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BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. CONCLUSIONS The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage-derived products as therapy for lung cancer. [ABSTRACT FROM AUTHOR]

Health information systems to monitor vaccine safety are used in industrialized countries to detect adverse medical events related to vaccinations or to prove the safety of vaccines. There are no such information systems in the developing world, but they are urgently needed. A large linked database for the monitoring of vaccine-related adverse events has been established in Khanh Hoa province, Viet Nam. Data collected during the first 2 years of surveillance, a period which included a mass measles vaccination campaign, were used to evaluate the system. For this purpose the discharge diagnoses of individuals admitted to polyclinics and hospitals were coded according to the International Classification of Diseases (ICD)-10 guidelines and linked in a dynamic population database with vaccination histories. A case-series analysis was applied to the cohort of children vaccinated during the mass measles vaccination campaign. The study recorded 107,022 immunizations in a catchment area with a population of 357,458 and confirmed vaccine coverage of 87% or higher for completed routine childhood vaccinations. The measles vaccination campaign immunized at least 86% of the targeted children aged 9 months to 10 years. No medical event was detected significantly more frequently during the 14 days after measles vaccination than before it. The experience in Viet Nam confirmed the safety of a measles vaccination campaign and shows that it is feasible to establish health information systems such as a large linked database which can provide reliable data in a developing country for a modest increase in use of resources. Copyright © 2005 World Health Organization [ABSTRACT FROM AUTHOR]

Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the antitumor activity of the RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in KRASG12C-mutant non-small cell lung cancer (NSCLC). Broad-spectrum reversible RASGTP inhibition with or without concurrent covalent targeting of active RASG12C yielded superior and differentiated antitumor activity across diverse comutational KRASG12C-mutant NSCLC mouse models of primary or acquired RASG12C(ON) or RASG12C(OFF) inhibitor resistance. Interrogation of time-resolved single-cell transcriptional responses established an in vivo atlas of multimodal acute and chronic RAS pathway inhibition in the NSCLC ecosystem and uncovered a regenerative mucinous transcriptional program that supports long-term tumor cell persistence. In patients with advanced KRASG12C-mutant NSCLC, the presence of mucinous histologic features portended poor response to sotorasib or adagrasib. Our results have potential implications for personalized medicine and the development of rational RAS inhibitor-anchored therapeutic strategies. Significance: Our work reveals robust and durable antitumor activity of the preclinical RAS(ON) multiselective inhibitor RMC-7977 against difficult-to-treat subsets of KRASG12C-mutant NSCLC with primary or acquired RASG12C inhibitor resistance and identifies a conserved mucinous transcriptional state that supports RAS inhibitor tolerance. See related commentary by Marasco and Misale, p. 2018., (©2024 American Association for Cancer Research.)

Importance: The benefit of adenoidectomy on otologic outcomes after tympanostomy tube (TT) insertion is unclear. Results from prior work are challenging to interpret due to small sample sizes, heterogeneous study designs, and varying outcome measures., Objective: To evaluate the association between adenoidectomy and otologic outcomes using a US population-level sample of children who received TTs, producing generalizable results for widespread clinical application., Design, Setting, and Participants: A matched cohort study was conducted using claims data from the Merative MarketScan Research Databases. The study included 601 848 children who received TTs between January 1, 2007, and December 31, 2021. Children who received adenoidectomy and TTs simultaneously (Ad+TT) were identified irrespective of the number of prior TTs. Control participants who received TTs without adenoidectomy were matched based on sex, age at the time of the procedure, and the number of prior TT procedures., Exposures: Adenoidectomy without tonsillectomy was the primary exposure., Main Outcomes and Measures: The primary outcomes were repeat TT insertion and subsequent oral antibiotic prescriptions after TT insertions. Multivariable logistic regression was used to quantify the effects of adenoidectomy and covariates on each outcome. Stratified analyses were performed in children younger than 4 years and 4 years or older., Results: Overall, 601 848 children (median [IQR] age, 2 [1-4] years; range, 0-11 years; 351 078 [58.3%] male) who received TTs were identified. The Ad+TT cohort included 201 932 children, with an equal number in the matched cohort. In children younger than 4 years, Ad+TT was common and was associated with lower odds of subsequent oral antibiotics (odds ratio [OR], 0.59; 95% CI, 0.58-0.60) but higher odds of repeat TT insertions (OR, 1.24; 95% CI, 1.22-1.27). In children 4 years or older, Ad+TT was associated with lower odds of repeat TT insertions (OR, 0.78; 95% CI, 0.75-0.81) and subsequent oral antibiotics (OR, 0.63; 95% CI, 0.62-0.65)., Conclusions and Relevance: This study found that in children younger than 4 years, Ad+TT was commonly performed and may have had a secondary benefit of reducing subsequent oral antibiotic courses; however, it was not associated with a reduction in the risks of repeat TT insertions. In children 4 years or older, Ad+TT was associated with a reduction in the risk of repeat TT insertions and subsequent oral antibiotics. Given these findings, Ad+TT may be offered in children 4 years or older to improve otologic outcomes.

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB 1,2 . Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial 3 . Unbiased genetic screens identified loss of both of these tumour suppressor genes as independent drivers of resistance to PD-(L)1 inhibition, and showed that loss of Keap1 was the strongest genomic predictor of dual ICB efficacy-a finding that was confirmed in several mouse models of Kras-driven NSCLC. In both mouse models and patients, KEAP1 and STK11 alterations were associated with an adverse tumour microenvironment, which was characterized by a preponderance of suppressive myeloid cells and the depletion of CD8 + cytotoxic T cells, but relative sparing of CD4 + effector subsets. Dual ICB potently engaged CD4 + effector cells and reprogrammed the tumour myeloid cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that-together with CD4 + and CD8 + T cells-contributed to anti-tumour efficacy. These data support the use of chemo-immunotherapy with dual ICB to mitigate resistance to PD-(L)1 inhibition in patients with NSCLC who have STK11 and/or KEAP1 alterations., (© 2024. The Author(s).)

