate 93%). A total of fifteen patients asked to participate in the control groups declined participation. Of the included trismus patients, 51 patients had TMD and 78 patients had H&N cancer. All but one H&N cancer patient received treatment with external radiotherapy, in 29 cases followed by brachytherapy. Thirty-eight patients received chemotherapy in addition to radiotherapy and in 34 patients surgery was performed. The median time from completion of oncological treatment until inclusion in this study was 4 months with a range between 4 months left of treatment to 152 months after completion of treatment. Four patients were still under on-going oncological treatment when included in the study. For the TMD patients the treatment regimens varied depending on the underlying disease. Further clinical and socio-demographic characteristics of both trismus groups (TMD and H&N cancer) as well as of the age- and gender-matched control groups are shown in Tables 1 & 2. There was no statistically significant difference in comorbidity between the trismus groups and the control groups. The TMD patients were significantly younger than the H&N cancer patients, with an average age of 42 and 59 years, respectively. Compared to the H&N cancer patients, a larger proportion of TMD patients were female and had a longer duration of trismus.
Patient reported instruments All trismus patients reported significantly higher dysfunction in all 3 GTQ domains and more facial pain compared to the control groups (Table 3). All trismus patients also reported a significant impact on all 3 single items related to limitations in opening the mouth, as seen in
7
Table 3. The greatest dysfunction was found for TMD patients regarding Jaw related problems. When comparing the trismus subgroups, the TMD patients reported significantly more Jaw related problems and Muscular tension (2 of 3 domains) compared to the cancer group. They also experienced more facial pain in all aspects, i.e. right now, worst and average pain. However, there were no significant differences between TMD vs. H&N cancer patients regarding the impact on social, leisure, or family activities or work.
With the exception of General Health, the H&N cancer group scored significantly lower on all 8 SF-36 domains compared to the control group, thereby indicating a lower HRQL (Table 4). The TMD group scored significantly lower than the control group on the SF 36 domains PF, BP and SF. However, when comparing H&N cancer with TMD patients a more complex pattern emerged than that of the GTQ scores. H&N cancer patients reported lower levels (i.e. worse) in Role Limitations due to Physical Problems compared to the TMD patients. Cancer patients also scored lower on Physical Functioning as well as Social Functioning and Role Limitations due to Emotional Problems, although these differences were not statistically significant. The lowest scores for H&N cancer patients were observed for Role Limitations due to Physical Problems. TMD patients’ lowest score was found for Bodily Pain, this score was also statistically significant lower (worse) compared to H&N cancer patients.
According to HADS, there was a statistically significant difference in depression between H&N cancer patients and the control group. As seen in Table 5, no other statistically significant differences were observed.
8
Discussion Trismus is a common symptom often related to the treatment of head and neck (H&N) cancer or to temporomandibular disorders (TMD). The incidence of trismus after H&N oncology treatment has been reported to be as high as 42% (7). To the best of our knowledge the incidence of TMD in Sweden is unknown, but a study by Anastassaki-Köhler et al, including a total of 1704 subjects, showed that in the last two decades, an increase in the prevalence of TMD symptoms has been observed (19). Despite this, the effect of trismus symptomatology on HRQL and mental health is largely unexplored.
In the current study, as could be expected, trismus patients reported more symptoms and poorer HRQL compared to the control groups. Several components of the trismus symptomatology can explain these findings, but manifestations of the underlying disease itself (TMD/H&N cancer) might also contribute to the results. The H&N cancer group scored lower on all SF-36 domains compared to the control group, with the exception for General Health. This may be explained by the general characteristics of the questions in the GH domain, making it too blunt to distinguish between these patient groups.
When comparing the trismus subgroups, the TMD patients reported more severe trismus specific symptoms such as Jaw related problems, Muscular tension and Pain compared to the cancer patients. One explanation for this could be due to the TMD group being more heterogeneous including patients with arthritis, disc problems, muscular problems, trauma and luxation, conditions often involving pain and inflammation. The longer duration of trismus in the TMD group as well as the significant differences within the trismus group according to age and gender might also affect the results.
9
That TMD patients experienced more pain than H&N cancer patients was also demonstrated by the SF-36 Bodily Pain scores. The only other difference between the trismus groups regarding HRQL was found for the Role limitations due to Physical problems domain where the H&N cancer patients reported significantly more problems than the TMD group. Effects of the cancer disease itself, as well as long lasting side effects of treatment regimens, such as nutritional aspects and speech impairment, may affect the patient in a more radical and generalised way than TMD (20). This highlights that trismus must be assessed together with other aspects of the patients’ clinical condition.
The HADS scores demonstrated a statistically significant greater proportion of patients with depression among the H&N cancer patients compared to the control group. The higher level of depression in this group is not an unexpected finding and is probably rather related to the underlying cancer disease than to the trismus symptoms solely. The depression scores are in accordance with previous research, e.g. the results of a cross-sectional study by Rogers et al, including patients previously treated for H&N cancer (21). Several studies have previously suggested that mood disorders can play a role in the TMD symptomatology (22, 23) and that TMD is often co-existent with depression and anxiety (22, 24, 25). Also in the current study the proportion of TMD patients with scores indicating possible or probable anxiety was not negligible, 42%. The TMD patients further demonstrated higher depression scores compared to the control group, although the difference was not statistically significant, neither for depression, nor for anxiety. A possible explanation to the lack of significant differences between the TMD group and the controls might be that the control group was constituted of patients suffering from medical conditions possibly elevating the risk of developing mood disorders. The relationship between pain and mood disorder is complex. While pain itself can constitute a significant physical and psychological stressor
10
that may induce or aggravate psychological distress, mood disorders may also cause a dysfunctional response to pain (26).
One limitation of this study is the cross-sectional study design which precludes causal interpretations and provides no information about changes over time in study outcomes. Another limitation is the clinical heterogeneity between the H&N cancer patients and the TMD patients in the trismus group with statistically significant differences concerning age, gender and duration of trismus. Furthermore there is a clinical heterogeneity within the TMD group itself. Finally, results of a secondary analysis should be interpreted conservatively.
Conclusion Our main findings demonstrate that trismus may be associated with poorer HRQL and mental health in both H&N cancer and TMD patients. The implications are that patients with trismus should be approached in a holistic way with respect for the underlying cause, treating not only the physical aspects of trismus but also addressing the patients’ mental health. As stated earlier, trismus can be the result of several different etiologies, with their own unique features, making trismus research not only challenging but also imperative if we want to be able to provide the patients with targeted and personalized trismus therapy.
Conflict of interest statement None declared.
Acknowledgements This study was supported by the by the Swedish Cancer Society, Assar Gabrielsson Foundation, Göteborg, Lions Cancer Foundation West and the Research and Development Council (FoU),
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Västra Götaland County. We would like to thank Eva Edström at the Department of Oralfacial Pain, Gothenburg and Bodil Fagerberg-Mohlin, Department of Oral and Maxillofacial Surgery, Faculty of Odontology, Gothenburg University for expert advice and patient data collection as well as and Polymnia Nikolaidis, physiotherapist, for patient data collection in Stockholm.
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References 1. Kohler AA, Helkimo AN, Magnusson T, Hugoson A. Prevalence of symptoms and signs indicative of temporomandibular disorders in children and adolescents. A crosssectional epidemiological investigation covering two decades. Eur Arch Paediatr Dent. 2009 Nov;10 Suppl 1:16-25. 2. Dijkstra PU, Huisman PM, Roodenburg JL. Criteria for trismus in head and neck oncology. Int J Oral Maxillofac Surg. 2006 Apr;35(4):337-42. 3. Oakley M, Vieira AR. The many faces of the genetics contribution to temporomandibular joint disorder. Orthod Craniofac Res. [Review]. 2008 Aug;11(3):125-35. 4. Scott B, Butterworth C, Lowe D, Rogers SN. Factors associated with restricted mouth opening and its relationship to health-related quality of life in patients attending a Maxillofacial Oncology clinic. Oral Oncol. [Validation Studies]. 2008 May;44(5):430-8. 5. Stubblefield MD, Manfield L, Riedel ER. A preliminary report on the efficacy of a dynamic jaw opening device (dynasplint trismus system) as part of the multimodal treatment of trismus in patients with head and neck cancer. Arch Phys Med Rehabil. 2010 Aug;91(8):1278-82. 