@ARTICLE{10.3389/fonc.2022.1042479, AUTHOR={Palmerini, Emanuela and Sanfilippo, Roberta and Grignani, Giovanni and Buonadonna, Angela and Romanini, Antonella and Badalamenti, Giuseppe and Ferraresi, Virginia and Vincenzi, Bruno and Comandone, Alessandro and Pizzolorusso, Antonio and Brunello, Antonella and Gelsomino, Fabio and De Pas, Tommaso and Ibrahim, Toni and Gurrieri, Lorena and Grosso, Federica and Zanelli, Francesca and Pantaleo, Maria Abbondanza and Milesi, Laura and Ciuffreda, Libero and Ferrari, Vittorio and Marchesi, Emanuela and Quattrini, Irene and Righi, Alberto and Setola, Elisabetta and Carretta, Elisa and Casali, Paolo G. and Picci, Piero and Ferrari, Stefano}, TITLE={Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis}, JOURNAL={Frontiers in Oncology}, VOLUME={12}, YEAR={2022}, URL={https://www.frontiersin.org/articles/10.3389/fonc.2022.1042479}, DOI={10.3389/fonc.2022.1042479}, ISSN={2234-943X}, ABSTRACT={BackgroundAmong sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).MethodsA post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.ResultsThirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).ConclusionsTrabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.} }