Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer.

PURPOSE: To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients who received concurrent chemoradiotherapy (C-CRT). METHODS: Data of LA-NPC patients were examined before and after C-CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C-CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre-treatment Hb values and RIT status. RESULTS: Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre-C-CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. CONCLUSION: Low pre-C-CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA-NPC undergoing C-CRT.

Hemoglobin-to-platelet ratio in predicting the incidence of trismus after concurrent chemoradiotherapy.

OBJECTIVE: The significance of pre-hemoglobin-to-platelet ratio (HPR) in predicting the occurrence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma patients (LA-NPC) who received concurrent chemoradiotherapy (C-CRT). METHODS: The records of LA-NPC patients with oral examination before and after C-CRT were analyzed. Maximum mouth openings (MMO) were measured before and after C-CRT to confirm RIT status, with an MMO of ≤35 mm defined as RIT. HPR values were calculated on the first day of C-CRT. The relationship between the HPR values and RIT status was discovered using the receiver operating characteristic curve analysis. RESULTS: A total of 43 patients RIT cases among 198 individuals were diagnosed. The optimal HPR cutoff that stratified the patients into two groups was 0.54. RIT incidence was found to be significantly higher in the HPR ≤0.54 group than its HPR >0.54 counterpart(p < 0.001). Univariately T3-4 stage, mean masticator apparatus dose>57.2Gy, and pre-C-CRT MMO ≤40.7 mm were found as the other significant correlates of increased RIT rates(p < 0.05). All four variables seemed to be independently connected to greater RIT incidence in multivariate analysis (p < 0.05, for each). CONCLUSION: The risk of post-C-CRT RIT may be significantly increased when pre-treatment HPR levels are low.

The Prediction of Radiation-Induced Trismus by the Apparent Diffusion Coefficient Values of Masseter Muscles before Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinomas.

PURPOSE: Although the apparent diffusion coefficient (ADC) value from diffusion-weighted imaging can provide insights into various pathological processes, no studies have examined the relationship between the pre-concurrent chemoradiotherapy (CCRT) mean ADC (ADCmean) values of the masseter muscles and radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients. Therefore, the current research aimed to investigate the significance of pre-CCRT masseter muscle ADCmean values for predicting the RIT rates in LA-NPC patients treated with definitive CCRT. MATERIALS AND METHODS: The pre-CCRT ADCmean values of the masseter muscles and the post-CCRT RIT rates were evaluated. A receiver operating characteristic curve analysis was employed to determine the optimal ADCmean cutoff. The primary objective was to examine the relationship between the pre-CCRT masseter muscle ADCmean values and the post-CCRT RIT rates. RESULTS: Seventy-seven patients were included. The optimal ADCmean cutoff value was 1381.30 × 10-6 mm2/s, which divided the patients into two groups: an ADCmean < 1381.30 × 10-6 mm2/s (n = 49) versus an ADCmean > 1381.30 × 10-6 mm2/s (n = 28). A masseter muscle ADCmean > 1381.30 × 10-6 mm2/s was found to be associated with significantly higher RIT rates than an ADCmean < 1381.30 × 10-6 mm2/s (71.42% vs. 6.12%; p < 0.001). The multivariate analysis results confirmed a pre-CCRT masseter muscle ADCmean > 1381.30 × 10-6 mm2/s as an independent predictor of RIT. CONCLUSIONS: Our study presents the first evidence establishing a connection between elevated masseter muscle ADCmean values and higher RIT rates in LA-NPC patients following CCRT. If confirmed with further research, these findings may help to categorize the risk of RIT in these patients.

The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients.

BACKGROUND: We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). METHODS: We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. RESULTS: Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. CONCLUSION: The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Worth of pan-immune-inflammation value in trismus prediction after concurrent chemoradiotherapy for nasopharyngeal carcinomas.

