Wedge Resection versus Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors ≤8 mm.

The objective of this study was to evaluate the overall survival of patients with ≤8 mm non-small cell lung cancer (NSCLC) who undergo wedge resection versus stereotactic body radiation therapy (SBRT). Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score-matched analysis were performed to evaluate the overall survival of patients with ≤8 mm NSCLC in the National Cancer Database (NCDB) from 2004 to 2017 who underwent wedge resection versus patients who underwent SBRT. The above-mentioned matched analyses were repeated for patients with no comorbidities. Patients who were coded in the NCDB as having undergone radiation because surgery was contraindicated due to patient risk factors (e.g., comorbid conditions, advance age, etc.) and those with a history of prior malignancy were excluded from analysis. Of the 1505 patients who had NSCLC ≤8 mm during the study period, 1339 (89%) patients underwent wedge resection, and 166 (11%) patients underwent SBRT. In the unadjusted analysis, multivariable Cox modeling and propensity score-matched analysis, wedge resection was associated with improved survival when compared to SBRT. These results were consistent in a sensitivity analysis limited to patients with no comorbidities.

From Machine Learning to Patient Outcomes: A Comprehensive Review of AI in Pancreatic Cancer.

Pancreatic cancer is a highly aggressive and difficult-to-detect cancer with a poor prognosis. Late diagnosis is common due to a lack of early symptoms, specific markers, and the challenging location of the pancreas. Imaging technologies have improved diagnosis, but there is still room for improvement in standardizing guidelines. Biopsies and histopathological analysis are challenging due to tumor heterogeneity. Artificial Intelligence (AI) revolutionizes healthcare by improving diagnosis, treatment, and patient care. AI algorithms can analyze medical images with precision, aiding in early disease detection. AI also plays a role in personalized medicine by analyzing patient data to tailor treatment plans. It streamlines administrative tasks, such as medical coding and documentation, and provides patient assistance through AI chatbots. However, challenges include data privacy, security, and ethical considerations. This review article focuses on the potential of AI in transforming pancreatic cancer care, offering improved diagnostics, personalized treatments, and operational efficiency, leading to better patient outcomes.

Suicide among Cancer Patients: Current Knowledge and Directions for Observational Research.

Cancer is a major public health concern associated with an increased risk of psychosocial distress and suicide. The reasons for this increased risk are still being characterized. The purpose of this study is to highlight existing observational studies on cancer-related suicides in the United States and identify gaps for future research. This work helps inform clinical and policy decision-making on suicide prevention interventions and ongoing research on the detection and quantification of suicide risk among cancer patients. We identified 73 peer-reviewed studies (2010-2022) that examined the intersection of cancer and suicide using searches of PubMed and Embase. Overall, the reviewed studies showed that cancer patients have an elevated risk of suicide when compared to the general population. In general, the risk was higher among White, male, and older cancer patients, as well as among patients living in rural areas and with lower socioeconomic status. Future studies should further investigate the psychosocial aspects of receiving a diagnosis of cancer on patients' mental health as well as the impact of new treatments and their availability on suicide risk and disparities among cancer patients to better inform policies.

Clinical outcomes of radiation therapy for transgender and gender-expansive people with cancer.

Introduction: Approximately 1.6 million people in the US identify as transgender, many of whom undergo gender-affirming medical or surgical therapies. While transgender individuals are diagnosed with cancer at similar rates as those who are cisgender, the impacts of radiation therapy on outcomes of gender-affirming care in transgender, nonbinary, and gender-expansive people with cancer are understudied. We report on the experiences and outcomes of transgender and gender-expansive patients receiving radiation therapy for cancer treatment. Methods: This study is a multi-institutional retrospective review of patients evaluated from 2005-2019 identified as transgender or gender-expansive in the medical record and treated with radiation therapy. Results: We identified 23 patients who received radiation to 32 sites, including 12 (38%) to the brain, head, or neck, 8 (25%) to the thorax, and 7 (22%) to the pelvis. Seventeen patients (74%) received gender-affirming hormone therapy and 13 patients (57%) underwent gender-affirming surgery. Four patients had pelvic radiation before or after gender-affirming pelvic surgery, including two trans women who had pelvic radiation after vaginoplasty. Four patients had radiation to the chest or thorax and gender-affirming chest or breast surgery, including two trans men with breast cancer. Two pediatric patients developed hypopituitarism and hypogonadism secondary to radiation therapy and, as adults, changed their hormone replacement therapy to affirm their transgender identities. Discussion: Transgender people with cancer undergo radiation therapy for a wide range of cancers. Understanding their prior gender-affirming medical or surgical treatments and future gender affirmation goals may identify important considerations for their oncologic care.

