Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: Locoregional tumor control remains a significant challenge in the management of head and neck cancers. The systemic chemotherapies and high radiation doses often used to prevent recurrence carry significant side effects which limit treatment success and reduce patient quality of life. Surgically implanted devices, such as drug-eluting polymers and gold nanostars, have emerged as new therapeutic options for preventing locoregional recurrence and targeting radiation to areas at highest risk for treatment failure.
Objectives: To assess the efficacy of a chemotherapy-eluting, gold nanostar-embedded polymer in providing targeted treatment, minimizing systemic cisplatin exposure, and sensitizing tumors to radiation therapy.
Methods: Forty male HeJ mice were stratified into the following treatment arms: control polymer, polymer with gold nanostars (GNS), polymer with cisplatin (Pt), and polymer with GNS and Pt. These mice were implanted with squamous cell carcinoma in the flank region; after the tumors grew to a volume of 1 cm³, they were debulked by 50%. At this time, the respective polymers were surgically implanted for each treatment arm. Each of these mice was treated with radiotherapy (RT) at doses of 4 Gy for 1-4 treatments. An additional control arm of mice treated with radiation alone was also included. Tumor growth was measured weekly.
Results: Mice that received either GNS, Pt, or GNS and Pt combined with RT showed the best outcomes compared to RT alone, with some mice completely without tumor burden at 2 months post-treatment. Radiation regimens of 4Gy for 1 or 2 treatments paired with polymer implantation demonstrated a more effective response to tumor shrinkage than 4 treatments of 4 Gy radiation alone. Control mice that received tumor debulking and control polymer with neither cisplatin nor radiation fared the worst, with tumor relapse occurring within 10 days.
Conclusion: These results suggest that polymers with Pt and polymers with GNS both independently conferred radiation sensitivity. Importantly, treatment of mice with the implant combining Pt and GNS appeared to reduce the radiation dose required to achieve an effective tumor response. The clinical application of dissolvable chemotherapeutic delivery agents paves the way for more effective and less toxic treatment regimens that can be used to direct RT when placed by the surgeon intraoperatively. These advances ultimately enhance patient outcomes and survival rates. Further clinical research and trials are essential to validate these findings and optimize the application of this promising developing technology.