scholarly journals Establishment of an Academic Tissue Microarray Platform as a Tool for Soft Tissue Sarcoma Research

Sarcoma ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Che-Jui Lee ◽  
Agnieszka Wozniak ◽  
Thomas Van Cann ◽  
Iris Timmermans ◽  
Jasmien Wellens ◽  
...  

Soft tissue sarcoma (STS) is a heterogeneous family of rare mesenchymal tumors, characterized by histopathological and molecular diversity. Tissue microarray (TMA) is a tool that allows performing research in orphan diseases in a more efficient and cost-effective way. TMAs are paraffin blocks consisting of multiple small representative tissue cores from biological samples, for example, from multiple donors, diverse sites of disease, or multiple different diseases. In 2015, we began constructing TMAs using archival tumor material from STS patients. Specimens were well annotated in terms of histopathological diagnosis, treatment, and clinical follow-up of the tissue donors. Each TMA block contains duplicate or triplicate 1.0–1.5 mm tissue cores from representative tumor areas selected by sarcoma pathologists. The construction of TMAs was performed with TMA Grand Master (3DHistech). So far, we have established disease-specific TMAs from 7 STS subtypes: gastrointestinal stromal tumor (72 cases included in the array), alveolar soft part sarcoma (n = 12 + 47), clear cell sarcoma (n = 22 + 32), leiomyosarcoma (n = 55), liposarcoma (n = 42), inflammatory myofibroblastic tumor (n = 12 + 21), and alveolar rhabdomyosarcoma (n = 24). We also constructed a multisarcoma TMA covering a representative number of important histopathological subtypes on arrays for screening purposes, namely, angiosarcoma, dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxoid liposarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, with 7–11 individual cases per subtype. We are currently expanding the list of TMAs with additional sarcoma entities, considering the heterogeneity of this family of tumors. Our extensive STS TMA platform is suitable for rapid and cost-effective morphological, immunohistochemical, and molecular characterization of the tumor as well as for the identification of potential novel diagnostic markers and drug targets. It is readily available for collaborative projects with research partners.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11547-11547
Author(s):  
Jiayong Liu ◽  
Zhengfu Fan ◽  
Wei Guo ◽  
Tian Gao ◽  
Shu Li ◽  
...  

11547 Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, had been prove to be effective for the treatment of advanced or metastatic soft tissue sarcoma(STS) faild anthracycline chemotherapy. With the lack of prospective data of combination of PDL-1 inhibitor and antiangiogenic agent, we designed a phase 1b study to investigated the efficacy and safety of anlotinib plus TQB2450 in patients with STS. Methods: Eligible patients (age 18-70, ECOG 0-1, with histopathologically confirmed advanced STS, at least one measurable lesion according to RECIST 1.1, and previously received front-line anthracycline chemotherapy) were included and received anlotinib (12mg qd, D1-14, 21d/cycle) plus TQB2450 (1200 mg, IV, D1, 21d/cycle) until disease progression or intolerable toxicities.The primary endpoint was objective response rate (ORR), secondary endpoints included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR). Results: From January 2019 to January 2021, 30 pts were enrolled1, 12 alveolar soft part sarcoma and 18 others (7 synovial sarcoma, 4 leiomyosarcoma, 5 undifferentiated pleomorphic sarcoma, 1 fibrosarcoma and 1 epithelioid sarcoma). ORR by RECIST was 36.7%, DCR was 83.3%, 11/30 pts had PR, 14/30 (46.7%) had SD, 5/30 (16.7%) PD. Median PFS was 9.6 m in all pts and 4.9m. in non-ASPS, respectively. Median OS in non-ASPS was 10.27m, while mOS in all pts and both mPFS and mOS in ASPS had not been reached. Notably, to ASPS pts, ORR was 75%, and DCR was 100%. The most common 1-2 grade treatment-related adverse reaction (TRAE) was hypothyroidism (19/30,63.3%),hypercholesterolemia (16/30, 53.3%) and hypertriglyceridemia (16/30, 53.3%), the most common ≥3 grade TRAEs were hypertriglyceridemia (3/30, 10%). 6 SAE (20%) occurred, including 2 pneumothorax, 1 Immune associated hapatic injury, 1 hypotension, 1 Immune myocarditis and 1 diabetic ketoacidosis. Conclusions: The combination of anlotinib and TQB2450 showed promising activity in second-line treatment of advanced STS, especially in ASPS, with well tolerance and acceptable toxicity.


2019 ◽  
Vol 28 (2) ◽  
pp. 196-199
Author(s):  
Virginia Miller ◽  
Jason Shih Hoellwarth ◽  
Margaret Lydia Hankins ◽  
Richard McGough ◽  
Karen Schoedel

Tumor-to-tumor metastasis is an unusual phenomenon wherein one distinct malignancy is present within the substance of another independent tumor. This event is rare, difficult to detect with imaging, and, due to conflicting terminology in the literature, can be challenging to classify. This article reports the first documented case of tumor-to-tumor metastasis involving prostatic adenocarcinoma and myxoid liposarcoma, reviews the available literature for carcinoma metastatic to sarcoma, and discusses the current situation within the context of the established criteria for the classification of combination tumors.


Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Hiroshi Kobayashi ◽  
Keisuke Ae ◽  
Taisuke Tanizawa ◽  
Tabu Gokita ◽  
Noriko Motoi ◽  
...  

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST).Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma.Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n=5), synovial sarcoma (n=5), epithelioid sarcoma (n=2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n=1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas.Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST.


