HCC is a rare liver malignancy in children, with less than 1.5 cases per million children under 18 years [1]. Due to innovations of surgical strategies particularly in LT, outcomes of pediatric HCC seem to improve over the decades, with a prolonged 5-year OS rate up to 83% reported in previous studies [25, 26]. However, recurrence remains the major cause of death and the outcomes of RHCC remains dismal. The current study summarized our single-center experience of percutaneous US-guided RFA for RHCC in children.
Pediatric HCC is far less investigated compared to HCC in adults, which might be associated with the extreme low incidence rate. Previous studies indicate that salvage LT is superior to repeated liver resection, especially in terms of disease-free survival for RHCC [27, 28]. For children with isolated recurrence in the liver, chemoembolization temporization before LT or immediate LT were reported, but salvage LT is limited due to a scarcity of donor organs, a high cost, and a long waiting list [10]. Repeated liver resection, especially by laparoscopy, could achieve tumor eradication and provide favorable long-term outcomes [29–31]. However, repeated surgery either salvage LT or re-resection might not be an option for children with RHCC who cannot tolerate surgical stress. Radiotherapy, such as Yttrium-90 transarterial radioembolization (Y90-TARE) and SBRT, has been reported in the treatment of RHCC [32, 33]. For now, few studies have reported the use of Y90-TARE or SBRT in pediatric liver malignancy, which might be associated with radiation exposure, and the need of specialized equipment and technical expertise required for its safe use [34, 35]. TACE is an alternative treatment modality for childhood liver malignancy [7]. However, TACE is a radiation-guided procedure that cannot achieve tumor eradication, which might limit its use in children. Since 1990, the International Childhood Liver Tumor Strategy Group has launched a serial of clinical trials (SIOPELs) to investigate the utility of chemotherapy for pediatric HCC. Although responses to chemotherapy were observed, it failed to improve overall survival of pediatric HCC [2, 3]. In recent years several clinical trials have been launched to investigate novel cytotoxic agents for recurrent or refractory solid tumors in children [8, 9, 36]. With only a small proportion of patients with liver malignancy in these studies, the efficacy of these chemical agents could not be determined for pediatric HCC. Moreover, targeted therapy and immunotherapy have offered novel therapeutic opportunities for HCC, but current studies are mostly adult-based [37]. Recently a phase I study combining sorafenib and irinotecan in pediatric refractory liver cancer failed to meet the end point due to severe adverse events [38]. Therefore, further studies are needed to verify the potential value of systemic therapy in pediatric RHCC.
To date, no studies on the efficacy of percutaneous RFA have been conducted in the particular setting of pediatric RHCC. Hetzer et al. reported the utility of percutaneous stereotactic RFA for various liver masses in children [39]. Compared to their study, we adopted US-guided RFA, which was convenient and free of radiation. All tumors achieved CA with a 100% technical success rate and neither severe RFA-related adverse effects nor mortality were seen in our study, which supports the idea that percutaneous RFA is feasible and safe to treat pediatric RHCC.
We applied RFA combined with PEI to one tumor that located in the caudate lobe surrounded by the inferior vena cava, portal vein and bile duct. Our previous studies demonstrated that combination of RFA and PEI for tumors in the caudate lobe can achieve high treatment success rate, but tumor size larger than 2 cm increases the risk of LTP after RFA [40, 41]. The tumor was 4.6 cm in size and received ethanol volume of 10 ml before RFA. Although ICA was identified one month after RFA, the tumor achieved CA after repeated RFA, which indicated that for lesions adjacent to important structures, close follow-up is necessary to identify residual tumor in a timely manner.
In addition, three patients diagnosed as pulmonary metastasis of HCC received RFA treatment with palliative intent in our study. Previous study showed that aggressive management of intrahepatic lesions might provide survival benefits for synchronous HCC with pulmonary metastasis [42]. For patients in advanced stage, palliative treatment may improve outcomes by decreasing tumor burden and relieving symptoms [43]. Among these three patients, one patient received subsequent targeted therapy combined with immunotherapy, and died of pneumonia and asphyxia 20 months after RFA. One patient received subsequent chemotherapy and died of liver failure 10.8 months after RFA. The third patient did not receive treatment and died of tumor progression 6 months after RFA. The prognosis of patients with advanced-stage HCC is poor, and the utility of RFA needs further investigation in this setting.
Our study had some limitations. First, only 10 patients with RHCC after curative surgery who underwent percutaneous US-guided RFA were enrolled in this study. However, pediatric HCC is extremely rare and thus, it is difficult to collect a large sample size of patients. Secondly, retrospective data collected from a single institution might result in bias. Therefore, a properly designed prospective multicenter study is needed to determine the efficacy of RFA in this setting. Finally, there was no direct comparison to other treatment modalities in this single arm treatment study. Randomized controlled clinical trials are needed to provide a comparative evaluation of this technique for the treatment of pediatric RHCC.