Defining the clinical characteristics of mammary analog secretory carcinoma of the salivary gland: Analysis of the National Cancer Database.

Objectives: Mammary analog secretory carcinoma (MASC) is a classification of salivary gland tumors, recently included within the term secretory carcinoma. Previous descriptions of this diagnosis have largely consisted of case reports and case series with few studies investigating its clinical characteristics as compared to non-MASC tumors. Our objective was to use a large patient database to compare the clinical characteristics of mammary analog secretory carcinoma vs. non-mammary analog secretory carcinoma salivary gland tumors. Methods: The National Cancer Database was queried between September and October 2022 for histological diagnosis of mammary analog secretory carcinoma and non-MASC salivary tumors. Patients diagnosed with mammary analog secretory carcinoma and non-mammary analog secretory carcinoma salivary tumors between the period of 2004 through 2019 were included in this analysis. Various demographic and clinical variables were abstracted from the database and compared using Wilcoxon rank sum and chi-square tests. Survival was compared between cohorts using Cox proportional hazards regression. Results: Overall, compared to non-mammary analog secretory carcinoma diagnoses (n = 47668), mammary analog secretory carcinoma tumors (n = 384) affected younger individuals, displayed favorable pathologic staging and tumor grade, and were less likely to invade surrounding tissues. Patients with mammary analog secretory carcinoma tumors also received treatment more quickly following diagnosis compared to patients with non-mammary analog secretory carcinoma tumors. The risk of death was 4.3 times greater for non-mammary analog secretory carcinoma diagnoses when adjusted for patient variables (hazard ratio = 4.3, 95% confidence interval [2.37-7.71], p < 0.001). Conclusions: Clinically, mammary analog secretory carcinoma salivary tumors have a more indolent course compared to other salivary cancers. Additional studies are needed to determine the natural history of this tumor type.

Facial plating industry payments: An analysis of the open payments database.

Objective: To compare industry payments from facial plating companies to plastic surgery, oral and maxillofacial surgery (OMFS), and otolaryngology (OHNS). Methods: The Open Payments Database was queried from 2016 to 2021 to identify all industry disbursements related to facial plating products from Stryker, Zimmer Biomet, Depuy Synthes Products, Acumed, and KLS Martin. Total dollars, number of payments, and specialists paid were compared between plastic surgery, OMFS, and OHNS. Funding was correlated to estimated case volume and number of licensed surgeons determined by literature review. Results: From 2016 through 2021, OMFS received an average of $786,497 annually, followed by plastic surgery ($765,482), and OHNS ($184,484). On average, facial plating companies distributed 2256, 963, and 917 yearly payments to 699 oral and maxillofacial surgeons, 378 plastic surgeons, and 354 otolaryngologists, respectively. Total dollars, number of payments, and specialists paid were significantly different between specialties (p < .05). Facial trauma coverage is 39.6% by plastic surgery, 36.6% by OMFS, and 23.3% by OHNS. There are 7560 licensed oral and maxillofacial surgeons, 4948 plastic surgeons, and 11,778 otolaryngologists in the United States. Decreased payment to OHNS was more than could be accounted for by case volume alone. Conclusions: The facial plating industry allocates more funding dollars to OMFS and plastic surgery compared to OHNS. OMFS receives the greatest number of payments to the most specialists compared to plastic surgery and OHNS. Engagement between OHNS and the facial plating industry is a potential area of growth in the future.Level of evidence: Level 4.

Comparison of Voice Therapy Outcomes: Clinic vs Telehealth.

BACKGROUND: Voice therapy provides patients with valuable exercises and techniques to optimize vocal behaviors and improve their ability to communicate effectively and efficiently. These sessions were typically held by speech-language pathologists (SLPs) in clinic. During the COVID-19 pandemic, SLPs were provisionally able to provide billable voice therapy services in telehealth format. There is a lack of existing research studies comparing outcomes based on the format of voice therapy. METHODS: A retrospective chart review was performed on 101 patients who underwent voice therapy at a large academic institution in order to compare outcomes between clinic, telehealth, and mixed voice therapy formats. Demographics, dysphonia etiology, duration of symptoms, number of therapy sessions, and pre- and postvoice therapy scores using reflux symptom index (RSI), voice handicap index (VHI-10), consensus auditory-perceptual evaluation of voice (CAPE-V), and Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scoring were collected. Statistical comparisons were performed using Fisher's exact test and analysis of covariance. RESULTS: There were no statistically significant differences in pre- to postvoice therapy RSI, VHI-10, CAPE-V, or GRBAS scores based on format of voice therapy, after adjustment for number of therapy sessions received. There were no differences in these outcomes when comparing voice therapy by etiology of dysphonia. CONCLUSIONS: Overall, these data support the effectiveness of the telehealth voice therapy format. It is a promising platform for greater patient access to therapy. All formats of voice therapy were effective in improving key measures of voice perception.

Optical genome mapping in acute myeloid leukemia: a multicenter evaluation.

