Body Composition in Primary Hyperparathyroidism: A Potential Contributor to Weakness and Fatigue.

BACKGROUND: Primary hyperparathyroidism (PHPT) patients commonly report weakness and fatigue, though the underlying mechanisms are uncertain. Our purpose is to determine whether CT-derived muscle and adipose tissue metrics are associated with weakness and fatigue in PHPT patients. METHODS: For this retrospective study, cross-sectional muscle and adipose tissue metrics were derived from CTs in PHPT patients undergoing preoperative imaging within 1 year of parathyroid surgery. Skeletal muscle index (SMI) and visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio were calculated based on a single CT image at the level of the L3 vertebra. Established sex-specific SMI thresholds were used to define sarcopenia. Demographic and clinical data were collected from the electronic health record. When available, postoperative CT images were analyzed to assess for changes in body composition pre- and post-parathyroidectomy. RESULTS: The cohort comprised 53 PHPT patients (38 females, 15 males, mean age 61.4 years), of whom 24 (45%) reported weakness, 43 (81%) reported fatigue, and 31 (58%) met CT-based criteria for sarcopenia. Lower SMI was significantly associated with preoperative weakness in females but not males. For both weakness and fatigue, VAT/SAT ratios were higher in symptomatic females and lower in symptomatic males than their asymptomatic counterparts, though these differences were not statistically significant. In patients with postoperative CTs (n = 23), no significant changes in CT metrics were observed after parathyroidectomy. DISCUSSION: In females but not males with PHPT, subjective preoperative weakness was significantly associated with lower SMI. Effects of parathyroid hormone on skeletal muscle and visceral adiposity may differ by sex.

Evaluation of Hearing Loss: Understanding Audiologic Testing to Refine Image Interpretation.

The standard of reference for diagnosing and characterizing hearing loss is audiologic testing. The results of audiologic testing inform the imaging algorithm and the differential diagnosis for the underlying cause. Pure-tone audiometry tests the ability to hear tones across different frequencies, and the results are displayed as an audiogram. Tympanometry measures tympanic membrane compliance as a function of pressure to generate a tympanogram. Acoustic reflex testing helps differentiate third window lesions from other causes of conductive hearing loss. Clinical and audiologic assessment of sensorineural hearing loss helps in differentiating cochlear from retrocochlear causes. Symmetrical sensorineural hearing loss is typical of cochlear disease. Asymmetry increases the likelihood of a retrocochlear lesion, the most common of which among adults is vestibular schwannoma. Unlike patients with sensorineural hearing loss, who commonly have normal imaging studies, patients with conductive hearing loss are expected to have abnormal temporal bone CT studies. By incorporating the results of audiologic testing into their evaluation, radiologists can perform a more informed and more intentional search for the structural cause of hearing loss. The authors describe several audiogram configurations that suggest specific underlying mechanisms of conductive hearing loss. By providing a practical and accessible summary of the basics of audiologic testing, the authors empower the radiologist to leverage relevant clinical information and audiologic test results to interpret temporal bone imaging more confidently and more accurately, particularly temporal bone CT in the setting of conductive hearing loss. ©RSNA, 2024.

Radiographic Response Assessments and Standardized Imaging Interpretation Criteria in Head and Neck Cancer on FDG PET/CT: A Narrative Review.

INTRODUCTION: There is growing interest in the development and application of standardized imaging criteria (SIC), to minimize variability and improve the reproducibility of image interpretation in head and neck squamous cell carcinoma (HNSCC). METHODS: "Squamous cell carcinoma" AND "standardized interpretation criteria" OR "radiographic response assessment" were searched using PubMed and Google Scholar for articles published between 2009 and 2024, returning 56 publications. After abstract review, 18 were selected for further evaluation, and 6 different SICs (i.e., PERCIST, Porceddu, Hopkins, NI-RADS, modified Deauville, and Cuneo) were included in this review. Each SIC is evaluated in the context of 8 desired traits of a standardized reporting system. RESULTS: Two SICs have societal endorsements (i.e., PERCIST, NI-RADS); four can be used in the evaluation of locoregional and systemic disease (i.e., PERCIST, Hopkins, NI-RADS, Cuneo), and four have specific categories for equivocal imaging results (i.e., Porceddu, NI-RADS, modified Deauville, and Cuneo). All demonstrated areas for future improvement in the context of the 8 desired traits. CONCLUSION: Multiple SICs have been developed for and demonstrated value in HNSCC post-treatment imaging; however, these systems remain underutilized. Selecting an SIC with features that best match the needs of one's practice is expected to maximize the likelihood of successful implementation.

