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This article in the Journal of Neurological Surgery. Part B. Skull Base discusses the use of an endoscopic endonasal approach for resecting sellar germ cell tumors, which are rare pediatric intracranial neoplasms. The video presentation details the surgical steps involved in the resection of a persistent sellar tumor in a 10-year-old female who had undergone chemotherapy as per clinical trial guidelines. The key surgical steps highlighted include sphenoid body drill out, tumor resection, and reconstruction with a nasoseptal flap. [Extracted from the article]

The article "Decoding Mucosal Melanomas: Genetic Profiling for Advanced Therapeutic Strategies" published in the Journal of Neurological Surgery. Part B. Skull Base discusses the rare and aggressive nature of head and neck mucosal melanomas (HNMM). The study explores the somatic mutational landscape of HNMM patients using the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. The most common mutations identified in HNMM patients include NRAS, NF1, TERT, ROS1, KIT, TP53, BRAF, KMT2C, and KMT2D, with NRAS being the most prevalent. Understanding these genetic alterations may lead to the development of targeted therapies for HNMM. [Extracted from the article]

The article explores common mutations in nasopharyngeal carcinomas (NPC) and their potential for targeted therapy development. It highlights the prevalence of KMT2D, TP53, and CYLD mutations in NPC patients, with implications for treatment strategies. The study also discusses ongoing clinical trials for PD-1/PDL-1 checkpoint inhibitors and the need for further research on targeted therapies based on the identified mutations. [Extracted from the article]

The article explores genetic alterations in olfactory neuroblastoma (ONB), a rare malignant neoplasm with limited information on its somatic mutational landscape. The study aims to identify common mutations and genetic alterations to support the development of targeted therapies for ONB. Results show that TP53 and FRK mutations are prevalent in ONB, with FRK mutations predominantly consisting of in-frame deletions or alterations affecting the R181 protein. Understanding these mutational landscapes may guide drug development and accelerate the development of novel ONB-targeted therapy. [Extracted from the article]

The article "Comprehensive Genomic Profiling of Sinonasal Carcinomas" explores the somatic mutational landscape of sinonasal cancers, including squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. The study utilized the AACR Project GENIE database to identify common mutations and genetic alterations in sinonasal cancer patients. TP53, PIK3CA, and KMT2D were found to be the most common mutations across different subtypes, suggesting potential targets for therapy such as tazemetostat and cetuximab. The research aims to advance the development of novel preclinical models for testing targeted therapies in sinonasal carcinomas. [Extracted from the article]

The article "Genomic Characterization of Chordomas: Insights from a National Database" explores the somatic mutational landscape of chordoma patients using the AACR Project Genomics Evidence Neoplasia Information Exchange database. The study found significant mutations in genes such as PBRM1, ARID1A, TERT, TP53, SETD2, and NOTCH2, with potential co-occurrence patterns that may guide the development of novel therapies. While there are limited clinical trials for targeted therapies against these mutations, understanding these profiles could improve outcomes for chordoma patients. The research did not find significant differences between pediatric and adult patients in terms of clinical or genomic characteristics. [Extracted from the article]

Simple Summary: Chordoma is a rare, slow-growing tumor arising from remnants of the embryonic notochord. This study investigates genomic alterations in chordoma using a large national patient-level repository, the AACR Project GENIE. The goal was to identify mutations in key genes such as PBRM1, ARID1A, TERT, and TP53, which may influence tumor behavior, treatment response, and clinical outcomes. These findings contribute to an improved understanding of chordoma biology, highlighting potential biomarkers and therapeutic targets. Background: Chordoma is a rare primary tumor originating from embryonic notochord remnants, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to characterize the genetic alterations in chordoma using a large national patient-level genomic repository, the AACR Project GENIE, to identify potential therapeutic targets and improve disease modeling. Methods: A retrospective analysis of chordoma samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set at p < 0.05. Results: Frequent mutations were observed in genes associated with SWI/SNF complex affecting chromatin remodeling (SETD2, PBRM1, ARID1A). Mutations were also common among the TERT promoter regions, and cell cycle regulation (CDKN2A). Significant co-occurrences were identified among PBRM1, BRCA2, and KMT2D mutations. CDKN2A/B deletions were enriched in metastatic tumors, and pediatric cases demonstrated distinct mutation profiles compared to adults. Conclusions: This study provides a genomic profile of chordoma, identifying key mutations and potential therapeutic targets. These findings highlight the roles of chromatin remodeling and cell cycle pathways in chordoma biology, offering insights for future precision medicine approaches and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm3 (range, 1-117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, 18F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood 10B ratio was 3.5 (range, 2.0-8.7). Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response. This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer. [ABSTRACT FROM AUTHOR]

