Dose-volume factors correlating with trismus following chemoradiation for head and neck cancer

Abstract

Background: To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers.

Material and methods: All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations.

Results: Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearman's rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was with V68Gy to the ipsilateral medial pterygoid (Rs = 0.29).

Conclusion: Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

Conflict of interest statement

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Figures

Figure 1

The distribution of the mean dose for each muscle structure. The box plot shows the median, 25th and 75th percentiles. The whiskers indicate the 95% level and values outside that range are shown as red points.

Figure 2

Logistic fit based on mean dose for each muscle structure. There is significant correlation between trismus and mean dose to all muscles. Solid line indicates the best fit of the logistic model while the dashed lines indicate the 95% confidence level. Error bars on the x-axis corresponds to one standard deviation while the error bars on the y-axis represent the 95% confidence level using the exact binomial distribution.

Figure 3

Lyman-Kutcher-Burman model for trismus. The incidence of trismus as a function of the gEUD for the MI (A) and MPI (B). Solid line indicates the maximum-likelihood fit of the Lyman-Kutcher-Burman (LKB) to the original data. Dashed lines indicate the 95% significance level of the fit using a boot-strapped pseudo dataset derived from the original data. Both models clearly indicate that the correlation is driven by the higher doses, with a values much greater than 1, which, in contrast, would indicate a preference for the mean dose.

Figure 4

Combined gEUD scatter plot with MI versus MPI. A higher incidence of trismus is clearly observed for gEUD value of 50 Gy for MI (a = 6.8) and 65 Gy for MPI (a = 8.7) as indicated by the dashed lines. Red circles indicate patients who developed trismus (G ≥ 1) while blue dots represent patients without complications.