LAUSR

ABSTRACT This study investigated the anti-tumor effects of stereotactic body radiation therapy (SBRT) with thymosin alpha-1 (Tα1) in heavily pretreated, metastatic esophageal squamous cell carcinoma (mESCC) patients. Thirty-one patients with at least 2 metastatic sites were enrolled. SBRT was delivered with a daily fraction of 5.0 Gy for a total dosage of 25 Gy over one week to one metastatic lesion. Concurrent Tα1 (1.6mg subcutaneously) was administered twice a week with an interval of 3-4 days until tumor progression of other documented metastatic lesions. Anti-tumor effects (the primary endpoint) were evaluated by assessing the CT/MRI response of other distinct measurable lesions. Secondary endpoints included treatment safety, survival outcomes and immune-related blood parameters. This study was registered at ClinicalTrials.gov (NCT 02545751). Partial response occurred in three (9.7%) patients, and 11 (35.5%) patients had stable metastatic disease, which yielded a metastatic-lesion control rate of 45.2%. Seventeen (54.8%) patients were documented to have progressive disease in other metastatic lesions. The median overall survival and abscopal progression free survival (APFS) times were 5.2 and 2.9 months, respectively. Significant differences in survival outcomes were observed between the abscopal control group (without progression in the abscopal lesions at 12 weeks) and the non-control group (P = 0.035 and 0.044, respectively). Treatment-related toxicity was acceptable, and no grade 4 acute toxicity occurred. Immunomonitoring of lymphocytes showed that the proportion of CD8+ T cells after treatment was significantly different between the abscopal control group and the non-control group (P=0.047). In conclusion, the combination of SBRT with Tα1 produced encouraging effects in heavily pretreated, mESCC patients and further research on radiation enhanced immunotherapy is warranted.