---
title: "Immunotherapy-based salvage therapy in advanced soft tissue sarcoma: single-center retrospective f"
id: "frontiers-in-immunology-14-immunotherapy-based-salvage-therapy-in-advanced-soft-tissue-sarcoma-after-first"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-immunotherapy-based-salvage-therapy-in-advanced-soft-tissue-sarcoma-after-first"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1918276"
published_at: "2026-08-27T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Immunotherapy-based salvage therapy in advanced soft tissue sarcoma: single-center retrospective f
## Provenance & Clinical Metadata
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- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1918276)
- **Published At:** 2026-08-27T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source article title reports a retrospective, single-center analysis of **immunotherapy**-based salvage therapy in patients with advanced **soft tissue sarcoma**, with particular emphasis on **undifferentiated pleomorphic sarcoma**. - The available source text contains only website navigation and header material from the journal and does not include the study abstract, methods, results, or conclusions. - Key study elements that are not reported in the provided source include sample size, inclusion/exclusion criteria, patient demographics, prior therapies, specific immunotherapy regimens, dosing schedules, and treatment duration. - Outcome data are not available in the provided source: response rates, progression-free survival, overall survival, duration of response, and time to progression were not reported. - Safety and tolerability information—including immune-related adverse events, grade distribution, management strategies, and treatment-related discontinuations—are not present in the provided material. - Details on statistical methods, biomarker analyses, subgroup analyses (including outcomes for undifferentiated pleomorphic sarcoma), and follow-up duration are not reported in the source text. - The article provenance (journal name Frontiers in Immunology and article title) is present in the source header, but author names, institutional affiliations, funding, and conflicts of interest are not provided in the supplied content. - Because the supplied content lacks the body of the paper, readers should consult the full published article for validated data before applying findings to clinical practice or guideline development. - This summary strictly reflects the partial source content and explicitly notes absent details rather than inferring study results or recommendations.
## Clinical Analysis & Structured Key Points
Frontiers | Immunotherapy-based salvage therapy in advanced soft tissue sarcoma after first-line chemotherapy: a retrospective single-center analysis with emphasis on undifferentiated pleomorphic sarcoma ORIGINAL RESEARCH article Front. Immunol. , 27 August 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1918276 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Part of a Research Topic Immunotherapy in rare tumors: From bench to bedside Submission open 11k views 11 articles Editor & Reviewers Edited by A H Azizul Haque Reviewed by S J Seda Jeral A E Anthony Elias Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Figure 5 View in article Table 1 Results of Kaplan–Meier analysis. View in article Table 2 Baseline demographics and clinical characteristics of patients with advanced soft tissue sarcoma. View in article Table 3 Efficacy outcomes by treatment and histological subtype. View in article Table 4 Multivariable Cox proportional hazards model for PFS. View in article Table 5 Comparison of baseline characteristics and efficacy outcomes in patients with UPS across treatment cohorts. View in article Table 6 Treatment-related adverse events (CTCAE version 5.0). View in article ORIGINAL RESEARCH article Front. Immunol. , 27 August 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1918276 Immunotherapy-based salvage therapy in advanced soft tissue sarcoma after first-line chemotherapy: a retrospective single-center analysis with emphasis on undifferentiated pleomorphic sarcoma Z L Zhichao Liao 1,2,3 † J H Junbo Huang 1,2,3 † H L Haotian Liu 1,2,3 C Z Chao Zhang 1,2,3 T L Ting Li 1,2,3 H W Hongyu Wang 1,2,3 Y L Yuanxin Liu 1,2,3 S R Sijia Ren 1,2,3 Z R Zhiwu Ren 1,2,3 H W Haixiao Wu 1,2,3 R X Ruwei Xing 1,2,3 S T Sheng Teng 1,2,3 J Z Jun Zhao 1,2,3 W X Wanyi Xiao 1,2,3 G Z Gengpu Zhang 1,2,3 Y Y Yun Yang 1,2,3 +8 more J Y Jilong Yang 1,2,3 * 1. Department of Bone and Soft Tissue Tumors, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 2. Tianjin’s Clinical Research Center for Cancer, Tianjin, China 3. State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, China See more Article metrics View details Abstract Introduction: Soft tissue sarcomas (STS) are rare mesenchymal malignancies with limited treatment options in advanced stages. Anthracycline-based chemotherapy remains the standard of care but yields modest outcomes with significant toxicity, underscoring the need for more effective strategies. Methods: We retrospectively analyzed 56 patients with advanced STS who received PD-1 inhibitor-based therapy at Tianjin Medical University Cancer Institute and Hospital between January 2021 and January 2026. Treatment regimens included immunotherapy alone or in combination with chemotherapy or targeted therapy. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival outcomes were analyzed by Kaplan–Meier analysis; factors associated with prognosis were identified by a Cox proportional hazards regression model. Outcomes were compared with a historical cohort of 53 patients treated with chemotherapy alone. Results: A total of 56 patients were included, and the median follow-up time in the immunotherapy cohort was 19.2 months (range, 1.32–52.8 months). Patients with UPS had a longer median PFS than those with non-UPS histology (P = 0.045). Patients receiving immunotherapy combined with chemotherapy had longer median PFS (P = 0.047) and median OS (P = 0.046) compared with those receiving immunotherapy without chemotherapy. Multivariable Cox regression identified UPS histology (P = 0.023) and immunotherapy combined with chemotherapy (P = 0.047) as factors associated with PFS in advanced STS. Compared with 53 patients who received chemotherapy alone, the immunotherapy-based comprehensive treatment group had longer median PFS in the overall population (P = 0.023); the pure chemoimmunotherapy group (n = 22) also showed longer PFS (P = 0.014). This association was also observed in the UPS subgroup (P = 0.006). Treatment-related adverse events were predominantly grade 1–2; no grade 4–5 severe adverse events or treatment-related deaths occurred. Discussion: Immunotherapy-based regimens, particularly chemoimmunotherapy, showed a suggested PFS benefit over conventional chemotherapy in advanced STS, with UPS showing a suggested association with disease control. The safety profile was acceptable. Nevertheless, the limitations inherent to the retrospective design, historical controls, modest sample size, and immature overall survival data warrant cautious interpretation. Introduction As rare tumors, sarcomas are a group of highly heterogeneous malignancies of mesenchymal origin with an overall incidence of approximately 5 per 100,000. They are generally classified into soft tissue sarcomas (STS) and bone sarcomas. The latest (5th edition) WHO Classification of Soft Tissue and Bone Tumours describes more than 150 distinct subtypes, of which approximately 70 are STS, accounting for about 1% of adult malignancies ( 1 ). Most soft tissue sarcomas metastasize hematogenously to the liver and lungs, which contributes to the difficulty of achieving a cure ( 2 , 3 ). The majority of STS occur sporadically and without identifiable causes—a circumstance likely attributable to low statistical power for characterizing risk factors resulting from their low incidence and misclassification of histology. Nevertheless, several associated or predisposing factors have been identified, including genetic predisposition, prior treatments, specific diseases, environmental carcinogens, and trauma ( 4 ). Surgery with negative margins (R0 resection) is the cornerstone of treatment for localized STS, whereas the management of advanced disease remains challenging owing to its rarity as well as clinical and biological heterogeneity. For patients with advanced STS, palliative surgical resection is also a preferred option, and anthracycline-based palliative therapy remains the standard first-line treatment ( 5 , 6 ). In this patient population, median progression-free survival (PFS) ranges from 1.6 to 6.8 months and median overall survival (OS) from 10.7 to 19.7 months, while the toxicity of chemotherapy limits its clinical application ( 7 – 11 ). Therefore, more effective treatment strategies beyond conventional chemotherapy and palliative surgery are urgently needed for patients with advanced STS. Immune checkpoint inhibitors (ICIs) have achieved breakthroughs in several solid tumors. Sarcomas, however, have traditionally been regarded as “cold tumors” lacking cytotoxic lymphocytes within the tumor core, and were initially considered poorly responsive to immunotherapy ( 12 ). As the tumor microenvironment (TME) across different STS subtypes has been further characterized, it has become increasingly clear that, given the high heterogeneity of STS, immune infiltration may vary substantially among subtypes. Meanwhile, cellular-level studies have shown that certain sarcoma subtypes possess relatively high immunogenicity, leading to the hypothesis that some sarcomas may respond to immunotherapy ( 13 ). Previous research has demonstrated that bone sarcomas respond poorly to immunotherapy and the overall objective response rate (ORR) for STS is below 15% ( 14 – 16 ). Our previous study showed similar results. In that early analysis, no statistically significant difference was found between bone sarcoma and STS patients in median PFS (P = 0.52) or median OS (P = 0.49). For the overall cohort, the median PFS was 6 months, median OS was 16 months, ORR was 10.8%, and disease control rate (DCR) was 18.9%. Subgroup trends suggested a tendency toward poorer PFS in bone sarcoma patients and a more favorable prognosis in relatively immunotherapy-sensitive STS subtypes, though neither reached statistical significance, warranting further validation with larger sample sizes. The core mechanisms underlying the limited efficacy of ICIs may involve low immunogenicity of bone sarcomas, insufficient