Primary clear cell adenocarcinoma of the lung: a national analysis.

Background: Primary clear cell adenocarcinoma of the lung (CCAL) is a rare form of lung cancer with poorly understood clinical features. We sought to investigate the clinicopathological characteristics and independent prognostic factors of primary CCAL. Methods: Overall survival (OS) of patients with CCAL in the National Cancer Database (NCDB) from 2004 to 2017 was compared to lung adenocarcinoma using Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score matching. Independent prognostic indicators for patients with CCAL were determined using multivariable Cox proportional hazards analysis. Results: A total of 1,396 CCAL and 462,360 lung adenocarcinoma patients were included in our analysis. When compared to patients diagnosed with lung adenocarcinoma, those diagnosed with CCAL were more likely to be younger, white, reside farther from a hospital, have higher Charlson/Deyo comorbidity condition (CDCC) scores, have private insurance, have T1, N0, M0 status. In unadjusted analysis, patients with CCAL had better survival than those with lung adenocarcinoma, although no significant differences in survival were found between the two groups with multivariable Cox proportional hazards and propensity score-matched analyses. Conclusions: In this national analysis, we found that the clinicopathological characteristics of CCAL are distinct from those of lung adenocarcinoma, but CCAL is not itself an independent predictor of survival after multivariable adjustment or propensity score-matched analysis.

Intrinsic and extrinsic regulation of rhabdomyolysis susceptibility by Tango2.

Rhabdomyolysis is a clinical emergency characterized by severe muscle damage, resulting in the release of intracellular muscle components, which leads to myoglobinuria and, in severe cases, acute kidney failure. Rhabdomyolysis is caused by genetic factors linked to increased disease susceptibility in response to extrinsic triggers. Recessive mutations in TANGO2 result in episodic rhabdomyolysis, metabolic crises, encephalopathy and cardiac arrhythmia. The underlying mechanism contributing to disease onset in response to specific triggers remains unclear. To address these challenges, we created a zebrafish model of Tango2 deficiency. Here, we demonstrate that the loss of Tango2 in zebrafish results in growth defects, early lethality and increased susceptibility of skeletal muscle defects in response to extrinsic triggers, similar to TANGO2-deficient patients. Using lipidomics, we identified alterations in the glycerolipid pathway in tango2 mutants, which is critical for membrane stability and energy balance. Therefore, these studies provide insight into key disease processes in Tango2 deficiency and have increased our understanding of the impacts of specific defects on predisposition to environmental triggers in TANGO2-related disorders.

Risk of suicide among stroke survivors in the United States.

BACKGROUND: Stroke is the largest cause of disability and the 5th leading cause of death in the United States. Suicide is the 12th leading cause of death in the United States. However, little is known about the risk of suicide among people with a prior stroke. OBJECTIVES: Using Multiple Cause of Death data (1999-2020) from the Centers for Disease Control and Prevention WONDER database, we examined via cross-sectional analysis the risk of suicide among survivors of stroke as compared to the general U.S. population and among subgroups within the United States. METHODS: We assessed disparities in suicide rate among patients with stroke stratified by sex, race, urbanization levels, and census regions using the CDC WONDER multiple cause of death database. Standardized mortality rates were calculated to compare the suicide rate of stroke patients with the rates among demographic-matched cohorts and the general United States population. RESULTS: As compared to the general population, stroke survivors had an elevated risk of suicide. Black stroke survivors had a lower rate of suicide as compared to the general population, while White stroke survivors and those in nonmetropolitan areas had an elevated risk compared to the general population. CONCLUSION: There was a slightly elevated risk of suicide among people with a prior stroke in the United States. This risk may be elevated among White people and among people living in nonmetropolitan areas.

Deaths Due to COVID-19 in Patients With Cancer During Different Waves of the Pandemic in the US.