Context and Objective: The genetic profile of prolactinomas remains poorly understood. Our objective is to identify somatic genetic alterations associated with prolactinomas and to report the identification of an activating ESR1 mutation (ESR1Y537S) in an aggressive prolactinoma., Setting: Brigham and Women's Hospital., Design: Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation (CNV)., Results: Twenty subjects (mean age 38.6 years; 12 women and 8 men) were included in this study. A somatic ESR1Y537S mutation was identified in an aggressive prolactinoma in a post-menopausal woman. No SF3B1 or other somatic mutations were identified. The median number of CNV events identified in our samples was 46; the prolactinoma with ESR1Y537S had the highest number with 233 events. In breast cancer, ESR1Y537S has been shown to activate estrogen receptor alpha independent of ligand binding. In patients with resistant breast cancer and ESR1Y537S, elacestrant, a second-line ER degrader, improves progression-free survival. Therefore, given the lack of response to multimodality therapies, elacestrant was initiated in this patient after the third cycle of radiotherapy. Elacestrant, along with radiotherapy, controlled tumor growth and significantly reduced prolactin levels., Conclusion: Molecular profiling allowed the identification of ESR1Y537S, in an aggressive prolactinoma. ESR1Y537S was not detected early in the course of the disease and is likely conferring tumor aggressiveness. This finding emphasizes the significance of estrogen receptor signaling in prolactinomas. It also allowed the use of targeted therapy with successful control of disease progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Editor's Note. - RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics . These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.

Positron emission tomography/computed tomography (PET/CT) using [18F]-fluoro-2-deoxy-D-glucose (FDG) has become the mainstay imaging modality for evaluating oncology patients with certain cancers. The most common FDG PET/CT applications include staging/restaging, assessing response to therapy and detecting tumor recurrence. It is important to be aware of potential pitfalls and technical artifacts on PET/CT in the chest and abdomen to ensure accurate interpretation, avoid unnecessary intervention and optimize patient care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chest radiography is one of the most commonly performed imaging tests, and benefits include accessibility, speed, cost, and relatively low radiation exposure. Lung cancer is the third most common cancer in the United States and is responsible for the most cancer deaths. Knowledge of the role of chest radiography in assessing patients with lung cancer is important. This article discusses radiographic manifestations of lung cancer, the utility of chest radiography in lung cancer management, as well as the limitations of chest radiography and when computed tomography (CT) is indicated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Imaging plays a key role in clinical staging of lung cancer and guiding therapy. A thorough understanding of the staging system including the nomenclature and updates is necessary to tailor treatment plans and optimize patient care. The 9th edition of the Tumor, Node, Metastasis staging system for lung cancer has no changes for T classification and subdivides N2 and M1c categories. In nodal staging, N2 splits into N2a, ipsilateral mediastinal single station involvement and N2b, ipsilateral mediastinal multiple stations involvement. In the staging of multiple extrathoracic metastases, M1c splits into M1c1, multiple extrathoracic metastases in one organ system and M1c2, multiple extrathoracic metastases in multiple organ systems. Awareness of the proposed changes in TNM-9 staging classification is essential to provide methodical and accurate imaging interpretation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To understand attentional preferences for normal and microtia ears., Methods: Eye-tracking technology was used to characterize gaze preferences. A total of 71 participants viewed images of 5 patients with unilateral microtia. Profile images of patient faces and isolated ears including normal, microtia, and post-reconstruction microtia ears were shown. Total time of fixation in predefined areas of interest (AOI) was measured. Inferential statistics were used to assess significance of fixation differences between AOIs within and between facial or auricular features., Results: The ear received most visual attention in lateral view of the face (1.91 s, 1.66-2.16 s) [mean, 95% CI], followed by features of the "central triangle"-the eyes (1.26 s, 1.06-1.46), nose (0.48 s, 0.38-0.58), and mouth (0.15 s, 0.15-0.20). In frontal view, microtia ears received less attention following surgical reconstruction (0.74 s vs. 0.4 s, p < 0.001). The concha was the most attended feature for both normal (2.97 s, 2.7-3.23) and reconstructed microtia ears (1.87 s, 1.61-2.13). Scars on reconstructed ears altered the typical visual scanpath., Conclusion: The ear is an attentional gaze landmark of the face. Attention to microtia ears, both pre- and post-reconstruction, differs from gaze patterns of normal ears. The concha was the most attended to subunit of the ear. Attentional gaze may provide an unbiased method to determine what is important in reconstructive surgery., Level of Evidence: NA Laryngoscope, 134:3136-3142, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The pericardium comprises a double-walled fibrous-serosal sac that encloses the heart. Reflections of the serosal layer form sinuses and recesses. With advances in multidetector computed tomography (CT) technology, pericardial recesses are frequently detected with thin-section CT. Knowledge of pericardial anatomy on imaging is crucial to avoid misinterpretation of fluid-filled pericardial sinuses and recesses as adenopathy/pericardial metastasis or aortic dissection, which can impact patient management and treatment decisions. The authors offer a comprehensive review of pericardial anatomy and its variations observed on CT, potential pitfalls in image interpretation, and implications for the pulmonologist with respect to unnecessary diagnostic procedures or interventions., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Drug-induced lung disease is commonly encountered, especially in the oncology setting. Diagnosis is challenging because clinical and radiologic findings are nonspecific, often overlapping with other lung pathologies in these patients due to underlying neoplasia, infection, or other treatment effects such as radiotherapy. Furthermore, oncology patients often receive multiple antineoplastic agents concurrently, and virtually every agent has an association with lung injury. In this article, we will review a variety of antineoplastic agents that are associated with drug-induced injury and discuss incidence, their typical timing of onset, and imaging features., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lung cancer remains one of the leading causes of mortality worldwide, as well as in the United States. Clinical staging, primarily with imaging, is integral to stratify patients into groups that determine treatment options and predict survival. The eighth edition of the tumor, node, metastasis (TNM-8) staging system proposed in 2016 by the International Association for the Study of Lung Cancer remains the current standard for lung cancer staging. The system is used for all subtypes of lung cancer, including non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumors., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Lung cancer is the leading cause of cancer deaths in men and women in the United States. Accurate staging is needed to determine prognosis and devise effective treatment plans. The International Association for the Study of Lung Cancer (IASLC) has made multiple revisions to the tumor, node, metastasis (TNM) staging system used by the Union for International Cancer Control and the American Joint Committee on Cancer to stage lung cancer. The eighth edition of this staging system includes modifications to the T classification with cut points of 1 cm increments in tumor size, grouping of lung cancers associated with partial or complete lung atelectasis or pneumonitis, grouping of tumors with involvement of a main bronchus regardless of distance from the carina, and upstaging of diaphragmatic invasion to T4. The N classification describes the spread to regional lymph nodes and no changes were proposed for TNM-8. In the M classification, metastatic disease is divided into intra- versus extrathoracic metastasis, and single versus multiple metastases. In order to optimize patient outcomes, it is important to understand the nuances of the TNM staging system, the strengths and weaknesses of various imaging modalities used in lung cancer staging, and potential pitfalls in image interpretation.