6. Bensadoun RJ, Riesenbeck D, Lockhart PB, et al. A systematic review of trismus induced by cancer therapies in head and neck cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. [Review]. 2010 Aug;18(8):1033-8. 7. Johnson J, van As-Brooks CJ, Fagerberg-Mohlin B, Finizia C. Trismus in head and neck cancer patients in Sweden: incidence and risk factors. Med Sci Monit. [Research Support, Non-U.S. Gov't]. 2010 Jun;16(6):CR278-82. 8. Teguh DN, Levendag PC, Voet P, et al. Trismus in patients with oropharyngeal cancer: relationship with dose in structures of mastication apparatus. Head & neck. 2008 May;30(5):622-30. 9. Bhatia KS, King AD, Paunipagar BK, et al. MRI findings in patients with severe trismus following radiotherapy for nasopharyngeal carcinoma. Eur Radiol. 2009 Nov;19(11):2586-93. 10. Sweden OS. Statistics - Health and Medical Care.Cancer Incidence in Sweden. 2009. 11. Kent L, M., Brennan MT, Noll JL, et al. Radiation-induced trismus in head and neck cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2008 Mar;16(3):305-9. 12. Johnson J, Carlsson S, Johansson M, et al. Development and validation of the Gothenburg Trismus Questionnaire (GTQ). Oral Oncol. [Research Support, Non-U.S. Gov't Validation Studies]. 2012 Aug;48(8):730-6. 13. Taft C, Karlsson J, Sullivan M. Performance of the Swedish SF-36 version 2.0. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. [Research Support, Non-U.S. Gov't Validation Studies]. 2004 Feb;13(1):251-6. 14. Gandek B, Sinclair SJ, Kosinski M, Ware JE, Jr. Psychometric evaluation of the SF-36 health survey in Medicare managed care. Health Care Financ Rev. [Evaluation Studies Research Support, U.S. Gov't, Non-P.H.S.]. 2004 Summer;25(4):5-25. 15. Zigmond A, Snaith R. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361-70. 16. Pauli N, Johnson J, Finizia C, Andrell P. The incidence of trismus and long-term impact on health-related quality of life in patients with head and neck cancer. Acta oncologica. [Research Support, Non-U.S. Gov't]. 2013 Aug;52(6):1137-45.
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17. Hilgers FJ, Ackerstaff AH, Aaronson NK, Schouwenburg PF, Van Zandwijk N. Physical and psychosocial consequences of total laryngectomy. Clin Otolaryngol Allied Sci. 1990 Oct;15(5):421-5. 18. Chaturvedi SK, Shenoy A, Prasad KM, Senthilnathan SM, Premlatha BS. Concerns, coping and quality of life in head and neck cancer patients. Support Care Cancer. 1996 May;4(3):186-90. 19. Anastassaki Kohler A, Hugoson A, Magnusson T. Prevalence of symptoms indicative of temporomandibular disorders in adults: cross-sectional epidemiological investigations covering two decades. Acta Odontol Scand. 2012 May;70(3):213-23. 20. Oskam IM, Verdonck-de Leeuw IM, Aaronson NK, et al. Prospective evaluation of health-related quality of life in long-term oral and oropharyngeal cancer survivors and the perceived need for supportive care. Oral Oncol. 2013 Jan 11. 21. Rogers SN, Rajlawat B, Goru J, Lowe D, Humphris GM. Comparison of the domains of anxiety and mood of the University of Washington Head and Neck Cancer Questionnaire (UW-QOL V4) with the CES-D and HADS. Head & neck. [Comparative Study]. 2006 Aug;28(8):697-704. 22. Vimpari SS, Knuuttila ML, Sakki TK, Kivela SL. Depressive symptoms associated with symptoms of the temporomandibular joint pain and dysfunction syndrome. Psychosom Med. 1995 Sep-Oct;57(5):439-44. 23. Rollman GB, Gillespie JM. The role of psychosocial factors in temporomandibular disorders. Curr Rev Pain. 2000;4(1):71-81. 24. Macfarlane TV, Gray RJM, Kincey J, Worthington HV. Factors associated with the temporomandibular disorder, pain dysfunction syndrome (PDS): Manchester case-control study. Oral Dis. [Comparative Study]. 2001 Nov;7(6):321-30. 25. Kindler S, Samietz S, Houshmand M, et al. Depressive and anxiety symptoms as risk factors for temporomandibular joint pain: a prospective cohort study in the general population. J Pain. [Research Support, Non-U.S. Gov't]. 2012 Dec;13(12):1188-97. 26. Von Korff M, Simon G. The relationship between pain and depression. Br J Psychiatry Suppl. 1996 Jun(30):101-8. 27. Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM Classification of malignant tumours. 7th ed. New York: Blackwell; 2009.
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Table 1. MIO, duration of trismus and socio-demographic characteristics of the trismus groups and the control groups TMD
H&N cancer
TMD Patients
TMD Controls
H&N cancer Patients
H&N cancer Controls
No.=51
No.=51
No. =78
No.=78
TMD vs. H&N cancer
p TMD vs. cont.
H&N cancer vs. cont.
Mean (SD) Median (range) MIO
Age
28.5 (5.6)
N/A
28.7 (6.5)
N/A
30.0 (10-35)
N/A
30.0 (10-35)
N/A
42 (14.5)
42 (14.4)
59 (14.0)
59 (13.6)
43 (16-78)
43 (16-77)
59 (23-87)
59 (24-89)
***
No. of patients (%) Male
11 (22)
11 (22)
41 (53)
41 (53)
Female
40 (78)
40 (78)
37 (47)
37 (47)
Smoker
10 (20)
10 (20)
20 (26)
15 (19)
**
Duration of trimsus (years) 0-
Joakim Johnson, M.D. Ph.D.1, Mia Johansson M.D. Ph.D.2, Anna Rydén Ph.D. 3, Erik Houltz M.D. Ph.D.4, Caterina Finizia M.D. Professor1
1
Dept. of Otorhinolaryngology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg,
2
Sahlgrenska University Hospital, Gothenburg, Sweden
Dept. of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska
University Hospital, Gothenburg, Sweden AstraZeneca, R&D, Mölndal, Sweden 4 Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital/Mölndal 3
Keywords: Trismus, Gothenburg Trismus Questionnaire, Health-Related Quality of Life, H&N cancer, Temporomandibular disorders, mental health Corresponding author: Mia Johansson M.D. Ph.D Department of Oncology Blå stråket 2 Sahlgrenska University Hospital, SU/S SE-413 45 Gothenburg, Sweden Tel +46-31-3421000 Fax +46-31-827843 E-Mail: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.23816
Abstract Background: Trismus is a common symptom often related to the treatment of head and neck (H&N) cancer and to temporomandibular disorders (TMD). The aim of the present study was to measure the impact of trismus on health related quality of life (HRQL) and mental health in patients with H&N cancer and TMD. Materials and Methods: We used the criteria for trismus of maximum interincisal opening (MIO) ≤35 mm and the study subjects responded to the following instruments; The Gothenburg Trismus Questionnaire (GTQ), the Short-Form 36 Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). The study also comprised an age- and gender-matched control group without trismus. Results: Trismus patients reported significantly more dysfunction in all GTQ domains and more facial pain compared to the control group. The patients with H&N cancer and trismus scored significantly lower on all SF-36 domains except General Health compared to the control group, and the TMD patients with trismus scored significantly lower in three of the eight domains in SF-36. According to the HADS, a greater proportion of H&N cancer patients with trismus displayed more depression compared to the control group. Conclusion: The results showed that trismus is associated with a significant impact on HRQL and that patients with trismus should be approached in a holistic way with respect for the underlying cause, treating not only the physical aspects of trismus but also addressing the patients’ mental health.
2
Introduction Trismus is the limited ability to open the mouth and can be measured objectively by Maximal Interincisal Opening (MIO) ≤ 35 mm (1, 2). It can be caused by jaw related conditions often referred to as temporomandibular disorders (TMD), which are a collection of medical and dental conditions affecting the temporomandibular joint (TMJ) and ⁄or the muscles of mastication as well as contiguous tissue components (3, 4). Trismus can also result from surgery in the TMJ area, local or metastatic tumor growth of head and neck (H&N) tumors damaging critical structures necessary for chewing, including the masseter and pterygoid muscles, nerve supply and innervation, supportive tissue and the TMJ (5). Moreover, trismus can also occur as a debilitating side effect of H&N oncology treatment, especially radiotherapy (6, 7) with a steep dose-effect relationship with increased probability of trismus with increasing radiation doses (8). Magnetic resonance imaging after radiotherapy demonstrates abnormalities in multiple structures involved in the chewing apparatus, which implies multifactorial mechanisms behind this condition (9).
In Sweden, approximately 1,200 men and women are diagnosed with H&N cancer annually. Of these, a vast majority receive radiotherapy and/or chemotherapy whilst the remaining undergo surgery and/or additional radiotherapy (10). A recent prospective study from our research group including 75 H&N cancer patients showed that the incidence of trismus was 9% pre-treatment and as high as 38% 6 months post-treatment (14). Trismus impacts heavily on many aspects of daily life, such as chewing ability, diet, eating difficulties, inability to practice effective oral hygiene, visiting the dentist, pain, speech and therefore might impair health related quality of life (HRQL) (4, 11).
3
Patient reported outcome (PRO) instruments are becoming increasingly important and reliable measures of how patients experience their symptoms and is an important part of modern cancer research. Due to the scarcity of trismus-specific PRO instruments, our research group developed and validated a comprehensive disease-specific self-administered instrument, the Gothenburg Trismus Questionnaire (GTQ). The GTQ measures symptoms and impact of trismus and is currently available in Swedish and English (12). In current literature several articles have studied trismus and its causes but few, if any, have specifically explored its effect on HRQL or mental health, both important factors in modern patient care. Therefore, the aim of this study was to evaluate how trismus symptomatology is related to HRQL and mental health among patients treated for H&N cancer and patients with TMD.
