Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival

Italiano, Antoîne; Toulmonde, Maud; Cioffi, Angela; Penel, Nicolas; Isambert, Nicolás; Bompas, Emmanuelle; Duffaud, Florence; Patrikidou, Anna; Lortal, Barbara; Cesne, Axel Le; Blay, Jean‐Yves; Maki, Robert G.; Schwartz, Gary K.; Antonescu, Cristina R.; Singer, Samuel; Coindre, Jean‐Michel; Bui, Binh

doi:10.1093/annonc/mdr485

Cited by 122 publications

(95 citation statements)

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“…The overall objective response rate of 37% in our study was significantly higher than in WDLPS/DDLPS, which was 12% in the largest series reported to date [2]. The median OS of patients with advanced PLPS (14 months) was comparable to that of other sarcoma subtypes.…”

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confidence: 50%

“…The median OS of patients with advanced PLPS (14 months) was comparable to that of other sarcoma subtypes. Recent studies have shown that a subset of PLPS is characterized by mutations or deletions affecting the tumor suppressor NF1 gene and up to 60% of PLPS exhibit TP53 mutation [1][2][3]. The NF1-encoded protein, neurofibromin, plays a crucial role in the regulation of the mTOR and of the MAPK pathways [4,5].…”

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Advanced pleomorphic liposarcomas: clinical outcome and impact of chemotherapy

et al. 2012

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Advanced pleomorphic liposarcomas: clinical outcome and impact of chemotherapy

et al. 2012

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“…Second, while surgery with or without radiotherapy is the usual treatment for localized WDLPS/DDLPS, the therapeutic options for patients with advanced disease are very limited. The classical antimitotic treatments such as doxorubicin or ifosfamide show low response rates [24]. Therefore, there is an urgent need for novel targeted therapies against WDLPS/DDLPS.…”

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confidence: 99%

A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions

et al. 2012

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While surgery is the usual treatment for localized well-differentiated and dedifferentiated liposarcomas (WDLPS/DDLPS), the therapeutic options for patients with advanced disease are limited. The classical antimitotic treatments are most often inefficient. The establishment of genetically characterized cell lines is therefore crucial for providing in vitro models for novel targeted therapies. We have used spectral karyotyping, fluorescence in situ hybridization with whole chromosome painting and locus-specific probes, and array-comparative genomic hybridization to identify the chromosomal and molecular alterations of a novel cell line established from a recurring sclerosing WDLPS. The karyotype was hypertriploid and showed multiple structural anomalies. All cells retained the presence of a giant marker chromosome that had been previously identified in the primary cell cultures. This giant chromosome contained high-level amplification of chromosomal regions 12q13-21 and lacked the alpha-satellite centromeric sequences associated with WDLPS/DDLPS. The 12q amplicon was large, containing 370 amplified genes. The DNA copy number ranged from 3 to 57. The highest levels of amplification were observed at 12q14.3 for GNS, WIF1, and HMGA2. We analyzed the mRNA expression status by real-time reverse transcription polymerase chain reaction for six genes from this amplicon: MDM2, HMGA2, CDK4, TSPAN31, WIF1, and YEATS4. mRNA overexpression was correlated with genomic amplification. A second amplicon originating from 10p11-14 was also present in the giant marker chromosome. The 10p amplicon contained 62 genes, including oncogenes such as MLLT10, previously described in chimeric fusion with MLL in leukemias, NEBL, and BMI1.

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“…In contrast WDLPS are unlikely to metastasize and have a slower rate of local progression, and may benefit more from active surveillance 44 . Since prognoses and treatment for WDLPS and DDLPS are quite different 22 , accurate diagnosis is crucial for the selection of appropriate treatment 45 .…”

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confidence: 99%

Can Abdominal Computed Tomography Imaging Help Accurately Identify a Dedifferentiated Component in a Well-Differentiated Liposarcoma?

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Wang

Varma

et al. 2016

Journal of Computer Assisted Tomography

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Purpose To assess the ability of CT to differentiate an atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) from a WDLPS with a dedifferentiated component (DDLPS) within it. Materials and Methods Forty-nine untreated patients with abdominal atypical lipomatous tumors/well-differentiated liposarcomas who had undergone contrast-enhanced CT were identified using an institutional database. Three radiologists who were blinded to the pathology findings evaluated all the images independently to determine whether a dedifferentiated component was present within the WDLPS. The CT images were evaluated for fat content (≤25% or >25%); presence of ground-glass density, enhancing and/or necrotic nodules; presence of a capsule surrounding the mass; septations; and presence and pattern of calcifications. A multivariate logistic regression model with generalized estimating equations was used to correlate imaging features with pathology findings. Kappa statistics were calculated to assess agreement between the three radiologists. Results On the basis of pathological findings, 12 patients had been diagnosed with DDLPS within a WDLPS and 37 had been diagnosed with WDLPS. The presence of an enhancing or a centrally necrotic nodule within the atypical lipomatous tumor was associated with dedifferentiated liposarcoma (p = 0.02 and p = 0.0003, respectively). The three readers showed almost perfect agreement in overall diagnosis (kappa r = 0.83; 95% confidence-interval 0.67 to 0.99). Conclusion An enhancing or centrally necrotic nodule may be indicative of a dedifferentiated component in well-differentiated liposarcoma. Ground-glass density nodules may not be indicative of dedifferentiation.

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Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival

Abstract: Chemotherapy was associated with clinical benefit in 46% of patients with advanced WDLPS/DDLPS. OS remains poor, even though visceral metastatic disease is less frequent than in other sarcomas.

Cited by 122 publications

References 35 publications

Advanced pleomorphic liposarcomas: clinical outcome and impact of chemotherapy

Advanced pleomorphic liposarcomas: clinical outcome and impact of chemotherapy

A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions

Can Abdominal Computed Tomography Imaging Help Accurately Identify a Dedifferentiated Component in a Well-Differentiated Liposarcoma?

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