Favorable response to nivolumab combined with radiotherapy for retroperitoneal leiomyosarcoma.

Retroperitoneal sarcoma (RPS) is a biologically heterogeneous tumor and rare malignant mesenchymal soft-tissue neoplasm. Although the 5-year overall survival rate for RPS is approximately 60%-70%, it is quite low for unresectable tumors. Surgery is a standard treatment for RPS. Immune checkpoint inhibitors (ICIs) have shown promising effects against various tumor types; however, the efficacy of ICIs for RPS is unclear and the combination of ICIs with other drugs or treatments has been considered. We report the case of a 71-year-old woman with dual primary cancer, retroperitoneal leiomyosarcoma, and malignant melanoma in the lower leg. Retroperitoneal leiomyosarcoma was considered inoperable and managed with palliative radiotherapy. However, subsequent treatment with nivolumab for melanoma resulted in significant shrinkage of the retroperitoneal leiomyosarcoma. The genomic analysis revealed a low TMB and poor CD8 score. These findings suggest that the retroperitoneal leiomyosarcoma would be immunologically cold. We report an unexpectedly successful treatment of RPS with ICI therapy after radiotherapy. There have been few reports on the detailed genetic profiles of sarcomas that respond to ICI therapy. Our findings suggest that the combination of radiotherapy and ICIs has therapeutic potential for immunologically cold tumors and may be a useful treatment strategy for RPS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-025-00771-0.