Genomic analysis of radiation-induced osteosarcoma in the maxilla

Abstract

Radiation-induced osteosarcoma (RIOS) is a rare and refractory late-stage complication of radiotherapy for head and neck cancer. Unlike de novo osteosarcoma, there are only a few treatment options for RIOS owing to its rapid progression, particularly in elderly who have received multimodal treatments including full-dose radiation and chemotherapies. Recently, genomic analysis has emerged as a potential approach to identify specific therapeutic targets for rare and refractory cancers such as RIOS. A 61-year-old male who developed RIOS of the maxilla 14 years after surgery and postoperative radiotherapy for hard palate squamous cell carcinoma. The patient initially received chemotherapies, and local control of RIOS was achieved by extended total maxillectomy with removal of the orbital content. However, multiple lung metastases occurred 8 months after surgery. To identify specific therapeutic targets for multiple distant metastases observed after chemotherapies, genomic analysis of the surgical specimens was performed, which revealed that the tumor mutational burden was 4muts/MB, the microsatellite status was stable, CCNE1 and KEL were amplified, and TP53 K321fs*15 was mutated. Therefore, Wee1 inhibitors were proposed as specific therapeutic targets. Although we identified several ongoing clinical trials using Wee1 inhibitors abroad, we were unable to propose a treatment option to the patient because such clinical trials are not available in Japan yet. Therefore, accumulating additional genomic data by genomic analysis could help in the development of new treatment options for RIOS in the future.

Keywords

• Radiation-induced osteosarcoma
• Genomic analysis
• Therapeutic target