Objective: To identify and analyse ongoing nutrition-related surveillance programmes led and/or funded by national authorities in countries in South-East Asian and Western Pacific Regions., Methods: We systematically searched for publications in PubMed® and Scopus, manually searched the grey literature and consulted with national health and nutrition officials, with no restrictions on publication type or language. We included low- and middle-income countries in the World Health Organization South-East Asia Region, and the Association of Southeast Asian Nations and China. We analysed the included programmes by adapting the United States Centers for Disease Control and Prevention's public health surveillance evaluation framework., Findings: We identified 82 surveillance programmes in 18 countries that repeatedly collect, analyse and disseminate data on nutrition and/or related indicators. Seventeen countries implemented a national periodic survey that exclusively collects nutrition-outcome indicators, often alongside internationally linked survey programmes. Coverage of different subpopulations and monitoring frequency vary substantially across countries. We found limited integration of food environment and wider food system indicators in these programmes, and no programmes specifically monitor nutrition-sensitive data across the food system. There is also limited nutrition-related surveillance of people living in urban deprived areas. Most surveillance programmes are digitized, use measures to ensure high data quality and report evidence of flexibility; however, many are inconsistently implemented and rely on external agencies' financial support., Conclusion: Efforts to improve the time efficiency, scope and stability of national nutrition surveillance, and integration with other sectoral data, should be encouraged and supported to allow systemic monitoring and evaluation of malnutrition interventions in these countries., ((c) 2023 The authors; licensee World Health Organization.)

Radiation therapy using conventional or newer high-precision dose techniques, including three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, four-dimensional conformational radiotherapy, and proton therapy, is an important component of treating patients with lung cancer. Knowledge of the radiation technique used and the expected temporal evolution of radiation-induced lung injury, as well as patient-specific parameters such as previous radiotherapy, concurrent chemoradiotherapy, or immunotherapy, is important in image interpretation. This review discusses factors that affect the development and severity of radiation-induced lung injury and its radiological manifestations, as well as the differences between conventional and high-precision dose radiotherapy techniques.

Mediastinal masses present a diagnostic challenge due to their diverse etiologies. Accurate localization and internal characteristics of the mass are the two most important factors to narrow the differential diagnosis or provide a specific diagnosis. The International Thymic Malignancy Interest Group (ITMIG) classification is the standard classification system used to localize mediastinal masses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two most commonly used imaging modalities for characterization of the mediastinal masses.

Lung cancer continues to be the most common cause of cancer-related death worldwide. In the past decade, with the implementation of lung cancer screening programs and advances in surgical and nonsurgical therapies, the survival of patients with lung cancer has increased, as has the number of imaging studies that these patients undergo. However, most patients with lung cancer do not undergo surgical re-section, because they have comorbid disease or lung cancer in an advanced stage at diagnosis. Nonsurgical therapies have continued to evolve with a growing range of systemic and targeted therapies, and there has been an associated evolution in the imaging findings encountered at follow-up examinations after such therapies (e.g., with respect to posttreatment changes, treatment complications, and recurrent tumor). This AJR Expert Panel Narrative Review describes the current status of nonsurgical therapies for lung cancer and their expected and unexpected imaging manifestations. The goal is to provide guidance to radiologists regarding imaging assessment after such therapies, focusing mainly on non-small cell lung cancer. Covered therapies include systemic therapy (conventional chemotherapy, targeted therapy, and immunotherapy), radiotherapy, and thermal ablation.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database., Methods: Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival., Results: A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]: 1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001)., Conclusions: In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor., (© 2023 Wiley Periodicals LLC.)

