CME 5 Session - EANM'16

(1)
ESTRO/Dosimetry & Oncology: Radiobiology/Radiation Biology Markers of Radiation Damage

Educational objectives
  1. Radiation exposure response of tissue, repair and recovery mechanisms
  2. Response at cellular level, induction of bystander and abscopal effects
  3. Intercellular signaling pathways
  4. Immunologic response to radiation
  5. Options for long-lasting synergetic effects from radiation and immunotherapy
  6. Clinical possibilities for imaging repair and recovery processes 

Summary:
Radiation exposure induces a wide range of effects in tissue. Radiation damage to the genome varies between well and reliably repairable defects to complex unrepairable multi-strand breaks. In all cases this leads to cell signaling cytokines, either to commence the repair process or to bring the cell into apoptosis or some other form of cell death. Radiation may result in damage mediated by a bystander like effect away from the irradiated field. Over the last decade there has been a re-emergence of immune modulating therapies as anti-cancer treatment modalities. There is growing pre-clinical data and a number of case reports which suggest the presence of abscopal effects when radiotherapy is co-administered with immune checkpoint inhibitors, suggesting that this combination may lead to an enhanced tumour response outside of the primary treatment field. Radiotherapy (RT) but also radionuclide therapy (e.g. with 223Ra) affects both the tumour and its micro-environment, leading to the release of tumour-associated antigens, damage molecular patterns (DAMPs) and the upregulation of immunomodulatory cell surface molecules, thereby starting an antitumour immune response. Abscopal or bystander effects can be induced in unexposed cells neighboring to irradiated cells. This could cause more response to radiation than what would be expected for a heterogeneous dose distribution. This heterogeneity on dose delivery is inherently coupled to radionuclide therapy where only a proportion of the cell population is targeted. Short-ranged particle emitters, like low energy beta’s or alpha’s, are specifically sensitive for these effects.

Key Words:

Abscopal / bystander effects, Dose response, Immunologic response, radiotherapy, radionuclide

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