Organ-specific response to [Lu]DOTATATE peptide receptor radionuclide therapy (PRRT) assessed by sequential [Ga]DOTATOC PET/CT in patients with metastatic small intestine neuroendocrine tumors.

Purpose: To evaluate organ-specific response to [Lu]DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) in patients with small intestine neuroendocrine tumor (SiNET) through [Ga]DOTATOC PET/CT, and to analyze tumor uptake and functional volume variations at different metastatic sites in relation to disease progression during clinical follow-up after treatment.

Methods: A retrospective analysis was conducted on 33 metastatic patients. PET/CT were performed pre-treatment (PET0), mid-treatment after two PRRT cycles (PET2), and post-treatment (PET4).

Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas.

Introduction: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement.

PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

Background: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value.

Methods: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers.

Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes.

Silencing of genes by promoter hypermethylation shapes tumor microenvironment and resistance to immunotherapy in clear-cell renal cell carcinomas.

The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial.

Mesenchymal-like Tumor Cells and Myofibroblastic Cancer-Associated Fibroblasts Are Associated with Progression and Immunotherapy Response of Clear Cell Renal Cell Carcinoma.

Unlabelled: Immune checkpoint inhibitors (ICI) represent the cornerstone for the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease, highlighting the need to precisely understand the plasticity of cancer cells and their cross-talk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial-to-mesenchymal transition gradient and a novel inflamed state.

Racial Disparities in MiT Family Translocation Renal Cell Carcinoma.

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort.

SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance.

Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs.

Immune Checkpoint Therapy Combinations in Adult Advanced MiT Family Translocation Renal Cell Carcinomas.

Background: There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC).

Methods: This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included.

Molecular analysis for refractory rare cancers: Sequencing battle continues - learnings for the MOSCATO-01 study.

Background: For patients with metastatic rare cancers, treatments are limited. How systematic tumor sequencing can improve therapeutic possibilities in this population?

Patients And Methods: Patients with rare cancer were identified in the MOSCATO-01 trial. Patients' outcome was measured by progression-free survival (PFS) and overall survival (OS).

An Enhancer Demethylator Phenotype Converged to Immune Dysfunction and Resistance to Immune Checkpoint Inhibitors in Clear-Cell Renal Cell Carcinomas.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of patients with clear-cell renal cell carcinomas (ccRCC). Although analyses of transcriptome, genetic alterations, and the tumor microenvironment (TME) have shed light into mechanisms of response and resistance to these agents, the role of epigenetic alterations in this process remains fully unknown.

Experimental Design: We investigated the methylome of six ccRCC cohorts as well as one cell line dataset.

Early identification of heart failure deterioration through respiratory monitoring with adaptive servo-ventilation.

Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep-disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity.

The LncRNA LENOX Interacts with RAP2C to Regulate Metabolism and Promote Resistance to MAPK Inhibition in Melanoma.

Unlabelled: Tumor heterogeneity is a key feature of melanomas that hinders development of effective treatments. Aiming to overcome this, we identified LINC00518 (LENOX; lincRNA-enhancer of oxidative phosphorylation) as a melanoma-specific lncRNA expressed in all known melanoma cell states and essential for melanoma survival in vitro and in vivo. Mechanistically, LENOX promoted association of the RAP2C GTPase with mitochondrial fission regulator DRP1, increasing DRP1 S637 phosphorylation, mitochondrial fusion, and oxidative phosphorylation.

Efficacy of Cabozantinib in Metastatic MiT Family Translocation Renal Cell Carcinomas.

Background: MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this subgroup is unclear.

Methods: We performed a multicenter, retrospective, international cohort study of patients with TRCC treated with cabozantinib.

Genetic landscape of indolent and aggressive Kaposi sarcomas.

Background: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown.

Objectives: To explore the tumour mutational burden in indolent and aggressive KS.

F-DOPA PET/CT at the Forefront of Initial or Presurgical Evaluation of Small-Intestine Neuroendocrine Tumors.

Our objective was to compare the respective value of Ga-DOTATOC and F-DOPA PET/CT for initial staging or presurgical work-up of patients with small-intestine neuroendocrine tumors (SiNETs). This was a retrospective, multicenter, noninterventional investigation involving 53 non-surgically treated SiNET patients who underwent both Ga-DOTATOC and F-DOPA PET/CT within a 6-mo interval without surgical intervention or therapeutic change between the 2 PET/CT studies. Percentage detection rate was calculated according to per-region and per-lesion analyses.

Impact of the app-based and nurse-led supportive care program AKO@dom on dose intensity of oral-targeted therapies in patients with metastatic renal cell cancer: a multicentric observational retrospective study.

Background: Tyrosine kinase inhibitors (TKIs) remain a cornerstone of metastatic kidney cancer (mRCC). Adverse events (AEs) may lead to dose downregulation, and optimal management of AEs is needed to maintain an efficient dose intensity (DI). The aim of our study was to evaluate the impact of an app-based and nurse-led supportive-care program on DI in mRCC patients.

Immune-Desert Tumor Microenvironment in Thoracic SMARCA4-Deficient Undifferentiated Tumors with Limited Efficacy of Immune Checkpoint Inhibitors.

Background: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Data linking BAF alterations with tumor microenvironment (TME) and efficacy of immune checkpoint inhibitors (ICI) are contradictory. The TME of SMARCA4-UT and their response to ICI are unknown.

Renal cell carcinoma in children and adolescents: a retrospective study of a French-Italian series of 93 cases.

Aims: Renal cell carcinomas (RCCs) represent 2-5% of kidney malignancies in children and adolescents. Appropriate diagnostic and classification are crucial for the correct management of the patients and in order to avoid inappropriate pre-operative chemotherapy, which is usually recommended if a Wilms' tumour is suspected.

Methods And Results: A French-Italian series of 93 renal cell carcinomas collected from 1990 to 2019 in patients aged less than 18 years was reclassified according to the 2016 World Health Organization (WHO) classification and the latest literature.

Natural History and Treatment Strategies of Advanced PEComas: A Systematic Review.

PEComas is a family of rare mesenchymal tumors. This systematic review aims to better understand the natural history of advanced PEComas. After a search on the PubMed database and main oncology meeting libraries according to the PRISMA guidelines, 88 articles reported in the English literature were included.

Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions.

Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas.