• biomarker
• caldesmon
• hormone receptor
• leiomyosarcoma
• NLR
• PLR
• trabectedin
• vimentin

Soft-tissue sarcomas (STSs) are rare tumours and include a large variety of different histological entities, among which leiomyosarcomas (LMSs) are one of the most frequent. LMSs could arise from the retroperitoneum, the uterus, the limbs, and from other less frequent sites. Uterine LMSs (ULMSs) usually show different behaviour than LMSs of other sites, but this difference is not fully understood yet. Trabectedin has shown activity and efficacy in the treatment of advance, pre-treated LMSs, both uterine and non-uterine, but no validated predictive biomarkers of its efficacy are known. The development of predictive biomarkers could be helpful to select patients with higher probability to have a good clinical outcome from trabectedin use. The aim of the study is then to find possible biomarkers for further study and validation in prospective studies.
A retrospective analysis of all patients with uterine and non-uterine LMSs treated with trabectedin as per standard guidelines in our centre was performed. Trabectedin efficacy, expressed in terms of progression-free survival (PFS) and overall survival (OS), was correlated with clinical, laboratory, and pathology characteristics.
No difference in terms of PFS and OS was found when comparing uterine and non-uterine LMSs. Studying laboratory parameters in the entire population, PFS was found to be better in patients with lower neutrophil-to-lymphocyte ratio (NLR < 2.5) (11.83 vs 3.43 months, p = 0.0143) and lower platelet-to-lymphocyte ratio (PLR < 182) (14 vs 4.17 months, p = 0.0163). Lower NLR and PLR were also associated with a statistically significant better overall survival (17.43 vs 10.7 months, p = 0.0313, and 29.3 versus 15.03 months, p = 0.0278, respectively).
Studying pathology parameters in the global population, immunohistochemistry positivity for caldesmon was associated with a better PFS (18.3 versus 3.93 months, p = 0.0242) and OS (34.03 versus 6.23 months, p = 0.001). Vimentin expression was associated with a worse OS (3.3 vs 20 months, p = 0.001), whereas no statistically significant difference in PFS was observed (2.46 vs 9.2 months, p = 0.0928). The expression of oestrogen and/or progesterone receptors was associated with a better PFS (18.03 vs 7.17 months, p = 0.0479), but no association with a better OS was found (23.8 vs 17.43 months, p = 0.2185).
This retrospective study gives a basis for further study of laboratory parameters, such as NLR and PLR, and pathological features, such as caldesmon, vimentin, and sexual hormone receptors expression, as predictive biomarkers of trabectedin efficacy in LMSs.