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. 2024 Aug;9(8):103645.
doi: 10.1016/j.esmoop.2024.103645. Epub 2024 Aug 16.

Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma

A Dufresne  1 , S Pokras  2 , A Meurgey  3 , S Chabaud  4 , M Toulmonde  5 , E Bompas  6 , A Le Cesne  7 , Y-M Robin  8 , F Duffaud  9 , T Valentin  10 , S El Zein  11 , A Leroux  12 , P Dubray-Longeras  13 , N Firmin  14 , G de Pinieux  15 , S Noal  16 , C Delfour  17 , J Bollard  18 , L Tonon  19 , A Biette  20 , N Gadot  21 , V Attignon  18 , M Jean-Denis  20 , M Woessner  2 , E Klohe  2 , T Thayaparan  2 , I Eleftheriadou  2 , K Blouch  2 , M J Nathenson  2 , J-Y Blay  22
Affiliations

Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma

A Dufresne et al. ESMO Open. 2024 Aug.

Abstract

Background: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed.

Patients and methods: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes.

Results: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting.

Conclusions: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes.

Keywords: HLA subtypes; NY-ESO-1 expression; adoptive T-cell therapy; metastatic synovial sarcoma.

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Figures

Figure 1
Figure 1
CONSORT diagram of primary and exploratory patient populations. CONSORT, Consolidated Standards of Reporting Trials; HLA, human leukocyte antigen; IHC, immunohistochemistry; NY-ESO-1, New York esophageal squamous cell carcinoma 1.
Figure 2
Figure 2
OS according to NY-ESO-1 positivity by IHC in the primary cohort. All multivariate analysis P values were calculated by Wald chi-square test. CI, confidence interval; HR, hazard ratio; IHC, immunohistochemistry; NE, not evaluable; NY-ESO-1, New York esophageal squamous cell carcinoma 1; OS, overall survival; SS, synovial sarcoma. aFinal model is estimated on 105 patients and 85 deaths due to missing values.
Figure 3
Figure 3
OS according to dual positivity in the primary (A) and exploratory (B) cohorts. Data show median OS for patients who were positive for NY-ESO-1 and had HLA-A subtype A∗02 versus those who were negative for NY-ESO-1 and had other HLA-A subtypes (with unadjusted HR and P values). CI, confidence interval; HLA, human leukocyte antigen; HLA-A, human leukocyte antigen-A; HR, hazard ratio; IHC, immunohistochemistry; NY-ESO-1, New York esophageal squamous cell carcinoma 1; OS, overall survival.
Supplementary Figure 1
Supplementary Figure 1
Supplementary Figure 2
Supplementary Figure 2
See this image and copyright information in PMC

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