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The Development of Simple Daily Jaw Exercises for Patients Receiving Radical Head and Neck Radiotherapy
Journal of Medical Imaging and Radiation Sciences
Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
Journal de l’imagerie médicale et des sciences de la radiation
www.elsevier.com/locate/jmir
The Development of Simple Daily Jaw Exercises for Patients Receiving Radical Head and Neck Radiotherapy Tracey Rose, MSc, RTT, DCR(T)a,*, Pamela Leco, MD, FRCPCa, and Jane Wilson, MD, FRCPCa a
The BC Cancer Agency Centre for the Southern Interior, Kelowna, British Columbia, Canada
ABSTRACT Introduction: Patients who receive radical radiotherapy to the head and neck may suffer from the late side effect of trismus due to radiation of the jaw. Trismus is progressive once it starts, and can be debilitating due to difficulty eating and inability to perform proper dental hygiene. Although radiotherapy to the temporomandibular joint can restrict mouth opening, the pterygoid musclesdwhich are responsible for lateral and protrusive motions of the jawdare more sensitive to radiation. Therefore, damage to these muscles will also limit mouth opening. Method: A series of simple jaw exercises was designed to help patients maintain jaw mobility and reduce the effect of trismus. In the study, one group of patients used the exercises and the other did not. To assess whether trismus was occurring, dental gap measurements (measurements taken with a ruler from upper incisor to lower incisor, or gum-to-gum) were taken at the start of radiotherapy treatment and again at scheduled follow-up appointments. Results: There was an overall statistically significant difference between the dental gap measurements of the jaw exercise and the nojaw exercise group (P ¼ .01, assuming the statistical significance level is .05). Patients who performed the jaw exercises were able to open their mouths wider than the patients who did not do them. Although there appeared to be a difference in decreasing dental gap across time between the two groups in the study, the Wald test did not find this to be statistically significant (P ¼ .1). The use of chemotherapy was not statistically significant; that is, chemotherapy could not be linked with trismus in this study (P ¼ .6171). Conclusion: The results of this study demonstrate that jaw exercises can be a useful aid to help prevent side effects of trismus due to radiotherapy treatment. Although it is not possible to accurately quantify the effect in this study due to the use of a compensator technique, this intervention was easy to implement and simple for patients to undertake. The jaw exercises continue to be used in the Cancer Centre for the Southern Interior, and a recent revision to the jaw exercises was made with the collaboration of the dental department.
RE´SUME´ Introduction: Les patients qui rec¸oivent de la radiothe´rapie a` la teˆte et au cou peuvent ressentir des effets secondaires tardifs sous forme de trismus en raison de l’irradiation de la maˆchoire. Le trimus, lorsqu’il se de´clenche, est progressif et peut avoir des effets de´bilitants pour le patient, en raison de la difficulte´ qu’il e´prouve a` se nourrir et de l’incapacite´ de pratiquer une bonne hygie`ne dentaire. Bien que la radiothe´rapie de l’articulation temporomandibulaire puisse restreindre l’ouverture de la bouche, les muscles pte´rygo€ıdes, responsables des mouvements late´raux et en protrusion de la maˆchoire, sont plus sensibles au rayonnement, de sorte que les dommages a` ces muscles limiteront aussi l’ouverture de la bouche. Me´thode: Une se´rie d’exercices simples de la maˆchoire a e´te´ conc¸ue pour favoriser la conservation de la mobilite´ de la maˆchoire et la re´duction des effets du trismus. Dans le cadre de l’e´tude, un groupe de patients a effectue´ les exercices tandis que l’autre servait de te´moin. Pour de´terminer l’incidence de trismus, des mesures de l’ouverture de la bouche (mesures avec une re`gle depuis les incisives supe´rieures jusqu’aux incisives infe´rieures ou de la gencive a` la gencive) ont e´te´ prises au de´but des traitements de radiothe´rapie et lors d’une visite de controˆle poste´rieure au traitement. Re´sultats: L’e´tude a permis de constater une diffe´rence statistiquement significative entre les mesures prises chez les membres du groupe qui effectuaient les exercices et les membres du groupe te´moin (P ¼ 0,01 en supposant que le niveau de signification statistique se situe a` 0,05). Les patients qui ont effectue´ les exercices de maˆchoires e´taient en mesure d’ouvrir plus grand la bouche que ceux qui ne les avaient pas faits. Bien qu’il semble y avoir une diffe´rence dans la diminution de l’ouverture de la bouche au fil du temps entre les deux groupes de l’e´tude, le test de Wald n’a pas permis d’e´tablir que cette diffe´rence e´tait statistiquement significative (P ¼ 0,1). L’utilisation de la chimiothe´rapie n’a pas e´te´ juge´e statistiquement significative, l’e´tude n’ayant pas permis d’e´tablir de lien entre la chimiothe´rapie et le trismus (P ¼ 0,6171). Conclusion: Les re´sultats de cette e´tude de´montrent que les exercices de la maˆchoire peuvent eˆtre un adjuvant utile pour aider a` pre´venir
* Corresponding author. The BC Cancer Agency Centre for the Southern Interior, 399 Royal Avenue, Kelowna, B.C. V1Y 5L3. Tel: 250-712-3900. E-mail address: [email protected] (T. Rose). 1939-8654/09/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi: 10.1016/j.jmir.2009.01.002
les effets secondaires du trismus cause´ par la radiothe´rapie. Bien qu’il ne soit pas possible de quantifier avec exactitude les effet dans cette e´tude en raison de l’utilisation d’une technique de compensation, cette intervention a e´te´ facile a` mettre en œuvre et simple pour les
patients. Les exercices de la maˆchoire continuent d’eˆtre utilise´s dans le centre de cance´rologie et des modifications ont re´cemment e´te´ apporte´es aux exercices avec l’aide du de´partement de me´decine dentaire.
