TY - JOUR
T1 - A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl)
AU - Palmerini, Emanuela
AU - Gambarotti, Marco
AU - Italiano, Antoine
AU - Nathenson, Michael J.
AU - Ratan, Ravin
AU - Dileo, Palma
AU - Provenzano, Salvatore
AU - Jones, Robin L.
AU - DuBois, Steven G.
AU - Martin-Broto, Javier
AU - de Alava, Enrique
AU - Baldi, Giacomo G.
AU - Grignani, Giovanni
AU - Ferraresi, Virginia
AU - Brunello, Antonella
AU - Paoluzzi, Luca
AU - Bertulli, Rossella
AU - Hindi, Nadia
AU - Montemurro, Michael
AU - Rothermundt, Christian
AU - Cocchi, Stefania
AU - Salguero-Aranda, Carmen
AU - Donati, Davide
AU - Martin, Juan D.
AU - Abdelhamid Ahmed, Amr H.
AU - Mazzocca, Alessandro
AU - Carretta, Elisa
AU - Cesari, Marilena
AU - Pierini, Michela
AU - Righi, Alberto
AU - Sbaraglia, Marta
AU - Laginestra, Maria A.
AU - Scotlandi, Katia
AU - Dei Tos, Angelo P.
AU - Ibrahim, Toni
AU - Stacchiotti, Silvia
AU - Vincenzi, Bruno
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/4
Y1 - 2023/4
N2 - Background: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. Methods: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres 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: In total, 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 localised 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.
AB - Background: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. Methods: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres 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: In total, 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 localised 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.
KW - BCOR::CCNB3
KW - Bone sarcoma
KW - CIC::DUX4
KW - Pediatric tumors
KW - RNA-seq
KW - Soft tissue sarcoma
KW - Ultra rare sarcoma
KW - Undifferentiated round cell sarcoma
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U2 - 10.1016/j.ejca.2023.01.003
DO - 10.1016/j.ejca.2023.01.003
M3 - Article
C2 - 36791667
AN - SCOPUS:85147828337
SN - 0959-8049
VL - 183
SP - 11
EP - 23
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -