Citations

Background: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer arising from the mucosal lining of the nasopharynx, for which systemic therapeutic options remain scarce, reflecting the limited characterization of its genomic profile. This study utilized a large patient-level genomic repository to characterize genetic alterations, identify potential therapeutic targets, and improve disease modeling in NPC. Methods: A retrospective analysis of NPC 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 identified in KMT2D (20%), TP53 (16%), CYLD (9.6%), NFKBIA (6.4%), and PIK3CA (5.6%), implicating the p53, NF-κB, and PI3K pathways in NPC development. Notably, significantly distinct mutational profiles were observed based on both sex and race, with female patients exhibiting higher frequencies of PIK3C2G, ETV6, and CDKN1B mutations and non-Asian patients showing enrichment in KDM5A, CCND2, and TP53 mutations. Conclusions: This study presents a detailed genomic profile of NPC, identifying key mutations within established cancer-associated pathways. The identification of frequently mutated pathways (p53, NF-κB, and PI3K) suggests potential targets for novel therapies. Furthermore, distinct mutational landscapes in female and Asian NPC patients offer possibilities for precision therapeutic interventions.

The role of second-look endoscopy and debridement (SLED) remains uncertain in children due to the perceived need for additional general anesthesia following their initial functional endoscopic sinus surgery (FESS) while mitigating risks and healthcare costs. This comprehensive review synthesizes current evidence on SLED in children, focusing on its practice pattern and treatment outcomes. This review was designed and performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Protocol. Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed. A total of 53 relevant, unique articles were initially identified; 12 articles were ultimately deemed appropriate for inclusion in final analysis. The most common indication for FESS was chronic rhinosinusitis or recurrent sinus infections while that for SLED under general anesthesia varied from institutional practice patterns to surgeon preference. No meaningful comparison of outcomes was possible as the “success rates” of FESS with or without SLED were largely based on unvalidated questionnaires and equally subjective surgeon assessments. Even when looking at outcomes based on revision rates, FESS with SLED was considered successful between 60.5% and 95.6% of the time, with a mean of 84.2%, while FESS without SLED was successful between 71.0% to 96.4% of the time, with a mean of 86.3%. However, no randomized, controlled studies were available in the pediatric literature pertaining to FESS with or without SLED. Moreover, it became apparent that previous conclusions on the utility of SLED were based on the outcomes of FESS following one single SLED under general anesthesia vs. no SLED. As such, there is an unmet need to examine the utility of serial, office-based SLED in children to better elucidate its utility in pediatric FESS.

AbstractObjectiveThe primary goal of this study was to measure health‐state utility values (HUVs) in patients with facial paralysis before and after treatment. A secondary objective was to compare these values with those of other chronic diseases and currently available treatments.Study DesignA retrospective chart review.SettingA tertiary medical center.MethodsAdults with flaccid and non‐flaccid facial paralysis were included. Baseline demographics, medical comorbidities, facial paralysis history, treatment details, and disease‐specific quality‐of‐life scores were collected. Utility values were derived using the Short‐Form 6D health index at baseline and after treatment.ResultsThe mean baseline Short‐Form 6D utility value for patients with facial paralysis (n = 134) was 0.73 (± 0.14) (95% confidence interval [CI]: 0.71‐0.75). Baseline utility values significantly correlated with disease‐specific quality of life as measured by the Facial Clinimetric Evaluation Scale (r = 0.400; P < .001), but not with Sunnybrook Facial Grading Scale or Synkinesis Assessment Questionnaire scores. Post‐treatment utility values showed a mean improvement of 0.03 (95% CI: −0.01 to 0.08; P = .14) in the overall cohort. The flaccid group showed a greater average improvement compared to the non‐flaccid group (0.05 [± 0.17] vs 0.02 [± 0.17]; P = .62).ConclusionPatients with flaccid and non‐flaccid facial paralysis reported HUVs that were significantly lower than the US population norm. Treatment improved utility values in both groups. These findings provide initial data for future cost‐effectiveness analyses of surgical and non‐surgical treatment options for facial paralysis.

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.