Introduction
open the mouth or the temporomandibular joint (TMJ). It could also be attributed to fibrosis from surgery scarring. In addition, radiotherapy causes fibrosis and contracture within the treatment area from damage to the blood supply; there is evidence that stiffness or fusion of the TMJ occurs, as referred to in Dijikstra et al [2]. Combining surgery and radiation exacerbates the risk of a patient developing trismus [3, 4]. Additionally, trismus itself may cause degenerative effects in the TMJ similar to arthritis, which could become permanent over time [5]. During radiotherapy, there is no significant change in a patient’s ability to open his or her mouth. Trismus arises sometime after the initial treatment, as muscle cells have a slow mitotic rate [3]. Evidence suggests that the most rapid decrease in mouth opening from trismus occurs 1–9 months after finishing the treatment course. There ensues a slower progression of the effect over the next 12–24 months. After 4 years, the mean decrease in mouth opening has been measured at 32% [6]. Goldstein et al noted that over 6–12 months, 86% of postradiotherapy patients had diminished mouth opening from when treatment began, although they did observe that there was also a noticeable change in jaw mobility during the course of treatment [7]. A systematic review in 2004 stated that the reduction in mouth opening after radiotherapy to the jaw was 18% (standard deviation: 17%) [8]. A consequence of increasing radiation dose to the jaw is a decrease in the ability to open the mouth. However, the pterygoid muscles are more sensitive to dose than the TMJs. Increasing dose to the TMJ does not increase mandibular dysfunction as it does with the pterygoid muscle. The effect of the radiation on the TMJs is a decrease in mouth opening, but the effect on the pterygoid muscles results in a reduction of lateral and protrusive jaw movements [7], which is painfully restricting for the patient. Grandi et al used the same quantification method as Goldstein et al, and supports that irradiation of the pterygoid muscles causes the observed limitation of mouth opening [9]. It is sometimes possible to exclude the TMJ in a radiotherapy treatment plan, but not the pterygoid muscles due to their anatomical position. Mouth opening effects from radiation appear to be the same, despite changes in wedge orientation. If the dose to one muscle is decreased by turning the wedge, the resultant increase in dose to another muscle negates the initial advantage [7]. The use of a compensator technique improves this effect by evening out the dose to the jaw muscles [10]. As described previously, there would have been some uneven doses to these muscles, which could potentially increase side effects. New advances in radiotherapy technology such as three-dimensional conformal radiotherapy and intensity-modulated radiation therapy address this problem [11].
Cancer of the head and neck accounts for 6% of all cancers. Approximately 4,600 patients in Canada are diagnosed with head and neck cancer each year. The most common pathology of these tumours is squamous cell or adenocarcinoma, and these types of cancer are more frequently found in males than females [1]. At the British Columbia Cancer Agency, patients diagnosed with cancer of the head and neck can expect to receive multidisciplinary care from a range of professionals, including surgical oncologists, radiation and medical oncologists, radiation therapists, and dietitians. The recommended treatment will depend on the initial stage of the disease on presentation, but will likely include a combined modality approach to treatment to improve survival and control the progression of local disease. This might be a course of radiotherapy, a combination of surgery followed by chemotherapy and radiotherapy, or a course of radiotherapy and concurrent chemotherapy as a primary treatment. Standard treatment is 6–7 weeks of daily radiotherapy 5 days per week, and three to seven cycles of chemotherapy, dependent on the regimen being used. Commonly, concurrent chemotherapy regimens include the use of single agent Cisplatin or Carboplatin, occasionally combined with 5-fluorouracil. Combined Modality Treatment Side Effects Patients who receive daily radiotherapy combined with several cycles of chemotherapy will incur unpleasant side effects. These side effects will have acute and late presentations and are exacerbated by the toxicity of the combined treatments. Acute side effects within the treatment area include inflammation of the skin, drying of the skin progressing to moist desquamation of the skin, mucositis, dysphagia, thick saliva, and hoarseness. Consequently, patients will have difficulty eating and weight loss may occur. Late side effects, which may occur months to years after the treatment is over, may include necrosis of the tissue or bone and trismus. Trismus Trismus is a progressive contraction of the muscles used for mastication, which results in restriction of mouth opening. It can be caused by muscle, nerve, or joint damage. This could be due to surgery, tetanus, or trauma. To assess a patient’s ability to open his or her mouth, dental gap measurements are commonly used in clinical research. The patient is asked to open their mouth the maximum amount possible, and then a measurement in millimetres is made using a ruler or caliper. This measurement is taken from the top incisor to the bottom incisor or gum-to-gum in edentulous patients. In head and neck cancer, trismus could occur due to invasion by tumour in or around the muscles that are used to
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
33
After trismus occurs, it is progressive, long-lasting, and affects the patient’s quality of life. For example, there will be difficulty eating and inability to perform proper oral hygiene, which has increased importance when patients also have xerostomia (another side effect from radiotherapy treatment) [5]. Preventive measures are imperative to try to counteract this side effect. Investigations including the use of pentoxifylline and electrotherapy to treat fibrosis continue; meanwhile, a series of jaw exercises is a simple preventive measure of trismus. However, the effectiveness of exercise therapy is dependent on patient compliance [8, 11]. Exercises need to be repeated on a daily basis. Studies that mention the use of jaw exercises recommend repetitions of anywhere from 3 times per day to 10–12 times per day [9, 12]. Ideally, patients need to continue with their exercises throughout their lives; this should be emphasized to them. Patient compliance should be monitored at follow-up appointments to ensure the exercises are being done [4]. Reinforcing the use of the exercises and using moist, warm heat before and after exercise, combined with anti-inflammatory and muscle relaxant medications, may help with patient compliance. Patients can use tongue depressors taped together to help with the mouth opening exercises. Patients will be able to monitor their own progress when they are able to increase the number of blades that they can hold in their mouth [3]. Nevertheless, it might be difficult for patients who are edentulous to use tongue depressors or other devices as a form of mouth-opening exercise because they will likely have ill-fitting dentures, attributable to the radiotherapy treatment side effects [13]. The systematic review published in 2004 emphasizes the lack of uniform criteria to define trismus. It appears that there is still not enough knowledge regarding trismus and how it is affected by therapeutic interventions. Mouth opening should be measured to evaluate trismus. The maximal mouth opening, which is the maximum distance between incisor teeth, should be measured with a ruler in millimetres [8]. Kropmans et al analyzed the smallest statistically significant change in dental gap measurements and stress the importance of repeating measurements for accurate information [14]. Dijkstra et al propose that a patient who has a mouth opening of 35 mm or less (irrespective of their dental status) should be an indicator that the patient has trismus [13]. This study aims to evaluate whether the use of daily jaw exercises can decrease the late side effect of trismus that may occur after radical radiotherapy, with or without chemotherapy. The mobility of the jaw will be assessed using a series of dental gap measurements (i.e., the maximal mouth opening measurement from incisor to incisor, or gum-to-gum in edentulous patients) taken over time using a millimetre ruler. This will be used to determine if the use of jaw exercises decreases trismus. Materials and Methodology Eligibility Criteria 1. Patients were newly referred, belonging to one of two radiation oncologists specializing in head and neck cancer. 34