RadioGraphics Update: Parathyroid CT and Primary Hyperparathyroidism.

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.

Testing for Primary Hyperparathyroidism in 17,491 Patients With Hypercalcemia.

BACKGROUND: Primary hyperparathyroidism (PHPT) is underdiagnosed and associated with many adverse health effects. Historically, many hypercalcemic patients have not received parathyroid hormone (PTH) testing; however, underlying reasons are uncertain. Our goals are to determine the PTH testing rate among hypercalcemic individuals at a large academic health system and to assess for characteristics associated with testing versus not testing for PHPT to inform future strategies for closing testing gaps. METHODS: This retrospective study included adult patients with ≥1 elevated serum calcium result between 2018 and 2022. Based on the presence or absence of a serum PTH result, individuals were classified as "screened" versus "unscreened" for PHPT. Demographic and clinical characteristics of these groups were compared. RESULTS: The sample comprised 17,491 patients: 6567 male (37.5%), 10,924 female (62.5%), mean age 59 y. PTH testing was performed in 6096 (34.9%). Characteristics independently associated with the greatest odds of screening were 5+ elevated calcium results (odds ratio [OR] 5.02, P < 0.0001), chronic kidney disease (OR 3.63, P < 0.0001), maximum calcium >12.0 mg/dL (OR 2.48, P < 0.0001), and osteoporosis (OR 2.42, P < 0.0001). Characteristics associated with lowest odds of screening were age <35 y (OR 0.60, P < 0.0001), death during the study period (OR 0.68, P < 0.0001), age ≥85 y (OR 0.70, P = 0.0007), and depression (OR 0.84; P = 0.0081). CONCLUSIONS: Only 35% of hypercalcemic patients received PTH testing. Although the presence of PHPT-associated morbidity was generally associated with increased rates of screening, hypercalcemic patients with depression were 16% less likely to be tested.

Study protocol: phase II study to evaluate the effect of cetuximab monotherapy after immunotherapy with PD-1 inhibitors in patients with head and neck squamous cell cancer.

Background: Immunotherapy with programmed death receptor-1 (PD-1) inhibitors, as a single agent or in combination with chemotherapy, is the standard first-line treatment for recurrent or metastatic head and neck squamous cell cancer (R/M HNSCC). Unfortunately, there is no established second-line treatment for the many patients who fail immunotherapy. Cetuximab is the only targeted therapy approved in HNSCC but historically has a low response rate of 13%. Objectives: We hypothesize that cetuximab monotherapy following an immune checkpoint inhibitor (ICI) will lead to increased efficacy due to a potential synergistic effect on the antitumor immune response, as a result of activation effects of both treatments on innate and adaptative immune responses. To the authors' knowledge, this is the only ongoing prospective clinical study that evaluates the combination of cetuximab and ICIs administered sequentially. Methods and analysis: In this non-randomized, open-label, phase II trial, 30 patients with R/M HNSCC who have previously failed or could not tolerate a PD-1 inhibitor as a single agent or in combination with chemotherapy will subsequently be treated with cetuximab monotherapy. Outcomes of interest include overall response rate, duration of response, progression-free survival, overall survival, and treatment toxicity, as well as treatment outcome measured by a patient-reported outcome questionnaire. Saliva and blood will be collected for correlative studies to investigate the immune response status at the end of therapy with an ICI and the effect of cetuximab on the antitumor immune response. The results will be correlated with the response to cetuximab and the time window between the last administration of an ICI and the loading dose of cetuximab. The clinical study is actively recruiting. Ethics: This study was approved by the Wake Forest Comprehensive Cancer Center Institutional Review Board: IRB00065239. Clinical trial registration: This study is registered on ClinicalTrials.gov: NCT04375384.

