Supportive Care in Cancer

, Volume 16, Issue 3, pp 305–309 | Cite as

Radiation-Induced trismus in head and neck cancer patients

  • M. Louise Kent
  • Michael T. Brennan
  • Jenene L. Noll
  • Philip C. Fox
  • Stuart H. Burri
  • Jane C. Hunter
  • Peter B. Lockhart
Short Communication

Abstract

Purpose

To determine the incidence of trismus in patients who had previously received curative doses of radiation therapy (RT) for head and neck cancer. In addition, we assessed if trismus was associated with quality of life deficits and radiation toxicity.

Methods and materials

Between February, 2005 and December, 2006, 40 patients with histologically confirmed head and neck cancer who had received curative doses of RT to the area(s) of the masticatory muscles and/or the ligaments of the temporomandibular joint (TMJ) were enrolled in this study. Differences in trismus incidence were compared between cancer treatment modalities [i.e., RT vs RT/chemotherapy (CT) and conventional RT vs intensity modulated RT]. Quality of life (QOL) was measured by using four questions from the EORTC QLQ-C30 that address pain and difficulty opening the jaw. Scores regarding impaired eating as a result of decreased range of motion of the mouth were derived from the Modified Common Toxicity Criteria (CTCAE Version 3.0).

Results

Trismus was identified in 45% of subjects who had received curative doses of RT. No differences were noted in the incidence of trismus between RT and RT/CT or between conventional RT and intensity modulated RT (IMRT). Those with trismus demonstrated more QOL deficits than the non-trismus group.

Conclusions

Curative doses of RT for head and neck cancer result in trismus in a high percentage of patients, independent of other treatment modalities. Trismus has a negative impact on quality of life in this population.

Keywords

Quality of life Trismus Radiotherapy Head and neck neoplasms Masticatory muscles 

Introduction

Squamous cell carcinoma (SCC) of the head and neck accounts for greater than 90% of all upper aerodigestive tract malignancies and represents the sixth most common neoplasm [14, 18]. Radiotherapy (RT) is a major treatment modality for the management of head and neck malignancies; a primary therapy for many early stage malignancies, an adjuvant therapy following surgical resection, and curative as well as palliative therapy in conjunction with concurrent chemotherapy (CT) for late stage and unresectable head and neck malignancies [5, 8, 9, 15, 16, 17, 19]. A meta-analysis of 120 randomized trials and approximately 25,000 patients showed that the concomitant cisplatin-based RT/CT provided the most benefit for locoregional control and survival, both in head and neck squamous cell carcinomas and nasopharyngeal carcinomas [4] On the other hand, concomitant RT/CT has a higher level of toxicity compared to RT alone [4].

RT-induced oral complications are complex, dynamic pathobiological processes that lower the QOL and predispose patients to serious clinical disorders [3543] Direct cell damage, combined with regional loss of vascular perfusion puts irradiated patients at a significant risk for loss of salivary function, an increased caries rate, and bone and soft tissue necrosis [20]. The loss of function and range of mandibular motion from RT appears to be related to damage and fibrosis to the muscles of mastication [22]. Studies have demonstrated that an abnormal proliferation of fibroblasts is an important initial event in these reactions, although the molecular mechanisms are poorly understood [13]. Limitations in jaw opening have been reported in 6–86% of patients having received RT to the temporomandibular joint (TMJ) and/or masseter/pterygoid muscles, with a frequency and severity that is somewhat unpredictable [6, 23].

The primary goal of our study was to identify the incidence of trismus in patients who had been treated with RT for head and neck cancer. In addition, we examined if currently utilized treatment modalities for head and neck cancer [i.e., RT vs RT/CT and conventional RT vs intensity modulated radiotherapy (IMRT)] had an impact on the incidence of trismus. We also explored the relationship between trismus and quality of life deficits.

Materials and methods

Subjects were recruited for this retrospective cohort study from our hospital’s Cancer Center, Radiation Oncology Department, and Oral Medicine service. Eligible subjects were those who had completed curative doses of radiation therapy for histologically proven head and neck cancer. Inclusion criteria included patients who had received ≥55 Gy RT to the TMJ region and/or muscle(s) of mastication and who were ≥18 years of age. Patients with prior surgical resection for cancer and/or CT were also eligible. This study was approved by our Institutional Review Board, and written informed consent was obtained for each research participant. The following information was collected: demographics; primary tumor location; lymph node metastases (Y/N); surgical resection (Y/N); CT (Y/N); CT drugs; RT dose; type of RT (conventional RT vs IMRT); time period from completion of RT to study enrollment; measurement of mouth opening (maximum vertical dimension or MVD); measurement of lateral mandibular movement; dental caries (Y/N), and QOL, and radiation toxicity (trismus) measurements. We categorized trismus as a MVD < 35 mm and non-trismus as a MVD ≥ 35 mm in dentulous patients [10]. For edentulous patients, a MVD < 40 mm was documented as trismus and a MVD ≥ 40 mm as non-trismus.

