Radiobiology and modelling in Brachytherapy: A review inspired by the ESTRO Brachytherapy pre-meeting course

Brachytherapy (BT) plays a key role in cancer treatment by delivering a high dose to a small volume over a short time. The use of BT is currently validated in a wide range of cancers such as cervical, prostate and breast cancers while being a favourable choice for organ preservation, such as in penile or rectal cancer, or in the setting of reirradiation. Consideration of the radiobiology of BT is integral to the choices made around dose and fractionation and combination with other techniques such as external beam radiotherapy (EBRT). Much of the radiobiology of brachytherapy is based on historic data, but fortunately there is a drive to integrate translational research including radiobiologic parameters into modern BT research. In a changing therapeutic landscape moving to a high dose rate (HDR) based on high dose per fraction, it is important to ensure that the incorporation of new radiobiology knowledge helps to drive clinical practice. This manuscript takes the ESTRO Brachytherapy pre-meeting course (May 3, 2024 - Glasgow ESTRO meeting) as a base and develops the concepts to present an overview of radiobiology in brachytherapy. Presented are 3 different considerations: the fundamentals of BT radiobiology (BT radiobiology history, biology and BT, α/β and re-irradiation), the pre-clinical radiobiology approach (pulsed dose radiotherapy (PDR) vs HDR, BT vs best EBRT techniques, high dose regions and integrated boost) and clinical radiobiology approaches (optimal number of BT fractions, radiobiology in BR for cervical, prostate, breast, skin/H&N and gastro-intestinal cancers). Presented is an analysis of radiobiology and modelling in BT aiding the integration of scientific pre-clinical and clinical data to allow a better understanding of the use of radioactive sources for cancer treatment.