Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/1/cncr32508_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/2/cncr32508.pd

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma

International audienceBackground: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes.Methods: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype.Results: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR-18-+18), +8% (IQR 0-+24),-12% (IQR-20-3) and-11% (IQR-15-9), respectively (p=0.001). Median viable cells were 10%, 60%, 20% and 70% (p=0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p=0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without Manuscript Click here to view linked References proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect.Conclusion: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns

Desmoid tumors located in the abdomen or associated with adenomatous polyposis: French intergroup clinical practice guidelines for diagnosis, treatment, and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR)

International audienceIntroduction: Desmoid tumor (DT) of the abdomen is a challenging and rare disease. The level of evidence available to document their treatment is relatively low, however, recent publications of prospective studies have allowed to precise their management.Methods: This document is a summary of the French intergroup guidelines realized by all French medical and surgical societies involved in the management of DT located in the abdomen or associated with adenomatous polyposis. Recommendations are graded in four categories (A, B, C and D), according to the level of evidence found in the literature until January 2021.Results: When the diagnosis of DT is suspected a percutaneous biopsy should be performed when possible. A molecular analysis looking for pathogenic mutations of the CTNNB1 and APC genes should be systematically performed. When a somatic pathogenic variant of the APC gene is present, an intestinal polyposis should be searched. Due to a high rate of spontaneous regression, non-complicated DT should first benefit from an active surveillance with MRI within 2 months after diagnosis to assess the dynamic of tumor growth. The treatment decision must be discussed in an expert center, favoring the less toxic treatments which can include broad spectrum tyrosine kinase inhibitor or conventional chemotherapy (methotrexate-vinblastine). Surgery, outside the context of emergency, should only be considered for favorable location in an expert center.Conclusion: French guidelines for DT management were elaborated to help offering the best personalized therapeutic strategy in daily clinical practice as the DT therapeutic landscape is complexifying. Each individual case must be discussed within a multidisciplinary expert team

Identification of a novel translocation producing an in-frame fusion of TAF15 and ETV4 in a case of extraosseous Ewing sarcoma revealed in the prenatal period

Ewing sarcoma (ES) is a highly malignant round cell sarcoma, characterized by gene fusion involving FET (FUS, EWSR1, TAF15) and ETS family genes, respectively. The involvement of the EWSR1 gene has been reported in approximately 90% of cases of ES, with the EWSR1::FLI1 fusion being the most frequent. We report the case of a newborn with a localized soft tissue paravertebral neoplasm diagnosed prenatally. Histopathology and immunophenotype were consistent with a CD99 + , NKX2.2 + undifferentiated round cell sarcoma (URSC); whole-exome RNA-sequencing demonstrated an undescribed in-frame TAF15::ETV4 fusion transcript, while consensus clustering analysis showed high transcriptomic proximity to the ES group. Given clinical context, high tumor chemosensitivity to ES conventional drugs, morphological characteristics, nature of the fusion partners involved, and high transcriptomic proximity to bona fide ESs, this case may represent a new genetic variant of ES

Molecular classification of endometrial stromal sarcomas using RNA sequencing defines nosological and prognostic subgroups with different natural history.

International audienceA series of 42 patients tumors diagnosed as endometrial stromal sarcomas (ESS) based on 15 the morphology but negative for JAZF1 and/or YWHAE rearrangement in FISH was analyzed by 16 RNA-sequencing. A chromosomal rearrangement was identified in 31 (74%) of the cases and a 17 missense mutation in known oncogenes / tumor suppressor genes in 11 (26%). Cluster analyses on 18 the expression profiles from this series together with a control cohort composed of 5 samples of Low 19 Grade ESS harboring a JAZF1-SUZ12 fusion, 1 High Grade ESS harboring a BCOR-ITD, 2 uterine 20 tumors resembling ovarian sex cord tumors, 2 samples each of uterine leiomyoma and 21 leiomyosarcomas and a series of BCOR-rearranged family of tumor (N=8), indicated that tumors 22 could be gather in three distinct subgroups: one mainly composed of BCOR-rearranged samples 23 that contained 7 ESS samples; one mainly composed of JAZF1-fused ESS (N=15) and the last 24 composed of various molecular subtypes (N=19). These three subgroups display different gene 25 signatures, different in silico cell cycle scores, and very different clinical presentations, natural 26 history and survival (Log-rank test, P=0.004). While YWHAE-NUTM2 fusion genes may be present 27 in both high and low grade ESS, the high-grade presenting with an additional BCOR or BCORL1 28 gene mutations. RNAseq brings clinically relevant molecular classification, enabling to reclassify 29 diseases and to guide therapeutic strategy. 3

Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection

International audienceIntroduction: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR).Materials and Methods: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT.Results: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04).Conclusion: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors

Comprehensive Immune Profiling Unveils a Subset of Leiomyosarcoma with “Hot” Tumor Immune Microenvironment

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A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant‐type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma

Abstract Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant‐type hemispheric glioma (IHG). Like desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), these tumors mainly affect infants and are supratentorial. While DIG/DIA is characterized by BRAF or RAF1 alterations, IHG has been shown to have receptor tyrosine kinase (RTK) gene fusions ( ALK , ROS1 , NTRK1/2/3 , and MET ). However, in this rapidly evolving field, a more comprehensive analysis of infantile glial/glioneuronal tumors including clinical, radiological, histopathological, and molecular data is needed. Here, we retrospectively investigated data from 30 infantile glial/glioneuronal tumors, consecutively compiled from our center. They were analyzed by two experienced pediatric neuroradiologists in consensus, without former knowledge of the molecular data. We also performed a comprehensive clinical, and histopathological examination (including molecular evaluation by next‐generation sequencing, RNA sequencing, and fluorescence in situ hybridization [FISH] analyses), as well as DNA methylation profiling for the samples having sufficient material available. The integrative histopathological, genetic, and epigenetic analyses, including t‐distributed stochastic neighbor embedding (t‐SNE) analyses segregated tumors into 10 DIG/DIA (33.3%), six IHG (20.0%), three gangliogliomas (10.0%), two pleomorphic xanthoastrocytomas (6.7%), two pilocytic astrocytomas (6.7%), two supratentorial ependymomas, ZFTA fusion‐positive (6.7%), two supratentorial ependymomas, YAP1 fusion‐positive (6.7%), two embryonal tumors with PLAGL2‐family amplification (6.7%), and one diffuse low‐grade glioma, MAPK‐pathway altered. This study highlights the significant differential features, in terms of histopathology (leptomeningeal infiltration, intense desmoplasia and ganglion cells in DIG/DIA and necrosis, microvascular proliferation, and siderophages in IHG), and radiology between DIG/DIA and IHG. Moreover, these results are consistent with the literature data concerning the molecular dichotomy ( BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification

CNS neuroblastoma, FOXR2-activated and its mimics: a relevant panel approach for work-up and accurate diagnosis of this rare neoplasm

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“Hemispheric pilocytic astrocytoma” revisited: A comprehensive clinicopathological and molecular series emphasizing their overlap with other glioneuronal tumors

International audienceAbstract Pilocytic astrocytomas (PA) typically exhibit distinct clinical, radiological, histopathological, and genetic features. DNA-methylation profiling distinguishes PA according to their location (infratentorial, midline, hemispheric, or spinal). In the hemispheric location, distinguishing PA from glioneuronal tumors remains a common diagnostic challenge for neuropathologists. Furthermore, the current version of the DKFZ classifier seems to have difficulty separating them from gangliogliomas. In this study, after central radiological review, we identified a histopathologically defined set of PA (histPA, n = 11) and a cohort of DNA-methylation defined PA (mcPA, n = 11). Nine out of the 11 histPA matched the methylation class of hemispheric PA, whereas 2 cases were classified at the end of the study as dysembryoplastic neuroepithelial tumors. Similarly, the mcPA cohort contained tumors mainly classified as PA (7/11), but 4 cases were classified as glioneuronal. The analysis of the 16 tumors with an integrated diagnosis of PA revealed that they affect mainly children with a wide spectrum of radiological, histopathological (i.e. a predominantly diffuse growth pattern), and genetic characteristics (large range of mitogen-activated protein kinase alterations). Based on these results, we consider hemispheric PA to be different from their counterparts in other locations and to overlap with other glioneuronal tumors, reinforcing the necessity of interpreting all data to obtain an accurate diagnosis