Methods Study design and participants Patients with TMD or H&N cancer with trismus (MIO ≤ 35 mm) were asked to participate in the study. Patients with poor language comprehension and cognition were considered ineligible. Patients with TMD were seen by a stomatognatic physiologist and included at the Department of Orofacial Pain, Gothenburg. Patients with H&N cancer and trismus were included at the Department of Oral and Maxillofacial Surgery, Faculty of Odontology, Gothenburg University and the Department of Otorhinolaryngology at Sahlgrenska University Hospital, Gothenburg, and at the Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Patients were identified and considered eligible for the study at oncology grand rounds or at follow-up visits after termination of treatment when there were clinical signs of trismus (MIO ≤ 35 mm). The study also comprised an age- (5-year interval) and gender-matched control group of patients from the department of Otorhinolaryngology at Sahlgrenska University Hospital, Mölndal. The control patients demonstrated no subjective or
4
objective signs of trismus and answered the instruments in clinic. The study subjects responded to the following PRO instruments: the Gothenburg Trismus Questionnaire (GTQ) (12), the Short-Form 36 Health Survey (SF-36) (13, 14) and the Hospital Anxiety and Depression Scale (HADS) (15). Instruments were distributed to patients at the clinic and mailed back. Patients who had not returned their instruments within 2 weeks were reminded once by mail. The material in this paper is in part a secondary analysis of data previously published by our research group (16).
Gothenburg Trismus Questionnaire (GTQ) The GTQ is an instrument developed to serve as a screening tool and endpoint in intervention and jaw physiotherapy/rehabilitation studies in trismus patients (12). The instrument contains 21 items divided into three domains; Jaw related problems (items 1,2,3,4,5,6), Eating limitations (items 8,9,10,11) and Muscular tension (items 7,12,13). The remaining 8 items measure pain at different time points and limitations in mouth opening and its effects (Appendix A). A five-point Likert scale is used, except for certain items covering pain and limited mouth opening, for which a seven-point Likert scale is used. The questionnaire has a one-week recall period for the three domains, and the items covering pain and limitations in mouth opening refer to the situation as it is right now or with one month recall period.
Short-Form 36 Health Survey (SF-36) The SF-36 is a widely used generic instrument for measuring HRQL with a recall period of four weeks for the standard version (13, 14). The instrument contains 36 items in eight domains: Physical Functioning (PF, 10 items), Role limitations due to Physical problems (RP, four items), Bodily Pain (BP, two items), General Health (GH, five items), Vitality (VT, four items), Social Functioning (SF, two items), Role limitations due to Emotional problems (RE, three items), Mental Health (MH, five items) and one question concerning perceived health
5
during the last year. A score for each domain between 0 (worst possible) and 100 (best possible) is calculated using a standardised scoring system. The Swedish version has welldocumented reliability and validity (13).
Hospital Anxiety and Depression Scale (HADS) The HADS is an instrument used to detect mood disorders in somatically ill patients (15) and has frequently been employed in cancer studies, including H&N cancer (17, 18). The Swedish version has been documented in several studies. HADS consists of 14 items on a four-point response scale ranging from 0-3. The summary scale scores for anxiety (7 items) and depression (7 items) thus range from 0-21. Each person is also grouped according to a clinically tested classification of psychiatric morbidity. A scale score < 8 is within normal range, a score 8-10 indicates a possible mood disorder whilst a score >10 indicates a probable mood disorder.
Statistical methods Descriptive statistics were calculated according to standard procedures. The trismus and control patients were matched according to age and gender. Tests between patients and control groups were carried out with Wilcoxon signed rank test for continuous variables and The Sign Test for categorical variables. Tests between TMD and H&N cancer groups were carried out using the Mann-Whitney U test for continuous variables and Fisher’s Exact test for dichotomous variables and the Mantel–Haenszel Chi Square Exact test for ordered categorical variables. Level of significance was set at 5% throughout.
Ethical considerations The study was approved by the Regional Ethical Review Board at Gothenburg University and performed in accordance with the Declaration of Helsinki.
