Post-Stereotactic Body Radiotherapy Circulating Immune Cells and Local Tumor Control for Patients With Recurrent Hepatocellular Carcinoma

Abstract

Host immune status plays an important role in treatment outcome prediction and prognosis in patients with various cancers. However, the relationship between circulating immune cell and tumor control has not been well studied in hepatocellular carcinoma (HCC) after stereotactic body radiation therapy (SBRT).Patients with recurrent HCC received liver SBRT were eligible. Patients must be deemed surgically unresectable, and had Trans Arterial Chemotherapy Embolization (TACE). The local tumor control was defined as no disease progression by treatment response assessment CT or MRI around 3 months, largely according to mRECIST. Complete metabolic responses were defined either with no enhancement on MRI or no FDG activity. The risk factors of our interest included demographics factors, liver disease history, Child Pugh score, pathology stage, and prior treatments. The counts of whole leukocytes, lymphocyte and neutrophil pre- and post-SBRT were recorded from clinical laboratory. Leukopenia was graded according to CTCAE v 5.0. The associations of variables with in-field treatment response were analyzed using Chi-square test and one-way ANOVA.A total of 22 patients enrolled between August 2015 and September 2020. All patients had disease progression after TACE treatment and received 5 fractions of SBRT. Twenty patients received a definitive dose of 40-50 Gy. The local tumor was controlled in 86.4% (19/22), and increased to 90% (18/20) after excluding 2 patients receiving lower doses of palliative SBRT. There were 2 (10%), 5 (25%) and 13 (65%) defined as progressive disease, stable disease, partial response, and complete metabolic response, respectively. Large tumor/multiple tumor (P = 0.003), vascular invasion (P = 0.042), surgery history (P = 0.023), and BCLC stage (P = 0.040) were significantly associated with the tumor control, while age, gender, family history, heavy drinking, smoking history, BMI, ECOG, hepatitis, cirrhosis, Child Pugh score, portal vein tumor emboli, TNM, tumor size, and radiation dose were not. In 20 patients with complete blood testing peri-SBRT and uninterrupted radiation treatment, 17 (85%), 18 (90%), 13 (65%) and 9 (45%) patients had reduction in leukocyte, lymphocyte, neutrophil and monocyte after SBRT, respectively. Post-SBRT leukocyte counts (P = 0.036), pre-monocyte (P = 0.029), pre-lymphocyte (P = 0.073) and post- lymphocyte (P = 0.092) were associated with tumor control. The pre-RT leukocyte, neutrophil, post-RT neutrophil and monocyte were not.This limited study suggests that SBRT may provide excellent local tumor control for patients with recurrent HCC after surgical resection and TACE with no local treatment options. The significance in post-SBRT circulating immune cell suggest a role of immune function on radiation tumor control and a potential value of improving SBRT technique to decrease damage of immune cells. Further validation study with large sample size and longer follow-up is needed.