With subjects seated in the upright position, the TheraBite® range of motion scale was used to measure maximum vertical dimension (MVD) of the mouth and lateral mandibular motion. These measurements were performed by dentists and nurses trained in the use of this measurement tool. An oral examination was performed to assess clinically evident caries and for evidence of acute infection (i.e., extra- or intra-oral swelling, purulence).

Subjects answered four questions extrapolated from the QLQ-30 quality of life questionnaire developed by the EORTC [3]and were graded for trismus using the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Table 1) [11].
Table 1

Quality of life questions (QLQ-30) [3]

Modified common toxicity criteria for trismus [11]

During the past week

QOL 1: Did you have pain in your face when chewing?

1

2

3

4

QOL 2: Did you have difficulty opening your jaw normally?

1

2

3

4

QOL 3: Did you have burning, shooting, or shock-like pains in your mouth or face?

1

2

3

4

QOL 4: Are you taking any pain medicines for treatment of the mouth or face pain?

Y/N

 

 

 

0 No decreased ROM, 1 decreased ROM without impaired eating, 2 decreased ROM requiring small bites, soft foods or purees, 3 decreased ROM with inability to adequately aliment or hydrate orally

Statistical analysis

Descriptive statistics were utilized with variables reported as mean, SD, or proportion. Group comparisons used the following: (1) continuous variables (t test or nonparametric Mann–Whitney U test, when appropriate); (2) ordinal variables (Wilcoxon rank-sum test); and (3) dichotomous variables (chi-square or Fisher’s exact test, when appropriate).

Results

We collected data from a convenience sample of 40 patients who had received RT to the area of the TMJ and /or muscle(s) of mastication for head and neck cancer, 18 of whom met the criteria for trismus (Table 2). The mean MVD for the trismus group was 28 ± 9 mm, and the non-trismus group was 43 ± 6 mm (p < 0.0001) (Table 3). In addition, there was a significant decrease in right and left lateral mandibular movement in the trismus group. No significant differences were noted between demographic variables, primary site, the type/amount of RT received or in the treatment modalities between the trismus vs the non-trismus groups (Table 2). We enrolled patients from one month post-RT up to 10 years post-RT. There were no significant differences between the trismus vs non-trismus group in the duration from RT to study enrollment. The trismus group demonstrated more QOL deficits than the non-trismus group, including difficulties with eating (CTC score) and difficulty when opening the jaw (Table 3).
Table 2

Baseline characteristics of trismus vs non-trismus patients

Variable

Trismus (n = 18)

No trismus (n = 22)

P value

Male (n, %)

14, 78%

16, 73%

1.0

Age (mean ± SD)

56.4 ± 7.5

54.4 ± 13.1

0.55

Primary tumor locationa (n, %)

 Tongue

6, 33%

11, 50%

0.29

 Tonsil

5, 27.8%

5, 22.7%

0.73

 Oropharynx

3, 16.7%

2, 9.1%

0.64

 Floor of mouth

2, 11.1%

2, 9.1%

1.0

 Hypopharynx

2, 11.1%

1, 4.5%

0.58

 Salivary gland

1, 5.5%

2, 9.1%

1.0

 Nasopharynx

1, 5.5%

1, 4.5%

1.0

 Unknown

0, 0%

1, 4.5%

1.0

Lymph node metastases present (n, %)

12, 67%

14, 64%

0.84

Surgery (n, %)

14, 78%

15, 68%

0.72

Chemotherapy (n, %)

11, 61%

14, 64%

0.87

 None

7, 38.9%

8, 36.4%

 

 Cisplatin/carboplatin alone

5, 27.8%

10, 45.4%

 

 Cisplatin with Taxane and/or 5-FU

4, 22.2%

4, 18.2%

 

 Carbo with VP-16

1, 5.6%

0, 0%

 

 Erbitux

1, 5.6%

0, 0%

 

RT dose (GY, mean ± SD)

66 ± 5.1

65 ± 5.2

0.45

IMRTb (n, %)

9, 50%

15, 68%

0.24

Conventional RT (n, %)

9, 50%

7, 32%

0.24

Duration from RT (months)

21.9 ± 35.6

10.9 ± 16.7

0.24

aSome patients had multiple tumor sites

bIntensity Modulated Radiation Therapy

Table 3

Oral opening measurements, QOL, and toxicity outcomes in trismus vs non-trismus patients

Variable

Trismus (n = 18)

No trismus (n = 22)

P value

Maximal vertical dimension (mm, mean ± SD)

28.7 ± 7.7

43.3 ± 4.9

<0.0001

Right mandibular movement (mm, mean ± SD)

7.3 ± 2.4

9.5 ± 3.2

0.02

Left mandibular movement (mm, mean ± SD)

7.3 ± 2.0

9.7 ± 3.6

0.01

Clinical caries (n, %)

2, 11%

5, 23%

0.43

QOL 1 (1–4 scale, chewing pain)

1.2 ± 0.7

0.9 ± 0.7

0.19

QOL 2 (1–4 scale, difficulty opening)

2.4 ± 1.1

1.2 ± 0.9

0.0002

QOL 3 (1–4 scale, facial pain)

1.7 ± 0.9

1.3 ± 1.0

0.21

QOL 4 (Y/N use of pain meds for facial pain)