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Results Patient characteristics During the study period 138 patients were eligible for inclusion, and all accepted participation. However, nine patients failed to return their instruments, resulting in a final 129 participants (response rate 93%). A total of fifteen patients asked to participate in the control groups declined participation. Of the included trismus patients, 51 patients had TMD and 78 patients had H&N cancer. All but one H&N cancer patient received treatment with external radiotherapy, in 29 cases followed by brachytherapy. Thirty-eight patients received chemotherapy in addition to radiotherapy and in 34 patients surgery was performed. The median time from completion of oncological treatment until inclusion in this study was 4 months with a range between 4 months left of treatment to 152 months after completion of treatment. Four patients were still under on-going oncological treatment when included in the study. For the TMD patients the treatment regimens varied depending on the underlying disease. Further clinical and socio-demographic characteristics of both trismus groups (TMD and H&N cancer) as well as of the age- and gender-matched control groups are shown in Tables 1 & 2. There was no statistically significant difference in comorbidity between the trismus groups and the control groups. The TMD patients were significantly younger than the H&N cancer patients, with an average age of 42 and 59 years, respectively. Compared to the H&N cancer patients, a larger proportion of TMD patients were female and had a longer duration of trismus.
Patient reported instruments All trismus patients reported significantly higher dysfunction in all 3 GTQ domains and more facial pain compared to the control groups (Table 3). All trismus patients also reported a significant impact on all 3 single items related to limitations in opening the mouth, as seen in
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Table 3. The greatest dysfunction was found for TMD patients regarding Jaw related problems. When comparing the trismus subgroups, the TMD patients reported significantly more Jaw related problems and Muscular tension (2 of 3 domains) compared to the cancer group. They also experienced more facial pain in all aspects, i.e. right now, worst and average pain. However, there were no significant differences between TMD vs. H&N cancer patients regarding the impact on social, leisure, or family activities or work.
With the exception of General Health, the H&N cancer group scored significantly lower on all 8 SF-36 domains compared to the control group, thereby indicating a lower HRQL (Table 4). The TMD group scored significantly lower than the control group on the SF 36 domains PF, BP and SF. However, when comparing H&N cancer with TMD patients a more complex pattern emerged than that of the GTQ scores. H&N cancer patients reported lower levels (i.e. worse) in Role Limitations due to Physical Problems compared to the TMD patients. Cancer patients also scored lower on Physical Functioning as well as Social Functioning and Role Limitations due to Emotional Problems, although these differences were not statistically significant. The lowest scores for H&N cancer patients were observed for Role Limitations due to Physical Problems. TMD patients’ lowest score was found for Bodily Pain, this score was also statistically significant lower (worse) compared to H&N cancer patients.
According to HADS, there was a statistically significant difference in depression between H&N cancer patients and the control group. As seen in Table 5, no other statistically significant differences were observed.
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Discussion Trismus is a common symptom often related to the treatment of head and neck (H&N) cancer or to temporomandibular disorders (TMD). The incidence of trismus after H&N oncology treatment has been reported to be as high as 42% (7). To the best of our knowledge the incidence of TMD in Sweden is unknown, but a study by Anastassaki-Köhler et al, including a total of 1704 subjects, showed that in the last two decades, an increase in the prevalence of TMD symptoms has been observed (19). Despite this, the effect of trismus symptomatology on HRQL and mental health is largely unexplored.
In the current study, as could be expected, trismus patients reported more symptoms and poorer HRQL compared to the control groups. Several components of the trismus symptomatology can explain these findings, but manifestations of the underlying disease itself (TMD/H&N cancer) might also contribute to the results. The H&N cancer group scored lower on all SF-36 domains compared to the control group, with the exception for General Health. This may be explained by the general characteristics of the questions in the GH domain, making it too blunt to distinguish between these patient groups.
When comparing the trismus subgroups, the TMD patients reported more severe trismus specific symptoms such as Jaw related problems, Muscular tension and Pain compared to the cancer patients. One explanation for this could be due to the TMD group being more heterogeneous including patients with arthritis, disc problems, muscular problems, trauma and luxation, conditions often involving pain and inflammation. The longer duration of trismus in the TMD group as well as the significant differences within the trismus group according to age and gender might also affect the results.
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That TMD patients experienced more pain than H&N cancer patients was also demonstrated by the SF-36 Bodily Pain scores. The only other difference between the trismus groups regarding HRQL was found for the Role limitations due to Physical problems domain where the H&N cancer patients reported significantly more problems than the TMD group. Effects of the cancer disease itself, as well as long lasting side effects of treatment regimens, such as nutritional aspects and speech impairment, may affect the patient in a more radical and generalised way than TMD (20). This highlights that trismus must be assessed together with other aspects of the patients’ clinical condition.