Objectives: The objective of this study is to determine whether machine learning may be used for objective assessment of aesthetic outcomes of auricular reconstructive surgery., Methods: Images of normal and reconstructed auricles were obtained from internet image search engines. Convolutional neural networks were constructed to identify auricles in 2D images in an auto-segmentation task and to evaluate whether an ear was normal versus reconstructed in a binary classification task. Images were then assigned a percent score for "normal" ear appearance based on confidence of the classification., Results: Images of 1115 ears (600 normal and 515 reconstructed) were obtained. The auto-segmentation task identified auricles with 95.30% accuracy compared to manually segmented auricles. The binary classification task achieved 89.22% accuracy in identifying reconstructed ears. When the confidence of the classification was used to assign percent scores to "normal" appearance, the reconstructed ears were classified to a range of 2% (least like normal ears) to 98% (most like normal ears)., Conclusion: Image-based analysis using machine learning can offer objective assessment without the bias of the patient or the surgeon. This methodology could be adapted to be used by surgeons to assess quality of operative outcome in clinical and research settings., Level of Evidence: 4 Laryngoscope, 133:2413-2416, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To evaluate multi-parametric MRI for distinguishing stereotactic body radiation therapy (SBRT) induced pulmonary fibrosis from local recurrence (LR)., Materials and Methods: SBRT treated non-small cell lung cancer (NSCLC) patients suspected of LR by conventional imaging underwent MRI: T2 weighted, diffusion weighted imaging, dynamic contrast enhancement (DCE) with a 5-minute delayed sequence. MRI was reported as high or low suspicion of LR. Follow-up imaging ≥12 months or biopsy defined LR status as proven LR, no-LR or not-verified., Results: MRI was performed between 10/2017 and 12/2021, at a median interval of 22.5 (interquartile range 10.5-32.75) months after SBRT. Of the 20 lesions in 18 patients: 4 had proven LR, 10 did not have LR and 6 were not verified for LR due to subsequent additional local and/or systemic therapy. MRI correctly identified as high suspicion LR in all proven LR lesions and low suspicion LR in all confirmed no-LR lesions. All proven LR lesions (4/4) showed heterogeneous enhancement and heterogeneous T2 signal, as compared to the proven no-LR lesions in which 7/10 had homogeneous enhancement and homogeneous T2 signal. DCE kinetic curves could not predict LR status. Although lower apparent diffusion coefficient (ADC) values were seen in proven LR lesions, no absolute cut-off ADC value could determine LR status., Conclusion: In this pilot study of NSCLC patients after SBRT, multi-parametric chest MRI was able to correctly determine LR status, with no single parameter being diagnostic by itself. Further studies are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRASG12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRASG12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRASG12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies., Significance: In this work, we identify co-occurring genomic alterations in KEAP1, SMARCA4, and CDKN2A as independent determinants of poor clinical outcomes with KRASG12Ci monotherapy in advanced NSCLC, and we propose a framework for patient stratification and treatment personalization based on the comutational status of individual tumors. See related commentary by Heng et al., p. 1513. This article is highlighted in the In This Issue feature, p. 1501., (©2023 American Association for Cancer Research.)

Malignant mesothelioma is a rare tumor arising from the mesothelial cells that line the pleura, pericardium, peritoneum, and tunica vaginalis. Imaging plays a primary role in the diagnosis, staging, and management of malignant mesothelioma. Multimodality imaging, including radiography, computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), is used in a variety of scenarios, including diagnosis, guidance for tissue sampling, staging, and reassessment of disease after therapy. CT is the primary imaging modality used in staging. MRI has superior contrast resolution compared with CT and can add value in terms of determining surgical resectability in equivocal cases. MRI can further assess the degree of local invasion, particularly into the mediastinum, chest wall, and diaphragm, for malignant pleural and pericardial mesotheliomas. FDG PET/CT plays a role in the diagnosis and staging of malignant pleural mesothelioma (MPM) and has been shown to be more accurate than CT, MRI, and PET alone in the staging of malignant pleural mesothelioma. PET/CT can also be used to target lesions for biopsy and to assess prognosis, treatment response, and tumor recurrence., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

An integral part of managing patients with thymoma and thymic carcinoma is imaging. At diagnosis and staging, imaging helps demonstrate the extent of local invasion and distant metastases which allows the proper stratification of patients for therapy. For decades, the predominant staging system for thymic tumors was the Masaoka-Koga staging system. More recently, however, the International Association for the Study of Lung Cancer, the International Thymic Malignancies Interest Group (ITMIG), the European Society of Thoracic Surgeons, the Chinese Alliance for Research on Thymomas, and the Japanese Association of Research on Thymus partnered together to develop a tumor-node-metastasis (TNM) staging system specifically for thymic tumors based on a retrospective database of nearly 10,000 patients. The TNM 8 th edition defines specific criteria for thymic tumors. Imaging also serves to assess treatment response and detect recurrent disease after various treatment modalities. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is currently used to assess response to treatment. ITMIG recommends certain modifications to RECIST version 1.1, however, in thymic tumors due to unique patterns of spread. While there is often overlap, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) characteristics can help differentiate thymoma and thymic carcinoma, with newer CT and MRI techniques under evaluation showing encouraging potential., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-22-58/coif). EMM reports an honorarium for a lecture from each of the following companies: Boehringer Ingelheim, AstraZeneca, Merck Sharp and Dohme. The other authors have no conflicts of interest to declare., (2023 Mediastinum. All rights reserved.)

A wide variety of neoplastic and nonneoplastic conditions occur in the mediastinum. Imaging plays a central role in the evaluation of mediastinal pathologies and their mimics. Localization of a mediastinal lesion to a compartment and characterization of morphology, density/signal intensity, enhancement, and mass effect on neighboring structures can help narrow the differentials. The International Thymic Malignancy Interest Group (ITMIG) established a cross-sectional imaging-derived and anatomy-based classification system for mediastinal compartments, comprising the prevascular (anterior), visceral (middle), and paravertebral (posterior) compartments. Cross-sectional imaging is integral in the evaluation of mediastinal lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to characterize mediastinal lesions detected on radiography. Advantages of CT include its widespread availability, fast acquisition time, relatively low cost, and ability to detect calcium. Advantages of MRI include the lack of radiation exposure, superior soft tissue contrast resolution to detect invasion of the mass across tissue planes, including the chest wall and diaphragm, involvement of neurovascular structures, and the potential for dynamic sequences during free-breathing or cinematic cardiac gating to assess motion of the mass relative to adjacent structures. MRI is superior to CT in the differentiation of cystic from solid lesions and in the detection of fat to differentiate thymic hyperplasia from thymic malignancy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-22-53/coif). The authors have no conflicts of interest to declare., (2023 Mediastinum. All rights reserved.)

