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Preclinical and clinical programs must therefore not only demonstrate that hydrogels act as spacers and local delivery vehicles, but also define how tumor intrinsic factorsnotably histologic subtype (squamous cell carcinoma (SCC) versus adenocarcinoma (AC)) and HPV statusmodify radiosensitivity and the therapeutic benefit gained from hydrogel-mediated radiosensitization (see Table 3)
This spatial separation confines the high-dose radiation to the tumor, substantially reducing inadvertent exposure of radiosensitive tissues and mitigating the risk of long-term complications such as fibrosis, necrosis, fistula formation, and sexual dysfunction [156]
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