Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Outcomes and predictors of survival for tracheal cancer.

INTRODUCTION: Primary tracheal cancer is uncommon, with poor survival. While surgical resection is the mainstay of therapy, the role of chemotherapy and radiation is poorly defined. We aimed to study the impact of treatment modalities on survival. METHODS: Patients with primary tracheal cancer were identified from the National Cancer Database over 12 years, 2004-2015. Patient characteristics, tumor characteristics, treatment modalities, and survival were recorded. Factors associated with survival were assessed using Cox Regression. RESULTS: Of the 1726 patients identified, 59% were male, 83% White race, 62% had a comorbidity index of zero, median age 64 years, median tumor size 2.7 cm, and median survival was 28.5 months (89 months for patients undergoing surgical resection). Cox Regression for all patients found adenoid cystic carcinoma (ACC) (p < 0.001), radiation (p < 0.001), and surgical resection (p < 0.001) to be associated with improved survival, while increasing age (p < 0.001) decreased survival. For patients receiving resection, ACC (p < 0.001) was associated with improved survival, while increasing age (p < 0.001) and positive margins (p = 0.002) were associated with worse survival. For R0 resections, ACC (p < 0.001) was associated with improved survival, while increasing age (p < 0.001) decreased survival, with chemotherapy and radiation having no impact. For R1/2 resections, ACC (p < 0.001) and radiation (p < 0.001) were associated with improved survival, while increasing age (p < 0.001) decreased survival, with chemotherapy having no impact on survival. CONCLUSIONS: Primary tracheal cancer is highly lethal, with surgical resection leading to the best chance of survival. For patients undergoing resection, radiation provided survival benefits for R1/2 but not R0, while chemotherapy did not impact survival regardless of margin status.

A Practical Guide for Paid Family and Medical Leave in Radiology, From the AJR Special Series on DEI.

Paid family and medical leave (FML) has significant benefits to organizations, including improvements in employee recruitment and retention, workplace culture, and employee morale and productivity, and is supported by evidence for overall cost savings. Furthermore, paid FML related to childbirth has significant benefits to individuals and families, including but not limited to improved maternal and infant health outcomes and improved breastfeeding initiation and duration. In the case of nonchildbearing parental leave, paid FML is associated with more equitable long-term division of household labor and childcare. Paid FML is increasingly being recognized as an important issue in medicine, as evidenced by the recent passage of policies by national societies and governing bodies, including the American Board of Medical Specialties, American Board of Radiology, Accreditation Council for Graduate Medical Education (ACGME), American College of Radiology, and American Medical Association. Implementation of paid FML requires adherence to federal, state, and local laws as well as institutional requirements. Specific requirements pertain to trainees from national governing bodies, such as the ACGME and medical specialty boards. Flexibility, work coverage, culture, and finances are additional considerations for ensuring an optimal paid FML policy that accounts for concerns of all impacted individuals.

Standard Adult Gastric Emptying Scintigraphy Criteria Is Applicable for Partial Meal Ingestion.

BACKGROUND/AIMS: Gastric emptying scintigraphy is commonly performed to assess for dysmotility. A standardized meal with associated threshold criteria was established in 2000 to enable robust interpretation. However, no guidance is available to interpret results when patients do not ingest the entire meal. The purpose of this study is to determine the continued appropriateness of the threshold criteria in contemporary clinical practice and its relevance for partially ingested meals. METHODS: This retrospective study analyzed patients (n = 1365 total) who underwent solid-phase gastric emptying scintigraphy at an academic medical center. Patients were stratified based on their completion of the standard meal. Patients were further stratified into normal and delayed gastric emptying cohorts based on the current criteria. Percent gastric retention values at 1, 2, 3, and 4 h were compared. RESULTS: Median (95% upper reference) normal gastric retention values for the complete standard meal were 64% (87%) at 1 h, 25% (60%) at 2 h, 13% (54%) at 3 h and 4% (9%) at 4 h. Consumption of at least 50% of the standard meal yielded similar retention; 53% (86%) at 1 h, 19% (58%) at 2 h, 6% (29%) at 3 h and 3% (10%) at 4 h. There was no significant age- or gender-specific differences using the current criteria, and no differences were observed based on diabetic status. Retention values matched well with the current criteria and validated with data-driven clustering. CONCLUSION: Adult normative standards for gastric emptying scintigraphy are appropriate for differentiating normal and delayed populations and can be applied to partial meals with at least 50% completion.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer.

Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand the relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery by using ferumoxytol-enhanced MRI and macrin in an ATC mouse model. Materials and Methods ATC tumors were generated in 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors, or intravenously to model hematogenous metastasis, and prospectively enrolled randomly into treatment cohorts (n = 94 total; August 1, 2018, to January 15, 2020). Mice were treated with vehicle or combined serine/threonine-protein kinase B-Raf (BRAF) kinase inhibitor (BRAFi) and anti-PDL1 antibody (aPDL1). A subset was cotreated with therapies, including an approximately 70-nm model drug delivery nanoparticle (DDNP) to target TAM, and an antibody-neutralizing colony stimulating factor 1 receptor (CSF1R). Imaging was performed at the macroscopic level with ferumoxytol-MRI and microscopically with macrin. Genetically engineered BrafV600E/WT p53-null allografts were used and complemented by a GFP-transgenic derivative and human xenografts. Tumor-bearing organs were processed by using tissue clearing and imaged with confocal microscopy and MRI. Two-tailed Wilcoxon tests were used for comparison (≥five per group). Results TAM levels were higher in orthotopic thyroid tumors compared with pulmonary metastatic lesions by 79% ± 23 (standard deviation; P < .001). These findings were concordant with ferumoxytol MRI, which showed 136% ± 88 higher uptake in thyroid lesions (P = .02) compared with lung lesions. BRAFi and aPDL1 combination therapy resulted in higher tumor DDNP delivery by 39% ± 14 in pulmonary lesions (P = .004). Compared with the untreated group, tumors following BRAFi, aPDL1, and CSF1R-blocking antibody combination therapy did not show greater levels of TAM or DDNP (P = .82). Conclusion In a mouse model of anaplastic thyroid cancer, ferumoxytol MRI showed 136% ± 88 greater uptake in orthotopic thyroid tumors compared with pulmonary lesions, which reflected high vascularization and greater tumor-associated macrophage (TAM) levels. Serine/threonine-protein kinase B-Raf inhibitor and anti-programmed death ligand 1 antibody elicited higher local TAM levels and 43% ± 20 greater therapeutic nanoparticle delivery but not higher vascularization in pulmonary tumors. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Luker in this issue.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Pediatric Solid Gastric Emptying Scintigraphy: Normative Value Guidelines and Nonstandard Meal Alternatives.

INTRODUCTION: Adult standards for gastric emptying scintigraphy, including the type of meal and range of normative values for percent gastric emptying, are routinely used in pediatric practice, but to date have not been validated. The purpose of this study is to determine whether the use of adult criteria for gastric emptying scintigraphy is valid for children and whether alternative nonstandard meals can also be offered based on these criteria. METHODS: This retrospective study analyzed patients (n = 1,151 total) who underwent solid-phase gastric emptying scintigraphy. Patients were stratified into normal and delayed gastric emptying cohorts based on adult criteria, i.e., with normal gastric emptying defined as ≤10% gastric retention at 4 hours. Patients were further stratified based on the type of meal, namely complete or partial adult standard meals or alternative cheese-based meals. Percent gastric retention values at 1, 2, 3, and 4 hours were compared. RESULTS: The median (95% upper reference limit) percentage gastric retention values for the complete standard meal were 72% (93%) at 1 hour, 39% (65%) at 2 hours, 15% (33%) at 3 hours, and 6% (10 %) at 4 hours. By comparison, the values for cheese-based meals were 60% (87%) at 1 hour, 29% (61%) at 2 hours, 10% (30%) at 3 hours, and 5% (10%) at 4 hours. Consumption of at least 50% of the standard meal yielded similar retention percentages; 68% (89%) at 1 hour, 32% (57%) at 2 hours, 10% (29%) at 3 hours, and 5% (10%) at 4 hours. There were no significant age- or sex-specific differences using the adult criteria. DISCUSSION: The adult normative standards for gastric emptying scintigraphy are applicable for use in the pediatric population. These same standards can be also be applied to nonstandard meal options, including cheese-based alternative meals and partial standard meals.

Understanding the in vivo Fate of Advanced Materials by Imaging.

Engineered materials are ubiquitous in biomedical applications ranging from systemic drug delivery systems to orthopedic implants, and their actions unfold across multiple time- and length-scales. The efficacy and safety of biologics, nanomaterials, and macroscopic implants are all dictated by the same general principles of pharmacology as apply to small molecule drugs, comprising how the body affects materials (pharmacokinetics, PK) and conversely how materials affect the body (pharmacodynamics, PD). Imaging technologies play an increasingly insightful role in monitoring both of these processes, often simultaneously: translational macroscopic imaging modalities such as MRI and PET/CT offer whole-body quantitation of biodistribution and structural or molecular response, while ex vivo approaches and optical imaging via in vivo (intravital) microscopy reveal behaviors at subcellular resolution. In this review, the authors survey developments in imaging the in situ behavior of systemically and locally administered materials, with a particular focus on using microscopy to understand transport, target engagement, and downstream host responses at a single-cell level. The themes of microenvironmental influence, controlled drug release, on-target molecular action, and immune response, especially as mediated by macrophages and other myeloid cells are examined. Finally, the future directions of how new imaging technologies may propel efficient clinical translation of next-generation therapeutics and medical devices are proposed.