2. Treatment was prescribed with a radical intent. All patients received radical radiotherapy either with or without chemotherapy. 3. Treatment plans included were bilateral to the head and neck, with or without electron boosts. In addition, most plans in the jaw exercise group would have compensators used in the treatment plan, which makes the dose to the muscles of the jaw more even. Jaw Exercise Sheet In consultation with a physiotherapist and two radiation oncologists who specialize in head and neck cancer, a group of jaw exercises was devised. These exercises were for patients who were receiving radical radiotherapy, where the jaw would be included in the treatment area. Before this, some patients did receive verbal jaw exercise information from radiation oncologists and dentists, such as using increasing numbers of stacked tongue depressors to help open the mouth. It was felt that all patients receiving high doses of radiotherapy to the jaw were at risk of incurring trismus and therefore should all receive the same information. There was a need to standardize this approach, because patients receiving radiotherapy or chemotherapy are inundated with information leaflets and instructions. For this reason, it was necessary to make the jaw exercises easy to understand, simple to perform, and non–time consuming. Additionally, the exercises needed to be self-explanatory so that the radiation therapist who educated each new patient would be able to dispense the exercise sheet without detailed elaboration. Consequently, the jaw exercises were printed on a single sheet of paper. There are diagrams on one side with simple, concise instructions on the other side. Patients are asked to perform the exercises twice a day and to continue doing them until their first follow-up appointment, wherein the radiation oncologist would encourage them to continue using the exercises indefinitely (Figure 1). Data Collection Dental gap measurements were recorded by the radiation oncologist at the patients’ initial consultation, then at intervals during follow-up appointments. Specifically, the dental gap measurement is the maximal mouth opening measured from upper incisors to lower incisors, or from gum-to-gum in edentulous patients using a ruler with centimetres and millimetres. This method of measurement has been commonly used in the literature and is recommended in the systematic review by Dijikstra et al [8], who state that visual assessment of mouth opening is not accurate. Each patient had an initial dental gap measurement (month 0) and a maximum of 10 follow-up measurements with the first follow-up measurement occurring at approximately 1 month (month 1). Dental gap measurements were accumulated from the electronic patient records. Records were accessed from October 2002, which was 1 year before the instigation of the jaw exercises, so that there would be
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
Figure 1. Original Jaw Exercises. Ó PhysioTools Ltd.
a set of patients who had never seen the jaw exercise sheet. Patient entry into the study ended in December 2005, to allow 12 months of data collection and to end the study in 2006. Ethics
groups, and the Fisher’s exact test was used to see if there was a difference in the proportions of different genders in the groups. The effect of chemotherapy on trismus was analyzed using a linear mixed effects regression model [15]. Analyses were carried out in SAS version 9.1.3.
The British Columbia Cancer Agency Research Ethics Board gave approval for the study.
Results
Data Analysis Comparisons of the dental gap measurements between the two groups were made using the Wald test. The two-sample ttest was used to compare differences in age between the two
Over 3 years, data were accrued on 45 patients who received radical radiotherapy with or without chemotherapy for head and neck cancers. Table 1 demonstrates that the majority of patients in each group of no-jaw exercises and jaw exercises were male, and most patients were in the age range of
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
35
Male Female Age groups
40-59 60-79 80-99
Table 2 Primary Cancers No Jaw Exercises
Jaw Exercises
75% 25% 56% 38% 6%
72% 28% 59% 38% 3%
40–59 years. Table 2 shows the primary cancers that the patients had at presentation in the no jaw exercise and jaw exercise groups. Cancers of the tonsil and tongue were the most common cancers found in this population. Twenty-nine patients used daily jaw exercises and 16 patients did not use jaw exercises. Fifteen patients (52%) who used jaw exercises had chemotherapy. All but one of them (97%) had a virtual compensator used in their treatment plan. Seven of the patients that did not use jaw exercises had chemotherapy (44%) and six (38%) had a compensator used in their treatment plan. The line graph in Figure 2 plots the mean of the dental gap measurements at each point in time. It demonstrates that patients who did the jaw exercises had a larger dental gap than those patients who did not do the jaw exercises. The Wald test found an overall significant difference between the dental gap measurements of the jaw exercise and no-jaw exercise group (P ¼ .01, assuming the statistical significance level is .05). Also on this line graph, the dental gap appears to decrease over time for the patients who did not use jaw exercises. This does not seem to be the case for patients who did the jaw exercises, although the Wald test did not find an overall statistical significant difference regarding decreasing dental gap across time (P ¼ .1, assuming the statistical significance level is .05). A linear mixed-effect regression model was used for the first 18 months of data to analyze whether change in trismus scores over time is different in patients receiving or not receiving chemotherapy. The final interpretation of this model was that the change in scores over time in this case is not statistically significant (P ¼ .6171) (i.e., the use of chemotherapy does not result in the occurrence of more or less trismus). In addition, using the two-sample t-test it was possible to determine there was no difference between the mean age distributions between groups (P ¼ .88). Also, the distribution of males and females was not significantly different between groups (P ¼ .74 using Fisher’s exact test).
No Jaw Exercises
Jaw Exercises
31% 31% 6% 6% 13% 6% 6%
38% 17% 10% 14% 7% 10% 3%
Tonsil Tongue Oropharynx Larynx Primary unknown Floor of mouth/alveolus Other
radiotherapy to the jaw. Although statistically insignificant in this study, it is interesting to note that all patients who had radiotherapy to the jaw continued to lose the flexibility to open their mouths whether or not they had done the jaw exercises over the first 12–18 months after treatment. These results are similar to those by Wang et al and Sciubba and Golden. Wang et al used dental gap measurements to investigate the length of time and rate of occurrence of trismus on patients who had radiotherapy to the jaw. During 4 years, they reported that trismus occurred slowly at varying rates, but was most rapid up to 9 months after radiotherapy treatment. Sciubba and Golden noted that restriction of mouth opening from trismus is most obvious in the first 12 months after radiotherapy treatment. It appears that there was a persistent deterioration in mouth opening ability for the patients who did not do the jaw exercises for 24–36 months, whereas the patients who used the jaw exercises appear to start to regain some mobility in their jaws at this point. Grandi et al also recognized this trend. Additionally, using the functional cutoff recommended by Dijkstra et al of 35 mm and comparing data at 10–12 months, it appears that trismus is more prevalent in the patients who did not do jaw exercises. Further investigation of this effect is warranted. The method of acquiring data was uncomplicated. The radiation oncologists incorporated taking the dental gap
5
Dental Gap (cm)
Table 1 Patient Demographics
4
3
Discussion There were a total of 45 patients included in this study. As recommended in the systematic review by Dijkstra et al, trismus was calculated using dental gap measurements repeatedly over time. The results establish that the patients who did the jaw exercises were able to open their mouths wider than the patients who never did the jaw exercises after radical 36
No jaw exercise jaw exercise
2 0
1
2-3
4-5
6-7
8-9 10-12 13-15 16-18 18-24 24-36
time (month) Figure 2. Dental gap vs time.
