Metastatic Brain Irradiation-Induced Lymphocytosis Predicts Efficacy of Radiotherapy

Abstract

The prognosis of cancer depends on both tumor and patient biological characteristics. Within host biological variables, lymphocytopenia is associated with a poor prognosis in advanced cancer patients. Moreover, lymphocyte number has been proven to be influenced by both tumor growth and antitumor therapies, among them radiotherapy (RT) would represent the most lymphocytopenic treatment, particularly the pelvic irradiation. The present investigation was performed to evaluate the effects of brain irradiation on lymphocyte count in relation to the efficacy of treatment, and those induced by the pineal hormone melatonin (MLT) on the radiosensitivity of brain metastases due to radioresistant neoplasms. In a first study, we evaluated 70 solid tumor patients with brain metastases, who were treated by brain RT. In a second study, we evaluated the influence of a concomitant MLT administration (20 mg/day orally in the evening) in 14 patients treated by RT for brain metastases due to lung adenocarcinoma or large cell carcinoma, by comparing the results to those obtained in a control-group of 28 comparable patients treated by RT alone. In both studies, the dose of brain RT was 30 Gy. Patients who achieved an objective regression of brain metastases showed a statistically significant increase in lymphocyte mean number with respect to those found in patients who had no benefit. On the same way, the concomitant administration of MLT significantly increased the percent of partial or complete brain metastasis regression with respect to the results observed in patients treated by the only RT. The results of this preliminary study seem to suggest that brain irradiation-induced increase in lymphocyte amount may predict the efficacy of the treatment in patients with brain metastases due to solid neoplasms, and that the concomitant administration of neuroactive substances capable of modulating immune system and tissue radiosensitivity, such as the pineal indole MLT, may modulate the biological effects and the efficacy of brain irradiation.