The HADS scores demonstrated a statistically significant greater proportion of patients with depression among the H&N cancer patients compared to the control group. The higher level of depression in this group is not an unexpected finding and is probably rather related to the underlying cancer disease than to the trismus symptoms solely. The depression scores are in accordance with previous research, e.g. the results of a cross-sectional study by Rogers et al, including patients previously treated for H&N cancer (21). Several studies have previously suggested that mood disorders can play a role in the TMD symptomatology (22, 23) and that TMD is often co-existent with depression and anxiety (22, 24, 25). Also in the current study the proportion of TMD patients with scores indicating possible or probable anxiety was not negligible, 42%. The TMD patients further demonstrated higher depression scores compared to the control group, although the difference was not statistically significant, neither for depression, nor for anxiety. A possible explanation to the lack of significant differences between the TMD group and the controls might be that the control group was constituted of patients suffering from medical conditions possibly elevating the risk of developing mood disorders. The relationship between pain and mood disorder is complex. While pain itself can constitute a significant physical and psychological stressor
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that may induce or aggravate psychological distress, mood disorders may also cause a dysfunctional response to pain (26).
One limitation of this study is the cross-sectional study design which precludes causal interpretations and provides no information about changes over time in study outcomes. Another limitation is the clinical heterogeneity between the H&N cancer patients and the TMD patients in the trismus group with statistically significant differences concerning age, gender and duration of trismus. Furthermore there is a clinical heterogeneity within the TMD group itself. Finally, results of a secondary analysis should be interpreted conservatively.
Conclusion Our main findings demonstrate that trismus may be associated with poorer HRQL and mental health in both H&N cancer and TMD patients. The implications are that patients with trismus should be approached in a holistic way with respect for the underlying cause, treating not only the physical aspects of trismus but also addressing the patients’ mental health. As stated earlier, trismus can be the result of several different etiologies, with their own unique features, making trismus research not only challenging but also imperative if we want to be able to provide the patients with targeted and personalized trismus therapy.
Conflict of interest statement None declared.
Acknowledgements This study was supported by the by the Swedish Cancer Society, Assar Gabrielsson Foundation, Göteborg, Lions Cancer Foundation West and the Research and Development Council (FoU),
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Västra Götaland County. We would like to thank Eva Edström at the Department of Oralfacial Pain, Gothenburg and Bodil Fagerberg-Mohlin, Department of Oral and Maxillofacial Surgery, Faculty of Odontology, Gothenburg University for expert advice and patient data collection as well as and Polymnia Nikolaidis, physiotherapist, for patient data collection in Stockholm.
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References 1. Kohler AA, Helkimo AN, Magnusson T, Hugoson A. Prevalence of symptoms and signs indicative of temporomandibular disorders in children and adolescents. A crosssectional epidemiological investigation covering two decades. Eur Arch Paediatr Dent. 2009 Nov;10 Suppl 1:16-25. 2. Dijkstra PU, Huisman PM, Roodenburg JL. Criteria for trismus in head and neck oncology. Int J Oral Maxillofac Surg. 2006 Apr;35(4):337-42. 3. Oakley M, Vieira AR. The many faces of the genetics contribution to temporomandibular joint disorder. Orthod Craniofac Res. [Review]. 2008 Aug;11(3):125-35. 4. Scott B, Butterworth C, Lowe D, Rogers SN. Factors associated with restricted mouth opening and its relationship to health-related quality of life in patients attending a Maxillofacial Oncology clinic. Oral Oncol. [Validation Studies]. 2008 May;44(5):430-8. 5. Stubblefield MD, Manfield L, Riedel ER. A preliminary report on the efficacy of a dynamic jaw opening device (dynasplint trismus system) as part of the multimodal treatment of trismus in patients with head and neck cancer. Arch Phys Med Rehabil. 2010 Aug;91(8):1278-82. 6. Bensadoun RJ, Riesenbeck D, Lockhart PB, et al. A systematic review of trismus induced by cancer therapies in head and neck cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. [Review]. 2010 Aug;18(8):1033-8. 7. Johnson J, van As-Brooks CJ, Fagerberg-Mohlin B, Finizia C. Trismus in head and neck cancer patients in Sweden: incidence and risk factors. Med Sci Monit. [Research Support, Non-U.S. Gov't]. 2010 Jun;16(6):CR278-82. 8. Teguh DN, Levendag PC, Voet P, et al. Trismus in patients with oropharyngeal cancer: relationship with dose in structures of mastication apparatus. Head & neck. 2008 May;30(5):622-30. 9. Bhatia KS, King AD, Paunipagar BK, et al. MRI findings in patients with severe trismus following radiotherapy for nasopharyngeal carcinoma. Eur Radiol. 2009 Nov;19(11):2586-93. 10. Sweden OS. Statistics - Health and Medical Care.Cancer Incidence in Sweden. 2009. 11. Kent L, M., Brennan MT, Noll JL, et al. Radiation-induced trismus in head and neck cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2008 Mar;16(3):305-9. 12. Johnson J, Carlsson S, Johansson M, et al. Development and validation of the Gothenburg Trismus Questionnaire (GTQ). Oral Oncol. [Research Support, Non-U.S. Gov't Validation Studies]. 2012 Aug;48(8):730-6. 13. Taft C, Karlsson J, Sullivan M. Performance of the Swedish SF-36 version 2.0. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. [Research Support, Non-U.S. Gov't Validation Studies]. 2004 Feb;13(1):251-6. 14. Gandek B, Sinclair SJ, Kosinski M, Ware JE, Jr. Psychometric evaluation of the SF-36 health survey in Medicare managed care. Health Care Financ Rev. [Evaluation Studies Research Support, U.S. Gov't, Non-P.H.S.]. 2004 Summer;25(4):5-25. 15. Zigmond A, Snaith R. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361-70. 16. Pauli N, Johnson J, Finizia C, Andrell P. The incidence of trismus and long-term impact on health-related quality of life in patients with head and neck cancer. Acta oncologica. [Research Support, Non-U.S. Gov't]. 2013 Aug;52(6):1137-45.