Lack of Lymphocyte Recovery After Esophagectomy Predicts Overall and Recurrence-Free Survival.

BACKGROUND: Lymphocytes have become the target of cancer interventions through engineering or immune checkpoint antibodies. We previously found decreased lymphocyte counts to be a predictor of mortality and complications in trauma and cardiac surgery patients. We hypothesized lack of lymphocyte count recovery postoperatively would predict outcomes in esophagectomy patients. METHODS: A retrospective review of all patients undergoing esophagectomy for adenocarcinoma performed over 13 y at our center by a single surgeon after institutional review board approval was performed. Patients were grouped by postoperative lymphocytes counts: never low, low with recovery, and low without recovery. Resolution of lymphopenia was assessed by day 4. Primary end points were overall and recurrence-free survival. RESULTS: In total, 198 patients were included with a minimum 6-mo follow-up. Collectively the 5-y recurrence and overall survival rates were 36% and 50%, respectively. Recurrence was significantly higher at 5 y in patients with persistent lymphopenia (43%) compared with those who recovered (14% P = 0.0017) and those who never dropped (0% P = 0.0009). The persistent lymphopenia group had significantly lower survival (45%) compared with the two other groups (67% P = 0.0232). CONCLUSIONS: There is a significant decrease in the overall and recurrence-free survival in those patients whose lymphocyte count drops without recovery after their esophagectomy. These data imply differences in immune responses to the stress of surgery that can be measured with routine postoperative laboratory values and are indicative of overall outcomes.

Clinical Implementation of a Free-Breathing, Motion-Robust Dynamic Contrast-Enhanced MRI Protocol to Evaluate Pleural Tumors.

OBJECTIVE. The purpose of this study was to develop a motion insensitive clinical dynamic contrast-enhanced MRI (DCE-MRI) protocol to assess the response of pleural tumors in clinical trials. MATERIALS AND METHODS. Thirty-two patients with pleura-based lesions were administered contrast material and imaged with gradient-recalled echo DCE-MRI sequence variants: either a traditional cartesian k-space acquisition (FLASH), a time-resolved imaging with stochastic trajectories acquisition (TWIST), or a radial stack-of-stars acquisition (radial) sequence in addition to other standard-of-care imaging sequences. Each image acquisition's sensitivity to motion was evaluated by comparing the motion of the thoracic border in 3D throughout the acquisition. One-way ANOVA was used to compare the image quality between different acquisitions. The 95% CIs were calculated for mean thoracic border displacement. The effects of motion on kinetic parameter estimation were explored with simulations according to clinically acquired data. RESULTS. Radial was the most motion-robust sequence with subvoxel mean displacement in the superior-inferior direction (0.4 ± 1.2 [SD] mm). FLASH showed intermediate displacement (4.6 ± 2.0 mm), whereas TWIST was most sensitive to motion (6.4 ± 3.4 mm). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images acquired with the radial sequence were on par or better than the FLASH and TWIST sequences when reconstructed with an improved density compensation algorithm. Simulations showed that motion on scans showing pleural-based lesions can lead to markedly inaccurate kinetic parameter estimation and inappropriate kinetic model convergence within a nested model analysis. CONCLUSION. A practical radial k-space trajectory sequence that provides motion-insensitive pharmacokinetic parameters was incorporated as part of the DCE-MRI protocol of pleural tumors. Validation and usefulness in clinical trials assessing response to therapy is needed.

A Tailor-Made Exercise Program for Improving Balance and Mobility in Older Adults With Type 2 Diabetes.

Effectiveness of an exercise program designed for improving postural control and mobility in older adults with type 2 diabetes was investigated. Ninety-three adults 65 or older diagnosed with type 2 diabetes and able to walk unaided were recruited. The intervention group received exercise training focused on ankle strengthening and mobility twice per week for 10 weeks. The control group did not participate in any exercise program. After 10 weeks, the intervention group showed significantly greater improvement in the mean Sensory Organization Test composite score (4.4 vs. 0.3; p = 0.01) as well as visual ratio (0.1 vs. 0.002; p = 0.01) and vestibular ratio (0.1 vs. 0.003; p < 0.001) than the control group after adjusting for covariates. A greater trend of improvement in the Timed Up and Go and Single-Leg Stance Test was also found in the intervention group. Exercise training focusing on the ankle is effective in enhancing the postural stability of older adults with type 2 diabetes and can potentially be effective in improving single-leg standing balance and mobility. [Journal of Gerontological Nursing, 44(2), 41-48.].

