Integrated Radiobiotherapy: A State-Based Framework for Response-Adaptive Combination Oncology

Background: Cancer care increasingly requires coordinated use of systemic therapy, targeted radionuclide therapy (TRT), and external-beam radiotherapy (EBRT), yet clinical workflows often remain organized around static staging and sequential specialty handoffs. Approach: We propose Integrated Radiobiotherapy (IRBT), a state-based, response-adaptive research framework in which molecular imaging, systemic therapy, TRT, and EBRT can be evaluated as coordinated components of prospective studies. The framework uses shared selection criteria, response measures, and prespecified adaptation options-escalate, consolidate, switch, or de-escalate. The oligometastatic and oligoprogressive spectrum serves as a pragmatic clinical testbed, while two landmark 1995 papers provide historical context for the implementation discipline required. Key Recommendations: Trials should evaluate sequencing at clinically relevant decision points, use state-based endpoints that capture lesion-level control and spatial heterogeneity, establish minimum governance standards with multidisciplinary peer review and cumulative-toxicity safeguards, and address equity, ethics, and resource intensity as core implementation requirements. Conclusions: Although individual components-including oligometastatic stereotactic body radiotherapy, TRT, and adaptive EBRT-have prospective support, the fully integrated response-adaptive strategy remains unvalidated. IRBT offers a proposed structure and research agenda for multimodality oncology trials; it is not a clinical practice guideline or treatment mandate. "Those who cannot remember the past are condemned to repeat it."-George Santayana.