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Published on: February 6, 2019
The future is not always uniform: rethinking radiotherapy through spatial fractionation
Federico Iori1,2, Slavisa Tubin3, Waleed F Mourad4
1Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. federico.iori@ausl.re.it.
Nature Reviews. Clinical Oncology
|June 10, 2026
Summary
Spatially fractionated radiotherapy (SFRT) introduces dose heterogeneity to treat complex tumors when uniform irradiation is not feasible. This approach may enhance tumor regression and modulate the tumor microenvironment, but requires further research for mechanism and reproducibility.
Area of Science:
- Radiation Oncology
- Cancer Therapy
- Tumor Microenvironment
Background:
- Traditional radiotherapy aims for uniform dose delivery, which is limited for large or complex tumors due to normal tissue tolerance.
- Spatially Fractionated Radiotherapy (SFRT) offers an alternative by creating intentional dose heterogeneity within tumors.
Purpose of the Study:
- To review the principles, biological hypotheses, and clinical applications of SFRT.
- To discuss the potential benefits and limitations of SFRT in cancer treatment.
Main Methods:
- Review of preclinical and early clinical studies on SFRT.
- Summary of various SFRT approaches including GRID, lattice, biology-guided, minibeam, and microbeam radiotherapy.
Main Results:
- SFRT creates high-dose peaks and low-dose valleys, potentially preserving functions within the tumor microenvironment.
- Preclinical and early clinical data suggest SFRT may lead to rapid tumor regression and immune modulation.
Conclusions:
- SFRT is a promising strategy for complex tumors where uniform irradiation is challenging.
- Further research is needed to define mechanisms, optimize dosimetry, assess response, and ensure multicenter reproducibility.
