Fast mass spectrometry search and clustering of untargeted metabolomics data.

The throughput of mass spectrometers and the amount of publicly available metabolomics data are growing rapidly, but analysis tools such as molecular networking and Mass Spectrometry Search Tool do not scale to searching and clustering billions of mass spectral data in metabolomics repositories. To address this limitation, we designed MASST+ and Networking+, which can process datasets that are up to three orders of magnitude larger than those processed by state-of-the-art tools.

Impact of Treatment Modalities upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Adjuvant Therapy and Prognosticators of Survival in Head and Neck Mucosal Melanoma.

OBJECTIVES/HYPOTHESIS: To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN: Retrospective database study. METHODS: The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS: Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P < .001), female sex (HR 0.757; P = .006), paranasal sinus localization (HR 1.648; P < .001), T4 classification (HR 1.443; P < .001), N1 classification (HR 2.310; P < .001), M1 classification (HR 3.357; P < .001), and positive surgical margins (HR 1.454; P < .001) were survival prognosticators. Adjuvant radiotherapy use was negatively correlated with older age, oral cavity localization, and M0 or T3 tumors (all P < .05). Adjuvant immunotherapy use was positively correlated with younger age and M1 tumors (all P < .05). CONCLUSIONS: Although SR did not confer survival benefits in HNMM patients, SI and SRI yielded greater OS than surgery alone. SRI was associated with superior survival outcomes than SR. Certain demographic and clinical factors were associated with increased mortality risk. Patient age and certain tumor characteristics were predictors of adjuvant radiotherapy or immunotherapy use. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:584-592, 2022.

Determinants of Survival in Skull Base Chondrosarcoma: A National Cancer Database Study.

OBJECTIVE: Chondrosarcomas of the skull base are rare tumors most commonly treated surgically with or without adjuvant radiation therapy. Using the National Cancer Database (NCDB), we analyzed overall survival (OS), treatment modalities, and prognosticators. METHODS: The NCDB was queried for all cases of histologically confirmed skull base chondrosarcoma treated between 2004 and 2015, excluding patients with more than 1 malignant tumor, on palliative care, receiving unrelated concurrent treatments, or having less than 1 month of follow-up. The χ2 test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with the use of adjuvant radiation, OS, and survival time. RESULTS: A total of 498 patients with skull base chondrosarcoma were identified in the NCDB. Of them, 224 (45.0%) and 198 (39.8%) were treated with either surgery alone or surgery with adjuvant radiation therapy, respectively. Patients more likely to undergo surgery with adjuvant radiation had higher tumor grade (P = 0.008), later year of diagnosis (P = 0.002), positive surgical margins (P < 0.001), and treatment at an academic institution (P = 0.02). Patient, tumor, and socioeconomic factors associated with worse OS on multivariate analysis included the Charlson/Deyo Comorbidity Score ≥2 (P = 0.017), as well as clear cell (P = 0.02) and dedifferentiated (P = 0.006) histology. Age, tumor grade, tumor size, treatment modality, insurance status, facility type, and urban/rural population did not show a statistically significant impact on OS. CONCLUSION: The mainstay of treatment for skull base chondrosarcoma is surgery, with consideration of adjuvant radiation. This study demonstrated worse overall survival associated with more frail patients and aggressive histology types. It is important to consider these factors when planning the clinical management of these patients.

Characteristics and overall survival in pediatric versus adult pituitary adenoma: a National Cancer Database analysis.

