A Local Strategy Toward Concurrent Chemoradiotherapy Based on Fibrin Gel for Postsurgical Cancer Treatment

Abstract

Postoperative cancer recurrence and metastasis have always been huge challenges in cancer therapy. The concurrent cisplatin (CDDP)-based chemoradiotherapy regimen is a standard therapeutic strategy in some cancer treatments after surgical resection. However, severe side effects and unsatisfactory local tumor concentrations of CDDP have hampered the application of this concurrent chemoradiotherapy. Therefore, a superior option that can enhance CDDP-based chemoradiotherapy efficacy with milder concurrent therapy-related toxicity is highly desirable. We developed a platform based on fibrin gel (Fgel) loaded with CDDP to be implanted into the tumor bed after surgery combined with concurrent radiation therapy for the prevention of postoperative local cancer recurrence and distant metastasis. The postoperative subcutaneous tumor mouse models established by incomplete resection of primary tumors were used to evaluate the therapeutic advantages of this chemoradiotherapy regimen for postsurgical treatment. The local and sustained release of CDDP from Fgel could enhance the antitumor efficacy of radiation therapy in the residual tumor with lower systemic toxicity. The therapeutic benefits of this approach are demonstrated in breast cancer, anaplastic thyroid carcinoma, and osteosarcoma mouse models. Our work offers a general platform for concurrent chemoradiotherapy to prevent postoperative cancer recurrence and metastasis.