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17. Hilgers FJ, Ackerstaff AH, Aaronson NK, Schouwenburg PF, Van Zandwijk N. Physical and psychosocial consequences of total laryngectomy. Clin Otolaryngol Allied Sci. 1990 Oct;15(5):421-5. 18. Chaturvedi SK, Shenoy A, Prasad KM, Senthilnathan SM, Premlatha BS. Concerns, coping and quality of life in head and neck cancer patients. Support Care Cancer. 1996 May;4(3):186-90. 19. Anastassaki Kohler A, Hugoson A, Magnusson T. Prevalence of symptoms indicative of temporomandibular disorders in adults: cross-sectional epidemiological investigations covering two decades. Acta Odontol Scand. 2012 May;70(3):213-23. 20. Oskam IM, Verdonck-de Leeuw IM, Aaronson NK, et al. Prospective evaluation of health-related quality of life in long-term oral and oropharyngeal cancer survivors and the perceived need for supportive care. Oral Oncol. 2013 Jan 11. 21. Rogers SN, Rajlawat B, Goru J, Lowe D, Humphris GM. Comparison of the domains of anxiety and mood of the University of Washington Head and Neck Cancer Questionnaire (UW-QOL V4) with the CES-D and HADS. Head & neck. [Comparative Study]. 2006 Aug;28(8):697-704. 22. Vimpari SS, Knuuttila ML, Sakki TK, Kivela SL. Depressive symptoms associated with symptoms of the temporomandibular joint pain and dysfunction syndrome. Psychosom Med. 1995 Sep-Oct;57(5):439-44. 23. Rollman GB, Gillespie JM. The role of psychosocial factors in temporomandibular disorders. Curr Rev Pain. 2000;4(1):71-81. 24. Macfarlane TV, Gray RJM, Kincey J, Worthington HV. Factors associated with the temporomandibular disorder, pain dysfunction syndrome (PDS): Manchester case-control study. Oral Dis. [Comparative Study]. 2001 Nov;7(6):321-30. 25. Kindler S, Samietz S, Houshmand M, et al. Depressive and anxiety symptoms as risk factors for temporomandibular joint pain: a prospective cohort study in the general population. J Pain. [Research Support, Non-U.S. Gov't]. 2012 Dec;13(12):1188-97. 26. Von Korff M, Simon G. The relationship between pain and depression. Br J Psychiatry Suppl. 1996 Jun(30):101-8. 27. Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM Classification of malignant tumours. 7th ed. New York: Blackwell; 2009.
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Table 1. MIO, duration of trismus and socio-demographic characteristics of the trismus groups and the control groups TMD
H&N cancer
TMD Patients
TMD Controls
H&N cancer Patients
H&N cancer Controls
No.=51
No.=51
No. =78
No.=78
TMD vs. H&N cancer
p TMD vs. cont.
H&N cancer vs. cont.
Mean (SD) Median (range) MIO
Age
28.5 (5.6)
N/A
28.7 (6.5)
N/A
30.0 (10-35)
N/A
30.0 (10-35)
N/A
42 (14.5)
42 (14.4)
59 (14.0)
59 (13.6)
43 (16-78)
43 (16-77)
59 (23-87)
59 (24-89)
***
No. of patients (%) Male
11 (22)
11 (22)
41 (53)
41 (53)
Female
40 (78)
40 (78)
37 (47)
37 (47)
Smoker
10 (20)
10 (20)
20 (26)
15 (19)
**
Duration of trimsus (years) 0-
