Preoperative future liver remnant(FLR) augmentation with local tumor control and in-situ immunization for patients with advanced hepatocellular carcinoma (HCC)

Abstract

Purpose: Portal vein embolization(PVE) provokes tumor progression. Liver Cirrhosis(LC) decreases FLR regeneration capacity doubling the risk for patient dropout. Our aim was to turn weakness into a strength- develop method of FLR augmentation that converts aggressive tumor into a safe vaccine and prolonged waiting period for FLR regeneration into effective In situ immunization period Method: 3 initially unresectable patients due to small FLR with advanced hepatocellular carcinoma(HCC) and liver cirrhosis were treated. Selective transarterial chemoembolization with short term biodegradable starch microspheres(DSM-TACE), into tumor bearing liver to be resected, was followed by simultaneous PVE of latter. Upon completion of PVE selective intratumoral immunotherapy(HIT-IT) with antiPD-L1(atezolizumab 1200mg) into restored after DSM-TACE tumor arterial feeders (for selective connection with PD-L1 ligands located on tumor cells but not on normal human tissues) was done. DSM-TACE and HIT-IT was repeated one more time in all patients after postzenith decrease of T-cytotoxic cells level in peripheral blood had started. Anticancer immune response was investigated by comparison of initial histopathology specimen with specimens obtained just before second DSM-TACE+ HIT-IT and finally with specimen of resected tumor bearing liver. Latter were analyzed along with peripheral blood flow cytometry. Results: Predominantly T and NK cells response was observed. All patients had successfully underwent extended liver resection upon sufficient FLR regeneration. In all 3 cases we had achieved effective local tumor control via total or subtotal HCC necrosis, even more, in 1(33%) case planned amount of liver resection was decreased due to achieved tumor downsizing. There were no severe morbidity or Immune-related adverse events (irAEs). Conclusion: Herein we had proposed new aggressive but safe method of FLR augmentation for patients with HCC and liver cirrhosis that could potentially preclude drop out of patients during anticipated prolonged waiting period of FLR augmentation and possible improves long-term outcomes by means of tumor downsizing and HCC immunoscore conversion.