Author(s): Shohei Nakatani [sup.1], Mitsuru Ida [sup.1], Yuu Tanaka [sup.1], Naoko Okamoto [sup.1], Xiaoying Wang [sup.1], Hitomi Nakatani [sup.1], Mariko Sato [sup.1], Yusuke Naito [sup.1], Masahiko Kawaguchi [sup.1] Author Affiliations: [...], Purpose Patient-reported outcomes after surgery and anaesthesia have recently attracted attention. A recent systematic review and a consensus guideline recommend that patients' recovery can be adequately measured using the quality of recovery-15 (QoR-15) during the perioperative period; however, the Japanese version of the QoR-15 (QoR-15J) is not available. We aimed to translate the QoR-15 into Japanese and assess its validity. Methods After translating into Japanese, 205 patients who underwent various types of surgery under general anaesthesia were enrolled in the study. QoR-15J was evaluated before surgery and 24 h and 48 h after surgery. Additionally, 30 patients answered the QoR-15J at 25 h after surgery. We assessed the feasibility, reliability, validity, and responsiveness of the QoR-15J. Results One patient who did not undergo surgery and two patients who were discharged within 24 h were excluded. One hundred and eighty-seven patients answered the QoR-15J at 24 h after surgery (completion rate, 92.6%) and 183 patients with complete data were included in the final analysis. The Cronbach's alpha coefficient for internal reliability and Spearman rank correlation coefficient for test-retest reliability were 0.84 and 0.91, respectively. The Cohen effect size for all items was 1.42. Conclusions QoR-15 was translated into Japanese and the Japanese version's validity was assessed in patients undergoing various types of surgery under general anaesthesia. Our results suggest that QoR-15J is feasible, reliable, valid, and responsive.

Author(s): Mariko Sato [sup.1], Mitsuru Ida [sup.1], Yusuke Naito [sup.1], Masahiko Kawaguchi [sup.1] Author Affiliations: (1) grid.410814.8, 0000 0004 0372 782X, Department of Anesthesiology, Nara Medical University, , 840 Shijo-cho, [...], Purpose The development of a preoperative anesthesia clinic (PAC) can reduce the number of surgical cases canceled on the day of surgery. However, there are only a few studies on the details of cancellations in the operating room. This study aimed to assess the incidence and reasons for surgical cases canceled from admission to the operating room to the start of surgery. Methods This retrospective study involved patients who underwent anesthesia performed by anesthesiologists between January 2008 and March 2019. We focused on case cancellations occurring from admission to the operating room to the start of surgery. We classified the reasons for cancellation into four categories: insufficient preoperative anesthetic assessment, anesthetic issues/complications, medical problems related to patients' comorbidity, and others. We evaluated and compared the incidence and reasons for cancellation before and after the establishment of a PAC. Results Among a total of 48,089 scheduled surgery, 18 (0.037%, 95% confidence interval 0.019-0.055) cases were canceled. The total cancellation rate before and after the development of a PAC was not statistically significant (0.051% vs 0.022%, P = 0.10). Before the development of a PAC, the most common reason was insufficient preoperative anesthetic assessment in 46.1%, followed by anesthetic issues/complications (23.0%), medical problems related to patients' comorbidity (15.3%), and others (15.3%). After the development of a PAC, surgeries were canceled for medical problems related to patients' comorbidity (80.0%) and anesthetic issues/complications (20.0%). Conclusions The total incidence of surgical case cancellations was 0.037%. Before and after the development of a PAC, cancellation rate was comparable. After the development of a PAC, none case were canceled due to insufficient preoperative anesthetic assessment.

