# Schlafen 11 as a prognostic and potentially predictive biomarker in soft tissue sarcoma: evidence from a real-world cohort

## TL;DR

This study shows that SLFN11 is a promising biomarker for predicting outcomes and treatment response in soft tissue sarcoma patients undergoing chemotherapy.

## Contribution

The study provides real-world evidence that SLFN11 is both a prognostic and potentially predictive biomarker in soft tissue sarcoma.

## Key findings

- SLFN11 expression correlates with tumor regression in neoadjuvant chemotherapy.
- SLFN11-high tumors show significantly longer survival in adjuvant and palliative chemotherapy.
- SLFN11 remains independently predictive of improved outcomes across multiple treatment settings.

## Abstract

Soft tissue sarcomas (STS) carry a high risk of relapse or metastasis even after complete resection. (Neo-)adjuvant chemotherapy benefits only a subset of patients, underscoring the need for predictive biomarkers. Schlafen 11 (SLFN11) has emerged as a marker of sensitivity to DNA-damaging agents. This study evaluated SLFN11 as a prognostic and predictive biomarker for (neo-)adjuvant chemotherapy in STS.

SLFN11 expression was assessed by immunohistochemistry in 242 patients with STS across different disease stages, using the H-score and percentage of positive tumor cells. Sub-cohorts included patients receiving neoadjuvant therapy (n = 33), primary resection (n = 193), palliative first-line chemotherapy (n = 26), or a palliative salvage therapy with trabectedin (n = 22). Associations between SLFN11 levels, clinicopathological features, and survival were analyzed.

In the neoadjuvant cohort, SLFN11 expression correlated with pathological tumor regression after chemotherapy alone (rho = 0.73, p = 0.016) and chemotherapy ± radiotherapy (rho = 0.62, p = 0.011). Among primarily resected STS treated with adjuvant chemotherapy ± radiotherapy, SLFN11-high tumors were associated with significantly longer overall survival (OS) (p = 0.007) and disease-free survival (DFS) (p = 0.022). SLFN11 was independently associated with improved outcome (OS: HR 0.06, p = 0.002; DFS: HR 0.08, p = 0.004). In the palliative first-line chemotherapy cohort, SLFN11-high tumors showed improved OS (p = 0.005) and progression-free survival (PFS) (p = 0.024), and SLFN11 remained independently predictive (OS: HR 0.11, p = 0.001). In the trabectedin cohort, SLFN11-high tumors demonstrated longer OS (p = 0.04) and PFS (p = 0.024).

SLFN11 is a prognostic and potentially predictive biomarker in STS in the context of chemotherapy. Our results support a prospective validation, standardization of SLFN11 assessment, and consecutive clinical implementation.