CINSARC in high-risk soft tissue sarcoma patients treated with neoadjuvant chemotherapy: Results from the ISG-STS 1001 study

Background The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001). Patients and Methods Patients with available pre-treatment samples, treated with 3 cycles of either standard (ST) preoperative or histotype-tailored (HT) chemotherapy, were scored according to CINSARC (low-risk, C1; high-risk, C2). The 10-year overall survival probability (pr-OS) according to SARCULATOR was calculated, and patients were classified accordingly (low-risk, Sarc-LR, 10-year pr-OS>60%; high-risk, Sarc-HR, 10-year pr-OS<60%). Survival functions were estimated using the Kaplan-Meier method and compared using log-rank test. Results Eighty-six patients were included, 30 C1 and 56 C2, 49 Sarc-LR and 37 Sarc-HR. A low level of agreement between CINSARC and SARCULATOR was observed (Cohen's Kappa = 0.174). The 5-year relapse-free survival in C1 and C2 were 0.57 and 0.55 (p = 0.481); 5-year metastases-free survival 0.63 and 0.64 (p = 0.740); 5-year OS 0.80 and 0.72 (p = 0.460). The 5-year OS in C1 treated with ST and HT chemotherapy was 0.84 and 0.76 (p = 0.251) respectively; in C2 treated it was 0.72 and 0.70 (p = 0.349). The 5-year OS in Sarc-LR treated with S and HT chemotherapy was 0.80 and 0.82 (p = 0.502) respectively; in Sarc-HR it was 0.70 and 0.61 (p = 0.233). Conclusions Our results, although constrained by the small size of the series, suggest that CINSARC has weak prognostic power in high-risk, localized STS treated with neoadjuvant chemotherapy.