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Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
Schlafen 11 as a prognostic and potentially predictive biomarker in soft tissue sarcoma: evidence from a real-world
Adrian Georg Simon1, Su Ir Lyu1, David Stahl2,3,4
1Institute of Pathology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
Background:
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.
Materials And Methods:
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.
Results:
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).
Conclusion:
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.
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