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
measurements during the patient’s first consultation, and from then on in regular follow-up appointments. It was also simple to instigate the use of the jaw exercises into the standard patient education given to each patient by the radiation therapists. The exercises are accompanied by diagrams and clear instructions, which meant that the radiation therapists did not have to go over them in detail with the patients. Healthcare professionals should be aware that the jaw exercises with side-to-side motions are equally as important as the ones that open the mouth. The pterygoid muscles are unavoidably irradiated using standard radiotherapy techniques and are more sensitive than the TMJs. Keeping the pterygoid muscles mobile by performing side-to-side motion of the jaw will facilitate the mouth opening. The study did have several limitations, which make the results less clear-cut. Patients within the British Columbia Cancer Agency received different chemotherapy regimes during the study. These regimens had different toxicities, which could affect the resultsdespecially if there was a significant mucosal toxicity, which made it painful for the patients to open their mouths for measurements. Furthermore, nearly half of the patients in the study (49%) received no chemotherapy and had radiotherapy only. A larger patient population would allow for some data of statistical significance to be accrued in these subsets of patients. The population was not randomized, which meant that there were variables that differed between the groups; most notable was that one of the groups had a higher rate of compensator use than the other, which restricts the conclusions that can be made regarding the results from this study. This study relied on patient compliance to undertake the jaw exercises on a regular basis and some patients probably did not do what was requested of them. This would potentially decrease the effect in the average, so that the observed effect in the study could in reality be even higher. Measurements that were recorded by the radiation oncologists in the patients’ chart were erratic, resulting in some patients having fewer data than others over time. Most notably, the baseline assessment measurement was often missing. This makes the results less accurate, although it is difficult to fully assess the impact on results.
Conclusion The results of this study demonstrate that jaw exercises can be a useful aid to help prevent side effects of trismus resulting from radiotherapy treatment. The use of the jaw exercises complements the use of the compensator technique. This intervention was well received by staff and patients in the Cancer Centre for the Southern Interior and has continued to be used for all head and neck patients receiving radiotherapy to the jaw since its implementation. In 2007, after collaboration
with the dental department, the jaw exercises were revised. After this revision, it was agreed that the dentists would add the jaw exercise sheet to the package that they give to all new head and neck patients. This seemed a more appropriate appointment to impart the information to the patients, especially as the new patients meet the dental team before the radiation therapists. The jaw exercise sheet remains available on the treatment machines so that the radiation therapists are able to ensure edentulous patientsdand any patients who did not see the dentist prior to starting radiotherapydwill still receive them. Although it is not possible to accurately quantify the value of their use from this study alone, there is enough evidence to signify the importance of daily jaw exercises for patients receiving radical radiotherapy to the jaw. Further randomized studies with a larger patient population are warranted. References [1] Head and Neck: BC Cancer Agency. Available at: http://www.bccancer. bc.ca/PPI/TypesofCancer/HeadnNeck/default.htm. Accessed September 6, 2008. [2] Dijkstra, P. U., Kropmans, T. J., & Tamminga, R. Y. (1992). Modified use of a dynamic bite openerdtreatment and prevention of trismus in a child with head and neck cancer: a case report. Cranio 10, 327–329. [3] Harrison, J. S., Dale, R. A., Haveman, C. W., & Redding, S. W. (2003). Oral complications in radiation therapy. Gen Dent 51, 552– 560; quiz 561. [4] Maureen, S. (2004). The expanding role of dental oncology in head and neck surgery. Surg Oncol Clin N Am 13, 37–46. [5] Sciubba, J. J., & Goldenberg, D. (2006). Oral complications of radiotherapy. Lancet Oncol 7, 175–183. [6] Wang, C. J., Huang, E. Y., Hsu, H. C., Chen, H. C., Fang, F. M., & Hsiung, C. Y. (2005). The degree and time-course assessment of radiation-induced trismus occurring after radiotherapy for nasopharyngeal cancer. Laryngoscope 115, 1458–1460. [7] Goldstein, M., Maxymiw, W. G., Cummings, B. J., & Wood, R. E. (1999). The effects of antitumor irradiation on mandibular opening and mobility: a prospective study of 58 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88, 365–373. [8] Dijkstra, P. U., Kalk, W. W. I., & Roodenburg, J. L. N. (2004). Trismus in head and neck oncology: a systematic review. Oral Oncol 40, 879–889. [9] Grandi, G., Silva, M. L., Streit, C., & Wagner, J. C. (2007). A mobilization regimen to prevent mandibular hypomobility in irradiated patients: an analysis and comparison of two techniques. Med Oral Patol Oral Cirugia Bucal 12, E105–E109. [10] Wilson, J., Webb, W., Mason, D., & Araujo, C. (2004). Virtual compensation in head and neck radiotherapy. Radiother Oncol (CARO 2004) 72(Suppl 1), abstract 179. [11] Vissink, A., Burlage, F. R., Spijkervet, F. K. L., Jansma, J., & Coppes, R. P. (2003). Prevention and treatment of the consequences of head and neck radiotherapy. Crit Rev Oral Biol Med 14, 213–225. [12] McLaughlin, M. P. (1999). The management of side effects of head and neck radiotherapy. Cancer Res Ther Control 9, 267–271. [13] Dijkstra, P. U., Huisman, P. M., & Roodenburg, J. L. N. (2006). Criteria for trismus in head and neck oncology. Int J Oral Maxillofac Surg 35, 337–342. [14] Kropmans, T. J., Dijkstra, P. U., Stegenga, B., Stewart, R., & de Bont, L. G. (1999). Smallest detectable difference in outcome variables related to painful restriction of the temporomandibular joint. J Dent Res 78, 784–789. [15] Diggle, P. J., Heagerty, P. J., Liang, K. Y., & Zeger, S. L. (2002). Analysis of Longitudinal Data. 2nd ed. Oxford: Oxford University Press.
