Optimal Percent Myxoid Component to Predict Outcome in High-Grade Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma

Lee, Ann Y.; Agaram, Narasimhan P.; Qin, Li‐Xuan; Kuk, Deborah; Curtin, Christina; Brennan, Murray F.; Singer, Samuel

doi:10.1245/s10434-015-5063-5

Cited by 37 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B) (p=0.021). To further test the importance of this grouping, we performed a multivariate analysis adjusting for tumor size, the most important known clinical predictor in myxofibrosarcoma (4, 23–25). Both variables were independent predictors of DSS: tumor size as a continuous variable had a hazard ratio of 1.15 (p=0.010) and cluster 1 vs cluster 2 membership had a hazard ratio of 5.26 (p=0.014).…”

Section: Resultsmentioning

confidence: 99%

“…Formerly known as a myxoid variant of malignant fibrous histiocytoma (a classification representing undifferentiated pleomorphic sarcomas), myxofibrosarcoma is currently regarded as a distinct fibroblastic/myofibroblastic tumor type defined by cellular pleomorphism, a curvilinear vascular pattern, and a myxoid stromal component (1–3). While the mainstay of therapy is surgical resection, and 5-year disease-specific survival (DSS) after surgery for primary high-grade myxofibrosarcoma is 60–70%, approximately 30–40% of high-grade tumors metastasize to lung, bone, or lymph nodes (4–7). Once myxofibrosarcoma has metastasized, conventional chemotherapy and radiation therapy are largely palliative, and metastasis eventually leads to disease-related death.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma

et al. 2016

Self Cite

View full text Add to dashboard Cite

Myxofibrosarcoma is a common mesenchymal malignancy with complex genomics and heterogeneous clinical outcomes. Through gene-expression profiling of 64 primary high-grade myxofibrosarcomas, we defined an expression signature associated with clinical outcome. The gene most significantly associated with disease-specific death and distant metastasis was ITGA10 (integrin-α10). Functional studies revealed that myxofibrosarcoma cells strongly depended on integrin-α10, whereas normal mesenchymal cells did not. Integrin-α10 transmitted its tumor-specific signal via TRIO and RICTOR, two oncoproteins that are frequently co-overexpressed through gene amplification on chromosome 5p. TRIO and RICTOR activated RAC/PAK and AKT/mTOR to promote sarcoma cell survival. Inhibition of these proteins with EHop-016 (RAC inhibitor) and INK128 (mTOR inhibitor) had anti-tumor effects in tumor-derived cell lines and mouse xenografts, and combining the drugs enhanced the effects. Our results demonstrate the importance of integrin-α10/TRIO/RICTOR signaling for driving myxofibrosarcoma progression and provide the basis for promising targeted treatment strategies for patients with high-risk disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, malignancies, which were rich in mucous matrix, usually exhibited insufficient glucose transporter expression and showed low FDG uptake [ 34 ]. In addition, a study by Lee AY, et al showed that myxofibrosarcomas with a higher proportion of mucus are associated with a better prognosis [ 35 ]. Therefore, we speculate that this is the reason why the PET/CT imaging features of these tumors tend to be benign ones.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of soft tissue and bone sarcomas from benign lesions utilizing 18F-FDG PET/CT-derived parameters

et al. 2020

View full text Add to dashboard Cite

Background Accurate differentiation between malignant and benign changes in soft tissue and bone lesions is essential for the prevention of unnecessary biopsies and surgical resection. Nevertheless, it remains a challenge and a standard diagnosis modality is urgently needed. The objective of this study was to evaluate the usefulness of 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT-derived parameters to differentiate soft tissue sarcoma (STS) and bone sarcoma (BS) from benign lesions. Methods Patients who had undergone pre-treatment 18 F-FDG PET/CT imaging and subsequent pathological diagnoses to confirm malignant (STS and BS, n = 37) and benign ( n = 33) soft tissue and bone lesions were retrospectively reviewed. The tumor size, PET and low-dose CT visual characteristics, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneous factor (HF) of each lesion were measured. Univariate and multivariate logistic regression analyses were conducted to determine the significant risk factors to distinguish sarcoma from benign lesions. To establish a regression model based on independent risk factors, and the receiver operating characteristic curves (ROCs) of individual parameters and their combination were plotted and compared. Conventional imaging scans were re-analyzed, and the diagnostic performance compared with the regression model. Results Univariate analysis results revealed that tumor size, SUVmax, MTV, TLG, and HF of 18 F-FDG PET/CT imaging in the STS and BS group were all higher than in the benign lesions group (all P values were < 0.01). The differences in the visual characteristics between the two groups were also all statistically significant ( P < 0.05). However, the multivariate regression model only included SUVmax and HF as independent risk factors, for which the odds ratios were 1.135 (95%CI: 1.026 ~ 1.256, P = 0.014) and 7.869 (95%CI: 2.119 ~ 29.230, P = 0.002), respectively. The regression model was constructed using the following expression: Logit ( P ) = − 2.461 + 0.127SUVmax + 2.063HF. The area under the ROC was 0.860, which was higher than SUVmax (0.744) and HF (0.790). The diagnostic performance of the regression model was superior to those of individual parameters and conventional imaging. Conclusion The regression model including SUVmax and HF based on 18 F-FDG PET/CT imaging may be useful for differentiating STS and BS from benign lesions.