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 40-40 ◽  
Author(s):  
Erlinda Maria Gordon ◽  
Kamalesh Kumar Sankhala ◽  
Nathan Stumpf ◽  
Joshua Ravicz ◽  
Suzan Arasheben ◽  
...  

40 Background: To restore innate tumor surveillance that is lost in cancer patients, a tumoricidal agent may have synergistic activity with an immune checkpoint inhibitor. Herein, we report on a retrospective analysis of our clinical experience using trabectedin, an alkylating agent, and nivolumab, a PD-1 inhibitor in advanced soft tissue sarcoma. Methods: Twenty previously treated STS patients received trabectedin (1.5 mg/m2 continuous intravenous infusion, CIV, for 24 hours) every 3 weeks, and nivolumab (3 mg/kg IV over 30 minutes) every 2 weeks. Safety/toxicity was analyzed using the NIH/NCI CTCAE v.4.03. Tumor responses were assessed by RECIST v1.1 and immune-related response criteria (irRECIST). Results: Histologic subtypes in 20 patients include undifferentiated pleomorphic sarcoma (UPS; n = 7), leiomyosarcoma (n = 5), synovial sarcoma (n = 2), myxoid liposarcoma (n = 4) and chondrosarcoma (n = 2). All patients had metastatic disease and a median of 4 lines of prior chemotherapy. Safety analysis (n = 20): Grade 3 treatment emergent adverse events include anemia (n = 2), fatigue (n = 1), decreased platelet count (n = 1), decreased granulocyte count (n = 1) and increased creatine kinase (n = 1). Efficacy analysis (n = 17): Seventeen patients were followed for at least 6 months and their results are reported here. There were 4 partial responses (UPS = 1, myxoid liposarcoma = 1, chondrosarcoma = 1, leiomyosarcoma = 1), 7 stable disease, and 6 progressive disease, with best overall response rate of 23.5%, median progression free survival (PFS) of > 11.6 months (range: 2.3- > 16.9 months), median overall survival (OS) of > 14.2 months (4.5- > 24.0 months), 6 month PFS rate of 64.7%, and 6 month OS rate of 94.1%. In a Phase 3 study, the median PFS was 4.2 months using trabectedin alone (Demetri et al., 2015). Conclusions: Taken together, the data suggest that paired administration of trabectedin and nivolumab is safe, and that this chemo-/immuno-therapy approach has synergistic activity.


Sarcoma ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Julian F. Guest ◽  
Monica Panca ◽  
Erikas Sladkevicius ◽  
Nicholas Gough ◽  
Mark Linch

Background. Doxorubicin/ifosfamide is a first-line systemic chemotherapy for the majority of advanced soft tissue sarcoma (ASTS) subtypes. Trabectedin is indicated for the treatment of ASTS after failure of anthracyclines and/or ifosfamide; however it is being increasingly used off-label as a first-line treatment. This study estimated the cost effectiveness of these two treatments in the first-line management of ASTS in Italy, Spain, and Sweden.Methods. A Markov model was constructed to estimate the cost effectiveness of doxorubicin/ifosfamide compared to trabectedin monotherapy, defined as the cost per QALY gained, in each country.Results. First-line treatment with doxorubicin/ifosfamide resulted in lower two-year healthcare costs and more QALYs than first-line treatment with trabectedin monotherapy in all three countries. Probabilistic sensitivity analysis showed that at a cost per QALY threshold of €35,000, >90% of a cohort would be cost effectively treated with doxorubicin/ifosfamide compared to trabectedin monotherapy in all three countries.Conclusion. Within the model’s limitations, first-line treatment of patients with ASTS with doxorubicin/ifosfamide instead of trabectedin monotherapy affords a cost-effective use of publicly funded healthcare resources in Italy, Spain, and Sweden and is therefore the preferred treatment in all three countries. These findings support the recommendation that trabectedin should remain a second-line treatment.


2019 ◽  
Vol 9 ◽  
pp. 35-43 ◽  
Author(s):  
Alessandro Gronchi ◽  
Nadia Hindi ◽  
Josefina Cruz ◽  
Jean-Yves Blay ◽  
Antonio Lopez-Pousa ◽  
...  

2021 ◽  
pp. 107815522110001
Author(s):  
Aparna Sharma ◽  
Babita Kataria ◽  
Bivas Biswas ◽  
Sameer Bakhshi ◽  
Deepam Pushpam

Introduction Soft tissue sarcoma(STS) is a rare and heterogeneous group of disorders with dismal outcomes in metastatic setting. Pazopanib and oral metronomic chemotherapy (OMT) have been evaluated as therapeutic options in this cohort. Materials and methods We conducted a retrospective, single center study evaluating 45 patients with unresectable and/or metastatic STS, who received pazopanib or oral metronomic regimen as per instituitonal protocol between January 2013 and December 2019. An informal cost minimisation analysis was conducted for both OMT and pazopanib arms, considering equivalent outcomes for both (PFS and OS). Results Median PFS in OMT and Pazopanib groups was 4.13 months and 3.53 months,respectively (HR1.31, 95% CI:0.68–2.51, p = 0.41) Only one patient in the OMT group achieved an objective response (partial response) and no objective response was noted in the pazopanib group. The incidence of grade III/IVtoxicities was higher with pazopanib than with OMT (p = 0.08). There were no toxicity related deaths noted in either arm. Conclusions Our study demonstrates that OMT have a similar progression free survival (PFS) and overall survival (OS) in metastatic STS. This study raises the possibility that OMT might be an equally efficacious and less toxic alternative to pazopanib, without compromising survival outcome especially in LMIC.


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