Advanced radiotherapy and systemic therapy in head and neck adenoid cystic carcinoma: Current progress and future integrated strategies.

Head and neck adenoid cystic carcinoma (HNACC) remains a therapeutic challenge because of its infiltrative behavior, perineural tropism, and high propensity for distant metastasis. Although surgery combined with radiotherapy remains the standard local approach, treatment outcomes remain suboptimal in patients with unresectable tumors, advanced local disease, or anatomically complex lesions. Advances in radiotherapy, including MRI-guided radiotherapy, FLASH radiotherapy, and proton or carbon-ion therapy, are reshaping local treatment by improving dose precision, normal tissue sparing, and opportunities for treatment individualization. However, systemic therapy continues to face a therapeutic ceiling: conventional chemotherapy provides limited benefit, targeted therapy mainly achieves disease stabilization, and immunotherapy is constrained by the immune-cold microenvironment of HNACC. Emerging biomarkers and molecular targets, particularly NOTCH and TROP2(trophoblast cell-surface antigen 2), together with antibody-drug conjugates and other precision strategies, are beginning to expand the therapeutic landscape. Future management of HNACC will likely rely on integrated strategies that combine precision radiotherapy, biomarker-guided systemic therapy, and modulation of the tumor microenvironment to overcome both local and distant treatment failure.