Association of CT-Derived Skeletal Muscle and Adipose Tissue Metrics with Frailty in Older Adults.

RATIONALE AND OBJECTIVES: Tools are needed for frailty screening of older adults. Opportunistic analysis of body composition could play a role. We aim to determine whether computed tomography (CT)-derived measurements of muscle and adipose tissue are associated with frailty. MATERIALS AND METHODS: Outpatients aged ≥ 55 years consecutively imaged with contrast-enhanced abdominopelvic CT over a 3-month interval were included. Frailty was determined from the electronic health record using a previously validated electronic frailty index (eFI). CT images at the level of the L3 vertebra were automatically segmented to derive muscle metrics (skeletal muscle area [SMA], skeletal muscle density [SMD], intermuscular adipose tissue [IMAT]) and adipose tissue metrics (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT]). Distributions of demographic and CT-derived variables were compared between sexes. Sex-specific associations of muscle and adipose tissue metrics with eFI were characterized by linear regressions adjusted for age, race, ethnicity, duration between imaging and eFI measurements, and imaging parameters. RESULTS: The cohort comprised 886 patients (449 women, 437 men, mean age 67.9 years), of whom 382 (43%) met the criteria for pre-frailty (ie, 0.10 < eFI ≤ 0.21) and 138 (16%) for frailty (eFI > 0.21). In men, 1 standard deviation changes in SMD (ß = -0.01, 95% confidence interval [CI], -0.02 to -0.001, P = .02) and VAT area (ß = 0.008, 95% CI, 0.0005-0.02, P = .04), but not SMA, IMAT, or SAT, were associated with higher frailty. In women, none of the CT-derived muscle or adipose tissue metrics were associated with frailty. CONCLUSION: We observed a positive association between frailty and CT-derived biomarkers of myosteatosis and visceral adiposity in a sex-dependent manner.

Sinonasal organized hematoma: Case report and review of the literature.

Sinonasal organized hematoma is a rare condition characterized by an organizing blood clot in the sinonasal cavity, which consists of blood products, fibrin, and dilated blood vessels. As a benign entity with an aggressive imaging appearance, it is important to differentiate sinonasal organized hematoma from malignancies affecting the paranasal sinuses and nasal cavities to guide appropriate management. In this report, we discuss the clinical presentation and diagnostic evaluation of an 82-year-old male with a left maxillary sinus organized hematoma and provide a comprehensive review of the relevant literature.

A New (Digital) Era in Medical Journalism: Leveraging Social Media and Other Online Tools to Increase Reach and Engagement.

Social media is a popular communication and marketing tool in modern society, with the power to reach and engage large audiences. Many members of the medical and radiology communities have embraced social media platforms, particularly X (formerly known as Twitter), as an efficient and economic means for performing patient outreach, disseminating research and educational materials, building networks, and promoting diversity. Editors of medical journals with a clear vision and relevant expertise can leverage social media and other digital tools to advance the journal's mission, further their interests, and directly benefit journal authors and readers. For editors, social media offers a means to increase article visibility and downloads, expand awareness of volunteer opportunities, and use metrics and other feedback to inform future initiatives. Authors benefit from broader dissemination of their work, which aids establishment of a national or international reputation. Readers can receive high-quality high-yield content in a digestible format directly on their devices while actively engaging with journal editors and authors in the online community. The authors highlight the multifaceted benefits of social media engagement and digital tool implementation in the context of medical journalism and summarize the activities of the RadioGraphics Social Media and Digital Innovation Team. By enumerating the social media activities of RadioGraphics and describing the underlying rationale for each activity, the authors present a blueprint for other medical journals considering similar initiatives. ©RSNA, 2023.

