Hyalinization-based pathologic response and immune infiltration following neoadjuvant radiotherapy with or without immune-checkpoint blockade in localized undifferentiated pleomorphic sarcoma.
| Title: | Hyalinization-based pathologic response and immune infiltration following neoadjuvant radiotherapy with or without immune-checkpoint blockade in localized undifferentiated pleomorphic sarcoma. |
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| Authors: | Traweek RS; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Zoghbi M; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Lazcano R; Department of Pathology, Massachusetts General Hospital, Boston, USA.; Cope BM; Department of Surgery, Keesler Medical Center, Biloxi, USA.; Bishop AJ; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Farooqi A; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Mitra D; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Yoder AK; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Guadagnolo BA; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Ingram DR; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Wani K; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Shamsutdinova D; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Lazar AJ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.; Wang WL; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Scally CP; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Keung EZ; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Torres KE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Hunt KK; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Ratan R; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Livingston JA; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Nakazawa MS; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Araujo DM; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Patel S; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Ravi V; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Conley AP; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Zarzour MA; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Somaiah N; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Roland CL; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.; Nassif Haddad EF; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: efnassif@mdanderson.org. |
| Source: | ESMO open [ESMO Open] 2025 Jul; Vol. 10 (7), pp. 105493. Date of Electronic Publication: 2025 Jun 24. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 101690685 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2059-7029 (Electronic) Linking ISSN: 20597029 NLM ISO Abbreviation: ESMO Open Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021 : [London] : Elsevier; Original Publication: London : BMJ, [2016]- |
| MeSH Terms: | Neoadjuvant Therapy*/methods ; Immune Checkpoint Inhibitors*/therapeutic use ; Immune Checkpoint Inhibitors*/pharmacology ; Sarcoma*/pathology ; Sarcoma*/therapy ; Sarcoma*/mortality; Humans ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; Adult |
| Abstract: | Background: Standard-of-care treatment of localized undifferentiated pleomorphic sarcoma (UPS) involves preoperative radiotherapy (RT) and surgery. Combination of RT with immune-checkpoint blockade (ICB) represents a promising new strategy.; Methods: Our primary objective was to assess survival outcomes and pathologically documented response in patients receiving RT with or without ICB or chemotherapy.; Results: In a retrospective cohort of 68 patients with primary or locally recurrent UPS who received neoadjuvant RT with or without ICB, the ICB group had greater tumor hyalinization than the non-ICB group (89% compared with 30%, P = 0.018). In the non-ICB group, 19/37 patients (51%) achieved hyalinization-based pathologic response (HPR; >30% tumor hyalinization), compared with 9/11 patients (82%) in the ICB group. At a median of 48 months, patients achieving HPR had longer overall survival rate (100% versus 64.1%, P = 0.035) and recurrence-free survival rate (67.1% versus 35.6%, P = 0.004) than those who did not. Among patients who did not receive ICB, chemotherapy with RT was associated with higher tumor necrosis compared with RT alone (80% compared with 20%, P = 0.01), and more patients in the chemotherapy group achieved HPR.; Conclusions: HPR was significantly associated with improved overall and recurrence-free survival, regardless of treatment, although use of ICB led to better outcomes. These findings support the need to explore the role of ICB with chemotherapy and RT to enhance UPS treatment strategies.; (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.) |
| Grant Information: | K12 CA088084 United States CA NCI NIH HHS; P50 CA221707 United States CA NCI NIH HHS; P50 CA272170 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: hyalinization-based pathologic response; immune-checkpoint blockade; radiotherapy; undifferentiated pleomorphic sarcoma |
| Substance Nomenclature: | 0 (Immune Checkpoint Inhibitors) |
| Entry Date(s): | Date Created: 20250625 Date Completed: 20250723 Latest Revision: 20260408 |
| Update Code: | 20260408 |
| PubMed Central ID: | PMC12256315 |
| DOI: | 10.1016/j.esmoop.2025.105493 |
| PMID: | 40561658 |
| Database: | MEDLINE |
Journal Article