A Global CollaboRAtive Study of CIC-Rearranged, BCOR::CCNB3-Rearranged and Other Ultra-Rare Unclassified Undifferentiated Round Cell Sarcomas (GRACefUl)
Background: Undifferentiated round cell sarcomas (URCSs) represent a diagnostic challenge and their optimal treatment is unknown. We aimed to define clinical characteristics, treatment and outcome of URCS patients.
Methods: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centers were retrospectively identified. Based on molecular assessment, cases were classified as follows 1) CIC -rearranged round cell sarcomas, 2) BCOR::CCNB3-rearranged round cell sarcomas, 3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.
Results: 148 patients were identified [88/148 (60%) CIC -rearranged sarcoma (median age 32 years, range 7-78), 33/148 (22%) BCOR :: CCNB3-rearranged (median age 17 years, range 5-91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4-70)]. One hundred-one (68.2%) cases presented with localized disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5-98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7-51.3) in CIC -rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1-90.6; p<0.0001).
Conclusions: This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.
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Funding Information: This work was supported by the the Carisbo Foundation Call for Translational and Clinical Medical Research
Conflict of Interests: EP has served on advisory boards for Daiichy Sankyo, Deciphera Pharmaceuticals, Eusa Pharma, and SynOx Therapeutics outside the submitted work. SGD has received consulting fees from Amgen, Bayer, and Jazz as well as travel expenses from Loxo, Roche, and Salarius. No other conflict of interest to declare.
Ethical Approval: Local ethics committee approval was obtained at each participating centre.
Palmerini, Emanuela and Gambarotti, Marco and Italiano, Antoine and Nathenson, Michael and Ratan, Ravin and Dileo, Palma and Provenzano, Salvatore and Jones, Robin Lewis and DuBois, Steven G. and Martin-Broto, Javier and de Alava, Enrique and Baldi, Giacomo Giulio and Grignani, Giovanni and Ferraresi, Virginia and Brunello, Antonella and Paoluzzi, Luca and Bertulli, Rossella and Hindi, Nadia and Montemurro, Michael and Rothermundt, Christian and Cocchi, Stefania and Salguero-Arand, Carmen and Donati, Davide Maria and Diaz Martin, Juan and Abdelhamid Ahmed, Amr and Mazzocca, Alessandro and Carretta, Elisa and Cesari, Marilena and Pierini, Michela and Righi, Alberto and Sbaraglia, Marta and Maria Antonella, Laginestra and Scotlandi, Katia and Dei Tos, Angelo Paolo and Ibrahim, Toni and Stacchiotti, Silvia and Vincenzi, Bruno, A Global CollaboRAtive Study of CIC-Rearranged, BCOR::CCNB3-Rearranged and Other Ultra-Rare Unclassified Undifferentiated Round Cell Sarcomas (GRACefUl). Available at SSRN: https://ssrn.com/abstract=4197931 or http://dx.doi.org/10.2139/ssrn.4197931
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