Exceptional response to cetuximab monotherapy after failure of immunotherapy with a checkpoint inhibitor in a patient with metastatic head and neck squamous cell cancer: case report and review of the literature.

Immunotherapy with PD-1 inhibitors monotherapy or combined with chemotherapy comprises the first-line palliative treatment for patients with recurrent or metastatic head and neck squamous cell cancers (R/M HNSCC). The established survival advantage among responders is overshadowed by the high percentage of patients failing the standard PD-1 inhibitor-based treatments. Salvage therapies are direly needed. However, no current standards are available. We present the case of a 65-year-old patient with heavily pretreated laryngeal squamous cell carcinoma who had an exceptional response to cetuximab monotherapy following the failure of immunotherapy with the PD-1 inhibitor nivolumab. We reviewed the literature for other cases of exceptional response to cetuximab, clinical studies investigating the combined or sequential administration of cetuximab and PD-1 inhibitors, and the mechanistic rationale for consideration of cetuximab as a potential salvage treatment after immunotherapy with PD-1 inhibitors. In addition to the specific epidermal growth factor receptor inhibitory effect, cetuximab, as an immunoglobulin G1 isotype, binds NK cells and elicits antibody-dependent cellular toxicity, triggering a domino of immunostimulatory, and immunoinhibitory effects that actually might decrease the cetuximab anticancer efficacy. However, in a tumor microenvironment exposed to previous treatment with a PD-1 inhibitor, the effects of the PD-1 inhibitor followed by cetuximab on innate and adaptative immune response appear to synergize. Specifically, persistent immune checkpoint inhibitors' consequences may negate downstream immunosuppressive effects of cetuximab caused through PD-1/PD-L1 upregulation, making it a more potent treatment option. Besides the potential synergistic effect on antitumor immune response with previous immune checkpoint inhibitors therapy, cetuximab is the only targeted agent approved for treating R/M HNSCC, making it a most advantageous candidate for further treatment validation studies as salvage treatment post-immunotherapy.

Brain Metastasis Incidence and Patterns of Presentation After Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Potential Argument for Brain Magnetic Resonance Imaging Surveillance.

Purpose: Brain metastases (BMs) are a common source of morbidity and mortality. Guidelines do not advise brain surveillance for locally advanced non-small cell lung cancer (LA-NSCLC). We describe the incidence, time to development, presentation, and management of BMs after definitive chemoradiotherapy (CRT). Methods and Materials: We reviewed records of patients with LA-NSCLC treated with CRT within the period from 2013 to 2020. Descriptive statistics were used to characterize the population and the Kaplan-Meier method was used to estimate time to BM. Fisher exact tests and Wilcoxon rank-sum tests were used to compare outcomes between symptomatic and asymptomatic patients. Results: A total of 219 patients were reviewed including 96 with squamous cell carcinoma, 88 with adenocarcinoma, and 35 with large cell/not otherwise specified (LC/NOS). Thirty-nine patients (17.8%) developed BMs: 35 (90%) symptomatic and 4 (10%) asymptomatic. The rate of BM was highest in LC/NOS (34.3%) and adenocarcinoma (23.9%). Ninety percent of BMs occurred within 2 years. All asymptomatic patients underwent stereotactic radiosurgery alone, compared with 40% of symptomatic patients (P = .04). Symptomatic patients were more likely to require hospitalization (65.7% vs 0%, P = .02), craniotomy (25.7% vs 0%, not significant), and steroids (91.4% vs 0%, P < .001). Cumulative BM volume was higher for symptomatic patients (4 vs 0.24 cm3, P < .001) as was median greatest axial dimension (2.18 vs 0.52 cm, P < .001). Conclusions: We identified a high rate of BMs, particularly in LC/NOS and adenocarcinoma histology NSCLC. The majority were symptomatic. These results provide rationale for post-CRT magnetic resonance imaging brain surveillance for patients at high risk of BM.

