Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas

Lagarde, Pauline; Przybył, Joanna; Brulard, Céline; Pérot, Gaëlle; Pierron, Gaëlle; Delattre, Olivier; Sciot, Raf; Woźniak, Agnieszka; Schöffski, Patrick; Terrier, Philippe; Neuville, Agnès; Coindre, Jean‐Michel; Italiano, Antoîne; Orbach, Daniel; Dębiec‐Rychter, Maria; Chibon, Fréderic

doi:10.1200/jco.2012.46.0147

Cited by 144 publications

(131 citation statements)

References 32 publications

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“…Nevertheless, all parameters being equal, the outcome of adult patients with RMS is less favorable. Beyond the obvious difference in therapeutic approaches and management, the genomics of A‐RMS and E‐RMS should be compared between adult and children, similar to that performed for synovial sarcoma 42. Sharing the same classification would allow easier comparison between clinical presentation and behavior in adults and children.…”

Section: Discussionmentioning

confidence: 99%

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

et al. 2018

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Five‐year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients’ characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E‐RMS) for 21% of patients, alveolar (A‐RMS) for 35% of patients, and “adult‐type” P‐RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A‐RMS: 18%; E‐RMS: 17%; and P‐RMS 65%. With a median follow‐up of 8.5 years, 5‐year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E‐RMS, A‐RMS, and P‐RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A‐RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes.

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Section: Discussionmentioning

confidence: 99%

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

et al. 2018

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“…The same group assessed GI in SS and has shown that a high GI score of 2 predicts for a very poor metastasis-free survival in both pediatric and adult SS. 10 Indeed, the GI was higher in adults, indicating greater genomic instability, which offers a possible biological explanation for the poorer outcome in adults with SS. 7,11,13 Age as a prognostic factor has been clearly shown in several cancer registry series.…”

Section: Epidemiology Biology and Predictors Of Outcomementioning

confidence: 99%

“…9 However, the better outcome in younger patients in part is probably explained by SS biology, in particular, the role of the genomic index (GI). 10 Despite all the recent gains in knowledge, in particular, around biology, and a more defined role for chemotherapy, the outcome for SS has not significantly changed or, indeed, improved over recent years. Certainly, a recent report from the English national cancer registry on overall survival in the UK gives a 5-year relative survival of 57%, which compares with other population-based series and has not significantly changed over the past 20-year period in the UK.…”

Section: Introductionmentioning

confidence: 99%

Synovial sarcoma: current perspectives

Brennan¹

2016

COAYA

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Synovial sarcoma (SS) is a distinct soft tissue sarcoma, occurring across all ages, from young children to the elderly, but the incidence of SS peaks in young adults. Recently, its biology, specifically the biomarker genomic index, may prove to be the most important prognostic marker, explaining findings such as the positive effect of younger age on outcome. While believed to be a chemosensitive soft tissue sarcoma, surgery remains the most important modality of treatment for many people, especially in localized disease, plus or minus radiotherapy to improve local control. Moving forward, the demonstration that SS has multiple therapeutic targets such as vascular endothelial growth factor, and new emerging targets, allows us to start to consider different systemic therapeutic interventions other than just chemotherapy. This is particularly important for advanced/metastatic SS which, with conventional chemotherapy only, continues to have a very poor outcome. The way forward, therefore, is an all-age trial combining perhaps anti-angiogenesis agents with chemotherapy, focusing on those SS cases whose outcome, as determined by biology, site, or metastatic status, is poor with just conventional sarcoma chemotherapy. This also allows prospective evaluation of the role of genomic index and other biomarkers.

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“…The aim of this study was to identify predictive biomarkers for response to TKI treatment in sarcoma, with a particular focus on synovial sarcoma, which is one of the most common soft tissue sarcomas in adolescents and young patients 14) . A magnetic bead-based assay was performed to identify predictive biomarkers in synovial sarcoma, and a meta-analysis was conducted to identify the gene expression pattern of the candidate biomarkers.…”

Section: Western Blottingmentioning

confidence: 99%

“…We used two microarray data sets as follows: 57 samples from GSE 54187 20) and 92 samples from GSE40025 14) . The microarray data were normalized and standardized using the Linear Models for Microarray Data (Limma) package (http:// bioconductor.org/packages/limma/) 21) .…”

Section: Meta-analysismentioning

confidence: 99%

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

Qiao

Kito²,

Takai³

et al. 2017

J. Electrophor

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SUMMARYSarcoma is a rare malignancy with an aggressive clinical course. Tyrosine kinase inhibitors (TKIs) have emerged as effective drugs in targeted therapy for malignancies; in particular, pazopanib was recently approved for the treatment of sarcoma. However, as only a limited proportion of patients exhibit favorable response to treatment with TKIs, predictive biomarkers of response to these drugs are urgently needed. In this study, we attempted to identify predictive biomarkers for response to TKIs in synovial sarcoma. We performed a magnetic bead-based assay (Bio-Plex) using synovial sarcoma cell culture supernatant and validated the results by ELISA and western blotting. Cellular protein and mRNA expression levels of candidate biomarkers were evaluated by western blotting and RT-PCR. Gene expression profiling of candidate biomarkers was conducted by meta-analysis of publicly available gene expression data from 149 patients with synovial sarcoma. We found that follistatin (FST) was significantly highly expressed in TKI-resistant cells. Moreover, cell proliferation was decreased following gene silencing of FST. Meta-analysis revealed that the mRNA expression of FST varied among the 149 patients with synovial sarcoma, and that 23 genes were co-expressed with FST; these included genes encoding receptor tyrosine kinase-like orphan receptor 1, Sal-like protein 4, and signal transducer CD24. This study suggested that FST represents a candidate predictive biomarker for response to treatment with TKIs in synovial sarcoma. Secretomics is a promising approach for predictive biomarker exploration. The utility of FST as a predictive biomarker for response to treatment with TKIs in synovial sarcoma should be further validated using clinical samples.

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Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas

Cited by 144 publications

References 32 publications

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Synovial sarcoma: current perspectives

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

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