Reproducible Abscopal Responses in Radiation Oncology: Treatment Design, Biomarkers, and Clinical Translation

Radiotherapy has long been viewed as a local treatment, yet under selected conditions it may be associated with tumor regression outside the irradiated field, commonly described as the abscopal effect. Although this phenomenon has generated strong interest, especially in the era of immune checkpoint blockade and stereotactic radiotherapy, it remains inconsistent, difficult to attribute with confidence, and challenging to translate into routine practice. In many settings, the key issue is no longer whether abscopal responses can occur, but under what biological and treatment conditions they can be generated reproducibly and interpreted rigorously.This Research Topic focuses on the practical and translational challenge of making abscopal responses more predictable, measurable, and clinically actionable in radiation oncology. Rather than broadly covering radiation-induced tumor immunology, this collection seeks studies that clarify which radiotherapy design variables, disease settings, biomarkers, and trial strategies are most relevant to the generation and validation of true out-of-field antitumor responses. We particularly welcome work that helps distinguish mechanistic signal from anecdotal observation and that provides a clearer framework for patient selection, treatment optimization, and endpoint definition.To capture the most clinically and scientifically actionable aspects of this field, we welcome articles including but not limited to the following topics:• Effects of dose, fractionation, target selection, field size, treatment volume, and modality on abscopal response generation.• Sequencing of radiotherapy with immune checkpoint inhibitors or other immunomodulatory approaches when abscopal outcomes are an explicit endpoint.• Biomarkers, tissue and blood correlates, imaging, radiomics, and translational models linked to prediction, attribution, or monitoring of abscopal responses.• Biological and clinical factors associated with resistance, non-reproducibility, or false attribution of out-of-field responses.• Clinical trial design, response assessment, prospective cohorts, and real-world studies evaluating abscopal outcomes in metastatic or oligometastatic disease.• Preclinical and translational studies that directly inform reproducibility and clinical implementation in radiation oncology.By prioritizing reproducibility, attribution, and treatment design, this collection aims to help define when the abscopal effect is biologically credible, clinically meaningful, and operationally useful. We invite Original Research, Clinical Trial reports, Reviews, Systematic Reviews, Methods, Case Series, and high-value Clinical Case Reports that provide clear mechanistic, biomarker, or treatment-design insight.Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.Topic Editor Panagiotis Balermpas received research grants from ViewRay, Inc., Siemens Healthineers and MSD, and serves on the MSD advisory board. The other Topic Editors declare no competing interests with regard to the Research Topic subject Topic editors: Jayant Sharad Vaidya, Pedro C Lara, Panagiotis Balermpas Source: https://www.frontiersin.org/research-topics/85485/reproducible-abscopal-responses-in-radiation-oncology-treatment-design-biomarkers-and-clinical-translation