3, 17%

4, 18%

1.0

CTC score (0–3 scale, difficulty eating)

1.5 ± 0.7

0.5 ± 0.8

0.0004

Discussion

Overall, our findings demonstrate a high frequency of trismus in head and neck cancer patients after RT by comparison with numerous other studies. A study of 48 consecutive patients treated with curative therapy for maxillary sinus carcinoma reported that few patients (n = 3, 6%) developed trismus [6]. Other studies have found limited mouth opening (<40 mm) in 10 out of 39 patients (26%) who received 66–72 Gy [12] and 9% of a larger retrospective study of 212 patients, 21 of whom developed trismus during or after treatment [7]. The highest percentage of trismus reported was 86% in a prospective study of 58 subjects with RT to the TMJ or the pterygoid muscle, while 6 patients (10%) had no difference, and 2 patients (3%) had greater jaw opening post-RT [23]. These wide differences in the reported frequency of trismus appear to be related to variabilities in the definitions and the measurement of trismus and limited follow-up for this often late-onset oral complication. In addition, most studies were completed before the widespread use of IMRT and before the greater acceptance of concurrent or concomitant CT. The present study suggests that the incidence of trismus is not influenced by different treatment modalities. Therefore, there does not appear to be increased trismus from IMRT compared to conventional RT or from the addition of concurrent CT.

Trismus tends to develop early in the posttreatment period (although it may not appear until up to 3–6 months later), and it frequently becomes a lifelong problem. The direct effect of radiation on muscle ultimately results in fibrosis and contracture with a gradual onset noted at about 9 weeks after treatment is completed. The damage has been reported to progress for the next 9 months at a rate of 2–4% loss of interincisal opening per month, with a more protracted loss of opening in later years. At 4 years, the reduction in mean interincisal opening has been measured at 32% [21, 22]. As trismus has been reported to develop anywhere from 9 weeks to 9 months post-RT and is commonly not assessed until approximately 6 months post-RT, we compared MVD measurement of patients who had completed RT within 6 months to patients more than 6 months. We found no significant differences in MVD in these two groups in the present study, with 37.5 ± 9.8 mm in the <6 months group and 36.0 ± 9.7 mm in the >6 months group. These findings may point to the importance of earlier assessment of this oral toxicity from RT.

Limited jaw opening and function interfere with oral hygiene, speech, and nutritional intake contributing to weight loss, difficulties in examination of the oropharynx and obtaining adequate dental treatment. These factors may have a negative impact on quality of life [6], and may contribute to depression. Our study confirms the relationship between trismus and QOL deficits (i.e., opening difficulty and dietary limitations).

Several mechanical methods have been advocated for the treatment of trismus such as the use of tongue depressors and finger stretching, spring appliances, acrylic cones/wedges, and clothes pegs, but none has been shown to be effective in adequately sized and controlled studies. Furthermore, the issue of compliance with any of these approaches has not been addressed on a long-term basis.

In the present study, we also examined how many patients treated with IMRT developed trismus compared to patients treated with conventional RT. There was no significant difference in the MVD between the 16 patients treated with IMRT compared to the 24 treated with conventional RT, 38.8 ± 9.0 mm vs 33.7 ± 10.1 mm, respectively, p = 0.11. Due to the small sample size of the present study, the possibility of a type II error must not be overlooked.

Radiation oncology textbooks often fail to mention trismus as a sequela of RT in head and neck cancer patients [1, 2]. This contributes to a lack of recognition of the significance and the extent of this condition. There has been an ongoing attempt by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) to develop “late effects in normal tissue” (LENT) morbidity scales, and the National Cancer Institute consensus conferences have introduced the SOMA (subjective, objective, management, analysis) classification for late toxicity. However, both are focused on major organ and dermatological injuries, and trismus is not addressed. This should be corrected in future revisions of these scales.

The main limitation of the present study was the small sample size. A more thorough QOL assessment would provide a broader understanding of the impact of trismus on QOL. In addition, trismus was measured at only one time point, and doses to the specific muscle groups were not completed. The present study was retrospective; prospective collection of data in a large cohort study would provide a better understanding of the incidence, risk factors, progression, and severity of trismus over time.

Conclusions

Considering the high percentage of trismus in the present study and the QOL deficits associated with trismus, increased efforts for patient education and prevention and early treatment options are warranted. Larger prospective trials for the prevention and treatment of trismus are needed to improve management of this oral sequela often seen after treatment for head and neck cancer.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. Louise Kent
    • 1
    • 4
  • Michael T. Brennan
    • 1
  • Jenene L. Noll
    • 1
  • Philip C. Fox
    • 1
  • Stuart H. Burri
    • 2
  • Jane C. Hunter
    • 3
  • Peter B. Lockhart
    • 1
  1. 1.Department of Oral MedicineCarolinas Medical CenterCharlotteUSA
  2. 2.Department of Radiation OncologyCarolinas Medical CenterCharlotteUSA
  3. 3.Department of OtolaryngologyCarolinas Medical CenterCharlotteUSA
  4. 4.Department of Oral MedicineCarolinas Medical CenterCharlotteUSA

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