Genomic divergence across ecological gradients in the Central African rainforest songbird (Andropadus virens).

The little greenbul, a common rainforest passerine from sub-Saharan Africa, has been the subject of long-term evolutionary studies to understand the mechanisms leading to rainforest speciation. Previous research found morphological and behavioural divergence across rainforest-savannah transition zones (ecotones), and a pattern of divergence with gene flow suggesting divergent natural selection has contributed to adaptive divergence and ecotones could be important areas for rainforests speciation. Recent advances in genomics and environmental modelling make it possible to examine patterns of genetic divergence in a more comprehensive fashion. To assess the extent to which natural selection may drive patterns of differentiation, here we investigate patterns of genomic differentiation among populations across environmental gradients and regions. We find compelling evidence that individuals form discrete genetic clusters corresponding to distinctive environmental characteristics and habitat types. Pairwise FST between populations in different habitats is significantly higher than within habitats, and this differentiation is greater than what is expected from geographic distance alone. Moreover, we identified 140 SNPs that showed extreme differentiation among populations through a genomewide selection scan. These outliers were significantly enriched in exonic and coding regions, suggesting their functional importance. Environmental association analysis of SNP variation indicates that several environmental variables, including temperature and elevation, play important roles in driving the pattern of genomic diversification. Results lend important new genomic evidence for environmental gradients being important in population differentiation.

Robot-Assisted Training for People With Spinal Cord Injury: A Meta-Analysis.

OBJECTIVE: To investigate the effects of robot-assisted training on the recovery of people with spinal cord injury (SCI). DATA SOURCES: Randomized controlled trials (RCTs) or quasi-RCTs involving people with SCI that compared robot-assisted upper limbs or lower limbs training with a control of other treatment approach or no treatment. We included studies involving people with complete or incomplete SCIs. STUDY SELECTION: We searched MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (Cochrane Library), and Embase to August 2016. Bibliographies of relevant articles on the effect of body-weight-supported treadmill training on subjects with SCI were screened to avoid missing relevant articles from the search of databases. DATA EXTRACTION: All kinds of objective assessments concerning physical ability, mobility, and/or functional ability were included. Assessments could be clinical tests (ie, 6-minute walk test, FIM) or laboratory tests (ie, gait analysis). Subjective outcome measures were excluded from this review. DATA SYNTHESIS: Eleven RCT studies involving 443 subjects were included in the study. Meta-analysis was performed on the included studies. Walking independence (3.73; 95% confidence interval [CI], -4.92 to -2.53; P<.00001; I2=38%) and endurance (53.32m; 95% CI, -73.15 to -33.48; P<.00001; I2=0%) were found to have better improvement in robot-assisted training groups. Lower limb robot-assisted training was also found to be as effective as other types of body-weight-supported training. There is a lack of upper limb robot-assisted training studies; therefore, performing a meta-analysis was not possible. CONCLUSIONS: Robot-assisted training is an adjunct therapy for physical and functional recovery for patients with SCI. Future high-quality studies are warranted to investigate the effects of robot-assisted training on functional and cardiopulmonary recovery of patients with SCI.

Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI.

PURPOSE: To determine optimal parameters for acquisition and processing of dynamic contrast-enhanced MRI (DCE-MRI) to detect small changes in near normal low blood-brain barrier (BBB) permeability. METHODS: Using a contrast-to-noise ratio metric (K-CNR) for Ktrans precision and accuracy, the effects of kinetic model selection, scan duration, temporal resolution, signal drift, and length of baseline on the estimation of low permeability values was evaluated with simulations. RESULTS: The Patlak model was shown to give the highest K-CNR at low Ktrans . The Ktrans transition point, above which other models yielded superior results, was highly dependent on scan duration and tissue extravascular extracellular volume fraction (ve ). The highest K-CNR for low Ktrans was obtained when Patlak model analysis was combined with long scan times (10-30 min), modest temporal resolution (<60 s/image), and long baseline scans (1-4 min). Signal drift as low as 3% was shown to affect the accuracy of Ktrans estimation with Patlak analysis. CONCLUSION: DCE acquisition and modeling parameters are interdependent and should be optimized together for the tissue being imaged. Appropriately optimized protocols can detect even the subtlest changes in BBB integrity and may be used to probe the earliest changes in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis.