A gap analysis integrating In vitro - Research in HDR interventional radiotherapy (Modern Brachytherapy): Challenges, limitations, and future directions

• This is the first gap analysis dedicated to ∗in vitro∗ studies using HDR interventional radiotherapy (IRT, brachytherapy). • All reviewed studies employed 2D monolayer cultures; no study integrated relevant 3D models such as spheroids or organoids. • Most studies focused on cytotoxicity and α/β ratio modeling, while other biological endpoints remain underexplored. • Dosimetric inaccuracies due to non-standard platforms were frequently reported and corrected via Monte Carlo simulations. • The analysis highlights the need for experimental frameworks combining radiobiology, 3D dosimetry, and biomimetic models.