show abstract

“…18 F-FDG is an analog of glucose and previous studies claimed that lesions with abundant in ltration of in ammatory cells or ones containing giant cells can display upregulation of hexokinase-2, leading to high FDG a nity [34]. Conversely, malignancies, which were rich in mucous matrix, usually exhibited insu cient glucose transporter expression and showed low FDG uptake [35].In addition, a study by Lee AY, et al showed that myxo brosarcomas with a higher proportion of mucus are associated with a better prognosis [36]. Therefore, we speculate that this is the reason why the PET/CT imaging features of these tumors tend to be benign ones.…”

Section: Discussionmentioning

confidence: 97%

Differentiation of soft tissue and bone sarcomas from benign lesions utilizing 18F- FDG PET/CT-derived parameters

Chen

Feng

Xie

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Accurate differentiation between malignant and benign changes in soft tissue and bone lesions is essential for the prevention of unnecessary biopsies and surgical resection. Nevertheless, it remains a challenge and a standard diagnosis modality is urgently needed. The objective of this study was to evaluate the usefulness of 18F-fluorodeoxyglucose (18F-FDG) PET/CT-derived parameters to differentiate soft tissue sarcoma (STS) and bone sarcoma (BS) from benign lesions. Methods: Patients who had undergone pre-treatment 18F-FDG PET/CT imaging and subsequent pathological diagnoses to confirm malignant (STS and BS, n = 37) and benign (n = 33) soft tissue and bone lesions were retrospectively reviewed. The tumor size, PET and low-dose CT visual characteristics, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneous factor (HF) of each lesion were measured. Univariate and multivariate logistic regression analyses were conducted to determine the significant risk factors to distinguish sarcoma from benign lesions. To establish a regression model based on independent risk factors, and the receiver operating characteristic curves (ROCs)of individual parameters and their combination were plotted and compared. Conventional imaging scans were re-analyzed, and the diagnostic performance compared with the regression model.Results: Univariate analysis results revealed that tumor size, SUVmax, MTV, TLG, and HF of 18F-FDG PET/CT imaging in the STS and BS group were all higher than in the benign lesions group (all P values were <0.01). The differences in the visual characteristics between the two groups were also all statistically significant (P <0.05). However, the multivariate regression model only included SUVmax and HF as independent risk factors, for which the odds ratios were 1.135 (95%CI: 1.026~1.256, P = 0.014) and 7.869 (95%CI: 2.119~29.230, P = 0.002), respectively. The regression model was constructed using the following expression: Logit (P) = -2.461+0.127SUVmax+2.063HF. The area under the ROC was 0.860, which was higher than SUVmax (0.744) and HF (0.790). The diagnostic performance of the regression model was superior to those of individual parameters and conventional imaging.Conclusion: The regression model including SUVmax and HF based on 18F-FDG PET/CT imaging may be useful for differentiating STS and BS from benign lesions.

show abstract

Optimal Percent Myxoid Component to Predict Outcome in High-Grade Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma

Cited by 37 publications

References 19 publications

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma

Differentiation of soft tissue and bone sarcomas from benign lesions utilizing 18F-FDG PET/CT-derived parameters

Differentiation of soft tissue and bone sarcomas from benign lesions utilizing 18F- FDG PET/CT-derived parameters

Contact Info

Product

Resources

About