Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods: We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage (p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL (p < 0.01). However, a negative association between EZH2 and age (p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = −0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.

Purpose: To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

Background/Objectives: We aimed to compare the salivary gland volume changes following intensity-modulated radiation therapy (IMRT) alone versus IMRT/intensity-modulated proton therapy (IMPT) combination in oropharyngeal cancer (OPC). Methods: We retrospectively reviewed 78 OPC patients who underwent definitive RT with ipsilateral neck irradiation. RT techniques were either IMRT alone or IMRT/IMPT combination. Salivary gland volumes over time in relation to dry mouth symptom were evaluated. Results: Patients’ characteristics were well balanced between groups. The mean dose to the ipsilateral parotid gland (PG) was significantly lower in IMRT alone than in IMRT/IMPT combination, while those to the contralateral PG and submandibular glands (SMGs) were significantly higher in IMRT alone. The volume ratio of ipsilateral PG showed an initial sharp decline, reaching 0.74, and stabilized thereafter. The ipsilateral SMG showed a continuous decline until 24 months and reached approximately 0.47 by 48 months. The contralateral PG/SMG showed initial decline and subsequent recovery to the initial volume by 48 months. There were no significant differences in salivary gland volume changes between groups. Within 6 months, 60.3% of patients experienced dry mouth symptom, and the dry mouth incidence decreased to 41.0% in 12 months and remained stable thereafter. There were no significant differences in dry mouth symptom between groups. The volume reduction in the ipsilateral salivary glands was greater in patients with dry mouth symptom. Conclusions: No significant differences in salivary gland volume changes and dry mouth symptom were apparent between groups. The critical factor in salivary gland volume change was the delivered dose to the salivary glands, not the RT techniques.

This study investigated the impact of implant materials on Hounsfield Unit (HU) distortion and dose calculation accuracy in radiotherapy planning. Standardized cubic phantoms (1 cm³) of PEEK, titanium mesh, and titanium solid were fabricated and scanned using 120 kV and 140 kV extended CT protocols, with and without iterative metal artifact reduction (iMAR). HU profiles were analyzed to quantify imaging artifacts, and VMAT (Volumetric Modulated Arc Therapy) plans were generated for dosimetric verification. Absolute point dose differences and gamma pass rates (3%/3 mm, global normalization, 10% threshold) were compared between calculated and measured doses. PEEK exhibited HU variations within 3% and gamma pass rates consistently above 96%, confirming its suitability as a radiotherapy-compatible implant material. Titanium mesh demonstrated reduced HU distortion compared with titanium solid, with gamma pass rates of 97–98% meeting the clinical acceptance threshold (≥95%). In contrast, the titanium solid showed severe HU distortion with gamma pass rates as low as 89%, falling below the clinical criterion. The effect of iMAR varied: partial improvement for the titanium solid at 120 kV, deterioration at 140 kV, and negligible influence for PEEK and titanium mesh. Overall, PEEK demonstrated the most stable performance, while titanium mesh was superior to solid titanium.

Purpose This study aimed to evaluate the risk of locoregional failure after reduced dose selective neck irradiation (RD-SNI) in patients with oropharyngeal cancer (OPC).Materials and Methods Between 2008 and 2022, 342 OPC patients underwent definitive radiation therapy (with or without concurrent systemic therapy). The doses of 67.2-68.4 Gy to gross tumor volume (GTV), 56-60 Gy to high-risk clinical target volumes (CTV-HR), and 32-36 Gy to low-risk clinical target volumes (CTV-LR) were irradiated. The same target delineation and dosing policy were applied to all patients regardless of human papillomavirus (HPV) status. Oncological outcomes including failure patterns were also investigated.Results With a median follow-up of 60.3 months (range, 1.4 to 196.6 months), the 3- and 5-year locoregional control, distant metastasis-free survival, disease-free survival, and overall survival rates were 91.6%/90.7%, 83.7%/80.7%, 78.7%/74.8%, and 91.0%/85.8%, respectively. The HPV-positive patients exhibited significantly better outcomes. Treatment failure occurred in 61 patients (17.8%); 37 (10.8%) had distant metastasis, 22 (6.4%) had local failure, and eight (2.3%) had regional failure. GTV failure was significantly more common in HPV-negative patients (p=0.003). Among the 27 patients with locoregional failure, either GTV and/or CTV-HR failure occurred in 22 (81.5%), with CTV-LR failure in one (3.7%), and out-target regional (OTR) failure in five (18.5%). Only five failures (1.5%) could be attributed to the current RD-SNI policy: one CTV-LR failure (0.3%) reflecting the RD policy and four OTR failures (1.2%) reflecting the SNI policy.Conclusion Excellent oncological outcomes were achieved with the current RD-SNI policy.