Meng LL, Ma L, Qu BL, Di YP. Spatially fractionated radiotherapy: Integrated dose heterogeneity and radiobiology for bulky tumor. World J Clin Oncol 2026; 17(6): 118731 [DOI: 10.5306/wjco.118731]
Corresponding Author of This Article
Yu-Peng Di, MD, Department of Radiotherapy, Air Force Medical Center, Air Force Medical University, No. 28 Fucheng Road, Beijing 100142, China. diyupeng0723@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jun 24, 2026; 17(6): 118731 Published online Jun 24, 2026. doi: 10.5306/wjco.118731
Spatially fractionated radiotherapy: Integrated dose heterogeneity and radiobiology for bulky tumor
Ling-Ling Meng, Lin Ma, Bao-Lin Qu, Yu-Peng Di
Ling-Ling Meng, Department of Radiotherapy, Chinese PLA General Hospital, Beijing 100853, China
Lin Ma, Bao-Lin Qu, Department of Radiation Oncology, Senior Department of Oncology, The First Medical Center of PLA General Hospital, Beijing 100853, China
Yu-Peng Di, Department of Radiotherapy, Air Force Medical Center, Air Force Medical University, Beijing 100142, China
Co-first authors: Ling-Ling Meng and Lin Ma.
Co-corresponding authors: Bao-Lin Qu and Yu-Peng Di.
Author contributions: Meng LL and Ma L performed the literature search and drafted the original manuscript contributed equally to this work thus qualified as the co-first authors of the paper; Di YP provided data validation and contributed to writing the initial draft; Qu BL and Di YP conceptualized the study, provided critical revisions, and finalized the manuscript thus qualified as the co-corresponding authors of the paper; and all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Corresponding author: Yu-Peng Di, MD, Department of Radiotherapy, Air Force Medical Center, Air Force Medical University, No. 28 Fucheng Road, Beijing 100142, China. diyupeng0723@126.com
Received: January 12, 2026 Revised: February 21, 2026 Accepted: May 8, 2026 Published online: June 24, 2026 Processing time: 164 Days and 5.4 Hours
Abstract
Spatially fractionated radiotherapy (SFRT) offers a promising investigational strategy to address the dilemma of maximizing tumor ablation while sparing adjacent normal tissues through controlled intra-tumoral dose heterogeneity. This approach utilizes partial-volume high-dose exposure, hypothesized to leverage the regenerative capacity of normal tissues-as suggested by low toxicity rates observed in preliminary cohorts like the SBRT-PATHY pilot study. Furthermore, SFRT is thought to potentially contribute to tumor control through putative pathways including tumor necrosis factor-alpha/ceramide-mediated bystander cytotoxicity and immunogenic cell death-induced immune responses. While early clinical observations in bulky tumors (> 8 cm) indicate encouraging response rates with manageable toxicity, the transition from these mechanistic hypotheses and small-scale exploratory data to standardized clinical practice requires further validation through robust, randomized trials.
Core Tip: Spatially fractionated radiotherapy (SFRT) offers a novel solution to the clinical challenge of treating bulky tumors. By creating controlled dose heterogeneity (“peaks” and “valleys”), SFRT leverages the regenerative capacity of normal tissues to maximize sparing while potentially triggering systemic antitumor immunity via bystander and abscopal effects. This article critically examines the dual mechanistic pathways of SFRT-integrating physical dose modulation with biological signaling-and reviews emerging clinical evidence suggesting its potential to safely expand the therapeutic index for difficult-to-treat malignancies.
