@article{ccdadfecd52d4144b348959e26ddeff9,
title = "A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma",
abstract = "Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial (NCT03307616) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.",
author = "Roland, {Christina L.} and {Nassif Haddad}, {Elise F.} and Keung, {Emily Z.} and Wang, {Wei Lien} and Lazar, {Alexander J.} and Heather Lin and Manoj Chelvanambi and Parra, {Edwin R.} and Khalida Wani and Guadagnolo, {B. Ashleigh} and Bishop, {Andrew J.} and Burton, {Elizabeth M.} and Hunt, {Kelly K.} and Torres, {Keila E.} and Feig, {Barry W.} and Scally, {Christopher P.} and Lewis, {Valerae O.} and Bird, {Justin E.} and Ravin Ratan and Dejka Araujo and Zarzour, {M. Alexandra} and Shreyaskumar Patel and Robert Benjamin and Conley, {Anthony P.} and Livingston, {J. Andrew} and Vinod Ravi and Tawbi, {Hussein A.} and Lin, {Patrick P.} and Moon, {Bryan S.} and Satcher, {Robert L.} and Bilal Mujtaba and Witt, {Russell G.} and Traweek, {Raymond S.} and Brandon Cope and Rossana Lazcano and Wu, {Chia Chin} and Xiao Zhou and Mohammad, {Mohammad M.} and Chu, {Randy A.} and Jianhua Zhang and Ashish Damania and Pranoti Sahasrabhojane and Taylor Tate and Kate Callahan and Sa Nguyen and Davis Ingram and Rohini Morey and Shadarra Crosby and Grace Mathew and Sheila Duncan and Lima, {Cibelle F.} and Blay, {Jean Yves} and Fridman, {Wolf Herman} and Kenna Shaw and Ignacio Wistuba and Andrew Futreal and Nadim Ajami and Wargo, {Jennifer A.} and Neeta Somaiah",
note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",
year = "2024",
doi = "10.1038/s43018-024-00726-z",
language = "English (US)",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
}