Introduction: There is a dearth of data on cancer care in the incarcerated population, despite being the leading cause of illness-related death in United states' prisons. We retrospectively reviewed the demographic and clinicopathologic characteristics of incarcerated individuals who received radiation therapy at a large safety-net hospital., Methods: Following IRB approval, we identified 80 incarcerated patients who presented for radiation therapy between January 2003 and May 2019. Descriptive statistics on the patients, tumor types and stage, treatment factors, and follow-up rates were analyzed., Results: 80 individuals with 82 cancer diagnoses presented for radiation oncology consultation over the study period. The median age was 54 years (range, 46-64). Patients of White, Black, and "other" races comprised 61.3% (n=49), 28.8% (n=23), and 10% (n=8), respectively. Most patients were male (n=75, 93.8%) and English speakers (n=76, 95%). Moreover, 50% (n=40) had a substance use disorder history and 75% (n=60) had a smoking history. The three most common cancer types were prostate (n=12, 14.6%), gastrointestinal (n=14, 17.1%), thoracic (n=17, 20.7%), and head and neck (n=21, 25.6%). The distribution of tumor stage (AJCC) was I (n=12, 14.6%), II (n=12, 14.6%), III (n=14, 17.1%), IV (n=38, 46.3%), and unknown/unavailable (n=6, 7.3%). Of the cohort, 65 patients with 66 cancers (80.5%) received radiation. Among them, the 6-month, 1-year, and 5-year follow-up rates were 41.5%, 27.7%, and 3.1%, respectively. Subset analysis limited to stage I-III patients (n=30) revealed 6-month, 1-year and 5-year follow-up rates of 41.9%, 22.6%, and 3.2%, respectively., Conclusions: This study highlights inequalities in cancer stage at diagnosis among a vulnerable patient population that is largely excluded from clinical research. Majority of the incarcerated patients presented with stage III & IV cancers and have poor follow up rates even among those with early-stage disease. Efforts to understand and mitigate persistent health inequalities among incarcerated patients are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To examine the relationship between hospital safety-net burden and (1) receipt of surgery after chemoradiation (trimodality therapy) and (2) survival in esophageal cancer patients., Methods: The National Cancer Database was queried to identify 22,842 clinical stage II to IVa esophageal cancer patients diagnosed in 2004 to 2015. The treatment facilities were categorized by proportion of uninsured/Medicaid-insured patients into percentiles. No safety-net burden hospitals (0-37th percentile) treated no uninsured/Medicaid-insured patients, whereas low (38-75th percentile) and high (76-100th percentile) safety-net burden hospitals treated a median (range) of 8.8% (0.87%-16.7%) and 23.6% (16.8%-100%), respectively. Adjusted odds ratios and hazard ratios with 95% confidence intervals were computed, adjusting for patient, tumor, and treatment characteristics., Results: Compared to no safety-net burden hospital patients, high safety-net burden hospital patients were significantly more likely to be young, Black, and low-income. Age, female sex, Black race, Hispanic ethnicity, nonprivate insurance, lower income, higher comorbidity score, upper esophageal location, squamous cell histology, higher stage, time to treatment, and treatment at a community program or a low-volume facility were associated with lower odds of receiving trimodality therapy. Adjusting for these factors, high safety-net burden hospital patients were less likely to receive surgery after chemoradiation versus no safety-net burden hospital patients (adjusted odds ratio 0.77 [95% confidence interval 0.68-0.86], P < .0001); no difference was detected comparing low safety-net burden hospitals versus no safety-net burden hospitals (adjusted odds ratio 1.01 [0.92-1.11], P = .874). No significant survival difference was noted by safety-net burden (low safety-net burden hospitals versus no safety-net burden hospitals: adjusted hazard ratio 1.01 [0.96-1.06], P = .704; high safety-net burden hospital versus no safety-net burden hospitals: adjusted hazard ratio 0.99 [0.93-1.06], P = .859)., Conclusion: Adjusting for patient, tumor, and treatment factors, high safety-net burden hospital patients were less likely to undergo surgery after chemoradiation but without significant survival differences., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This analysis investigates whether research productivity during medical school predicts future research productivity during radiation oncology residency., Methods and Materials: At our institution, there have been 20 medical students who graduated between 2005 and 2015 and subsequently completed their residency training in radiation oncology. We built a database of all PubMed-indexed publications in which these former students were the first author or coauthor. Mean publication rates with 95% confidence intervals (95% CI) were computed. The paired t test and McNemar-Bowker test of symmetry were used to examine differences in first-author and coauthor publications between the medical school and residency periods. An ordinal logistic regression model was employed to measure the odds ratio of publishing during residency versus during medical school. A Spearman correlation coefficient was calculated for the relationship between the number of publications during medical school and the number during residency., Results: A total of 14 and 60 first-author publications (46 and 117 coauthor publications) were identified for 20 individuals during medical school and residency, respectively. There was an average of 0.7 (95% CI, 0.17-1.23) first-author publications during medical school and 3.08 (95% CI, 1.56-4.44) first-author publications during residency ( P  = .003). Only 15% (3/20) had ≥2 publications during medical school, and 50% (10/20) had ≥2 publications during residency ( P  = .012). The Spearman correlation coefficient between research publications before and during residency was .457 ( P  = .043). The mean number of coauthor publications during medical school and residency was 2.3 (95% CI, 0.92-3.68) and 5.85 (95% CI, 3.50-8.20), respectively ( P  = .004)., Conclusions: Based on this retrospective analysis from our institution, student research productivity during medical school, as defined by the number of first-author publications, does correlate with future research productivity during radiation oncology residency., (© 2023 The Authors.)

Purpose: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown., Methods and Materials: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms., Results: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol., Conclusions: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This study evaluates the impact of depth of invasion (DOI) on local recurrence (LR) in node-negative oral tongue squamous cell carcinoma (SCC)., Methods: Fifty-one patients were retrospectively reviewed from an institutional database. Patients were evaluated for local control (LC). Cox-proportional hazards modeling was used to calculate hazard ratios., Results: There were 84.3% T1/2 and 15.7% T3/4 classification tumors. The 3-year overall survival rate was 97.9%. Local failure rate was 5.7% with a 3-year LC of 93.6%. On Univariate analysis, increased hazard of LR was noted with each unit increase in DOI (HR 1.40, 95% CI 1.07-1.83, p = 0.014). Age, sex, T classification, margins ≥5 mm, lymphovascular invasion (LVI) and perineural invasion (PNI), and adjuvant treatment were not associated with LR. On Multivariate analysis, adjusting for age and adjuvant treatment, results for DOI remained significant (aHR 1.46, 95% CI 1.08-1.98, p = 0.013)., Conclusion: On evaluation of our institutional dataset increasing DOI was associated with increased hazard of local recurrence with oral tongue SCC., (© 2022 Wiley Periodicals LLC.)

The purpose of this study was to determine the negative predictive value (NPV) of a 12- to 14-wk posttreatment PET/CT for 2-y progression-free survival (PFS) and locoregional control (LRC) in patients with p16-positive locoregionally advanced oropharyngeal cancer (LA-OPC). Study was a secondary endpoint in NRG-HN002, a noncomparative phase II trial in p16-positive LA-OPC, stage T1-T2, N1-N2b or T3, N0-N2b, and ≤10 pack-year smoking. Patients were randomized in a 1:1 ratio to reduced-dose intensity-modulated radiotherapy (IMRT) with or without cisplatin. Methods: PET/CT scans were reviewed centrally. Tumor response evaluations for the primary site, right neck, and left neck were performed using a 5-point ordinal scale (Hopkins criteria). Overall scores were then assigned as negative, positive, or indeterminate. Patients with a negative score for all 3 evaluation sites were given an overall score of negative. The hypotheses were NPV for PFS and LRC at 2-y posttreatment ≤ 90% versus >90% (1-sided P value, 0.10). Results: A total of 316 patients were enrolled, of whom 306 were randomized and eligible. Of these, 131 (42.8%) patients consented to a posttherapy PET/CT, and 117 (89.3%) patients were eligible for PET/CT analysis. The median time from the end of treatment to PET/CT scan was 94 d (range, 52-139 d). Estimated 2-y PFS and LRC rates in the analysis subgroup were 91.3% (95% CI, 84.6, 95.8%) and 93.8% (95% CI, 87.6, 97.5%), respectively. Posttreatment scans were negative for residual tumor for 115 patients (98.3%) and positive for 2 patients (1.7%). NPV for 2-y PFS was 92.0% (90% lower confidence bound [LCB] 87.7%; P = 0.30) and for LRC was 94.5% (90% LCB 90.6%; P = 0.07). Conclusion: In the context of deintensification with reduced-dose radiation, the NPV of a 12- to 14-wk posttherapy PET/CT for 2-y LRC is estimated to be >90%, similar to that reported for patients receiving standard chemoradiation. However, there is insufficient evidence to conclude that the NPV is >90% for PFS., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

At our institution, students can be mentored by radiation oncology faculty through structured research programs, such as the Medical Student Summer Research Program (MSSRP). The purpose of this study is to report the research productivity of students who engaged in radiation oncology research mentorship, whether through the MSSRP or other avenues of research mentorship. We compiled a database of abstracts and manuscripts co-authored by 58 students who conducted research with radiation oncology faculty from 2005 to 2020. The means, medians, ranges, and interquartile ranges (IQR) of co-authorships and first authorships were calculated for the overall cohort and compared for MSSRP and non-MSSRP students, who matched into radiation oncology and those who did not, and male versus female students. Among all 58 students, 106 abstracts and 70 manuscripts were identified. Of those students, 54 (93.1%) published at least one abstract or manuscript. The mean number of abstract co-authorships per student was 3.07 (median 2, range 0-25, IQR 0-4), and the mean number of manuscript co-authorships per student was 2.22 (median 1, range 0-18, IQR 1-3). There were no significant differences in research output between MSSRP and non-MSSRP students or male and female students. However, the students who matched into radiation oncology published more co-author (3.67 vs. 1.63, p = 0.01) and first-author (1.62 vs. 0.53, p = 0.006) manuscripts than those who did not. Further research is warranted to assess whether skills gained from student-directed research translate into residency and beyond., (© 2021. American Association for Cancer Education.)

Objectives: To present recommendations for the coordinated evaluation and management of the hearing and reconstructive needs of patients with microtia and aural atresia., Methods: A national working group of 9 experts on microtia and atresia evaluated a working document on the evaluation and treatment of patients. Treatment options for auricular reconstruction and hearing habilitation were reviewed and integrated into a coordinated care timeline., Results: Recommendations were created for children with microtia and atresia, including diagnostic considerations, surgical and non-surgical options for hearing management and auricular reconstruction, and the treatment timeline for each option. These recommendations are based on the collective opinion of the group and are intended for otolaryngologists, audiologists, plastic surgeons, anaplastologists, and any provider caring for a patient with microtia and ear canal atresia. Close communication between atresia/hearing reconstruction surgeon and microtia repair surgeon is strongly recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer [BK] declared a past collaboration with the author [KC] to the handling editor at the time of review., (© 2022 Truong, Liu, Kohn, Chinnadurai, Zopf, Tribble, Tanner, Sie and Chang.)

Lung cancer is a leading cause of cancer-related mortality worldwide. Imaging is integral in accurate clinical staging to stratify patients into groups to predict survival and determine treatment. The eighth edition of the tumor, node, and metastasis (TNM-8) staging system proposed by the International Association for the Study of Lung Cancer in 2016, accepted by both the Union for International Cancer Control and the American Joint Committee on Cancer, is the current standard method of staging lung cancer. This single TNM staging is used for all histologic subtypes of lung cancer, including nonsmall cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumor, and it addresses both clinical and pathologic staging. Familiarity with the strengths and limitations of imaging modalities used in staging, the nuances of TNM-8, its correct nomenclature, and potential pitfalls are important to optimize patient care. In this article, we discuss the role of computed tomography (CT) and positron emission tomography/CT in lung cancer staging, as well as current imaging recommendations pertaining to TNM-8., Competing Interests: None declared., (Thieme. All rights reserved.)

Particulate-bound mercury (PBM) is a global environmental concern owing to its large dry deposition velocities and scavenging coefficients, both of which drive Hg into terrestrial and marine ecosystems. PBM observation studies have been widely conducted over East Asia, but comparable studies in Peninsular Southeast Asia (PSEA) remain scarce. This is the first study reporting PBM concentrations for Ho Chi Minh City (HCMC), the biggest metropolitan area in Vietnam. A total of 222 samples were collected in 2018 and contained an average PBM 10 (particulate matter - PM with diameter ≤10 μm) concentration and Hg mass fraction (i.e. PBM/PM) of 67.3 ± 45.9 pg m -3 and 1.18 ± 1.12 μg g -1 , respectively. Although PBM concentration was lower than those reported in Chinese megacities, the Hg mass fraction was similar to those in China, suggesting strong enrichment from anthropogenic Hg emissions in HCMC. Traffic-induced particulate emission and deposition processes were major factors governing PBM temporal variation at our site. In addition, the prevailing southwest monsoon winds brought air masses that passed through industrial areas and were associated with a higher Hg mass fraction. Statistically significant positive correlations (R 2  = 0.11-0.52, p < 0.01) were observed for PBM with PM and the Hg mass fraction, indicating similar PM and Hg sources or oxidized Hg adsorption onto PM via gas-particle partitioning. Moreover, PCA results revealed a higher contribution of primary sources than secondary sources to PBM concentration variability in HCMC. A health risk assessment indicated that the PBM concentrations at HCMC posed minimal non-carcinogenic risks (HI < 1) for children and adults, but dermal contact may act as an important exposure route since lightweight clothing is common among residents. This PBM dataset over PSEA, a region with high atmospheric Hg emissions, provides a valuable resource for the Hg scientific community to improve our understanding of Hg biogeochemical cycle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The normal immune system identifies and eliminates precancerous and cancerous cells. However, tumors can develop immune resistance mechanisms, one of which involves the exploitation of pathways, termed immune checkpoints, that normally suppress T-cell function. The goal of immune checkpoint inhibitor (ICI) immunotherapy is to boost T-cell-mediated immunity to mount a more effective attack on cancer cells. ICIs have changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and numerous ICIs have now been approved as first-line treatments for NSCLC by the U.S. Food and Drug Administration. ICIs can cause atypical response patterns such as pseudoprogression, whereby the tumor burden initially increases but then decreases. Therefore, response criteria have been developed specifically for patients receiving immunotherapy. Because ICIs activate the immune system, they can lead to inflammatory side effects, termed immune-related adverse events (irAEs). Usually occurring within weeks to months after the start of therapy, irAEs range from asymptomatic abnormal laboratory results to life-threatening conditions such as encephalitis, pneumonitis, myocarditis, hepatitis, and colitis. It is important to be aware of the imaging appearances of the various irAEs to avoid misinterpreting them as metastatic disease, progressive disease, or infection. The basic principles of ICI therapy; indications for ICI therapy in the setting of NSCLC; response assessment and atypical response patterns of ICI therapy, as compared with conventional chemotherapy; and the spectrum of irAEs seen at imaging are reviewed. An invited commentary by Nishino is available online. © RSNA, 2022.

Recent studies have shown that using international guidelines to diagnose metabolic syndrome (MetS) may underestimate its prevalence in different Asian populations. This study aims to determine the validity of anthropometric indicators and appropriate cut-off values to predict MetS for Vietnamese adults. We analyzed data on 4701 adults across four regions of Vietnam. Four conventional and five novel anthropometric indexes were calculated. The area under a receiver operating characteristic (ROC) curve (AUC) and Youden's J statistic were applied to evaluate the diagnostic ability and optimal cut-off values. Regardless of diagnostic criteria and gender, Abdominal volume index (AVI), Body roundness index (BRI), and Waist-height ratio (WHtR) had the highest AUC values, followed by Body mass index (BMI) and Waist-hip ratio (WHR). However, it was seen that differences among the AUC values of most indices were minor. In men, using International Diabetes Federation (IDF) criteria, the threshold of indices was 3.86 for BRI, 16.20 for AVI, 0.53 for WHtR, 22.40 for BMI, and 0.90 for WHR. In women, the threshold for these figures were 3.60, 12.80, 0.51, 23.58, and 0.85, respectively. It is recommended that health personnel in Vietnam should apply appropriate thresholds of anthropometry, which are lower than current international guidelines, for MetS screening to avoid under-diagnosis.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-22-3/coif). “The Series Dedicated to the 11th International Thymic Malignancy Interest Group Annual Meeting (Virtual ITMIG 2021)” was commissioned by the editorial office without any funding or sponsorship. MZ serves as an unpaid Associate Editor-in-Chief of Mediastinum from February 2020 to January 2024. ACR serves as an unpaid Associate Editor of Mediastinum from July 2021 to June 2023. MS served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Mediastinum from June 2021 to May 2023. ACR received Transplant Scholarly Time award “Unique Gene Expression Signatures in Lung Explants of Patients with Shortened Telomeres and their Prognostic Significance”, funded by Mayo Clinic Transplant Center, 2021-2023 and reported grant “Differential expression of inflammatory genes aids in the diagnosis of antibody mediated and acute rejection and their distinction from morphologic mimics in lung allografts” funded by DLMP Research Fund, 2019-2021, royalty for Contribution of medical educational material to up-to-date and honorarium from the College of American Pathologists for lecture. HW reports grants or contracts from ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune BMS, Clovis Oncology Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, Helsinn, participation on Advisory Boards of AstraZeneca, Xcovery, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn, Merck, Takeda, Genentech/Roche, Cellworks and she is a president of the International Association for the Study of Lung Cancer (IASLC) and a member of Executive committee of ECOG-ACRIN. MS reports paid lectures for Boehringer Ingelheim, AstraZeneca Pharma Poland, Roche Polska, MSD Polska and she is a Secretary of the International Thymic Malignancy Interest Group, Chair of Thymic and Mediastinal Working Group in European Society of Pathology, Member of Main Revisory Board in the Polish Society of Pathology. The authors have no other conflicts of interest to declare.

