Extracranial Abscopal Effects Induced by Brain Radiation in Advanced Lung Cancer

An extracranial abscopal effect induced by central nervous system (CNS)-radiation therapy is considered an unusual event because of the belief that brain has a distinctive immune microenvironment. Regular immune responses from radiation therapy or other interventions were thought to be very limited in the CNS. In addition, CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounters with CNS antigens. Moreover, the traditional assumption is that nascent tumor-associated antigens produced by radiation therapy could not pass through the blood-brain barrier back into the rest of the body to modulate the immune system and induce extracranial abscopal responses. Emerging data from a small number of case series and individual case reports of various malignancies have radically altered our earlier understanding by revealing that the CNS is neither isolated nor passive in its interactions with the body's immune system. Furthermore, current data indicate that the CNS is both immune-competent and interacts actively with the peripheral immune system. Therefore, radiation treatment to ≥1 location of CNS metastases can induce abscopal responses in tumors away from the treated CNS metastatic sites. These observations suggest the abscopal effect traverses the blood-brain barrier. In this article, we reviewed and assessed the clinical evidence of extracranial abscopal responses of CNS-radiation therapy in patients with advanced lung cancer.