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.