Best Overall Response-associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE
The study, “Best Overall Response-associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE,” is an exploratory analysis of tumor samples from the patients that were treated with doxorubicin in the ANNOUNCE clinical trial to identify potential predictive markers. The investigators sequenced the RNA of 259 pretreatment tumor samples to look for RNA expression patterns in tumors that responded to doxorubicin and those that did not. A best overall response-associated RNA signature to doxorubicin (REDSARC) was created by evaluating tumors with radiographic response (shrinking of the tumor measured by imaging) versus progression. The analyses indicated there was an association between the best overall response signature and histologic subtype and tumor grade. It also indicated that REDSARC was also predictive for progression-free (PFS) and overall survival (OS). A refined 25-gene signature was identified and applied to the samples where it was predictive of PFS and OS in leiomyosarcoma, liposarcoma, and other sarcoma subtypes, but not in undifferentiated pleomorphic sarcoma. These results show that after further testing and refinement that the REDSARC signature could be used guide the use of doxorubicin in sarcomas.