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Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
Journal de l’imagerie médicale et des sciences de la radiation
www.elsevier.com/locate/jmir
The Development of Simple Daily Jaw Exercises for Patients Receiving Radical Head and Neck Radiotherapy Tracey Rose, MSc, RTT, DCR(T)a,*, Pamela Leco, MD, FRCPCa, and Jane Wilson, MD, FRCPCa a
The BC Cancer Agency Centre for the Southern Interior, Kelowna, British Columbia, Canada
ABSTRACT Introduction: Patients who receive radical radiotherapy to the head and neck may suffer from the late side effect of trismus due to radiation of the jaw. Trismus is progressive once it starts, and can be debilitating due to difficulty eating and inability to perform proper dental hygiene. Although radiotherapy to the temporomandibular joint can restrict mouth opening, the pterygoid musclesdwhich are responsible for lateral and protrusive motions of the jawdare more sensitive to radiation. Therefore, damage to these muscles will also limit mouth opening. Method: A series of simple jaw exercises was designed to help patients maintain jaw mobility and reduce the effect of trismus. In the study, one group of patients used the exercises and the other did not. To assess whether trismus was occurring, dental gap measurements (measurements taken with a ruler from upper incisor to lower incisor, or gum-to-gum) were taken at the start of radiotherapy treatment and again at scheduled follow-up appointments. Results: There was an overall statistically significant difference between the dental gap measurements of the jaw exercise and the nojaw exercise group (P ¼ .01, assuming the statistical significance level is .05). Patients who performed the jaw exercises were able to open their mouths wider than the patients who did not do them. Although there appeared to be a difference in decreasing dental gap across time between the two groups in the study, the Wald test did not find this to be statistically significant (P ¼ .1). The use of chemotherapy was not statistically significant; that is, chemotherapy could not be linked with trismus in this study (P ¼ .6171). Conclusion: The results of this study demonstrate that jaw exercises can be a useful aid to help prevent side effects of trismus due to radiotherapy treatment. Although it is not possible to accurately quantify the effect in this study due to the use of a compensator technique, this intervention was easy to implement and simple for patients to undertake. The jaw exercises continue to be used in the Cancer Centre for the Southern Interior, and a recent revision to the jaw exercises was made with the collaboration of the dental department.
RE´SUME´ Introduction: Les patients qui rec¸oivent de la radiothe´rapie a` la teˆte et au cou peuvent ressentir des effets secondaires tardifs sous forme de trismus en raison de l’irradiation de la maˆchoire. Le trimus, lorsqu’il se de´clenche, est progressif et peut avoir des effets de´bilitants pour le patient, en raison de la difficulte´ qu’il e´prouve a` se nourrir et de l’incapacite´ de pratiquer une bonne hygie`ne dentaire. Bien que la radiothe´rapie de l’articulation temporomandibulaire puisse restreindre l’ouverture de la bouche, les muscles pte´rygo€ıdes, responsables des mouvements late´raux et en protrusion de la maˆchoire, sont plus sensibles au rayonnement, de sorte que les dommages a` ces muscles limiteront aussi l’ouverture de la bouche. Me´thode: Une se´rie d’exercices simples de la maˆchoire a e´te´ conc¸ue pour favoriser la conservation de la mobilite´ de la maˆchoire et la re´duction des effets du trismus. Dans le cadre de l’e´tude, un groupe de patients a effectue´ les exercices tandis que l’autre servait de te´moin. Pour de´terminer l’incidence de trismus, des mesures de l’ouverture de la bouche (mesures avec une re`gle depuis les incisives supe´rieures jusqu’aux incisives infe´rieures ou de la gencive a` la gencive) ont e´te´ prises au de´but des traitements de radiothe´rapie et lors d’une visite de controˆle poste´rieure au traitement. Re´sultats: L’e´tude a permis de constater une diffe´rence statistiquement significative entre les mesures prises chez les membres du groupe qui effectuaient les exercices et les membres du groupe te´moin (P ¼ 0,01 en supposant que le niveau de signification statistique se situe a` 0,05). Les patients qui ont effectue´ les exercices de maˆchoires e´taient en mesure d’ouvrir plus grand la bouche que ceux qui ne les avaient pas faits. Bien qu’il semble y avoir une diffe´rence dans la diminution de l’ouverture de la bouche au fil du temps entre les deux groupes de l’e´tude, le test de Wald n’a pas permis d’e´tablir que cette diffe´rence e´tait statistiquement significative (P ¼ 0,1). L’utilisation de la chimiothe´rapie n’a pas e´te´ juge´e statistiquement significative, l’e´tude n’ayant pas permis d’e´tablir de lien entre la chimiothe´rapie et le trismus (P ¼ 0,6171). Conclusion: Les re´sultats de cette e´tude de´montrent que les exercices de la maˆchoire peuvent eˆtre un adjuvant utile pour aider a` pre´venir
* Corresponding author. The BC Cancer Agency Centre for the Southern Interior, 399 Royal Avenue, Kelowna, B.C. V1Y 5L3. Tel: 250-712-3900. E-mail address: [email protected] (T. Rose). 1939-8654/09/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi: 10.1016/j.jmir.2009.01.002
les effets secondaires du trismus cause´ par la radiothe´rapie. Bien qu’il ne soit pas possible de quantifier avec exactitude les effet dans cette e´tude en raison de l’utilisation d’une technique de compensation, cette intervention a e´te´ facile a` mettre en œuvre et simple pour les
patients. Les exercices de la maˆchoire continuent d’eˆtre utilise´s dans le centre de cance´rologie et des modifications ont re´cemment e´te´ apporte´es aux exercices avec l’aide du de´partement de me´decine dentaire.
