Comprehensive Molecular Genetic Analysis in Glioma Patients by Next Generation Sequencing.

BACKGROUND: Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies. METHODS: We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools. RESULTS: A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials. CONCLUSION: We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.

Establishment of tumor microenvironment-preserving organoid model from patients with intracranial meningioma.

BACKGROUND: Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment. METHODS: The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing. RESULTS: MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression. CONCLUSION: Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.

Salivary ultrasonography and histopathologic evaluation of secondary Sjögren's syndrome in rheumatoid arthritis patients.

Novel modalities, such as salivary ultrasonography (SGUS) and shear wave elastography (SWE), have previously been introduced to evaluate Sjögren's syndrome (SS). However, in secondary SS (sSS), the diagnostic performance of SGUS and its relationship with clinicopathological characteristics have not yet been clearly defined. In this study, we aimed to investigate sSS in RA patients using SGUS and SWE and sought to determine its pathological correlations. Thirty-one RA patients who presented with sicca symptoms were included to be evaluated on SS, and were compared with 18 primary SS (pSS) patients. All subjects were assessed through SGUS, SWE, and conventional diagnostic approaches for SS, including minor salivary gland biopsy (MSGB). In SGUS evaluation, two separate scoring systems, suggested by Hocevar and OMERACT, were used. Among 31 RA patients with sicca symptoms, 19 (61.2%) were diagnosed as sSS. Similar to pSS, SGUS showed good diagnostic performance (sensitivity 68.4% and 78.9%, and specificity 91.7% and 75.0% for Hocever and OMERACT, respectively) in differentiating sSS from RA patients with simple sicca symptoms. The sSS and pSS patients exhibited significantly higher lymphoid infiltration areas in MSGB than RA patients without SS. Focus score and lymphoid infiltration areas correlated well with sonographic severity. Severity of fibrosis in MSGB showed better positive correlation with SWE than with SGUS. Similar to pSS, SGUS shows good diagnostic performance for sSS in RA patients. SWE reflects histopathologic chronicity of MSGB well in both pSS and sSS.

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor.

BACKGROUND: The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). METHODS: A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary's Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. RESULTS: Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. CONCLUSIONS: We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor's molecular pathology.

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea.

BACKGROUND: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. METHODS: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. RESULTS: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. CONCLUSIONS: Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Periodontitis deteriorates renal fibrosis and macrophage infiltration in rats with chronic kidney disease.

OBJECTIVE: The objective of this study was to examine the effect of periodontitis on renal function and morphology in rats with or without nephrectomy (Nx)-induced chronic kidney disease (CKD). METHODS: Rats were divided into sham surgery (Sham), Sham with tooth ligation (ShamL), Nx, and NxL groups. Periodontitis was induced by tooth ligation at 16-week olds. Creatinine, alveolar bone area, and renal histopathology were analyzed at 20-week olds. RESULTS: Creatinine did not differ between the Sham and ShamL groups or between the Nx and NxL groups. The ShamL and NxL groups (both p = 0.002) had less alveolar bone area than the Sham group. The NxL group had fewer glomeruli than the Nx group (p < 0.000). The periodontitis groups demonstrated more tubulointerstitial fibrosis (Sham vs. ShamL p = 0.002, Nx vs. NxL p < 0.000) and macrophage infiltration (Sham vs. ShamL p = 0.002, Nx vs. NxL p = 0.006) than the groups without periodontitis. Only the NxL group had greater renal TNFα expression than the Sham group (p < 0.003). CONCLUSIONS: These suggest that periodontitis increases renal fibrosis and inflammation in the presence or absence of CKD but does not affect renal function. Periodontitis also increases TNFα expression in the presence of CKD.

Alveolar bone and tibia responses to hormonal and mineral abnormalities in rats with chronic kidney disease: A pilot study.

OBJECTIVES: As the impact of chronic kidney disease (CKD) severity on different bone types remains unclear, we induced increasing levels of CKD severity in a rat model and investigated hormone and mineral levels as well as alveolar and tibia bone histomorphology. METHODS: Rats were divided into sham operation (sham), 4/6 nephrectomy (4/6Nx), 5/6Nx, and 4/6Nx with hyperphosphorous (HP) diet (4/6NxHP). At week 20, BUN, FGF23, PTH, and P were estimated in plasma. Bone parameters were evaluated by microCT, and osteoclasts and osteoid areas were evaluated by TRAP and H&E stains, respectively. RESULTS: The 4/6NxHP and 5/6Nx groups had elevated PTH, and the 4/6NxHP group alone had elevated P. Compared to the 4/6Nx group, the 4/6NxHP group demonstrated increased FGF23 and P. In the alveolar bone, the 4/6NxHP group had reduced bone volume and BMD compared to the sham and 4/6Nx groups. In the tibia cortical bone, bone surface density was higher in the 4/6NxHP group compared to the sham group. Tibia cortical bone volume was negatively correlated with FGF23 and P. Moreover, alveolar bone volume was negatively correlated with FGF23, PTH, and P. CONCLUSIONS: Our results demonstrate that hormone and mineral levels vary with CKD severity, and alveolar bone loss strongly correlates with these hormone and mineral alterations.

