Dose-Volume Correlates of Patient-Reported Trismus in Long-Term Oropharyngeal Cancer Survivors after IMRT

Abstract

The purpose of the current study was to ascertain the dose-toxicity relationship in the development of self-reported trismus in long-term survivors following intensity modulated radiation therapy (IMRT) for oropharyngeal carcinoma (OPC). Self-reported mouth opening was ascertained from a cross-sectional survey of OPC survivors treated from January 2000 to April 2014 on an IRB approved protocol. The survey is a single item inquiring on the presence and severity of trismus, based on the number of vertically stacked fingers that could be fit between the central incisors or gums. Trismus classification were coded as follows: 3 or more fingers “no trismus,” at least 2 fingers “mild” trismus, only one finger “moderate” trismus, and the inability to fit any fingers “severe” trismus. Treatment plans were restored, and dose-volume histograms (DHVs) were generated for the following regions of interest (ROI): medial pterygoid (MP), lateral pterygoid (LP) and masseter (M) muscles with ipsilateral (I) or contralateral (C) designation relative to the primary tumor. Patient and treatment characteristics were further characterized by trismus presence and severity stratification utilizing the Kruskal-Wallis and Pearson’s chi-square test for group mean and categorical variables, respectively. Mean RT dose (Dmean) of individual ROIs was calculated and compared collectively across patient subgroups based on presence of trismus using the Kruskal-Wallis test, then investigated further via Pairwise Wilcoxon rank-sum test. Recursive partitioning analysis (RPA) was used to identify dose-volume parameters associated with persistent trismus. Of 587 eligible patients, the majority (84%) were male with mean age of 57.7. The large majority of patients had cancer of the base of tongue (49%) or tonsil (45%). A total of 37.5%, 17%, 22%, and 24% of patients underwent concurrent chemoradiation (CCRT), induction chemotherapy (IC), IC + CCRT and RT alone, respectively. The mean IMRT dose of 68.12 Gy. One hundred sixty-four of the 587 (30%) participants self-reported any degree of trismus. The advanced T stage, receipt of CCRT, and higher total RT dose were associated with higher grade of trismus. Comparison of mean RT dose between trismus and no trismus subgroups was highly significant (p<0.05) across all ROIs. On multivariate analysis, there was an association between presence of trismus and mean dose to the ILP and CMP with p values of <0.01 and 0.02, respectively. RPA showed DVH-derived parameters; ILP Dmean and V27 were associated with RT-attributed persistent trismus, specifically V27 ≥ 98.6 and Dmean of 61 Gy. Dose to muscles of mastication plays a significant role in the development of trismus following RT with 30% of this large survivorship cohort of OPC patients reported trismus after IMRT. Care should be taken by clinicians to avoid unnecessarily RT dose, when feasible, to these structures in an attempt to decrease the incidence of this treatment sequelae.