immune infiltration within the TME, and activation of immunosuppressive pathways ( 17 , 18 ), as well as substantial variability in tumor mutational burden (TMB) across subtypes—tumors with higher TMB harbor more neoantigens and exhibit greater immunogenicity (e.g., undifferentiated pleomorphic sarcoma, UPS) ( 19 , 20 ). Moreover, differential treatment responses have also been observed to potentially correlate with the abundance and maturation status of tertiary lymphoid structures ( 21 , 22 ). Nevertheless, the role of biomarkers in sarcoma immunotherapy and the relationship between predictive markers and prognosis remain unclear ( 23 ). Unlike bone sarcomas, certain STS subtypes exhibit high PD-L1 expression and immune cell infiltration, suggesting potential sensitivity to immunotherapy. Previous clinical studies have also demonstrated better responses to immunotherapy in select subtypes compared with others; this phenomenon has likewise been observed in patients with locally advanced or systemic progression ( 24 – 27 ). However, direct data in other researches comparing the efficacy, prognostic factors, and outcomes of immunotherapy-based comprehensive treatment versus conventional chemotherapy in advanced STS remain insufficient. Currently, only reviews comparing different single-arm studies are available, with some studies suggesting advantages in PFS and OS for immunotherapy-based combination strategies with an acceptable safety profile, whereas others do not support this conclusion—and direct comparative analyses are lacking ( 28 – 32 ). Hence, this study retrospectively analyzed latest five-year clinical data (2021-2026) to explore the efficacy, factors associated with prognosis, and safety of immunotherapy-based comprehensive treatment, and compared these outcomes with those of conventional chemotherapy in advanced STS, aiming to provide evidence for individualized treatment of advanced STS. Materials and methods Study objectives The primary endpoint of this study was PFS in advanced STS patients who received immunotherapy. Secondary endpoints included ORR, DCR, OS, and safety. In addition, we sought to identify factors associated with prognosis by statistically analyzing all available clinicopathological variables, with the goal of informing new treatment strategies for patients with advanced sarcoma. Patients and methods We retrospectively reviewed patients with American Joint Committee on Cancer (AJCC) stage IV soft tissue sarcoma and ECOG performance status scores of 0–3 treated at our center between January 2021 and January 2026, selecting those who had received immunotherapy or immunotherapy-based combination regimens such as chemoimmunotherapy. All patients had pathologically confirmed disease, and each had at least one measurable target lesion for response evaluation. Immunotherapeutic agents included sintilimab, camrelizumab, tislelizumab, pembrolizumab, and toripalimab. Some patients concurrently received conventional chemotherapy, targeted therapy, or both. Chemotherapy regimens included doxorubicin plus ifosfamide (AI) and others; targeted therapy regimens included anlotinib, among others. The historical chemotherapy cohort was assembled from patients with AJCC stage IV soft tissue sarcoma who received first-line anthracycline-based chemotherapy at our center between January 2011 and December 2019. Inclusion criteria were: (1) pathologically confirmed advanced/metastatic STS without prior systemic treatment, (2) ECOG PS 0–3, (3) at least one measurable lesion per RECIST 1.1, (4) at least 2 cycles of chemotherapy received. Patients who had received prior immunotherapy, targeted therapy, or any investigational agent were excluded. Both the immunotherapy cohort and the historical chemotherapy cohort required a minimum of two treatment cycles for inclusion in the efficacy analysis, to ensure adequate treatment exposure for response evaluation. All patients in the immunotherapy cohort had previously received and progressed on first-line anthracycline-based chemotherapy prior to initiating immunotherapy-based treatment as second-line salvage therapy. Based on the specific second-line regimen received, these patients were further categorized into four subgroups: immunotherapy monotherapy (n = 7), targeted therapy plus immunotherapy (n = 9), chemotherapy plus targeted therapy plus immunotherapy (n = 18), and chemoimmunotherapy (n = 22). For the primary analysis, these subgroups were consolidated into two strategies: immunotherapy with chemotherapy (n = 40, combining the chemoimmunotherapy and chemotherapy + targeted therapy + immunotherapy subgroups) and immunotherapy without chemotherapy (n = 16, combining the immunotherapy monotherapy and targeted therapy + immunotherapy subgroups). The choice of regimen in the salvage setting was primarily guided by the patient’s tolerance to prior first-line chemotherapy: patients who had tolerated it well typically received immunotherapy combined with chemotherapy, whereas those with poor tolerance received immunotherapy alone or with targeted therapy, depending on their clinical status. Radiological data, including computed tomography (CT), magnetic resonance imaging (MRI), and B-scan ultrasonography, were reviewed. The collected data were grouped by age, gender, pathological subtype, and