Introduction
open the mouth or the temporomandibular joint (TMJ). It could also be attributed to fibrosis from surgery scarring. In addition, radiotherapy causes fibrosis and contracture within the treatment area from damage to the blood supply; there is evidence that stiffness or fusion of the TMJ occurs, as referred to in Dijikstra et al [2]. Combining surgery and radiation exacerbates the risk of a patient developing trismus [3, 4]. Additionally, trismus itself may cause degenerative effects in the TMJ similar to arthritis, which could become permanent over time [5]. During radiotherapy, there is no significant change in a patient’s ability to open his or her mouth. Trismus arises sometime after the initial treatment, as muscle cells have a slow mitotic rate [3]. Evidence suggests that the most rapid decrease in mouth opening from trismus occurs 1–9 months after finishing the treatment course. There ensues a slower progression of the effect over the next 12–24 months. After 4 years, the mean decrease in mouth opening has been measured at 32% [6]. Goldstein et al noted that over 6–12 months, 86% of postradiotherapy patients had diminished mouth opening from when treatment began, although they did observe that there was also a noticeable change in jaw mobility during the course of treatment [7]. A systematic review in 2004 stated that the reduction in mouth opening after radiotherapy to the jaw was 18% (standard deviation: 17%) [8]. A consequence of increasing radiation dose to the jaw is a decrease in the ability to open the mouth. However, the pterygoid muscles are more sensitive to dose than the TMJs. Increasing dose to the TMJ does not increase mandibular dysfunction as it does with the pterygoid muscle. The effect of the radiation on the TMJs is a decrease in mouth opening, but the effect on the pterygoid muscles results in a reduction of lateral and protrusive jaw movements [7], which is painfully restricting for the patient. Grandi et al used the same quantification method as Goldstein et al, and supports that irradiation of the pterygoid muscles causes the observed limitation of mouth opening [9]. It is sometimes possible to exclude the TMJ in a radiotherapy treatment plan, but not the pterygoid muscles due to their anatomical position. Mouth opening effects from radiation appear to be the same, despite changes in wedge orientation. If the dose to one muscle is decreased by turning the wedge, the resultant increase in dose to another muscle negates the initial advantage [7]. The use of a compensator technique improves this effect by evening out the dose to the jaw muscles [10]. As described previously, there would have been some uneven doses to these muscles, which could potentially increase side effects. New advances in radiotherapy technology such as three-dimensional conformal radiotherapy and intensity-modulated radiation therapy address this problem [11].
Cancer of the head and neck accounts for 6% of all cancers. Approximately 4,600 patients in Canada are diagnosed with head and neck cancer each year. The most common pathology of these tumours is squamous cell or adenocarcinoma, and these types of cancer are more frequently found in males than females [1]. At the British Columbia Cancer Agency, patients diagnosed with cancer of the head and neck can expect to receive multidisciplinary care from a range of professionals, including surgical oncologists, radiation and medical oncologists, radiation therapists, and dietitians. The recommended treatment will depend on the initial stage of the disease on presentation, but will likely include a combined modality approach to treatment to improve survival and control the progression of local disease. This might be a course of radiotherapy, a combination of surgery followed by chemotherapy and radiotherapy, or a course of radiotherapy and concurrent chemotherapy as a primary treatment. Standard treatment is 6–7 weeks of daily radiotherapy 5 days per week, and three to seven cycles of chemotherapy, dependent on the regimen being used. Commonly, concurrent chemotherapy regimens include the use of single agent Cisplatin or Carboplatin, occasionally combined with 5-fluorouracil. Combined Modality Treatment Side Effects Patients who receive daily radiotherapy combined with several cycles of chemotherapy will incur unpleasant side effects. These side effects will have acute and late presentations and are exacerbated by the toxicity of the combined treatments. Acute side effects within the treatment area include inflammation of the skin, drying of the skin progressing to moist desquamation of the skin, mucositis, dysphagia, thick saliva, and hoarseness. Consequently, patients will have difficulty eating and weight loss may occur. Late side effects, which may occur months to years after the treatment is over, may include necrosis of the tissue or bone and trismus. Trismus Trismus is a progressive contraction of the muscles used for mastication, which results in restriction of mouth opening. It can be caused by muscle, nerve, or joint damage. This could be due to surgery, tetanus, or trauma. To assess a patient’s ability to open his or her mouth, dental gap measurements are commonly used in clinical research. The patient is asked to open their mouth the maximum amount possible, and then a measurement in millimetres is made using a ruler or caliper. This measurement is taken from the top incisor to the bottom incisor or gum-to-gum in edentulous patients. In head and neck cancer, trismus could occur due to invasion by tumour in or around the muscles that are used to
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After trismus occurs, it is progressive, long-lasting, and affects the patient’s quality of life. For example, there will be difficulty eating and inability to perform proper oral hygiene, which has increased importance when patients also have xerostomia (another side effect from radiotherapy treatment) [5]. Preventive measures are imperative to try to counteract this side effect. Investigations including the use of pentoxifylline and electrotherapy to treat fibrosis continue; meanwhile, a series of jaw exercises is a simple preventive measure of trismus. However, the effectiveness of exercise therapy is dependent on patient compliance [8, 11]. Exercises need to be repeated on a daily basis. Studies that mention the use of jaw exercises recommend repetitions of anywhere from 3 times per day to 10–12 times per day [9, 12]. Ideally, patients need to continue with their exercises throughout their lives; this should be emphasized to them. Patient compliance should be monitored at follow-up appointments to ensure the exercises are being done [4]. Reinforcing the use of the exercises and using moist, warm heat before and after exercise, combined with anti-inflammatory and muscle relaxant medications, may help with patient compliance. Patients can use tongue depressors taped together to help with the mouth opening exercises. Patients will be able to monitor their own progress when they are able to increase the number of blades that they can hold in their mouth [3]. Nevertheless, it might be difficult for patients who are edentulous to use tongue depressors or other devices as a form of mouth-opening exercise because they will likely have ill-fitting dentures, attributable to the radiotherapy treatment side effects [13]. The systematic review published in 2004 emphasizes the lack of uniform criteria to define trismus. It appears that there is still not enough knowledge regarding trismus and how it is affected by therapeutic interventions. Mouth opening should be measured to evaluate trismus. The maximal mouth opening, which is the maximum distance between incisor teeth, should be measured with a ruler in millimetres [8]. Kropmans et al analyzed the smallest statistically significant change in dental gap measurements and stress the importance of repeating measurements for accurate information [14]. Dijkstra et al propose that a patient who has a mouth opening of 35 mm or less (irrespective of their dental status) should be an indicator that the patient has trismus [13]. This study aims to evaluate whether the use of daily jaw exercises can decrease the late side effect of trismus that may occur after radical radiotherapy, with or without chemotherapy. The mobility of the jaw will be assessed using a series of dental gap measurements (i.e., the maximal mouth opening measurement from incisor to incisor, or gum-to-gum in edentulous patients) taken over time using a millimetre ruler. This will be used to determine if the use of jaw exercises decreases trismus. Materials and Methodology Eligibility Criteria 1. Patients were newly referred, belonging to one of two radiation oncologists specializing in head and neck cancer. 34
2. Treatment was prescribed with a radical intent. All patients received radical radiotherapy either with or without chemotherapy. 3. Treatment plans included were bilateral to the head and neck, with or without electron boosts. In addition, most plans in the jaw exercise group would have compensators used in the treatment plan, which makes the dose to the muscles of the jaw more even. Jaw Exercise Sheet In consultation with a physiotherapist and two radiation oncologists who specialize in head and neck cancer, a group of jaw exercises was devised. These exercises were for patients who were receiving radical radiotherapy, where the jaw would be included in the treatment area. Before this, some patients did receive verbal jaw exercise information from radiation oncologists and dentists, such as using increasing numbers of stacked tongue depressors to help open the mouth. It was felt that all patients receiving high doses of radiotherapy to the jaw were at risk of incurring trismus and therefore should all receive the same information. There was a need to standardize this approach, because patients receiving radiotherapy or chemotherapy are inundated with information leaflets and instructions. For this reason, it was necessary to make the jaw exercises easy to understand, simple to perform, and non–time consuming. Additionally, the exercises needed to be self-explanatory so that the radiation therapist who educated each new patient would be able to dispense the exercise sheet without detailed elaboration. Consequently, the jaw exercises were printed on a single sheet of paper. There are diagrams on one side with simple, concise instructions on the other side. Patients are asked to perform the exercises twice a day and to continue doing them until their first follow-up appointment, wherein the radiation oncologist would encourage them to continue using the exercises indefinitely (Figure 1). Data Collection Dental gap measurements were recorded by the radiation oncologist at the patients’ initial consultation, then at intervals during follow-up appointments. Specifically, the dental gap measurement is the maximal mouth opening measured from upper incisors to lower incisors, or from gum-to-gum in edentulous patients using a ruler with centimetres and millimetres. This method of measurement has been commonly used in the literature and is recommended in the systematic review by Dijikstra et al [8], who state that visual assessment of mouth opening is not accurate. Each patient had an initial dental gap measurement (month 0) and a maximum of 10 follow-up measurements with the first follow-up measurement occurring at approximately 1 month (month 1). Dental gap measurements were accumulated from the electronic patient records. Records were accessed from October 2002, which was 1 year before the instigation of the jaw exercises, so that there would be
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
Figure 1. Original Jaw Exercises. Ó PhysioTools Ltd.
a set of patients who had never seen the jaw exercise sheet. Patient entry into the study ended in December 2005, to allow 12 months of data collection and to end the study in 2006. Ethics
groups, and the Fisher’s exact test was used to see if there was a difference in the proportions of different genders in the groups. The effect of chemotherapy on trismus was analyzed using a linear mixed effects regression model [15]. Analyses were carried out in SAS version 9.1.3.
The British Columbia Cancer Agency Research Ethics Board gave approval for the study.
Results
Data Analysis Comparisons of the dental gap measurements between the two groups were made using the Wald test. The two-sample ttest was used to compare differences in age between the two
Over 3 years, data were accrued on 45 patients who received radical radiotherapy with or without chemotherapy for head and neck cancers. Table 1 demonstrates that the majority of patients in each group of no-jaw exercises and jaw exercises were male, and most patients were in the age range of
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Male Female Age groups
40-59 60-79 80-99
Table 2 Primary Cancers No Jaw Exercises
Jaw Exercises
75% 25% 56% 38% 6%
72% 28% 59% 38% 3%
40–59 years. Table 2 shows the primary cancers that the patients had at presentation in the no jaw exercise and jaw exercise groups. Cancers of the tonsil and tongue were the most common cancers found in this population. Twenty-nine patients used daily jaw exercises and 16 patients did not use jaw exercises. Fifteen patients (52%) who used jaw exercises had chemotherapy. All but one of them (97%) had a virtual compensator used in their treatment plan. Seven of the patients that did not use jaw exercises had chemotherapy (44%) and six (38%) had a compensator used in their treatment plan. The line graph in Figure 2 plots the mean of the dental gap measurements at each point in time. It demonstrates that patients who did the jaw exercises had a larger dental gap than those patients who did not do the jaw exercises. The Wald test found an overall significant difference between the dental gap measurements of the jaw exercise and no-jaw exercise group (P ¼ .01, assuming the statistical significance level is .05). Also on this line graph, the dental gap appears to decrease over time for the patients who did not use jaw exercises. This does not seem to be the case for patients who did the jaw exercises, although the Wald test did not find an overall statistical significant difference regarding decreasing dental gap across time (P ¼ .1, assuming the statistical significance level is .05). A linear mixed-effect regression model was used for the first 18 months of data to analyze whether change in trismus scores over time is different in patients receiving or not receiving chemotherapy. The final interpretation of this model was that the change in scores over time in this case is not statistically significant (P ¼ .6171) (i.e., the use of chemotherapy does not result in the occurrence of more or less trismus). In addition, using the two-sample t-test it was possible to determine there was no difference between the mean age distributions between groups (P ¼ .88). Also, the distribution of males and females was not significantly different between groups (P ¼ .74 using Fisher’s exact test).
No Jaw Exercises
Jaw Exercises
31% 31% 6% 6% 13% 6% 6%
38% 17% 10% 14% 7% 10% 3%
Tonsil Tongue Oropharynx Larynx Primary unknown Floor of mouth/alveolus Other
radiotherapy to the jaw. Although statistically insignificant in this study, it is interesting to note that all patients who had radiotherapy to the jaw continued to lose the flexibility to open their mouths whether or not they had done the jaw exercises over the first 12–18 months after treatment. These results are similar to those by Wang et al and Sciubba and Golden. Wang et al used dental gap measurements to investigate the length of time and rate of occurrence of trismus on patients who had radiotherapy to the jaw. During 4 years, they reported that trismus occurred slowly at varying rates, but was most rapid up to 9 months after radiotherapy treatment. Sciubba and Golden noted that restriction of mouth opening from trismus is most obvious in the first 12 months after radiotherapy treatment. It appears that there was a persistent deterioration in mouth opening ability for the patients who did not do the jaw exercises for 24–36 months, whereas the patients who used the jaw exercises appear to start to regain some mobility in their jaws at this point. Grandi et al also recognized this trend. Additionally, using the functional cutoff recommended by Dijkstra et al of 35 mm and comparing data at 10–12 months, it appears that trismus is more prevalent in the patients who did not do jaw exercises. Further investigation of this effect is warranted. The method of acquiring data was uncomplicated. The radiation oncologists incorporated taking the dental gap
5
Dental Gap (cm)
Table 1 Patient Demographics
4
3
Discussion There were a total of 45 patients included in this study. As recommended in the systematic review by Dijkstra et al, trismus was calculated using dental gap measurements repeatedly over time. The results establish that the patients who did the jaw exercises were able to open their mouths wider than the patients who never did the jaw exercises after radical 36
No jaw exercise jaw exercise
2 0
1
2-3
4-5
6-7
8-9 10-12 13-15 16-18 18-24 24-36
time (month) Figure 2. Dental gap vs time.
