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ImportanceCutaneous squamous cell carcinoma (CSCC) risk stratification is central to management, and physicians rely on tumor staging systems to estimate risk. The Brigham and Women’s Hospital (BWH) T staging system predicts risk based on 4 tumor risk factors (RFs). However, stage is not precisely associated with the number of RFs, as BWH stage T2b includes CSCCs with 2 and 3 RFs.ObjectiveTo determine how RF number is associated with the risk of recurrence, metastasis, and disease-related death.Design, Setting, and ParticipantsThis retrospective multination cohort study of CSCCs diagnosed between October 1, 1991, and July 19, 2023, was conducted at 12 centers in the US (10), Spain (1), and Brazil (1). Invasive CSCCs with confirmed negative margins longer than 14 days were included. Tumors were excluded if they were metastatic at presentation or received adjuvant therapy. Data were analyzed from October 2023 to August 2024.Interventions or ExposuresCSCCs were stratified by the number of the following RFs (0, 1, 2, 3, or 4): a diameter of 2 cm or larger, poorly differentiated histology, tumor extension beyond subcutaneous fat, and large caliber nerve invasion.Main Outcomes and MeasuresFive-year cumulative incidences of local recurrence, nodal metastasis, distant metastasis, and disease-specific death.ResultsA total of 16 844 CSCCs were included (5978 female individuals [35.5%]; median [IQR] age, 73.9 [65.7-81.8] years), with 0 (12 657 [75.1%]), 1 (2892 [17.2%]), 2 (1015 [6.0%]), 3 ( 225 [1.3%]) or 4 (55 [0.3%]) RFs. Median (IQ) follow up time was 33.6 (14.5-60.3) months. For local recurrence, the risk increased as the number of RF increased from 0 (1.7%; 95% CI, 1.5%-2.0%) to 1 (5.0%; 95% CI, 4.1%-5.9%) to 2 (8.8%; 95% CI, 7.0%-11.0%) to 3 (16.0%; 95% CI, 11.0%-22.0%) to 4 (33.0%; 95% CI, 19.0%-47.0%; P < .001 for between-group differences). This increase was also observed for nodal metastasis (0.6% [95% CI, 0.4%-0.7%] vs 3.6% [95% CI, 2.9%-4.4%] vs 11.0% [95% CI, 9.2%-13.0%] vs 20.0% [95% CI, 15.0%-26.0%] vs 28.0% [95% CI, 15.0%-42.0%], respectively; P < .001), distant metastasis (0.2% [95% CI, 0.1%-0.3%] vs 1.1% [95% CI, 0.7%-1.6%] vs 2.3% [95% CI, 1.4%-3.4%] vs 7.9% [95% CI, 4.6%-12.0%] vs 8.4% [95% CI, 2.6%-19.0%], respectively; P < .001), and disease-specific death (0.3% [95% CI, 0.2%-0.4%] vs 1.9% [95% CI, 1.4%-2.7%] vs 5.4% [95% CI, 4.0%-7.0%] vs 11.0% [95% CI, 6.7%-16.0%] vs 25% [95% CI, 12%-39%], respectively; P < .001). CSCCs with 3 RFs had higher cumulative incidences of local recurrence (1.6-fold), nodal metastasis (1.9-fold), distant metastasis (4.3-fold), and disease-specific death (1.9-fold) compared with those with 2 RFs.Conclusions and RelevanceThe results of this cohort study suggest that the number of RFs is an indicator of risk, and among BWH T2b tumors, those with 3 RFs represent a higher risk subset.

Importance Completion of the Human Genome Project prompted predictions that genomics would transform medicine, including through genomic screening that identifies potentially medically actionable findings that could prevent disease, detect it earlier, or treat it better. However, genomic screening remains anchored in research and largely unavailable as part of routine care. Objective To summarize 11 years of experience with genomic screening and explore the landscape of genomic screening efforts. Design, Setting, and Participants This cohort study was based in Geisinger’s MyCode Community Health Initiative, a genomic screening program in a rural Pennsylvania health care system in which patient-participants exomes are analyzed. Main Outcomes and Measures Genomic screen-positive rates were evaluated and stratified by condition type (cancer, cardiovascular, other) and US Centers for Disease Control and Prevention (CDC) Tier 1 designation. The proportion of participants previously unaware of their genomic result was assessed. Other large-scale population-based genomic screening efforts with genomic results disclosure were compiled from public resources. Results A total of 354 957 patients participated in Geisinger’s genomic screening program (median [IQR] age, 54 [36-69] years; 194 037 [59.7%] assigned female sex at birth). As of June 2024, 175 500 participants had exome sequencing available for analysis, and 5934 participants (3.4%) had a pathogenic variant in 81 genes known to increase risk for disease. Between 2013 and July 2024, 5119 results were disclosed to 5052 eligible participants, with 2267 (44.2%) associated with risk for cardiovascular disease, 2031 (39.7%) with risk for cancer, and 821 (16.0%) with risk for other conditions. Most results (3040 [59.4%]) were in genes outside of those with a CDC Tier 1 designation. Nearly 90% of participants (4425 [87.6%]) were unaware of their genomic risk prior to disclosure. In a survey of large-scale biobanks with genomic and electronic health record (EHR) data, only 25.0% (6 of 24) disclosed potentially actionable genomic results. Conclusions and Relevance In this large, genomics-informed cohort study from a single health system, 1 in 30 participants had a potentially actionable genomic finding. However, nearly 90% were unaware of their risk prior to screening, demonstrating the utility of genomic screening in identifying at-risk individuals. Most large-scale biobanks with genomic and EHR data did not return genomic results with potential medical relevance, missing opportunities to significantly improve genomic risk ascertainment for these individuals and to perform longitudinal studies of clinical and implementation outcomes in diverse settings.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Background: Both perineural and intravenous dexamethasone have been proposed as effective adjuncts that prolong the duration of peripheral nerve blocks. The authors sought to explore whether combining systemic with perineural dexamethasone yields any additive or synergistic effect on the characteristics and analgesic effects of peripheral nerve blocks. Methods: Adult patients having distal radius open reduction and internal fixation and/or carpometacarpal arthroplasty under supraclavicular block were randomized to intravenous dexamethasone, a combination of perineural plus intravenous dexamethasone, or no dexamethasone (control). Sensory block duration was set as the primary outcome. Secondary outcomes included motor block duration; postoperative rebound pain scores as well as worst pain at 8, 16, 24, 32, 40, and 48 h; opioid consumption at 0 to 24 and 25 to 48 h; incidence of nausea/vomiting; and presence of burning sensation in the blocked limb at 24 and 48 h. The null hypothesis was lack of difference in sensory block duration between the three groups. Results: A total of 104 patients were included in the analysis (intravenous dexamethasone, 37; intravenous plus perineural dexamethasone, 34; control, 33). Compared to intravenous dexamethasone alone, adding perineural dexamethasone did not yield any incremental benefits in any of the outcomes examined. The mean ± SD of sensory block duration was 21.3 ± 7.3 h in the intravenous dexamethasone group, 20.6 ± 6.1 h in the perineural plus intravenous group, and 16.8 ± 6.8 h in the control group. The mean difference (95% CI) of sensory block duration was significantly prolonged by 4.5 h (95% CI, 1.3 to 7.7; P = 0.006) in the intravenous dexamethasone group and 3.8 h (95% CI, 0.8 to 6.8; P = 0.015) in the perineural plus intravenous dexamethasone group compared to control; however, no difference was observed when the two dexamethasone groups were compared to each other (0.7 h [95% CI, –2.5 to 3.9]; P = 0.670). Compared to control, both intravenous and intravenous plus perineural dexamethasone similarly reduced 24-h pain scores and opioid consumption and decreased incidence of rebound pain. Conclusions: The authors’ findings suggest that intravenous dexamethasone alone is sufficient to improve analgesic outcomes for patients receiving supraclavicular block for upper extremity surgery. Combining the intravenous and perineural dexamethasone routes does not yield an additive or synergistic effect on the characteristics and analgesic effects of supraclavicular block.

Objectives Black/African American (B/AA) pancreatic ductal adenocarcinoma (PDAC) patients have worse clinical outcomes than White patients and are underrepresented in genomic databases. We aimed to expand our understanding of the PDAC somatic landscape from a diverse cohort. Materials and Methods Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity. Whole exome sequencing was performed on malignant and benign tissue. Bioinformatics analysis included deduction of genetic ancestry and somatic mutational analysis, with comparisons to public datasets. Results Out of 24 cases, 17 identified as B/AA race; genetic ancestry analysis confirmed proportions of Sub-Saharan African ancestry greater than 47%. The most commonly mutated genes included KRAS , TP53 , SMAD4 , and CDKN2A . Comparison of mutations in our cohort versus publicly available, predominantly White datasets showed higher mutation frequencies of ATM, RREB1, BRCA1/2, KDM6A, ARID1A, BRAF, and MYC ( P < 0.04). When cohorts were combined and analyzed by race, no mutation frequencies differences were observed, including KRAS . Conclusions Genomic analysis of PDAC tumors from B/AA and White patients demonstrate similarities in mutation frequencies. Larger studies are needed to further understand molecular characterizations across continental subpopulations. This study provides further rationale for equitable representation of diverse patients in genomic databases and clinical trials.

Introduction Artificial intelligence (AI), particularly large-language models like Chat Generative Pre-Trained Transformer (ChatGPT), has demonstrated potential in streamlining research methodologies. Systematic reviews and meta-analyses, often considered the pinnacle of evidence-based medicine, are inherently time-intensive and demand meticulous planning, rigorous data extraction, thorough analysis, and careful synthesis. Despite promising applications of AI, its utility in conducting systematic reviews with meta-analysis remains unclear. This study evaluated ChatGPT’s accuracy in conducting key tasks of a systematic review with meta-analysis. Methods This validation study used data from a published meta-analysis on emotional functioning after spinal cord stimulation. ChatGPT-4o performed title/abstract screening, full-text study selection, and data pooling for this systematic review with meta-analysis. Comparisons were made against human-executed steps, which were considered the gold standard. Outcomes of interest included accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for screening and full-text review tasks. We also assessed for discrepancies in pooled effect estimates and forest plot generation. Results For title and abstract screening, ChatGPT achieved an accuracy of 70.4%, sensitivity of 54.9%, and specificity of 80.1%. In the full-text screening phase, accuracy was 68.4%, sensitivity 75.6%, and specificity 66.8%. ChatGPT successfully pooled data for five forest plots, achieving 100% accuracy in calculating pooled mean differences, 95% CIs, and heterogeneity estimates ( I 2 score and tau-squared values) for most outcomes, with minor discrepancies in tau-squared values (range 0.01–0.05). Forest plots showed no significant discrepancies. Conclusion ChatGPT demonstrates modest to moderate accuracy in screening and study selection tasks, but performs well in data pooling and meta-analytic calculations. These findings underscore the potential of AI to augment systematic review methodologies, while also emphasizing the need for human oversight to ensure accuracy and integrity in research workflows.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.