Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.

The management of renal cell carcinoma (RCC) has advanced significantly in the past two decades. Many promising functional imaging modalities such as radiolabeled tracer targeting carbonic anhydrase IX and prostate-specific membrane antigen are under development to detect primary kidney tumors, stage systemic disease, and assess treatment response in RCC. Immune checkpoint inhibitors targeting PD-1 and cytotoxic T-cell lymphocyte-4 have changed the treatment paradigm in advanced RCC.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials And Methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively.

Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes.

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Patients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.

Liquid biopsy epigenomic profiling for cancer subtyping.

Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

Design, Setting, And Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection.

Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers for patients with mccRCC receiving systemic therapies, with a focus on immunotherapy-based regimens.

Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes.

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory stimuli that maintain immunosuppression ("brakes") and priming the immune system to target tumoral cells ("gas pedals").

Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition.

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC.

Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma.

Renal cell carcinoma (RCC) of variant histology comprises approximately 20% of kidney cancer diagnoses, yet the optimal therapy for these patients and the factors that impact immunotherapy response remain largely unknown. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based immune markers for patients with variant histology RCC, or any RCC histology with sarcomatoid differentiation, enrolled in a phase II clinical trial of atezolizumab and bevacizumab. Baseline circulating (plasma) inflammatory cytokines were highly correlated with one another, forming an "inflammatory module" that was increased in International Metastatic RCC Database Consortium poor-risk patients and was associated with worse progression-free survival (PFS; P = 0.

Functional assessment using 3D movement analysis can better predict health-related quality of life outcomes in patients with adult spinal deformity: a machine learning approach.

Introduction: Adult spinal deformity (ASD) is classically evaluated by health-related quality of life (HRQoL) questionnaires and static radiographic spino-pelvic and global alignment parameters. Recently, 3D movement analysis (3DMA) was used for functional assessment of ASD to objectively quantify patient's independence during daily life activities. The aim of this study was to determine the role of both static and functional assessments in the prediction of HRQoL outcomes using machine learning methods.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

Introduction: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy.

Germline variants associated with toxicity to immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types.

Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study.

Background: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19.

Methods: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021.

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity.

Purpose: To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations.

Methods: One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°).

Reliability assessment of cervical spine parameters measured on full-body radiographs in asymptomatic subjects and patients with spinal deformity.

Background: Cervical spinal alignment is usually assessed on full-body radiographs allowing for the concomitant evaluation of possible compensatory mechanisms that may occur at any level in the setting of postural malalignment.

Hypothesis: Cervical parameters measured on full-body radiographs are reliable.

Patients And Methods: A total of 70 subjects were included and divided in 3 groups: asymptomatic adults (n=21), adolescents with idiopathic scoliosis (n=20), and adults with spinal deformity (n=29), for whom full-body low-dose biplanar radiographs were obtained.

Gait kinematic alterations in subjects with adult spinal deformity and their radiological determinants.

Background: Adults with spinal deformity (ASD) are known to have postural malalignment affecting their quality of life. Classical evaluation and follow-up are usually based on full-body static radiographs and health related quality of life questionnaires. Despite being an essential daily life activity, formal gait assessment lacks in clinical practice.

Toward understanding the underlying mechanisms of pelvic tilt reserve in adult spinal deformity: the role of the 3D hip orientation.

Purpose: To explore 3D hip orientation in standing position in subjects with adult spinal deformity (ASD) presenting with different levels of compensatory mechanisms.

Methods: Subjects with ASD (n = 159) and controls (n = 68) underwent full-body biplanar X-rays with the calculation of 3D spinopelvic, postural and hip parameters. ASD subjects were grouped as ASD with knee flexion (ASD-KF) if they compensated by flexing their knees (knee flexion ≥ 5°), and ASD with knee extension (ASD-KE) otherwise (knee flexion < 5°).

What is the most reliable radiographic method to evaluate the longitudinal foot arch? Application in subjects with Adolescent Idiopathic Scoliosis.

Background: The foot arch is known to be altered in subjects with postural malalignment. Foot arch morphology can be studied simultaneously with body's balance by measuring foot radiographic parameters on full-body biplanar x-rays. There is no consensus on which is the most reliable method to use to draw the foot axes.