Although histopathological diagnosis is essential in decision of therapeutic strategy for gliomas, sometimes the tumors diagnosed in one histological entity show thoroughly different clinical courses. This phenomenon is believed to be due primarily to the presence of the genetic subgroup. In fact, relationship between treatment response and certain genetic characteristics is indicated (e.g. better chemosensitivity in glioma with losses of 1p/19q (−1p/19q)). It is highly likely that genetic classification of glioma is useful to select the adjuvant treatment. Additionally, gain of 7q (+7q) and −1p/19q are early events in 2 distinct tumor lineages, astrocytic tumors and oligodendroglial tumors, respectively, and these tumors obtain additional genetic aberration (−9p, 10q) with tumor progression. On the other hand, concerning the tumors without +7q or −1p/19q, little is known about clinically important genetic aberration. Therefore the study on such tumors could provide useful information for the prognosis prediction and the determination of treatment strategy. METHODS: We selected 39 cases of gliomas without +7q or −1p/19q from 200 adult supratentorial glioma cases surgically treated and analyzed chromosomal DNA copy number aberrations (CNAs) by comparative genomic hybridization (CGH) from 2005 to 2012. We correlated clinical features of these tumors with histological characteristics, CNAs and IDH1 status. RESULTS: The clinical course of gliomas without +7q or −1p/19q was not correlated with additional genetic aberration of -9p or 10q, which have been known as genetic markers for poor prognosis, and absence of +7q or −1p/19q was maintained at the time of recurrence. The tumors without +7q or −1p/19q showed relatively favorable prognosis although mutation of IDH1 was infrequent in these tumors (35.8 %). CONCLUSION: The gliomas without +7q or −1p/19q have clinical features distinct from the +7q and −1p/19q gliomas. Prognostic markers for each subgroups could help establish therapeutic strategy against the tumor. DNA methylation is a mechanism altering the normal state of cells implicated in many cancers. Currently the methylation status of MGMT is one of the most widely utilized clinical genetic tests performed on glioblastoma multiforme (GBM). While several global gene expression signatures have been developed, it is unclear if genome-wide DNA methylation signatures can predict prognosis in cancer. We used a computational algorithm (MethylMix) to analyze genome-wide DNA methylation in GBM data obtained from The Cancer Genome Atlas (TCGA). MethylMix identified a set of driver genes that met criteria for being both differential and functional. Differential refers to a difference in cancer methylation compared to normal tissue; functional refers to having a significant correlation with matched gene expression changes. We then used these MethylMix driver genes to build multivariate models of overall survival using linear regression and validated these models in independent data sets. Applying MethylMix and linear regression we identified a novel methylation signature predictive of overall survival, which we here define as the GLIOMETH signature. Interestingly, GLIOMETH did not include MGMT, suggesting that MGMT methylation is not essential to predict prognosis in GBM. GLIOMETH was prognostically significant even in a multivariate analysis with known prognostic covariates, including MGMT methylation. We validated GLIOMETH in two external DNA methylation data sets and two gene expression data sets, using a leveraging technique predicting methylation in terms of gene expression, showing also a significant survival correlation. Differential and functional DNA methylation is predictive of overall survival in GBM independent of known prognostic factors. We identified GLIOMETH as a DNA methylation signature that is predictive of overall survival in GBM, outperforming MGMT methylation. The GLIOMETH model validated across multiple independent DNA methylation and gene expression validation data sets demonstrating its robustness as an independent predictor of prognosis in GBM. Recent next-generation genomic studies of medulloblastoma have revealed an unexpected and overwhelming convergence of somatic alterations affecting chromatin-modifying genes. Estimates informed by next-generation sequencing implicate that at least one third of all medulloblastomas have somatic mutations in a chromatin modifier, including those targeting histone methyltransfereses, histone demethylases, and related chromatin modulators that collectively function to influence chromatin conformation associated gene expression states. These mutations occur across all four medulloblastoma subgroups although different sets of genes appear to be selectively altered in a subgroup-specific manner. Despite the abundance of evidence implicating deregulation of chromatin modifiers as a key event in medulloblastoma pathogenesis, the medulloblastoma epigenome remains largely unexplored, and studies cataloguing histone modification states on a genome-wide scale have yet to be reported. To comprehensively investigate the histone code in medulloblastoma and the consequences associated with mutations affecting histone-modifying genes, we have performed ChIP-sequencing on a set of well-characterized primary medulloblastoma specimens. Histone marks examined in this study include the six modifications mandated by the International Human Epigenome Consortium (IHEC), including H3K4me3, H3K9me3, H3K27me3, H3K27ac, H3K4me1 and H3K36me3. Chromatin isolates from primary fresh-frozen tissues representative of each medulloblastoma subgroup were immunoprecipitated with the indicated antibodies and sequenced with a HiSeq Illumina sequencer to obtain at least 10 million unique reads per ChIP experiment. Peak calling was performed using multiple publicly available tools and data integrated with existing ENCODE data for the same histone marks. Inter-subgroup comparisons of histone modification states revealed a wealth of distinguishing genomic regions that were highly correlated with alternative patterns of gene expression existing between the subgroups. Moreover, integration with existing mutational profiles demonstrated aberrant chromatin states that could be linked to underlying mutations in select chromatin modifiers. Ongoing work will focus on expanding the cohort and integration with all levels of ‘omic data.

Simple Summary: In post-irradiated recurrent head and neck cancer (R-HNC), the treatment safety margin is limited by accumulated toxicity. Despite the development of aggressive curative treatment methods, such as reirradiation with photon or particle beam therapy with or without chemotherapy, sufficient clinical outcomes have not been achieved in various prospective trials due to the limitations imposed by toxicity. Boron neutron capture therapy (BNCT), with its selective cell-by-cell dose delivery, may be an effective and safe treatment option for patients with a prior radiotherapy history, as the previous Phase II trial of BNCT in unresectable locally recurrent or locally R-HNC has shown encouraging results. In this study, we analyzed the results of a Japanese nationwide post-marketing surveillance of BNCT for R-HNC conducted under the national health insurance system and found that toxicity was well-tolerated with preferable efficacy. BNCT is suggested to be a promising treatment option in post-irradiated R-HNC. Background: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). Methods: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. Results: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. Conclusions: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting. [ABSTRACT FROM AUTHOR]