Quad-shot-immunotherapy: quad-shot radiotherapy with pembrolizumab for advanced/recurrent head and neck cancer.

Effective treatments for advanced/recurrent head and neck squamous-cell carcinoma are limited. For cases not curable by conventional local therapies, the immune checkpoint inhibitor pembrolizumab shows modest response rates. Quad-shot, a hypofractionated palliative radiotherapy regimen (14.8 Gy in four twice-daily fractions), can provide symptomatic relief, contributes to local control and may potentiate the effects of immune checkpoint inhibitors. In this study, 15 patients with advanced/recurrent head and neck squamous-cell carcinoma will be treated with pembrolizumab combined with up to three administrations of quad-shot before cycles four, eight and 13. Outcomes include disease response, survival and treatment toxicity. Correlative multiomics analysis of blood and saliva will identify molecular biomarkers of response to immune checkpoint inhibitor and the immune-related impact of quad-shot. Clinical trial registration: This study (WFBCCC 60320) is registered on NCT04454489 (ClinicalTrials.gov).

Advanced and recurrent head and neck cancers are difficult to treat. Most patients receive systemic therapies, such as chemotherapy or immunotherapy, with modest rates of cancer control. We aim to test the effectiveness of an immunotherapy drug called pembrolizumab in combination with a type of low-dose radiation therapy called quad-shot. Patients will receive pembrolizumab every 3 weeks and will be treated with one to three low-dose radiation therapy courses targeted at their cancer in the head and neck approximately every 12 weeks. We plan to measure how well the cancer responds to treatment, how long this response lasts, how long patients survive and treatment side effects.

Opportunistic CT Assessment of Parathyroid Glands: Utility of Radiologist-Recommended Biochemical Evaluation for Diagnosing Primary Hyperparathyroidism.

BACKGROUND. Existing gaps in primary hyperparathyroidism (PHPT) diagnosis and treatment have prompted calls for systemic change in the approach to this disease. One proposed change is opportunistic assessment for enlarged parathyroid glands on routine CT examinations, to target biochemical testing to individuals most likely to have un-diagnosed PHPT. OBJECTIVE. The purpose of our study was to assess the utility of a radiologist recommendation for biochemical testing in patients with a suspected enlarged parathyroid gland on routine CT for identifying previously undiagnosed PHPT. METHODS. This retrospective study included patients without known or suspected PHPT who underwent routine CT (i.e., performed for reasons other than known or suspected parathyroid disease) between August 2019 and September 2021 in which the clinical CT report included a radiologist recommendation for biochemical testing to evaluate for possible PHPT because of a suspected enlarged parathyroid gland. Neuroradiologists at the study institution included this recommendation on the basis of individual judgment without formal criteria. The EHR was reviewed to identify patients who underwent subsequent laboratory evaluation for PHPT. An endocrine surgeon used available laboratory results and clinical data to classify patients as having PHPT, secondary hyper-parathyroidism, or no parathyroid disorder independent of the CT findings. RESULTS. The sample comprised 39 patients (median age, 68 years; 20 women, 19 men) who received the radiologist recommendation for biochemical evaluation. Of these patients, 13 (33.3%) received the recommended biochemical evaluation. Of the 13 tested patients, three (23.1%) were classified as having PHPT, four (30.8%) as having secondary hyperparathyroidism, and six (46.2%) as having no parathyroid disorder. Thus, the number of patients needing to receive a radiologist recommendation for biochemical testing per correct PHPT diagnosis was 13.0, and the number of patients needing to undergo laboratory testing per correct PHPT diagnosis was 4.3. One of the three patients classified as having PHPT underwent surgical resection of the lesion identified by CT, which was shown on histopathologic evaluation to represent hypercellular parathyroid tissue. CONCLUSION. Radiologist recommendations for biochemical testing in patients with suspected enlarged parathyroid glands on routine CT helped to identify individuals with undiagnosed PHPT. CLINICAL IMPACT. Opportunistic assessment for enlarged parathyroid glands on routine CT may facilitate PHPT diagnosis.

