| Autor: |
Vaios EJ; Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA., Winter SF; Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA., Shih HA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA., Dietrich J; Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA., Peters KB; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., Floyd SR; Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA., Kirkpatrick JP; Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., Reitman ZJ; Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. |
| Abstrakt: |
Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined systemic therapy and SRS have contributed to a growing incidence of necrosis. The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway (cGAS-STING) represents a key biological mechanism linking radiation-induced DNA damage to pro-inflammatory effects and innate immunity. By recognizing cytosolic double-stranded DNA, cGAS induces a signaling cascade that results in the upregulation of type 1 interferons and dendritic cell activation. This pathway could play a key role in the pathogenesis of necrosis and provides attractive targets for therapeutic development. Immunotherapy and other novel systemic agents may potentiate activation of cGAS-STING signaling following radiotherapy and increase necrosis risk. Advancements in dosimetric strategies, novel imaging modalities, artificial intelligence, and circulating biomarkers could improve the management of necrosis. This review provides new insights into the pathophysiology of necrosis and synthesizes our current understanding regarding the diagnosis, risk factors, and management options of necrosis while highlighting novel avenues for discovery. |
