Raquibul Hannan, Chief of the Genitourinary Radiation Oncology Service at UT Southwestern Medical Center, shared on X:
“Excited to share our JAMA Oncology phase 2 trial of neoadjuvant SAbR for RCC with IVC tumor thrombus!
1-year RFS: 71.4%, meeting the prespecified criterion. Feasible with encouraging safety findings. Larger trials are next!”
Title: Neoadjuvant Stereotactic Ablative Radiotherapy Before Inferior Vena Cava Thrombectomy for Renal Cell Carcinoma/ A Phase 2 Nonrandomized Clinical Trial
Authors: Raquibul Hannan, Lin Lin, Ryan Assadi, Laurentiu M. Pop, Lily Robles, Faya Zhang, Oscar Mulvaney, Ang Gao, Payal Kapur, Ivan Pedrosa, Aurelie Garant, Daniel Yang, Chul Ahn, Michael Wait, Robert Timmerman, Vitaly Margulis
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For decades, renal cell carcinoma was considered largely radioresistant. When treated with conventional fractionated radiation – delivering small daily doses over several weeks – tumor cells were able to repair sublethal DNA damage between fractions, limiting therapeutic response.
This challenge was compounded by the tumor microenvironment. Genetic alterations, such as VHL gene inactivation, drive aberrant angiogenesis and produce chaotic, inefficient vascular networks. This results in significant areas of tumor hypoxia. Because conventional low-LET radiation relies heavily on molecular oxygen to fix DNA damage via reactive oxygen species, hypoxic regions showed marked resistance to standard treatment.
The introduction of Stereotactic Body Radiotherapy (SBRT) altered this clinical paradigm. By delivering highly focused, ablative doses of radiation in a small number of fractions, SBRT overcomes traditional mechanisms of radioresistance through key radiobiological pathways.
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