Comment on: VMAT with CCC Algorithm Optimizes Trismus Prevention: Dose–Response Analysis of Jaw Muscles Dmean and Dmax in T3–T4 Nasopharyngeal Carcinoma

Dear Editor,

We read with great interest the recent article by Chen and colleagues, which sought to establish dose-response relationships and propose clinically actionable thresholds for the prevention of radiation-induced trismus (RIT) using volumetric modulated arc therapy (VMAT) with collapsed-cone convolution (CCC) dose calculation. ¹ The authors deserve commendation for addressing a clinically under-recognized late complication of nasopharyngeal carcinoma (NPC) therapy, RIT, and for their pioneering attempt to derive preliminary dose-response thresholds for masticatory and suprahyoid musculature. Their focus on preserving functional organs represents a significant step toward patient-centered radiotherapy planning.

The first point of paramount significance lies in the study's novel inclusion of the jaw-opening muscles—the digastric, mylohyoid, and geniohyoid—as organs at risk (OARs). Historically, RIT research has predominantly emphasized the jaw-closing muscles (temporalis, masseter, and pterygoids), with most dose-constraint recommendations extrapolated from oropharyngeal IMRT cohorts rather than advanced nasopharyngeal carcinoma (NPC) populations. ² By identifying the digastric Dmean (≤26 Gy) and mylohyoid Dmean (≤28 Gy) as discriminatory parameters, the authors underscore the critical functional contribution of these smaller but indispensable muscles. This finding aligns with recent reports showing that the inferomedial muscle groups receive disproportionately higher incidental doses due to elective nodal coverage and tumor extension patterns in T3–T4 NPCs. ³ However, the authors’ reliance on a subjective “two-finger insertion” test for RIT assessment, rather than an objective interincisal distance measurement (typically <35 mm), may have introduced inter-observer variability and potentially underestimated mild-to-moderate functional impairment. ⁴ Incorporating standardized, quantitative evaluation methods would enhance measurement reliability and facilitate cross-study comparisons. Nevertheless, integrating jaw-opening muscle constraints into VMAT optimization may complement existing temporomandibular joint (TMJ)-based guidelines and lead to measurable improvements in post-treatment jaw mobility. Should these observations be confirmed by further prospective validation, such anatomical refinement could provide a foundation for next-generation contouring protocols and adaptive replanning strategies aimed at mitigating RIT.

The second key issue, however, concerns the methodological limitations that challenge the interpretation of the reported dose-response relationships. The study's cohort comprised exclusively T3–T4 NPC cases, in which high baseline trismus risk and tumor proximity to suprahyoid musculature create a “ceiling effect.” Consequently, the observed negative regression coefficient between digastric D-mean and RIT probability likely reflects confounding by indication: patients with greater tumor burden inherently receive higher muscle doses and are simultaneously more predisposed to RIT from tumor invasion and fibrosis.^3,5 The authors correctly acknowledge this paradox and the need for validation in larger, stage-diverse, prospective cohorts. Complementary use of objective mouth-opening measurements (eg, interincisal distance measured with a caliper) and multivariate correction for tumor extent, nodal dose, and concurrent toxicity indices would strengthen causal inference. Moreover, penalized regression or competing-risks modeling may improve robustness, given the modest sample size and intercorrelated dosimetric parameters.

In conclusion, Chen and colleagues advance the field by extending dosimetric evaluation to the functional jaw-opening unit and suggesting actionable mean-dose thresholds that could feasibly integrate into clinical VMAT planning. Future studies should validate these findings using standardized objective endpoints and incorporate functional imaging or radiomic biomarkers of muscular fibrosis.