Importance: With the ongoing relaxation of guidelines to prevent COVID-19 transmission, particularly in hospital settings, medically vulnerable groups, such as patients with cancer, may experience a disparate burden of COVID-19 mortality compared with the general population. Objective: To evaluate COVID-19 mortality among US patients with cancer compared with the general US population during different waves of the pandemic. Design, Setting, and Participants: This cross-sectional study used data from the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database to examine COVID-19 mortality among US patients with cancer and the general population from March 1, 2020, to May 31, 2022. The number of deaths due to COVID-19 during the 2021 to 2022 winter Omicron surge was compared with deaths during the preceding year's COVID-19 winter surge (when the wild-type SARS-CoV-2 variant was predominant) using mortality ratios. Data were analyzed from July 21 through August 31, 2022. Exposures: Pandemic wave during which the wild-type variant (December 2020 to February 2021), Delta variant (July 2021 to November 2021), or Omicron variant (December 2021 to February 2022) was predominant. Main Outcomes and Measures: Number of COVID-19 deaths per month. Results: The sample included 34 350 patients with cancer (14 498 females [42.2%] and 19 852 males [57.8%]) and 628 156 members of the general public (276 878 females [44.1%] and 351 278 males [55.9%]) who died from COVID-19 when the wild-type (December 2020-February 2021), Delta (July 2021-November 2021), and winter Omicron (December 2021-February 2022) variants were predominant. Among patients with cancer, the greatest number of COVID-19 deaths per month occurred during the winter Omicron period (n = 5958): at the peak of the winter Omicron period, there were 18% more deaths compared with the peak of the wild-type period. In contrast, among the general public, the greatest number of COVID-19 deaths per month occurred during the wild-type period (n = 105 327), and at the peak of the winter Omicron period, there were 21% fewer COVID-19 deaths compared with the peak of the wild-type period. In subgroup analyses by cancer site, COVID-19 mortality increased the most, by 38%, among patients with lymphoma during the winter Omicron period vs the wild-type period. Conclusions and Relevance: Findings of this cross-sectional study suggest that patients with cancer had a disparate burden of COVID-19 mortality during the winter Omicron wave compared with the general US population. With the emergence of new, immune-evasive SARS-CoV-2 variants, many of which are anticipated to be resistant to monoclonal antibody treatments, strategies to prevent COVID-19 transmission should remain a high priority.

Suicide Risk Among Patients With Heart Disease and Heart Failure.

Heart disease is the leading cause of death in the United States (US). Suicide is the 12th leading cause of death. However, little is known about the risk of suicide in patients with heart disease and heart failure. Using Multiple Cause of Death data from the Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) database, we used a cross-sectional analysis to examine the risk of suicide in patients with heart disease and heart failure as compared with the general US population and in subgroups within the US. We assessed suicide rate in patients with heart disease and heart failure in the US population as a whole and stratified by race, time, urbanization levels, and census regions using the CDC WONDER Multiple Cause of Death database. Standardized mortality rates were calculated as observed deaths divided by expected deaths. As compared with the general population, patients with heart disease and heart failure had an elevated risk of suicide. This was true across racial and geographic subgroups. There was an elevated risk of suicide in patients with heart disease and heart failure in the United States. For heart disease, there were particular elevations in the Western US, and there was a particular elevation in Black Americans compared with the age-matched population.

Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset.

Ubiquitin-proteasome system (UPS) dysfunction is associated with the pathology of a wide range of human diseases, including myopathies and muscular atrophy. However, the mechanistic understanding of specific components of the regulation of protein turnover during development and disease progression in skeletal muscle is unclear. Mutations in KLHL40, an E3 ubiquitin ligase cullin3 (CUL3) substrate-specific adapter protein, result in severe congenital nemaline myopathy, but the events that initiate the pathology and the mechanism through which it becomes pervasive remain poorly understood. To characterize the KLHL40-regulated ubiquitin-modified proteome during skeletal muscle development and disease onset, we used global, quantitative mass spectrometry-based ubiquitylome and global proteome analyses of klhl40a mutant zebrafish during disease progression. Global proteomics during skeletal muscle development revealed extensive remodeling of functional modules linked with sarcomere formation, energy, biosynthetic metabolic processes, and vesicle trafficking. Combined analysis of klh40 mutant muscle proteome and ubiquitylome identified thin filament proteins, metabolic enzymes, and ER-Golgi vesicle trafficking pathway proteins regulated by ubiquitylation during muscle development. Our studies identified a role for KLHL40 as a regulator of ER-Golgi anterograde trafficking through ubiquitin-mediated protein degradation of secretion-associated Ras-related GTPase1a (Sar1a). In KLHL40-deficient muscle, defects in ER exit site vesicle formation and downstream transport of extracellular cargo proteins result in structural and functional abnormalities. Our work reveals that the muscle proteome is dynamically fine-tuned by ubiquitylation to regulate skeletal muscle development and uncovers new disease mechanisms for therapeutic development in patients.

The Role of Artificial Intelligence in the Detection and Implementation of Biomarkers for Hepatocellular Carcinoma: Outlook and Opportunities.

Liver cancer is a leading cause of cancer-related death worldwide, and its early detection and treatment are crucial for improving morbidity and mortality. Biomarkers have the potential to facilitate the early diagnosis and management of liver cancer, but identifying and implementing effective biomarkers remains a major challenge. In recent years, artificial intelligence has emerged as a promising tool in the cancer sphere, and recent literature suggests that it is very promising in facilitating biomarker use in liver cancer. This review provides an overview of the status of AI-based biomarker research in liver cancer, with a focus on the detection and implementation of biomarkers for risk prediction, diagnosis, staging, prognostication, prediction of treatment response, and recurrence of liver cancers.

Machine Learning Improves the Prediction of Responses to Immune Checkpoint Inhibitors in Metastatic Melanoma.

Pretreatment LDH is a standard prognostic biomarker for advanced melanoma and is associated with response to ICI. We assessed the role of machine learning-based radiomics in predicting responses to ICI and in complementing LDH for prognostication of metastatic melanoma. From 2008-2022, 79 patients with 168 metastatic hepatic lesions were identified. All patients had arterial phase CT images 1-month prior to initiation of ICI. Response to ICI was assessed on follow-up CT at 3 months using RECIST criteria. A machine learning algorithm was developed using radiomics. Maximum relevance minimum redundancy (mRMR) was used to select features. ROC analysis and logistic regression analyses evaluated performance. Shapley additive explanations were used to identify the variables that are the most important in predicting a response. mRMR selection revealed 15 features that are associated with a response to ICI. The machine learning model combining both radiomics features and pretreatment LDH resulted in better performance for response prediction compared to models that included radiomics or LDH alone (AUC of 0.89 (95% CI: [0.76-0.99]) vs. 0.81 (95% CI: [0.65-0.94]) and 0.81 (95% CI: [0.72-0.91]), respectively). Using SHAP analysis, LDH and two GLSZM were the most predictive of the outcome. Pre-treatment CT radiomic features performed equally well to serum LDH in predicting treatment response.

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise in minimally invasive locoregional therapy, as the bulk of these tumors are usually in the liver. The aim of this review is to highlight the immunological therapeutic targets for primary liver cancers, the available immune-based approaches, and the contributions that interventional radiology can provide in the care of these patients.

Role of Adjuvant Chemotherapy in Early-Stage Combined Small Cell Lung Cancer.

BACKGROUND: The role of adjuvant therapy in completely resected primary tumors that have components of both non-small cell lung cancer and small cell lung cancer (combined SCLC) is poorly understood. We sought to determine the potential benefits of adjuvant chemotherapy in patients who undergo complete resection for early-stage combined SCLC. METHODS: Overall survival of patients with pathologic T1-2 N0 M0 combined SCLC who underwent complete resection in the National Cancer Database from 2004 to 2017, stratified by adjuvant chemotherapy vs surgery alone, was evaluated by multivariable Cox proportional hazards modeling and propensity score-matched analysis. Patients treated with induction therapy and those who died within 90 days of surgery were excluded from analysis. RESULTS: Of 630 patients who had pT1-2 N0 M0 combined SCLC during the study period, 297 patients (47%) underwent complete R0 resection. Adjuvant chemotherapy was administered to 63% of patients (n = 188), and 37% of patients underwent surgery alone (n = 109). In unadjusted analysis, the 5-year overall survival was 61.6% (95% CI, 50.8-70.7) for patients who underwent surgery alone and 66.4% (95% CI, 58.4-73.3) for patients who underwent adjuvant chemotherapy. In multivariable and propensity score-matched analysis, there were no significant differences in overall survival between adjuvant chemotherapy and surgery alone (adjusted hazard ratio, 1.16; 95% CI, 0.73-1.84). These findings were consistent when limited to patients who underwent lobectomies or to healthier patients who have at most 1 major comorbidity. CONCLUSIONS: In this national analysis, patients with pT1-2 N0 M0 combined SCLC treated with surgical resection alone have similar outcomes to those who undergo adjuvant chemotherapy.

Primary and Metastatic Lung Cancer: Rationale, Indications, and Outcomes of Thermal Ablation.

The widespread use of imaging as well as the efforts conducted through screening campaigns has dramatically increased the early detection rate of lung cancer. Historically, the management of lung cancer has heavily relied on surgery. However, the increased proportion of patients with comorbidities has given significance to less invasive therapeutic options like minimally invasive surgery and image-guided thermal ablation, which could precisely target the tumor without requiring general anesthesia or a thoracotomy. Thermal ablation is considered low-risk for lung tumors smaller than 3 cm that are located in peripheral lung and do not involve major blood vessels or airways. The rationale for ablative therapies relies on the fact that focused delivery of energy induces cell death and pathologic necrosis. Image-guided percutaneous thermal ablation therapies are established techniques in the local treatment of hepatic, renal, bone, thyroid and uterine lesions. In the lung, and specifically in the setting of metastatic disease, the 3 main indications for lung ablation are to serve as (1) curative intent, (2) as a strategy to achieve a chemo-holiday in oligometastatic disease, and (3) in oligoprogressive disease. Following these premises, the current paper aims to review the rationale, indications, and outcomes of thermal ablation as a form of local therapy in the treatment of primary and metastatic lung disease.

Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are often empirically used for patients with low-renin hypertension (LRH) or probable primary aldosteronism (PA) who decline surgery. However, the optimal approach to MRA therapy is unknown. Studies have shown that a rise in renin is an effective biomarker of prevention of cardiovascular complications of PA. This study aimed to determine whether empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin is associated with a decrease in blood pressure and/or proteinuria. METHODS: Retrospective single-center cohort study from 2005 to 2021 included adults with LRH or probable PA (renin activity <1.0 ng/ml/h and detectable aldosterone levels). All patients were empirically treated with an MRA, targeting renin ≥1.0 ng/ml/h. RESULTS: Out of 39 patients studied, 32 (82.1%) achieved unsuppressed renin. Systolic and diastolic blood pressure decreased from 148.0 and 81.2 to 125.8 and 71.6 mm Hg, respectively (P < 0.001 for both). Similar blood pressure reductions were seen whether patients had high (>10 ng/dl) or low (<10 ng/dl) aldosterone levels. The majority (24/39; 61.5%) of patients had at least one baseline anti-hypertensive medication stopped. Among the six patients who had detectable proteinuria and albumin-to-creatinine (ACR) measurements post-treatment, the mean ACR decreased from 179.0 to 36.1 mg/g (P = 0.03). None of the patients studied had to completely stop treatment due to adverse reactions. CONCLUSIONS: Empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin can safely and effectively improve blood pressure control and reduce proteinuria.

Role of Machine Learning-Based CT Body Composition in Risk Prediction and Prognostication: Current State and Future Directions.

CT body composition analysis has been shown to play an important role in predicting health and has the potential to improve patient outcomes if implemented clinically. Recent advances in artificial intelligence and machine learning have led to high speed and accuracy for extracting body composition metrics from CT scans. These may inform preoperative interventions and guide treatment planning. This review aims to discuss the clinical applications of CT body composition in clinical practice, as it moves towards widespread clinical implementation.

Image-Guided Percutaneous and Transarterial Therapies for Primary and Metastatic Lung Cancer.

Lung cancer is the leading cause of cancer mortality in the world. A significant proportion of patients with lung cancer are not candidates for surgery and must resort to other treatment alternatives. Rapid technological advancements in fields like interventional radiology have paved the way for valid treatment modalities like image-guided percutaneous and transarterial therapies for treatment of both primary and metastatic lung cancer. The rationale of ablative therapies relies on the fact that focused delivery of energy induces tumor destruction and pathological necrosis. Image-guided percutaneous thermal ablation therapies are established techniques in the local treatment of hepatic, renal, bone, thyroid, or uterine lesions. In the lung, the 3 main indications for lung ablation include local curative intent, a strategy to achieve a chemoholiday in oligometastatic disease, and recently, oligoprogressive disease. Transarterial therapies include a set of catheter-based treatments that involve delivering embolic and/or chemotherapeutic agents directed into the target tumor via the supplying arteries. This article provides a comprehensive review of the various techniques available and discusses their applications and associated complications in primary and metastatic lung cancer.

Role of artificial intelligence in risk prediction, prognostication, and therapy response assessment in colorectal cancer: current state and future directions.

Artificial Intelligence (AI) is a branch of computer science that utilizes optimization, probabilistic and statistical approaches to analyze and make predictions based on a vast amount of data. In recent years, AI has revolutionized the field of oncology and spearheaded novel approaches in the management of various cancers, including colorectal cancer (CRC). Notably, the applications of AI to diagnose, prognosticate, and predict response to therapy in CRC, is gaining traction and proving to be promising. There have also been several advancements in AI technologies to help predict metastases in CRC and in Computer-Aided Detection (CAD) Systems to improve miss rates for colorectal neoplasia. This article provides a comprehensive review of the role of AI in predicting risk, prognosis, and response to therapies among patients with CRC.