Sprouty2 Regulates Endocytosis and Degradation of Fibroblast Growth Factor Receptor 1 in Glioblastoma Cells.

The Sprouty (SPRY) proteins are evolutionary conserved modulators of receptor tyrosine kinase (RTK) signaling. SPRY2 inhibits fibroblast growth factor (FGF) signaling, whereas it enhances epidermal growth factor (EGF) signaling through inhibition of EGF receptor (EGFR) endocytosis, ubiquitination, and degradation. In this study, we analyzed the effects of SPRY2 on endocytosis and degradation of FGF receptor 1 (FGFR1) using two human glioblastoma (GBM) cell lines with different endogenous SPRY2 levels.

Liquid Biopsy versus CT: Comparison of Tumor Burden Quantification in 1065 Patients with Metastases.

Background Tumor fraction (TF) at liquid biopsy is a potential noninvasive marker for tumor burden, but validation is needed. Purpose To evaluate TF as a potential surrogate for tumor burden, assessed at contrast-enhanced CT across diverse metastatic cancers. Methods This retrospective monocentric study included patients with cancer and metastatic disease, with TF results and contemporaneous contrast-enhanced CT performed between January 2021 and January 2023.

Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics.

Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody.

Integration of pre-treatment computational radiomics, deep radiomics, and transcriptomics enhances soft-tissue sarcoma patient prognosis.

Our objective was to capture subgroups of soft-tissue sarcoma (STS) using handcraft and deep radiomics approaches to understand their relationship with histopathology, gene-expression profiles, and metastatic relapse-free survival (MFS). We included all consecutive adults with newly diagnosed locally advanced STS (N = 225, 120 men, median age: 62 years) managed at our sarcoma reference center between 2008 and 2020, with contrast-enhanced baseline MRI. After MRI postprocessing, segmentation, and reproducibility assessment, 175 handcrafted radiomics features (h-RFs) were calculated.

Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

Background: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors.

Methods: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden.

Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide.

Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures.

Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study.

Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions.

Radiomics and artificial intelligence for soft-tissue sarcomas: Current status and perspectives.

This article proposes a summary of the current status of the research regarding the use of radiomics and artificial intelligence to improve the radiological assessment of patients with soft tissue sarcomas (STS), a heterogeneous group of rare and ubiquitous mesenchymal malignancies. After a first part explaining the principle of radiomics approaches, from raw image post-processing to extraction of radiomics features mined with unsupervised and supervised machine-learning algorithms, and the current research involving deep learning algorithms in STS, especially convolutional neural networks, this review details their main research developments since the formalisation of 'radiomics' in oncologic imaging in 2010. This review focuses on CT and MRI and does not involve ultrasonography.

Initial Active Surveillance Strategy for Patients with Peripheral Sporadic Primary Desmoid-Type Fibromatosis: A Multicentric Phase II Observational Trial.

Background: Stabilization or spontaneous regressions are demonstrated in more than half of patients affected by primary desmoid-type fibromatosis (DF) in retrospective studies. The objective of this phase II study was to prospectively assess the behavior of primary sporadic DT managed by active surveillance (AS).

Methods: This prospective, multicenter, observational study (NCT01801176) included patients ≥18 years of age with primary sporadic DF located in an extremity or the abdominal/thoracic wall.

Imaging presentation of extraskeletal osteosarcomas on CT and MRI and correlation with patients outcome: A two-center retrospective study of 54 patients.

Purpose: The purpose of this study was to analyze the imaging features of extraskeletal osteosarcomas (ESOS) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate their associations with overall survival (OS) using uni- and multivariable survival analyses.

Materials And Methods: This two-center retrospective study included all consecutive adult patients between 2008 and 2021 with histopathologically-proven ESOS who underwent pre-treatment CT and/or MRI. Clinical and histological characteristics, ESOS presentation on CT and MRI, treatment and outcomes were reported.

Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy.

Purpose: The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation.

Experimental Design: This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1.

Soft-tissue sarcoma in adults: Imaging appearances, pitfalls and diagnostic algorithms.

