Hyalinization-based pathologic response and immune infiltration following neoadjuvant radiotherapy with or without immune-checkpoint blockade in localized undifferentiated pleomorphic sarcoma

R S Traweek; M Zoghbi; R Lazcano; B M Cope; A J Bishop; A Farooqi; D Mitra; A K Yoder; B A Guadagnolo; D R Ingram; K Wani; D Shamsutdinova; A J Lazar; W-L Wang; C P Scally; E Z Keung; K E Torres; K K Hunt; R Ratan; J A Livingston; M S Nakazawa; D M Araujo; S Patel; V Ravi; A P Conley; M A Zarzour; N Somaiah; C L Roland; E F Nassif Haddad

doi:10.1016/j.esmoop.2025.105493

Hyalinization-based pathologic response and immune infiltration following neoadjuvant radiotherapy with or without immune-checkpoint blockade in localized undifferentiated pleomorphic sarcoma

ESMO Open. 2025 Jun 24;10(7):105493. doi: 10.1016/j.esmoop.2025.105493. Online ahead of print.

Authors

R S Traweek¹, M Zoghbi², R Lazcano³, B M Cope⁴, A J Bishop⁵, A Farooqi⁵, D Mitra⁵, A K Yoder⁵, B A Guadagnolo⁵, D R Ingram⁶, K Wani⁶, D Shamsutdinova⁶, A J Lazar⁷, W-L Wang⁶, C P Scally¹, E Z Keung¹, K E Torres¹, K K Hunt¹, R Ratan², J A Livingston², M S Nakazawa², D M Araujo², S Patel², V Ravi², A P Conley², M A Zarzour², N Somaiah², C L Roland¹, E F Nassif Haddad⁸

Affiliations

¹ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
² Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
³ Department of Pathology, Massachusetts General Hospital, Boston, USA.
⁴ Department of Surgery, Keesler Medical Center, Biloxi, USA.
⁵ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁶ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
⁷ 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.
⁸ 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.

PMID: 40561658
DOI: 10.1016/j.esmoop.2025.105493

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.

Keywords: hyalinization-based pathologic response; immune-checkpoint blockade; radiotherapy; undifferentiated pleomorphic sarcoma.