OBJECTIVE: Pituitary adenomas in the pediatric population are extremely rare, resulting in limited information in the literature on these patients. In this study, data from the National Cancer Database (NCDB) to compare pituitary adenoma clinical presentations, treatment management patterns, and overall survival between pediatric and adult patients. METHODS: The NCDB was queried for all cases of histologically confirmed pituitary adenoma treated between 2004 and 2015. Patients were primarily stratified as either pediatric (< 18 years) or adult (≥ 18 years). Patient demographics/socioeconomics and resulting outcomes were then compared. RESULTS: 1893 pediatric and 77,993 adult patients with pituitary adenomas were evaluated. Average tumor size for pediatric and adult patients was 13.6 ± 13.2 mm and 20.1 ± 13.1 mm, respectively (p < 0.001). Pediatric patients were more likely to undergo gross total resection, less likely to receive adjuvant radiation, more likely to receive medical therapy, more likely to undergo active surveillance, and exhibited improved 5-year and 10-year overall survival (OS) (all p < 0.001). Temporal analysis demonstrated a significant increase in endoscopic approach over time (from 48 to 65%) in the pediatric population (R2 = 0.722, p = 0.03). On univariate analysis in the pediatric population, African American race compared to Caucasians (HR: 5.85, 95% CI 1.79-19.2, p < 0.003), patients with government insurance compared to those with private insurance (HR: 5.07, 95% CI 1.31-19.6, p < 0.02) and uninsured patients compared to those with private insurance (HR: 14.4, 95% CI 2.41-86.5, p < 0.003) were associated with decreased OS. Lastly, patients who underwent GTR had improved OS compared to those who underwent subtotal resection (HR: 0.08, 95% CI 0.008-0.93, p < 0.04) in the pediatric population. CONCLUSIONS: Compared to adults, children with pituitary adenomas more commonly underwent GTR, less frequently underwent adjuvant radiotherapy, more frequently underwent medical management and active surveillance, and had improved survival. Temporal analysis demonstrated increasing utilization of the endoscopic approach for surgical treatment of pediatric and adult pituitary adenoma patients. LEVEL OF EVIDENCE: Level III.

Treatment Modalities and Survival Outcomes for Sinonasal Diffuse Large B-Cell Lymphoma.

OBJECTIVES/HYPOTHESIS: This study utilizes a large population national database to comprehensively analyze prognosticators and overall survival (OS) outcomes of varying treatment modalities in a large cohort of sinonasal diffuse large B-cell lymphoma (SN-DLBCL) patients. STUDY DESIGN: Retrospective database study. METHODS: The National Cancer Database was queried for all SN-DLBCL cases diagnosed from 2004 to 2015. Kaplan-Meier log-rank test determined differences in OS based on clinical covariates. Cox proportional-hazards analysis was used to determine clinical and sociodemographic covariates predictive of mortality. RESULTS: A total of 2,073 SN-DLBCL patients were included, consisting of 48% female with a mean age of 66.0 ± 16.2 years. Overall, 82% of patients were Caucasian, 74% had early-stage disease, and 49% had primary tumors in the paranasal sinuses. Early-stage patients were more likely to receive multi-agent chemoradiotherapy compared to multi-agent chemotherapy alone (P < .001). Multivariable Cox proportional-hazards analysis revealed chemoradiotherapy to confer significantly greater OS improvements than chemotherapy alone (hazard ratio [HR]: 0.61; P < .001). However, subset analysis of late-stage patients demonstrated no significant differences in OS between these treatment modalities (P = .245). On multivariable analysis of chemotherapy patients treated post-2012, immunotherapy (HR = 0.51; P = .024) demonstrated significant OS benefits. However, subset analysis showed no significant advantage in OS with administering immunotherapy for late-stage patients (P = .326). Lastly, for all patients treated post-2012, those receiving immunotherapy had significantly improved OS compared to those not receiving immunotherapy (P < .001). CONCLUSIONS: Treatment protocol selection differs between early- and late-stage SN-DLBCL patients. Early-stage patients receiving chemotherapy may benefit from immunotherapy as part of their treatment paradigm. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2727-E2735, 2021.

Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon sinonasal malignancy and is even less common in the pediatric population. OBJECTIVE: The purpose of this study is to compare characteristics and outcomes of ENB between adult and pediatric patients. METHODS: The National Cancer Database was queried for patients with histologically proven ENB of the nasal cavity and paranasal sinuses, and then baseline characteristics, treatment, and survival data compared between the pediatric (age < 18 years) and adult (age ≥ 18 years) populations. RESULTS: 1411 patients were identified, with 45 in the pediatric cohort and 1366 in the adult cohort. Ten-year overall survival (OS) in the pediatric cohort was improved compared to the adult cohort, 87% and 66%, respectively (p < 0.05). Adjuvant chemotherapy was more commonly utilized in the pediatric cohort (p < 0.001). Race was associated with decreased OS in the pediatric cohort (p = 0.013). Pediatric patients had shorter length of stay (p = 0.009) and lived closer to their provider (p = 0.044) than adult ENB patients. CONCLUSION: Treatment of ENB in pediatric patients more commonly includes chemotherapy and more commonly occurs at academic medical centers. OS is improved in pediatric ENB compared to adults as well, but larger studies are necessary.

Characteristics and overall survival in pediatric versus adult skull base chordoma: a population-based study.

PURPOSE: Less than 5% of chordomas occur in pediatric patients. While many studies have explored the treatment and outcomes of skull base chordomas, few have focused on the differences between pediatric and adult populations. The aim of this study is to analyze the epidemiological variables and clinical outcomes between pediatric and adult skull base chordomas using a large-sample, population-based cancer database. METHODS: The National Cancer Database was queried between 2004 and 2015 for skull base chordomas. We stratified patients as pediatric (<18 years) and adults (≥18 years). We compared several clinical covariates between the two groups. RESULTS: Our cohort consisted of 658 patients, 61 pediatric (9.3%), and 597 adults (90.7%). Pediatric patients were more likely to have larger tumor size (41.4 ± 15.7 mm versus 34.1 ± 15.8 mm, p < 0.01) and universally treated at academic facilities. There was no significant difference in overall survival. CONCLUSIONS: Pediatric skull base chordomas are rare tumors that are managed with aggressive surgical resection, followed by radiation. While there may be difference between tumor presentation, outcomes between pediatric and adult patients are similar.

Treatment Analysis and Overall Survival Outcomes of Patients With Bilateral Vestibular Schwannoma.

OBJECTIVES: To investigate the clinical presentation, treatment breakdown, and overall survival (OS) outcomes of patients with neurofibromatosis type 2 (NF2)-associated bilateral vestibular schwannoma (NVS). METHODS: The 2004 to 2016 National Cancer Database was queried for patients with a diagnosis of VS. The "Laterality" code was used to stratify patients into sporadic unilateral vestibular schwannoma (UVS) and NVS. RESULTS: Of the 33,839 patients with VS, 155 (0.46%) were coded for NVS with an average age and tumor size of 37.4 ±â€Š20.5 years and 23.5 ±â€Š18.2 mm. Patients underwent observation (45.3%), surgery (29.3%), and radiotherapy (20.0%), and had a 5.8% 5-year mortality rate. Compared with UVS, NVS was negatively associated with receiving surgery (40.2% versus 29.3%, p = 0.02) while watchful observation was more prevalent (30.1% versus 45.3%, p = 0.001). In NVS, undergoing surgery was associated with larger tumor size (34.5 ±â€Š21.2 versus 17.8 ±â€Š13.3 mm, p = 0.001) and shorter diagnosis-to-treatment time (49.1 ±â€Š60.6 versus 87.0 ±â€Š78.5 d, p = 0.02), radiotherapy was associated with older age (44.4 ±â€Š18.9 versus 35.2 ±â€Š20.6 yr, p = 0.02) and longer diagnosis-to-treatment time (85.9 ±â€Š77.9 versus 53.9 ±â€Š65.5 d, p = 0.04), and observation was associated with smaller tumor size (17.8 ±â€Š15.9 versus 28.0 ±â€Š19.2 mm, p = 0.01). Kaplan-Meier log-rank analysis demonstrated similar 10-year OS between NVS and UVS patients (p = 0.58) without factoring the earlier age of presentation. Furthermore, there were no temporal changes in presentation/management of NVS, and OS was not dependent on the received treatment (p = 0.30). CONCLUSIONS: With younger age, larger tumors, and more conservative management, NVS's OS was not treatment-dependent and was similar to sporadic UVS, though the latter should not be interpreted as similar life expectancies due to the much earlier presentation.

Outcomes of Primary Versus Salvage Surgery for Sinonasal Malignancies: A Population-Based Analysis.

OBJECTIVES/HYPOTHESIS: There exists a lack of consensus on the optimal sequence of treatment for many sinonasal malignancies (SNMs). This study compares the overall survival (OS) outcomes for primary surgery (PS) versus salvage surgery (SS) in SNM patients across stage, histology, and primary site. STUDY DESIGN: Retrospective database review. METHODS: The National Cancer Database was queried for all SNM cases treated with multimodal surgical and nonsurgical therapy between 2004 and 2015. Logistic regression identified predictors of SS. Cox proportional hazards models evaluated predictors of mortality, and Kaplan-Meier log-rank test assessed OS outcomes. RESULTS: Our SNM cohort consisted of 3,011 patients (PS = 2,804; SS = 207). SS patients had significantly longer postoperative hospital stays (P = .009) and increased rates of 30-day (P < .001) and 90-day mortality (P < .001) compared to PS. On multivariate logistic regression, predictors of undergoing SS included sinonasal undifferentiated carcinoma histology (odds ratio = 2.72; 95% confidence interval [CI]: 1.16-6.66; P = .024). On multivariate Cox proportional hazards analyses among SS patients, late-stage disease (hazard ratio [HR] = 4.80; 95% CI: 1.46-15.8; P = .01) and positive surgical margins (HR = 2.31; 95% CI: 1.29-4.13; P = .005) portended significantly worse OS. In the propensity score-matched cohort controlling for stage and histology, PS had significantly improved OS compared to SS (P = .007). Compared to SS, PS also had improved OS in subgroup analyses for patients with late-stage disease (P = .026) and squamous cell carcinoma histology (P = .006). CONCLUSIONS: In our SMN cohort, PS resulted in improved OS outcomes compared to SS independent of stage and histology. Consideration may be given to primary surgical resection for SMN whenever feasible, though a targeted, individualized approach is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E710-E718, 2021.

Machine learning models to predict length of stay and discharge destination in complex head and neck surgery.

BACKGROUND: This study develops machine learning (ML) algorithms that use preoperative-only features to predict discharge-to-nonhome-facility (DNHF) and length-of-stay (LOS) following complex head and neck surgeries. METHODS: Patients undergoing laryngectomy or composite tissue excision followed by free tissue transfer were extracted from the 2005 to 2017 NSQIP database. RESULTS: Among the 2786 included patients, DNHF and mean LOS were 421 (15.1%) and 11.7 ± 8.8 days. Four classification models for predicting DNHF with high specificities (range, 0.80-0.84) were developed. The generalized linear and gradient boosting machine models performed best with receiver operating characteristic (ROC), accuracy, and negative predictive value (NPV) of 0.72-0.73, 0.75-0.76, and 0.88-0.89. Four regression models for predicting LOS in days were developed, where all performed similarly with mean absolute error and root mean-squared errors of 3.95-3.98 and 5.14-5.16. Both models were developed into an encrypted web-based interface: https://uci-ent.shinyapps.io/head-neck/. CONCLUSION: Novel and proof-of-concept ML models to predict DNHF and LOS were developed and published as web-based interfaces.

Short-Term Morbidity and Predictors of Adverse Events Following Esthesioneuroblastoma Surgery.

