Technological advances in external beam radiotherapy. Study of new treatment strategies.

This research covers the use of advanced technologies in external beam radiotherapy (EBRT), such as proton therapy for thoracic tumors, a central issue with significant implications for radiation oncology. By combining motion management, adaptive planning, and radiobiological modeling, my Ph.D. work aims to better understand the issue and prospect of proton therapy optimization. The primary objectives of this research are to evaluate the image-guided proton therapy (IGPT) procedures, determine the efficacy of online adaptive proton therapy (oAPT), and estimate secondary cancer risk using mechanistic models. To reach these objectives, my study uses a mixed-method approach involving systematic literature review, dosimetric simulation, and collaborative clinical research by leveraging multicentric scientific collaborations. Through the use of probabilistic robustness evaluation tools, computational-based secondary malignancy risk models, and comparative case studies, the study explores dose conformity, plan adaptation, and long-term biological outcomes. Key findings include the identification of persistent uncertainties in thoracic IGPT and evidence supporting the superiority of pencil-beam scanning proton therapy in mitigating secondary cancer induction in ultra-fractionated radiation therapy. These findings suggest that enhanced motion management and radiobiological modeling enhance the therapeutic index of proton therapy, indicating broader utility to treatment personalization. Findings from this research are expected to advance medical physics and radiation oncology, offering new knowledge on IGPT application particularly relevant for hybrid proton and photon therapy approaches.The work investigated how to develop hybrid treatments with radiobiological modeling for risk computation that identifies a solid basis for future studies in next-generation personalized Radio-oncology