T. Rose et al./Journal of Medical Imaging and Radiation Sciences 40 (2009) 32-37
measurements during the patient’s first consultation, and from then on in regular follow-up appointments. It was also simple to instigate the use of the jaw exercises into the standard patient education given to each patient by the radiation therapists. The exercises are accompanied by diagrams and clear instructions, which meant that the radiation therapists did not have to go over them in detail with the patients. Healthcare professionals should be aware that the jaw exercises with side-to-side motions are equally as important as the ones that open the mouth. The pterygoid muscles are unavoidably irradiated using standard radiotherapy techniques and are more sensitive than the TMJs. Keeping the pterygoid muscles mobile by performing side-to-side motion of the jaw will facilitate the mouth opening. The study did have several limitations, which make the results less clear-cut. Patients within the British Columbia Cancer Agency received different chemotherapy regimes during the study. These regimens had different toxicities, which could affect the resultsdespecially if there was a significant mucosal toxicity, which made it painful for the patients to open their mouths for measurements. Furthermore, nearly half of the patients in the study (49%) received no chemotherapy and had radiotherapy only. A larger patient population would allow for some data of statistical significance to be accrued in these subsets of patients. The population was not randomized, which meant that there were variables that differed between the groups; most notable was that one of the groups had a higher rate of compensator use than the other, which restricts the conclusions that can be made regarding the results from this study. This study relied on patient compliance to undertake the jaw exercises on a regular basis and some patients probably did not do what was requested of them. This would potentially decrease the effect in the average, so that the observed effect in the study could in reality be even higher. Measurements that were recorded by the radiation oncologists in the patients’ chart were erratic, resulting in some patients having fewer data than others over time. Most notably, the baseline assessment measurement was often missing. This makes the results less accurate, although it is difficult to fully assess the impact on results.
Conclusion The results of this study demonstrate that jaw exercises can be a useful aid to help prevent side effects of trismus resulting from radiotherapy treatment. The use of the jaw exercises complements the use of the compensator technique. This intervention was well received by staff and patients in the Cancer Centre for the Southern Interior and has continued to be used for all head and neck patients receiving radiotherapy to the jaw since its implementation. In 2007, after collaboration
with the dental department, the jaw exercises were revised. After this revision, it was agreed that the dentists would add the jaw exercise sheet to the package that they give to all new head and neck patients. This seemed a more appropriate appointment to impart the information to the patients, especially as the new patients meet the dental team before the radiation therapists. The jaw exercise sheet remains available on the treatment machines so that the radiation therapists are able to ensure edentulous patientsdand any patients who did not see the dentist prior to starting radiotherapydwill still receive them. Although it is not possible to accurately quantify the value of their use from this study alone, there is enough evidence to signify the importance of daily jaw exercises for patients receiving radical radiotherapy to the jaw. Further randomized studies with a larger patient population are warranted. References [1] Head and Neck: BC Cancer Agency. Available at: http://www.bccancer. bc.ca/PPI/TypesofCancer/HeadnNeck/default.htm. Accessed September 6, 2008. [2] Dijkstra, P. U., Kropmans, T. J., & Tamminga, R. Y. (1992). Modified use of a dynamic bite openerdtreatment and prevention of trismus in a child with head and neck cancer: a case report. Cranio 10, 327–329. [3] Harrison, J. S., Dale, R. A., Haveman, C. W., & Redding, S. W. (2003). Oral complications in radiation therapy. Gen Dent 51, 552– 560; quiz 561. [4] Maureen, S. (2004). The expanding role of dental oncology in head and neck surgery. Surg Oncol Clin N Am 13, 37–46. [5] Sciubba, J. J., & Goldenberg, D. (2006). Oral complications of radiotherapy. Lancet Oncol 7, 175–183. [6] Wang, C. J., Huang, E. Y., Hsu, H. C., Chen, H. C., Fang, F. M., & Hsiung, C. Y. (2005). The degree and time-course assessment of radiation-induced trismus occurring after radiotherapy for nasopharyngeal cancer. Laryngoscope 115, 1458–1460. [7] Goldstein, M., Maxymiw, W. G., Cummings, B. J., & Wood, R. E. (1999). The effects of antitumor irradiation on mandibular opening and mobility: a prospective study of 58 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88, 365–373. [8] Dijkstra, P. U., Kalk, W. W. I., & Roodenburg, J. L. N. (2004). Trismus in head and neck oncology: a systematic review. Oral Oncol 40, 879–889. [9] Grandi, G., Silva, M. L., Streit, C., & Wagner, J. C. (2007). A mobilization regimen to prevent mandibular hypomobility in irradiated patients: an analysis and comparison of two techniques. Med Oral Patol Oral Cirugia Bucal 12, E105–E109. [10] Wilson, J., Webb, W., Mason, D., & Araujo, C. (2004). Virtual compensation in head and neck radiotherapy. Radiother Oncol (CARO 2004) 72(Suppl 1), abstract 179. [11] Vissink, A., Burlage, F. R., Spijkervet, F. K. L., Jansma, J., & Coppes, R. P. (2003). Prevention and treatment of the consequences of head and neck radiotherapy. Crit Rev Oral Biol Med 14, 213–225. [12] McLaughlin, M. P. (1999). The management of side effects of head and neck radiotherapy. Cancer Res Ther Control 9, 267–271. [13] Dijkstra, P. U., Huisman, P. M., & Roodenburg, J. L. N. (2006). Criteria for trismus in head and neck oncology. Int J Oral Maxillofac Surg 35, 337–342. [14] Kropmans, T. J., Dijkstra, P. U., Stegenga, B., Stewart, R., & de Bont, L. G. (1999). Smallest detectable difference in outcome variables related to painful restriction of the temporomandibular joint. J Dent Res 78, 784–789. [15] Diggle, P. J., Heagerty, P. J., Liang, K. Y., & Zeger, S. L. (2002). Analysis of Longitudinal Data. 2nd ed. Oxford: Oxford University Press.
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