Background Soft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated. Methods Taking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out. Results Trabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series. Conclusions Taken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent.

A 65-year-old male patient with an 8-year history of poliostotic Paget's disease complained of shoulder pain that started 6 months prior to admission. An extensive lytic area was identified in the right proximal humerus along with Paget's disease. There was cortical destruction and a soft tissue mass. Following an incisional biopsy, a diagnosis of grade 2 chondrosarcoma associated with Paget's disease was made. The histologic identification of chondrosarcoma associated with Paget's disease is rare. However, the presence of a calcified matrix in a destructive lesion associated with Paget's disease should alert the radiologist and the pathologist to the possibility of a chondromatous differentiation taking place in the sarcoma associated with Paget's disease. The histologic evaluation of the lesion will form the basis for the diagnosis.

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e17030 Background: Urothelial carcinoma (UC) accounts for 90% of cases of bladder cancer. In advanced UC diagnosis, skeletal involvement is frequent. Here we report the establishment of a primary culture of bone metastasis (BM) from High Grade UC derived from 81 years-old patient with a previous diagnosis of papillary urothelial cancer in 2016. After 2 years, patient relapsed to bone and visceral sites and because of poor clinical condition, patient underwent palliative best supportive care. Methods: Patient-derived bone metastatic cell culture was obtained from a surgical specimen. Tumor cells were isolated by collagenase digestion. Cells were seeded on in vitro 2D plates or into 3D collagen scaffolds composed of bovine collagen type I. The establishment of tumor cell isolation was confirmed through the evaluation of cytomorphologic features and positive pan-citokeratin staining. Then, drug treatments was performed and cell survival was evaluated. The study was approved by Ethical Committee and patient signed an informed consent. Results: After a long-term culture, we were able to isolate from a 3D scaffold a tumor clone that successfully growth until passage 20. Stabilized cells generate spheroid-like aggregates, recreating acinar-structures typical of the primary papillary urothelial tumor. Next, we treated cells with: Gemcitabine (Gem), Carboplatin (Carbo), Docetaxel, Carbo+Gem and Bone targeted drugs (Zoledronic Acid and Denosumab). The most effective treatment was Gem+Carbo, in particular 24% of survival in 2D platform and 87% on 3D collagen scaffold. For all treatments, cells cultured on 3D scaffold were more resistant to drugs, mimicking more closely the in-vivo condition. Conclusions: We were able to isolate and establish a BM primary culture from UC using a 3D in-vitro collagen scaffold. This system can recreate microenvironmental conditions more similar to in-vivo ones and it promoted the isolation of tumor cell clones from stromal components of the heterogeneous primary culture. This cell line could be useful to investigate the molecular and genetic profile in order to identify promising molecular targets and to better understard the natural history of BM from UC.

Background: NTRK gene fusions resulting in the elevated expression of TRK kinases were discovered in a wide variety of tumor types but generally at a low frequency. FDA approved TRK inhibitors such as larotrectinib and entrectinib in patients with TRK fusion positive cancers, regardless of age or the tumor type.Methods: Formalin Fixed Paraffin Embedded (FFPE) samples of 599 Chinese sarcoma patients were collected from nearly 58 kinds of subtype of sarcoma for next-generation sequencing (NGS) assay with 638-gene panel. The testing was carried out by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China.Results: We analyzed 170 children (age 19 years) and 429 adults (age＞19 years). 24 patients were identified as NTRK fusion positive, with 12 children and 12 adults, which accounted to approximately 4.1% of the Chinese sarcoma patients in our cohort. NTRK fusions were found in 7.1% of children, including rhabdomyosarcoma (3%) and fibrosarcoma (50%), and 2.8% in adults, including rhabdomyosarcoma (14.3%), synovial sarcoma (3.7%), undifferentiated pleomorphic sarcoma (3.5%) and osteosarcoma (3.4%). 13 out of 24 patients harbored NTRK1 fusions, 2 with NTRK2 fusions, and the remained ones were NTRK3 fusions with 9 partners. LMNA (8/24), ETV6 (4/24), TPM3 (2/24) were the most common partners of NTRK fusion in this cohort. Moreover, we identified uncommon partner genes by NGS, including CHTOP, SLC28A3, LOXL1, LRRC28, ZNF704, SH2D2A and TPR. Based on the NGS results, several actionable genomic alterations including CDKN2A, BRCA2, and CDK4 were found in this study. We also found 10 patients harbored NTRK amplification in our cohort, who may also benefit from TRK kinases.