Impact of preoperative treatment on the CINSARC prognostic signature: translational research results from a phase 1 trial of the German Interdisciplinary Sarcoma Group (GISG 03)

Purpose: CINSARC (Complexity INdex in SARComas) is a prognostic signature for soft tissue sarcoma that determines the risk for recurrence and may serve to guide the decision for adjuvant chemotherapy. The aim of this study was to compare the CINSARC signature of pre- and posttreatment biopsies of sarcoma patients treated within a phase I trial evaluating preoperative sunitinib and irradiation. Methods: We retrieved 14 pairs of formalin-fixed paraffin-embedded blocks from pretreatment biopsies and posttreatment resection specimens and performed expression profiling of the 67 CINSARC signature genes. Results: In 5/14 patients, both probes were unsuitable for expression analysis because there was no (vital) tissue left in biopsies or resection specimens. Comparing the CINSARC risk classification before and after treatment in the remaining patients, 2/9 shifted from a high- to a low-risk classification for metastatic disease after preoperative treatment with radiation therapy plus sunitinib and 7/9 pairs of pre- and posttreatment biopsies revealed identical results. Conclusion: Concurrent radiation therapy and sunitinib leads to diverging results of prognostic gene array testing in a relevant proportion of sarcoma patients. These changes may reflect tumor heterogeneity, local treatment effects, or prognostic changes of the disease. Caution is advised in the selection of samples and interpretation of test results.