OBJECTIVE: Radiation-induced trismus (RIT), one of the rare but serious side effects of concurrent chemoradiotherapy (C-CRT), is difficult to predict with high accuracy. We aimed to examine whether the pretreatment pan-immune-inflammation value (PIV) measures predict RIT in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving C-CRT. METHODS: Data of patients with LA-NPC who underwent C-CRT and had maximum mouth openings (MMO) > 35 mm were reviewed. Any MMO of 35 mm or less after C-CRT was considered RIT. All PIV values were computed using the complete blood count test results: PIV = (Platelets × Monocytes × Neutrophils) ÷ Lymphocytes. The receiver operating characteristic analysis was employed to dissect a possible association between pre-treatment PIV readings and RIT status. Confounding variables were tested for their independent relationship with the RIT rates using logistic regression analysis. RESULTS: The research comprised 223 participants, and RIT was diagnosed in 46 (20.6%) at a median time from C-CRT to RIT of 10 months (range: 5-18 months). Pre-C-CRT PIV levels and RIT rates were analyzed using receiver operating characteristic curve analysis, with 830 being the optimal cutoff (area under the curve: 92.1%; sensitivity: 87.5%; specificity: 85.5%; Youden index: 0.730). RIT was significantly more prevalent in the PIV > 830 cohort than its PIV ≤ 830 counterpart (60.3% vs. 5%; hazard ratio 5.79; P < 0.001). Multivariate logistic regression analysis revealed that advanced T-stage (P = 0.004), masticatory apparatus dose V58Gy≥%32 (P = 0.003), and PIV > 830 (P < 0.001) were independently linked with significantly elevated rates of RIT. CONCLUSION: The presence of elevated pre-C-CRT PIV is a unique biological marker that independently predicts increased RIT rates in LA-NPC undergoing C-CRT.

Decreased Rates of Radiation-induced Trismus and Lowered Mastication Structure Doses in Patients Treated for Head and Neck Cancer During the Last Two Decades.

AIMS: To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. MATERIALS AND METHODS: This study investigated two HNC patient cohorts treated with RT in 2007-2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [Cohort 1]) and 2017-2020 (volumetric-modulated arc therapy [VMAT]; n =124 [Cohort 2]). All patients underwent RT without mastication structure-sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. RESULTS: Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. CONCLUSION: Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10-20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques.

The unique CARWL score stratifies locally advanced nasopharyngeal cancer patients receiving concurrent chemoradiotherapy into risk groups for radiation-induced trismus.

PURPOSE: To determine the utility of the novel CARWL score, which integrates C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in stratifying the locally advanced nasopharyngeal carcinoma (LA-NPC) patients into significantly different radiation-induced trismus (RIT) risk groups following definitive C-CRT. PATIENTS AND METHODS: This retrospective study analyzed the medical records of 286 LA-NPC patients who received C-CRT between January 2010 and December 2022. The maximum mouth opening (MMO) was measured before the C-CRT, at 1, 3, 6, 9, and 12 months, and every 6 months after that during the follow-up. Additionally, the CAR value just before the commencement of C-CRT and SWL defined as a weight loss > 5% in the preceding six months were documented for each patient. RIT was defined as a MMO ≤ 35 mm. RESULTS: The optimal CAR cut-off was 3.03 (area under the curve: 87.3%; sensitivity: 82.6%; specificity: 80.9%, J-index: 0.635), using receiver operating characteristic (ROC) curve analysis, with RIT incidence being the event. We stratified the patients into three CARWL score groups. CARWL-0: CAR < 3.0 and WL ≤ 5.0% (N = 92), CARWL-1: CAR < 3.0 and WL > 5.0% or CAR ≥ 3.0 (N = 99), and WL ≤ 5.0% and CARWL-2: CAR > 3.0 and WL > 5.0% (N = 95). The incidence of RIT increased significantly across CARWL score groups (8.7% for CARWL-0, 23.2% for CARWL-1, and 44.2% for CARWL-2; P < 0.001). CONCLUSION: The current study indicated that the novel CARWL scoring system is efficient in precisely stratifying LA-NPC patients into distinct RIT risk groups after C-CRT.

Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.