Radiographic and α-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: a multicenter study

Abstract

Background Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. Methods We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti–programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. Results We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558–0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785–0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. Conclusions In patients with unresectable HCC receiving combined TKI/anti–PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.

Hepatectomy After Conversion Therapy with Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitors and Anti-PD-1 Antibodies for Initially Unresectable Hepatocellular Carcinoma

“…pCR has been reported to be associated with excellent survival outcomes in patients with HCC treated with TACE or TKIs combined with anti-PD-1 antibodies. [30][31][32] Various factors influenced pCR, including HBV DNA load ≤ 1×10 2 IU/ mL, AFP ≤ 20 ng/mL, maximum tumor size ≤ 5 cm, multiple preoperative TACE sessions, and CR based on mRECIST. 33 In a study by Huang et al, 31 AFP before surgery, AFP response (a change from a positive status at baseline to a negative status before resection), and radiographic response were predictors of pCR in patients with HCC who received TKIs plus anti-PD-1 antibodies.…”

“…[30][31][32] Various factors influenced pCR, including HBV DNA load ≤ 1×10 2 IU/ mL, AFP ≤ 20 ng/mL, maximum tumor size ≤ 5 cm, multiple preoperative TACE sessions, and CR based on mRECIST. 33 In a study by Huang et al, 31 AFP before surgery, AFP response (a change from a positive status at baseline to a negative status before resection), and radiographic response were predictors of pCR in patients with HCC who received TKIs plus anti-PD-1 antibodies. In the current study, more single tumors, unilobar tumors, and PVTT were 1718 observed in patients with pCR, and multivariable logistic regression revealed that tumor number was related to pCR.…”

Cure can be Achieved by Conversion to Microwave Ablation following Atezolizumab-Bevacizumab Therapy in Unresectable Hepatocellular Carcinoma

“…Data from prospective, multicenter trials are needed to determine if this strategy is universally applicable. conversion is in fact not only limited to Atezolizumab-Bevacizumab but can also be achieved using other 12,13] Most reports on curative conversion employ surgical modalities to effect cure, with only a minority mentioning thermal ablative therapies like radiofrequency ablation (RFA) and microwave ablation (MWA). [8,10,14] This is understandable since thermal ablation is usually limited to smaller tumor sizes, and patients who undergo systemic therapy usually have large tumor sizes at the start of treatment.…”