This article provides an overview of the current knowledge regarding diagnostic imaging of patients with soft-tissue sarcomas, which is a heterogeneous group of rare mesenchymal malignancies. After an initial contextualization, diagnostic flow-chart based on initial radiological findings of soft-tissue masses (with specific focus on adipocytic soft-tissue tumors [STTs], hemorragic STTs and retroperitoneal STTs) are provided considering relevant results from novel researches, guidelines, and experts' viewpoints, with the aim to help radiologists and clinicians in their practice. Particularly, the central place of sarcoma reference centers in the diagnostic and therapeutic management is highlighted, as well as the pivotal role that radiologists should play to correctly identify patients with soft-tissue sarcoma at the initial stage of the disease.

Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer.

Breast cancer is one the most common cause of cancer death in women worldwide. We report here the first phase II study investigating a virus genetically engineered for tumor-selective replication in patients with breast cancer. Ten patients were treated with a combination of low-dose oral cyclophosphamide and intra-venous JX-594, a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF) and β-galactosidase.

Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume.

Background: Anti-PD-(L)1 treatment is indicated for patients with mismatch repair-deficient (MMRD) tumors, regardless of tumor origin. However, the response rate is highly heterogeneous across MMRD tumors. The objective of the study is to find a score that predicts anti-PD-(L)1 response in patients with MMRD tumors.

Pembrolizumab combined with low-dose cyclophosphamide and intra-tumoral injection of the toll-like receptor 4 agonist G100 in patients with advanced pretreated soft tissue sarcoma: results from the PEMBROSARC basket study.

Soft tissue sarcomas (STS) are heterogeneous mesenchymal tumors with limited therapeutic options in the advanced setting. Immune checkpoint inhibitors have been shown to have significant clinical activity in inflamed STS which are characterized by the presence of tertiary lymphoid structures (TLS). New strategies are needed to sensitize TLS-negative STS to immunotherapy.

Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma.

JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS.

Primary Soft-Tissue Lymphomas: MRI Features Help Discriminate From Other Soft-Tissue Tumors.

Objectives: MRI presentation of extra-nodal soft-tissue lymphomas (STLs) is scarcely reported and lacks of comparison with other soft-tissue tumors (STTs) including sarcomas (STS). Yet, suggesting this diagnosis on MRI would considerably reduce diagnostic intervals. Our aim was to investigate if conventional MRI could discriminate STLs from other STTs.

Distinct patterns of the natural evolution of soft tissue sarcomas on pre-treatment MRIs captured with delta-radiomics correlate with gene expression profiles.

Objectives: Radiomics of soft tissue sarcomas (STS) is assumed to correlate with histologic and molecular tumor features, but radiogenomics analyses are lacking. Our aim was to identify if distinct patterns of natural evolution of STS obtained from consecutive pre-treatment MRIs are associated with differential gene expression (DGE) profiling in a pathway analysis.

Methods: All patients with newly diagnosed STS treated in a curative intent in our sarcoma reference center between 2008 and 2019 and with two available pre-treatment contrast-enhanced MRIs were included in this retrospective study.

Ranking the most influential predictors of CT-based radiomics feature values in metastatic lung adenocarcinoma.

Purpose: To investigate which acquisition, post-processing, tumor, and patient characteristics contribute the most to the value of radiomics features (RFs) in lung adenocarcinoma in order to better understand and order the potential sources of bias in radiomics studies in a multivariate setting.

Methods: This single-center retrospective study included all consecutive patients with newly-diagnosed lung adenocarcinoma treated between December 2016 and September 2018 who had pre-treatment contrast-enhanced CT-scan showing ≥ 2 target lesions per response evaluation criteria in solid tumors (RECIST) v1.1.

Investigation of the surfactant distribution in oil-in-water emulsions during the crystallization of the dispersed phase via nuclear magnetic resonance relaxometry and diffusometry.

The crystallization of melt emulsions is of great interest to the food, cosmetic, and pharmaceutical industries. Surfactants are used in emulsions and suspensions to stabilize the dispersed phase; thus, questions arise about the liquid-liquid and solid-liquid interfaces of the droplets or particles and the distribution of the surfactant in the different phases (continuous and dispersed phase, interface). Nuclear magnetic resonance relaxation and diffusion measurements revealed that the internal and rotational mobility of surfactant molecules at the liquid-liquid interface decreases with increasing droplet sizes.

No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks' Outcome?

The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGéAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGéAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed.

Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort.

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781).

Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression.

Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently of PD-L1 expression status and CD8+ T-cell density.