INTRODUCTION: The short-term adverse events and predictors of morbidity in surgical resection of esthesioneuroblastoma (ENB) are largely unknown, and investigating these variables can help direct planning for at-risk patients. METHODS: The 2005-2017 National Surgical Quality Improvement Program database was queried to identify patients with a diagnosis of ENB undergoing skull base surgery for tumor resection. Information regarding demographics, patient morbidity score, pre-operative and intra-operative data, and post-operative outcomes were extracted. Cox proportional hazard analysis was utilized to assess complication and readmission/reoperation rates. RESULTS: A total of 95 patients undergoing skull base surgery for resection of ENB were included. Mean age, BMI, operation time, and post-operative length of stay (LOS) of the cohort were 53.6 ± 16.2 years, 29.1 ± 6.5, 392.0 ± 204.6 minutes, and 5.8 ± 4.6 days, respectively. In total, 31 patients (32.6%) experienced at least one 30-day adverse event, which included blood transfusion intra-operatively or within 72 hours from the operation (22.1%), readmission (10.7%), intubation >48 hours (7.4%), reintubation (4.2%), organ or space infection (4.2%), reoperation (4.0%), superficial or deep surgical site infection (2.1%), sepsis (2.1%), pulmonary embolism (1.1%), and myocardial infarction (1.1%). Patients who experienced at least one adverse event had significantly higher operation time (486.8 ± 230.4 vs. 347.5 ± 176.2 minutes, p = 0.002), LOS (9.2 ± 5.6 days vs. 4.2 ± 3.0, p < 0.001), and lower hematocrit (37.3 ± 5.9 vs. 41.2 ± 3.8, p < 0.001) and albumin levels (3.8 ± 0.6 vs. 4.2 ± 0.3, p = 0.009). Patients with a higher American Society of Anesthesiologists (ASA) score (HR = 2.39; p = 0.047) or longer operation time (HR = 1.004; p = 0.001) had a significantly higher risk for experiencing adverse events. Obesity was not associated with different intra- or post-operative outcomes, but older patients had shorter operations (p = 0.002) and LOS (p = 0.0014). CONCLUSION: Longer operation time and lower pre-operative hematocrit and albumin levels may all increase complication rates in ENB resection. Patients with high ASA score or more advanced age may have different short-term outcomes.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

OBJECTIVES: The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. STUDY DESIGN: A retrospective analysis using the National Cancer Database (NCDB). METHODS: The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. RESULTS: There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). CONCLUSIONS: Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:776-781, 2021.

Peer-to-Peer Contact Tracing: Development of a Privacy-Preserving Smartphone App.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is an urgent public health crisis, with epidemiologic models predicting severe consequences, including high death rates, if the virus is permitted to run its course without any intervention or response. Contact tracing using smartphone technology is a powerful tool that may be employed to limit disease transmission during an epidemic or pandemic; yet, contact tracing apps present significant privacy concerns regarding the collection of personal data such as location. OBJECTIVE: The aim of this study is to develop an effective contact tracing smartphone app that respects user privacy by not collecting location information or other personal data. METHODS: We propose the use of an anonymized graph of interpersonal interactions to conduct a novel form of contact tracing and have developed a proof-of-concept smartphone app that implements this approach. Additionally, we developed a computer simulation model that demonstrates the impact of our proposal on epidemic or pandemic outbreak trajectories across multiple rates of adoption. RESULTS: Our proof-of-concept smartphone app allows users to create "checkpoints" for contact tracing, check their risk level based on their past interactions, and anonymously self-report a positive status to their peer network. Our simulation results suggest that higher adoption rates of such an app may result in a better controlled epidemic or pandemic outbreak. CONCLUSIONS: Our proposed smartphone-based contact tracing method presents a novel solution that preserves privacy while demonstrating the potential to suppress an epidemic or pandemic outbreak. This app could potentially be applied to the current COVID-19 pandemic as well as other epidemics or pandemics in the future to achieve a middle ground between drastic isolation measures and unmitigated disease spread.