Evidence for Persistent Radiation-Related Injury to the Immune System in Patients With Local Breast Cancer

Abstract

Severe and prolonged lymphopenia is well described in the literature as a consequence of local radiation and is associated with early death and impaired responses to immunotherapy. In animals, localized radiation results in histologic changes in lymph nodes that are distant from the radiation field. The sustained effects of radiation on distant lymph nodes in humans has not been previously described. This study was designed to assess changes in lymph nodes architecture outside the radiation field in women with breast cancer months after radiation treatment. Seven women were enrolled on a protocol to collect a distal abdominal lymph node during breast reconstruction with a deep inferior epigastric perforators (DIEP) flap. Five patients previously received chest wall irradiation on average 608 days prior to reconstruction while two patients did not receive radiation. The abdominal lymph node was compared to the initial (pre-radiation) mastectomy surgery lymph node by a blinded hematopathologist. The lymph node cellularity was graded by density score. The five patients who underwent radiation had striking reductions in their lymph node cellularity: average baseline score of 3 ± 1.2 with post lymph node density score of 1.2 ± 0.5, when compared to the two unirradiated patients: average baseline score of 4 with post lymph node density score of 3 ± 1.4. This small study suggests that localized radiation may have long-term impacts on distal lymph node basins in humans as has been seen in animals. Future studies evaluating prolonged systemic lymphopenia following radiation are needed to document the long-term systemic effects of local radiation, and the overall implications of this finding.