Evidence for persistent radiation-related injury to the immune system in patients with local breast cancer.

Abstract

e15189 Background: Clinical data in multiple tumors has demonstrated that the inadvertent radiation of circulating lymphocytes causes grade III-IV lymphopenia which is associated with worse outcomes in cancer patients and failure to respond to immunologic interventions. Murine data from our lab demonstrated that radiation to the brain results in striking changes in the anatomy and cellularity of distant unirradiated lymph nodes. This study was designed to understand the relationship between local radiation and the depletion of distant unirradiated lymph nodes in humans which has not been previously studied. Methods: Adult women with breast cancer who had undergone prior mastectomy with pathology, labs, and radiation data available at our institution were enrolled at the time of their deep inferior epigastric perforator artery (DIEP) flap reconstruction. During reconstruction, a single abdominal lymph node was extracted, and subsequently formalin fixed. The pre- and post-treatment lymph nodes of radiated and non-radiated patients were presented in a blinded manner to the hematopathologist. The pathologist described each lymph node and graded the lymph node density as (1) low, (2) low-normal, (3) normal, or (4) high. Results: Seven women have been enrolled (median age 50; range 31-55) with AJCC tumor stages from 1a – 3b (five are hormone positive, and two are triple negative). The reconstruction was completed on average 488.71 + 224.57 days after initial mastectomy. Three of the women received neoadjuvant chemotherapy, and five received adjuvant chemotherapy. Five of the seven women had received radiation (mean 50.9 + 5.6 Gy). The baseline median LN density score in all patients was 4 (range 1-4), with a post mean LN density of 1.2 + 0.4 in the radiation group compared to a mean score of 3 + 1.4 in the control group. Conclusions: Systemic lymphocyte counts remain relatively stable but lymph node density is markedly lower than baseline in 80% of patients who received chest wall irradiation consistent with data from animal model studies. It is important to note that this effect on the nodes is seen long after the radiation has been completed. [Table: see text]