Bridging the Communication Gaps: A Prospective Single-Arm Pilot Study Testing the Feasibility of Interdisciplinary Radiotherapy Planning in Locally Advanced Lung Cancer.

RATIONALE AND OBJECTIVES: The treatment of locally advanced lung cancer (LALC) with radiotherapy (RT) can be challenging. Multidisciplinary collaboration between radiologists and radiation oncologists (ROs) may optimize RT planning, reduce uncertainty in follow-up imaging interpretation, and improve outcomes. MATERIALS AND METHODS: In this prospective clinical treatment trial (clinicaltrials.gov NCT04844736), 37 patients receiving definitive RT for LALC, six attending ROs, and three thoracic radiologists were consented and enrolled across four treatment centers. Prior to RT plan finalization, representative computed tomography (CT) slices with overlaid outlines of preliminary irradiation targets were shared with the team of radiologists. The primary endpoint was to assess feasibility of receiving feedback no later than 4 business days of RT simulation on at least 50% of plans. RESULTS: Thirty-seven patients with lung cancer were enrolled, and 35 of 37 RT plans were reviewed. Of the 35 patients reviewed, mean age was 69 years. For 27 of 37 plans (73%), feedback was received within 4 or fewer days (interquartile range 3-4 days). Thirteen of 35 cases (37%) received feedback that the delineated target potentially did not include all sites suspicious for tumor involvement. In total, changes to the RT plan were recommended for over- or undercoverage in 16 of 35 cases (46%) and implemented in all cases. Radiology review resulted in no treatment delays and substantial changes to irradiated volumes: gross tumor volume, -1.9 to +96.1%; planning target volume, -37.5 to +116.5%. CONCLUSION: Interdisciplinary collaborative RT planning using a simplified workflow was feasible, produced no treatment delays, and prompted substantial changes in RT targets.

Diagnostic performance of computed tomography features in detecting oropharyngeal squamous cell carcinoma extranodal extension.

OBJECTIVES: Accurate pre-treatment imaging determination of extranodal extension (ENE) could facilitate the selection of appropriate initial therapy for HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). Small studies have associated 7 CT features with ENE with varied results and agreement. This article seeks to determine the replicable diagnostic performance of these CT features for ENE. METHODS: Five expert academic head/neck neuroradiologists from 5 institutions evaluate a single academic cancer center cohort of 75 consecutive HPV + OPSCC patients. In a web-based virtual laboratory for imaging research and education, the experts performed training on 7 published CT features associated with ENE and then independently identified the "single most (if any) suspicious" lymph node and presence/absence of each of the features. Inter-rater agreement was assessed using percentage agreement, Gwet's AC1, and Fleiss' kappa. Sensitivity, specificity, and positive and negative predictive values were calculated for each CT feature based on histologic ENE. RESULTS: All 5 raters identified the same node in 52 cases (69%). In 15 cases (20%), at least one rater selected a node and at least one rater did not. In 8 cases (11%), all raters selected a node, but at least one rater selected a different node. Percentage agreement and Gwet's AC1 coefficients were > 0.80 for lesion identification, matted/conglomerated nodes, and central necrosis. Fleiss' kappa was always < 0.6. CT sensitivity for histologically confirmed ENE ranged 0.18-0.94, specificity 0.41-0.88, PPV 0.26-0.36, and NPV 0.78-0.96. CONCLUSIONS: Previously described CT features appear to have poor reproducibility among expert head/neck neuroradiologists and poor predictive value for histologic ENE. KEY POINTS: • Previously described CT imaging features appear to have poor reproducibility among expert head and neck subspecialized neuroradiologists as well as poor predictive value for histologic ENE. • Although it may still be appropriate to comment on the presence or absence of these CT features in imaging reports, the evidence indicates that caution is warranted when incorporating these features into clinical decision-making regarding the likelihood of ENE.