Prediction of BRAF V600E variant from cancer gene expression data.

Background: BRAF inhibitors have been approved for the treatment of melanoma, non-small cell lung cancer, and colon cancer. Real-time polymerase chain reaction or next-generation sequencing were clinically used for BRAF variant detection to select who responds to BRAF inhibitors. The prediction of BRAF variants using gene expression data might be an alternative test when the direct variant sequencing test is not feasible. In this study, we built a prediction model to detect BRAF V600 variants with mRNA gene expression data in various cancer types. Methods: We adopted a penalized logistic regression for the BRAF V600E variants prediction model. Ten times bootstrap resampling was done with a combined target variable and cancer type stratification. Data preprocessing included knnimputation for missing value imputation, YeoJohnson transformation for skewness correction, center, and scale for standardization, synthetic minority over-sampling technique for class imbalance. Hyperparameter optimization with a grid search was undertaken for model selection in terms of area under the precision-recall. Results: The area under the curve of the receiver operating characteristic curve on the test set was 0.98 in thyroid carcinoma, 0.90 in colon adenocarcinoma, and 0.85 in cutaneous melanoma. The area under the precision-recall of the test set was 0.98 in thyroid carcinoma, 0.71 in colon adenocarcinoma, and 0.65 in cutaneous melanoma. Conclusions: Our penalized logistic regression model can predict BRAF V600E variants with good performance in thyroid carcinoma, cutaneous melanoma, and colon adenocarcinoma.

Prediction of homologous recombination deficiency from cancer gene expression data.

OBJECTIVE: Homologous recombination deficiency (HRD) is the main mechanism of tumorigenesis in some cancers. HRD causes abnormal double-strand break repair, resulting in genomic scars. Some scoring HRD tests have been approved as companion diagnostics of polyadenosine diphosphate-ribose polymerase (PARP) inhibitor treatment. This study aimed to build an HRD prediction model using gene expression data from various cancer types. METHODS: The cancer genome atlas data were used for HRD prediction modeling. A total of 10,567 cases of 33 cancer types were included, and expression data from 5128 out of 20,502 genes were included as predictors. A penalized logistic regression model was chosen as a modeling technique. RESULTS: The area under the curve of the receiver operating characteristic curve of HRD status prediction was 0.98 for the training set and 0.93 for the test set. The accuracy of HRD status prediction was 0.93 for the training set and 0.88 for the test set. CONCLUSIONS: Our study suggests that the HRD prediction model based on penalized logistic regression using gene expression data can be used to select patients for treatment with PARP inhibitors.

Importance of lymph node ratio in HPV-related oropharyngeal cancer patients treated with surgery and adjuvant treatment.

OBJECTIVES: The pathologic nodal stage of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) patients is classified according to the number of lymph nodes (LNs), as revised in 2018. Previous studies showed that the LN ratio (LNR) could be also a significant prognostic factor in head and neck cancer, but there are few studies on the LNR in HPV-related [HPV(+)] OPC. The aim of the present study was to analyze the predictive value of the LNR for survival and recurrence in HPV(+) OPC patients. MATERIALS AND METHODS: HPV(+) OPC patients treated with surgery with or without postoperative radiotherapy from January 2000 to March 2019 were evaluated. The patients were divided into two sets of three groups, according to LN numbers based on pathologic nodal stages, and LNRs by a cutoff value of 0.05. The medical records were reviewed, and the overall survival (OS), disease-free survival, locoregional recurrence, and distant metastasis incidence were analyzed. RESULTS: Ninty patients were included and the median follow-up period was 38.2 months. There were no significant differences in OS in the LN number groups. However, there was a significant difference in OS in the LNR groups (P = 0.010). The incidence of distant metastasis in the LNR groups was significantly different (P = 0.005). CONCLUSION: The LNR in HPV(+) OPC patients may be a more useful tool to predict survival and distant metastasis than the LN number. Additional research and consensus on surgical pathology are needed before applying the LNR to adjuvant treatment decisions and pathologic nodal staging.

Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma.

Background: A high platelet−lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil−lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28−4.36 for DSS; HR 1.80, 95% CI 1.06−3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC.

Clinical feasibility of modified procarbazine and lomustine chemotherapy without vincristine as a salvage treatment for recurrent adult glioma.

Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.

Lack of Association between Chlamydophila psittaci and Ocular Adnexal MALT Lymphoma in Korean Patients-Is the Geographic or Genetic Difference Significant?

