Innovative radiotherapy approaches

Radiotherapy (RT) with concurrent chemotherapy is the standard of care for squamous-cell carcinoma of the anal canal (SCCAC), achieving favorable results in terms of local control and overall survival. However, locoregional failure remains common despite advances such as intensity-modulated radiotherapy (IMRT), which reduces toxicity but has limitations. Despite the benefits of IMRT, frequent and severe toxicities persist, affecting patients' quality of life. This review examines strategies to improve RT outcomes in anal cancer. These include risk-adapted target delineation, daily target volume adjustment, brachytherapy, magnetic resonance-guided linear accelerator for radiation therapy (MRI-Linac), and proton therapy. Risk-adapted delineation proposes personalized treatment volumes based on individual risk factors, potentially improving efficacy and safety. With image-guided implantation and intensity-modulated dose delivery, interventional RT (brachytherapy), including modern brachytherapy, offers advantages in dose escalation while minimizing toxicity. Proton therapy, which delivers energy at specific depths, shows promise in reducing toxicity, although further prospective studies are needed. Advanced RT delivery modalities, such as online adaptive RT and MRI-Linac, offer opportunities to improve treatment outcomes by accounting for daily anatomical variations and allowing personalized dose adjustments. The aim of the integration of these technologies is to achieve optimal therapeutic ratios, minimize toxicities, and improve patient outcomes in the treatment of anal cancer. To address the remaining challenges and optimize RT approaches for SCCAC, ongoing trials are investigating dose-volume stratification, adaptive treatment, and proton therapy.