treatment regimen for statistical comparison to identify prognostic factors and to assess whether immunotherapy, relative to conventional chemotherapy, offered advantages in efficacy and safety in stage IV STS. Ultimately, we aimed to analyze prognostic factors and identify STS subtypes sensitive to immunotherapy ( Figure 1 ). Figure 1 Flowchart of patient enrollment and treatment grouping for advanced soft tissue sarcoma. Immunotherapy cohort (2021–2026): A total of 81 candidate patients were initially screened. After excluding 20 patients with non-STS tumors and 5 patients who received fewer than 2 cycles of immunotherapy, 56 eligible patients with advanced STS were ultimately included. All patients in the immunotherapy cohort had received and progressed on prior first-line chemotherapy. Historical chemotherapy cohort (2011–2019): 53 patients with AJCC stage IV STS who received first-line chemotherapy were identified using comparable eligibility criteria. According to treatment regimen, the immunotherapy cohort was divided into 4 subgroups: immunotherapy monotherapy (n = 7), targeted therapy plus immunotherapy (n = 9), chemotherapy plus targeted therapy plus immunotherapy (n = 18), and pure chemoimmunotherapy (n = 22). Clinical data Demographic data for all patients included gender and age. Clinical data included diagnosis, primary tumor location, metastatic sites, survival status, date of death, prior treatment history, treatment dates (including drug names and number of cycles), dates of immune checkpoint inhibitor administration, concomitant medications given with ICIs, toxicities reported in patient records and historical laboratory data, ICI discontinuation dates, dates of disease progression, and dates of death. Immune-related toxicities were further evaluated, including the need for intervention. Imaging studies included CT, MRI, or ultrasound to assess the size of target lesions. Efficacy evaluation Tumor responses were rigorously re-evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Duration of response was calculated for patients achieving CR, PR, or SD until investigator-assessed progressive disease (PD) or documented intolerable treatment-related adverse events. The primary endpoint was PFS (from treatment initiation to disease progression or death); the secondary endpoints were OS (from treatment initiation to death from any cause), ORR (= CR + PR), and DCR (= CR + PR + SD). Safety and toxicity assessment Safety assessment: All patients were documented and reviewed in detail according to CTCAE version 5.0. Statistical analysis Statistical analysis: SPSS version 26.0 was used for data analysis. Baseline categorical variables were compared between cohorts using the chi-square test or Fisher’s exact test, as appropriate. Survival was assessed by the Kaplan–Meier method with curves drawn accordingly, and the log-rank test was used to identify factors influencing PFS and OS. Median follow-up time was estimated by the reverse Kaplan–Meier method. Multivariable prognostic analysis was performed using a Cox proportional hazards regression model to identify factors associated with PFS. Estimated effects of predictive variables were reported as hazard ratios (HRs) with 95% confidence intervals. A two-sided P 0.05). The grouping of different PD-1 inhibitors in the primary analysis was a pragmatic analytical decision, as the study was underpowered for agent-specific comparisons. A Kaplan-Meier analysis showed no statistically significant difference in PFS among the five PD-1 inhibitors used (P = 0.988; Table 1 ), although this finding should not be interpreted as demonstrating equivalence given the very small subgroups. Similarly, patients receiving concurrent targeted therapy were included in the immunotherapy-with-chemotherapy or immunotherapy-without-chemotherapy groups based on the rationale that the primary analytical focus was whether chemotherapy was combined with immunotherapy, rather than the presence of targeted agents. Notably, the “pure chemoimmunotherapy” subgroup (n = 22), which excluded patients receiving concurrent targeted therapy, provided an exploratory comparison with the historical chemotherapy group in the UPS subgroup, serving as a sensitivity analysis addressing the potential confounding effect of targeted therapy. Table 1 Variable mPFS (months) P mOS (months) P Histological subtype 0.045 0.632 UPS 7.984 20.895 Non-UPS 4.008 25.068 Primary site 0.220 0.287 Trunk 5.027 20.107 Extremities 6.045 26.875 Age 0.550 0.187 < 60 years 6.012 25.068 ≥ 60 years 8.969 20.107 Gender 0.135 0.215 Male 5.979 22.209 Female 6.045 23.819 Combined with chemotherapy 0.047 0.046 Yes 6.965 26.875 No 3.023 18.661 Combined with targeted therapy 0.493 0.560 Yes 5.947 22.341 No 6.965 22.209 PD-1 inhibitor 0.988 0.560 Camrelizumab 6.045 22.209 Pembrolizumab 6.045 28.550 Toripalimab 5.947 23.819 Tislelizumab 8.969 25.068 Sintilimab 5.979 18.661 Results of Kaplan–Meier analysis. Red values indicate statistically significant differences (P < 0.05). The statistical analysis was structured hierarchically. First, within the immunotherapy cohort (n = 56), survival outcomes were compared between the immunotherapy-with-chemotherapy and immunotherapy-without-chemotherapy groups, and between UP
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