Objectives/hypothesis: Post-tonsillectomy hemorrhage (PTH) is a potentially life-threatening complication. A recent meta-analysis suggests that ibuprofen may increase the risk of PTH. The aims of this study were to 1) re-evaluate the effect of ibuprofen on PTH given additional recent evidence and 2) to evaluate a potential dose effect of ibuprofen., Study Design: Meta-analysis and meta-regression; single-institution retrospective review., Methods: We conducted a systematic review of the literature and a meta-analysis of 12 studies comparing postoperative ibuprofen analgesia to non-nonsteroidal anti-inflammatory drug (NSAID) controls. Next, we performed a meta-regression analysis to assess for an effect of dose, if any, on rates of PTH. Five studies specifying a dose of 5 mg/kg (828 patients, 1,411 controls) and 7 studies using 10 mg/kg (5,633 patients, 7,656 controls) were included. We then conducted a novel single-institution, retrospective review of data for 1,046 patients prescribed intermediate-dose 7.5 mg/kg ibuprofen., Results: Ibuprofen was not associated with an increased rate of PTH (log odds ratio [OR], 0.21; 95% confidence interval [CI] -0.15, 0.57). Meta-regression showed that ibuprofen dose (5 and 10 mg/kg) did not have a statistically significant effect on PTH (OR, 1.32; 95% CI 0.30, 5.84). Uncontrolled, aggregate rates of PTH across all studies were 2.29% (N = 828) for 5 mg/kg and 4.65% (N = 5,633) for 10 mg/kg dosing. The rate of secondary hemorrhage in patients prescribed 7.5 mg/kg ibuprofen was 3.10% (N = 1,046)., Conclusion: We found no statistically significant increased risk of PTH when ibuprofen is prescribed at the low or high range of commonly used clinical dosages, compared to a non-ibuprofen regimen. Further studies with less heterogeneity are needed to determine if there is a clinically relevant dose-dependent difference in PTH with ibuprofen., Level of Evidence: 3 Laryngoscope, 132:1473-1481, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Besides anti-inflammatory medication, physical exercise represents a cornerstone of modern treatment for patients with axial spondyloarthritis (AS). Digital health apps (DHAs) such as the yoga app YogiTherapy could remotely empower patients to autonomously and correctly perform exercises., Objective: This study aimed to design and develop a smartphone-based app, YogiTherapy, for patients with AS. To gain additional insights into the usability of the graphical user interface (GUI) for further development of the app, this study focused exclusively on evaluating users' interaction with the GUI., Methods: The development of the app and the user experience study took place between October 2020 and March 2021. The DHA was designed by engineering students, rheumatologists, and patients with AS. After the initial development process, a pilot version of the app was evaluated by 5 patients and 5 rheumatologists. The participants had to interact with the app's GUI and complete 5 navigation tasks within the app. Subsequently, the completion rate and experience questionnaire (attractiveness, perspicuity, efficiency, dependability, stimulation, and novelty) were completed by the patients., Results: The results of the posttest questionnaires showed that most patients were already familiar with digital apps (4/5, 80%). The task completion rates of the usability test were 100% (5/5) for the tasks T1 and T2, which included selecting and starting a yoga lesson and navigating to an information page. Rheumatologists indicated that they were even more experienced with digital devices (2/5, 40% experts; 3/5, 60% intermediates). In this case, they scored task completion rates of 100% (5/5) for all 5 usability tasks T1 to T5. The mean results from the User Experience Questionnaire range from -3 (most negative) to +3 (most positive). According to rheumatologists' evaluations, attractiveness (mean 2.267, SD 0.401) and stimulation (mean 2.250, SD 0.354) achieved the best mean results compared with dependability (mean 2.000, SD 0.395). Patients rated attractiveness at a mean of 2.167 (SD 0.565) and stimulation at a mean of 1.950 (SD 0.873). The lowest mean score was reported for perspicuity (mean 1.250, SD 1.425)., Conclusions: The newly developed and tested DHA YogiTherapy demonstrated moderate usability among rheumatologists and patients with rheumatic diseases. The app can be used by patients with AS as a complementary treatment. The initial evaluation of the GUI identified significant usability problems that need to be addressed before the start of a clinical evaluation. Prospective trials are also needed in the second step to prove the clinical benefits of the app., (©Minh Tam Truong, Obioma Bertrand Nwosu, Maria Elena Gaytan Torres, Maria Paula Segura Vargas, Ann-Kristin Seifer, Marlies Nitschke, Alzhraa A Ibrahim, Johannes Knitza, Martin Krusche, Bjoern M Eskofier, Georg Schett, Harriet Morf. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.06.2022.)