Clamydophila psittaci (C. psittaci) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort (n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci-positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics.

OBJECTIVES: To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) METHODS: Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. RESULTS: This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72-0.80; p=0.04), stage (iAUC, 0.70-0.79; p=0.001), and combined models (iAUC, 0.76-0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. CONCLUSION: Integration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

Prognostic value of MRI-measured tumor thickness in patients with tongue squamous cell carcinoma.

This study aimed to assess the prognostic value of MRI-measured tumor thickness (MRI-TT) in patients with tongue squamous cell carcinoma (SCC). This single-center retrospective cohort study included 133 pathologically confirmed tongue SCC patients between January 2009 and October 2019. MRI measurements of tongue SCC were based on axial and coronal T2-weighted (T2WI) and contrast-enhanced T1-weighted (CE-T1WI) images. Two radiologists independently measured MRI-TT. Intraclass correlation coefficients (ICC) were calculated for inter-rater agreements. Spearman's rank correlation between MRI-TT and pathologic depth of invasion (pDOI) was assessed. Cox proportional hazards analyses on recurrence-free (RFS) and overall survival (OS) were performed for MRI-TT and pDOI. Kaplan-Meier survival curves were plotted with log-rank tests. The intra- and inter-rater agreements of MRI-TT were excellent (ICC: 0.829-0.897, all P < 0.001). The correlation between MRI-TT and pDOI was good (Spearman's correlation coefficients: 0.72-0.76, P < 0.001). MRI-TT were significantly greater than pDOI in all axial and coronal T2WI and CE-T1WI (P < 0.001). In multivariate Cox proportional hazards analysis, MRI-TT measured on axial CE-T1WI yielded a significant prognostic value for OS (hazards ratio 2.77; P = 0.034). MRI-TT demonstrated excellent intra- and inter-rater agreements as well as high correlation with pDOI. MRI-TT may serve as a prognostic predictor in patients with tongue SCC.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1.

BACKGROUND: There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As 'diffuse midline glioma' was recently defined, and there was no international guideline, trials and guidelines of 'diffuse intrinsic pontine glioma' or 'brain stem glioma' were thoroughly reviewed first. RESULTS: The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma's protocol is recommended. CONCLUSION: The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1.

BACKGROUND: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. RESULTS: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. CONCLUSION: The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

Analysis of PET parameters as prognosticators of survival and tumor extent in Oropharyngeal Cancer treated with surgery and postoperative radiotherapy.

BACKGROUND: Positron-emission tomography (PET) is widely used to detect malignancies, but consensus on its prognostic value in oropharyngeal cancer has not been established. The purpose of this study was to analyze the PET parameters associated with tumor extent and survival in resectable oropharyngeal cancer. METHODS: The PET parameters in oropharyngeal cancer patients with regional node metastasis who underwent surgery and postoperative radiotherapy between January 2005 and January 2019 were analyzed. We calculated the SUVmax, tumor-to-liver ratio (TLR), metabolic tumor volume (MTV, volume over SUV 2.5), and total lesion glycolysis (TLG, MTV x mean SUV) of the primary lesion and metastatic nodes. Histologic findings, patient survival, and recurrence were reviewed in the medical records. RESULTS: Fifty patients were included, and the PET parameters were extracted for 50 primary lesions and 104 nodal lesions. In the survival analysis, MTV and TLG of the primary lesions showed significant differences in overall survival (OS) and recurrence-free survival (RFS). In the multiple regression analysis, TLG of the primary lesion was associated with the depth of invasion (DOI). MTV of the nodes was a significant factor affecting extranodal extension (ENE). CONCLUSIONS: PET parameters could be related with OS, RFS, DOI of the primary tumor, and ENE. PET would be expected to be a useful diagnostic tool as a prognosticator of survival and pathologic findings in oropharyngeal cancer.

Proposal of a scoring system for predicting pathological risk based on a semiautomated analysis of whole slide images in oral squamous cell carcinoma.

BACKGROUND: The study aimed to evaluate the risk factors based on pathological findings comprehensively in oral squamous cell carcinoma (OSCC) using image analysis. METHODS: Scanned images of hematoxylin and eosin-, pan-cytokeratin-, CD3-, and CD8-stained slides of OSCC cases from 256 patients were analyzed, and six variables were obtained including the tumor-stroma ratio, tumor budding per tumor bed area, and tumor infiltrating lymphocytes-associated variables. We determined the "score" of all cases based on the variables, and all cases were classified into low-, intermediate-, and high-risk groups. RESULTS: A significant difference in prognosis was confirmed between the risk groups (p < 0.001), and even when evaluated within different tumor-node-metastasis (TNM) stages, the high-risk groups were associated with poor survival. CONCLUSIONS: We report our work on a possible descriptive model that can predict prognosis based on pathological and imaging findings regardless of the TNM stage.