Detection of hallmark genomic aberrations in acute myeloid leukemia (AML) is essential for diagnostic subtyping, prognosis, and patient management. However, cytogenetic/cytogenomic techniques used to identify those aberrations, such as karyotyping, fluorescence in situ hybridization (FISH), or chromosomal microarray analysis (CMA), are limited by the need for skilled personnel as well as significant time, cost, and labor. Optical genome mapping (OGM) provides a single, cost-effective assay with a significantly higher resolution than karyotyping and with a comprehensive genome-wide analysis comparable with CMA and the added unique ability to detect balanced structural variants (SVs). Here, we report in a real-world setting the performance of OGM in a cohort of 100 AML cases that were previously characterized by karyotype alone or karyotype and FISH or CMA. OGM identified all clinically relevant SVs and copy number variants (CNVs) reported by these standard cytogenetic methods when representative clones were present in >5% allelic fraction. Importantly, OGM identified clinically relevant information in 13% of cases that had been missed by the routine methods. Three cases reported with normal karyotypes were shown to have cryptic translocations involving gene fusions. In 4% of cases, OGM findings would have altered recommended clinical management, and in an additional 8% of cases, OGM would have rendered the cases potentially eligible for clinical trials. The results from this multi-institutional study indicate that OGM effectively recovers clinically relevant SVs and CNVs found by standard-of-care methods and reveals additional SVs that are not reported. Furthermore, OGM minimizes the need for labor-intensive multiple cytogenetic tests while concomitantly maximizing diagnostic detection through a standardized workflow.

Human Papillomavirus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer.

Human papillomavirus (HPV)-positive head and neck cancers, predominantly oropharyngeal squamous cell carcinoma (OPSCC), exhibit epidemiologic, clinical, and molecular characteristics distinct from those OPSCCs lacking HPV. We applied a combination of whole-genome sequencing and optical genome mapping to interrogate the genome structure of HPV-positive OPSCCs. We found that the virus had integrated in the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Integration of the virus occurred at essentially random sites within the genome. Focal amplification of the virus and the genomic sequences surrounding it often occurred subsequent to integration, with the number of tandem repeats in the chromosome accounting for the increased copy number of the genome sequences flanking the site of integration. In all cases, viral integration correlated with pervasive genome-wide somatic alterations at sites distinct from that of viral integration and comprised multiple insertions, deletions, translocations, inversions, and point mutations. Few or no somatic mutations were present in tumors with only episomal HPV. Our data could be interpreted by positing that episomal HPV is captured in the host genome following an episode of global genome instability during tumor development. Viral integration correlated with higher grade tumors, which may be explained by the associated extensive mutation of the genome and suggests that HPV integration status may inform prognosis. IMPLICATIONS: Our results indicate that HPV integration in head and neck cancer correlates with extensive pangenomic structural variation, which may have prognostic implications.

Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping.

Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid tumors. Using as little as 6.5 mg of input tumor tissue, we show successful extraction of high-molecular-weight genomic DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system's utility in identifying somatic SVs affecting functional and cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment.

In-depth analysis of thyroid cancer mortality.

BACKGROUND: There are reports of an increasing thyroid cancer mortality rate. This study aimed to analyze the latest trends in this rate over time and compare findings from different cancer registries. METHODS: Thyroid cancer incidence-based mortality (IBM) rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) program, including SEER-9, SEER-13, and SEER-18. The National Center for Health Statistics (NCHS) thyroid cancer mortality rate was acquired for comparison. Statistical analysis was performed using the JoinPoint software. RESULTS: NCHS data revealed an overall annual percent change (APC) over 1987 to 2017 of 0.61 (P < .01), and the value was nearly four times greater for males compared to females. The overall IBM APC values for SEER-9, SEER-13, and SEER-18 were also positive and statistically significant (P < .01). CONCLUSIONS: The increased thyroid cancer mortality rate observed in previous studies continues to be statistically significant based on updated NCHS and SEER IBM data.

Evidence of a positive association between malpractice climate and thyroid cancer incidence in the United States.

The incidence of thyroid cancer has risen dramatically in the past few decades. The cause of this is unclear, but several lines of evidence indicate it is largely due to overdiagnosis, the diagnosis of tumors that would have never manifest clinically if untreated. Practices leading to overdiagnosis may relate to defensive medicine. In this study, we evaluated the association between malpractice climate and incidence of thyroid, breast, prostate, colon, and lung cancer in U.S. states from 1999-2012 using publicly available government data. State-level malpractice risk was quantified as malpractice payout rate, the number of malpractice payouts per 100,000 people per state per year. Associations between state-level cancer incidence, malpractice payout rate, and several cancer risk factors were evaluated. Risk factors included several social determinants of health, including factors predicting healthcare access. States with higher malpractice payout rate had higher thyroid cancer incidence, on both univariate analysis (r = 0.51, P = 0.009, Spearman) and multivariate analysis (P<0.001, multilevel model). In contrast, state-level malpractice payout rate was not associated with incidence of any other cancer type. Malpractice climate may be a social determinant for being diagnosed with thyroid cancer. This may be a product of greater defensive medicine in states with higher malpractice risk, which leads to increased diagnostic testing of patients with thyroid nodules and potential overdiagnosis. Alternatively, malpractice risk may be a proxy for another, unmeasured risk factor.