The Genomic Grade Index predicts postoperative clinical outcome in patients with soft-tissue sarcoma

Bertucci, François; Nonneville, Alexandre de; Finetti, Pascal; Perrot, Delphine; Nilbert, Mef; Italiano, Antoîne; Cesne, Axel Le; Skubitz, Keith M.; Blay, Jean‐Yves; Birnbaum, Daniel

doi:10.1093/annonc/mdx699

Cited by 26 publications

(20 citation statements)

References 22 publications

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“…Nevertheless, there is no data on the prognostic value of baseline Hb levels and outcomes in sarcomas. The increasingly widespread use of molecular biology is now promoting a better understanding of the complexity of STS and making it possible to identify predictive signatures of the risk of metastatic recurrence in localized STS [51,52]. In vitro studies have suggested that cells with a deficient homologous recombination DNA repair pathway have a higher sensitivity to trabectedin [53], and retrospective studies have shown that BRCA1 (breast cancer gene 1) status may be predictive of trabectedin efficacy [54,55,56].…”

Section: Discussionmentioning

confidence: 99%

Validation of Neutrophil Count as An Algorithm-Based Predictive Factor of Progression-Free Survival in Patients with Metastatic Soft Tissue Sarcomas Treated with Trabectedin

Nonneville

Barbolosi

Andriantsoa

et al. 2019

Cancers

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Introduction: Based on a mathematical model of trabectedin-induced neutropenia, we assessed the predictive value of absolute neutrophil count (ANC) on progression-free survival (PFS) in an independent validation cohort of patients treated with trabectedin. Methods: We collected data from 87 patients in two expert centers who received at least two cycles of trabectedin for soft tissue sarcomas (STS) treatment. Correlations between ANC, patients’ characteristics, and survival were assessed, and a multivariate model including tumor grade, performance status, ANC, and hemoglobin level was developed. Results: Therapeutic ANC ≥ 7.5 G/L level was associated with shorter PFS: 3.22 months (95% confidence interval (CI), 1.57–4.87) in patients with ANC ≥ 7.5 G/L vs. 5.78 months (95% CI, 3.95–7.61) in patients with ANC < 7.5 G/L (p = 0.009). Age, primary localization, lung metastases, dose reduction, hemoglobin, and albumin rates were also associated with PFS. In multivariate analysis, ANC ≥ 7.5 G/L was independently associated with poor PFS and overall survival. Conclusion: We validated increased pre-therapeutic ANC as a predictive factor of short PFS in patients starting trabectedin for STS. ANC appears to have an impact on survival rates and may be used as a decision-making tool for personalizing second-line strategies in patients with metastatic STS.

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Section: Discussionmentioning

confidence: 99%

Validation of Neutrophil Count as An Algorithm-Based Predictive Factor of Progression-Free Survival in Patients with Metastatic Soft Tissue Sarcomas Treated with Trabectedin

Nonneville

Barbolosi

Andriantsoa

et al. 2019

Cancers

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“…In addition, it has been reported that isolated gains of 3p in ChRCC was correlated to sarcomatoid differentiation while gain of chromosome 21 was correlated to poor prognosis 34,35 . Moreover, since it is usually described that tumors showing segmental unbalances may have a higher aggressiveness than tumors showing gains or losses of whole chromosomes, 36,37 this raises the issue of histopathological features related to these segmental quantitative alterations. However, Sperga et al 26 did not observe any correlation of a combination of gains and losses in a series of 37 ChRCC to histological features or to prognosis.…”

Section: Discussionmentioning

confidence: 99%

Detection of tetraploidization in chromophobe renal cell carcinoma: Insights and pitfalls

Mauro¹,

Vignot

Roussel

et al. 2020

Genes Chromosomes & Cancer

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Chromosomal losses resulting in a marked hypodiploidy are a specificity of chromophobe renal cell carcinoma (ChRCC), the third most frequent type of kidney cancer. Its detection is useful in challenging cases. However some ChRCC, especially the eosinophilic variant, do not exhibit hypodiploidy and deserve to be better explored. Using comparative genomic hybridization (array-CGH) we observed chromosomal gains in five cases of nonmetastatic ChRCC. Our objective was to determine whether these apparent chromosomal gains were instead losses within a near-polyploid genome. We performed a retrospective and prospective molecular study of 26 cases of ChRCC retrieved among 643 renal tumors (2012-2019). All tumors were analyzed using array-CGH (Agilent) and array-CGH (Affymetrix) coupled to single nucleotide polymorphism analysis (array-SNP). In silico manual centralization of the fluorescence ratio, fluorescence in situ hybridization (FISH) and next generation sequencing were made in the five cases suspected of polyploidy. Tetraploidization was observed in 19% of our series of ChRCC. None of the methods used individually could identify both chromosomal losses and tetraploidy. Only the combination of manual recentring of array-CGH and FISH provided relevant results. B-allele frequency results indicated that tetraploidization occurred secondarily to chromosomal losses in four cases while it preceded losses in one case. Tetraploidization is a frequent but underestimated phenomenon in ChRCC that may be overlooked using the individual standard genomic methods. Its potential clinical consequences are not identified yet. Whether the mechanisms that induce chromosomal losses in ChRCC are the same that generate tetraploidization is not known.

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“…This variance in treatment response is linked with both intratumoral and intertumoral genomic heterogeneity, with subclonal tumor populations with distinct gene expression profiles that may correspond to their response to various treatment modalities. 4,13,[16][17][18][19] These findings provide insight into the potential to improve outcome by applying radiation dose heterogeneously, or "dose painting," based on the distinct subclonal populations throughout the tumor, rather than the typical homogenous dose distributions that are currently used.…”

Section: Genomicsmentioning

confidence: 99%

The Future of Radiation Oncology in Soft Tissue Sarcoma

et al. 2018

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Radiotherapy (RT) is an important component of the treatment of soft tissue sarcomas (STS) and has been traditionally incorporated with a homogenous approach despite the reality that STS displays a known heterogeneity in clinicopathologic features and treatment outcomes. In this article, we explore the principle components of personalized medicine, including genomics, radiomics, and treatment response, along with their impact on the future of radiation therapy for STS. We propose a shift in the treatment paradigm for STS from a one-size-fits-all technique to one that implements the tenets of personalized medicine and includes the framework for a potential clinical trial technique in this heterogeneous disease.

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The Genomic Grade Index predicts postoperative clinical outcome in patients with soft-tissue sarcoma

Cited by 26 publications

References 22 publications

Validation of Neutrophil Count as An Algorithm-Based Predictive Factor of Progression-Free Survival in Patients with Metastatic Soft Tissue Sarcomas Treated with Trabectedin

Validation of Neutrophil Count as An Algorithm-Based Predictive Factor of Progression-Free Survival in Patients with Metastatic Soft Tissue Sarcomas Treated with Trabectedin

Detection of tetraploidization in chromophobe renal cell carcinoma: Insights and pitfalls

The Future of Radiation Oncology in Soft Tissue Sarcoma

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