When chemotherapy fails, one-third of pediatric patients with liver cancer are not eligible for surgical resection, which is necessary for curative intent. While chemotherapy has a therapeutic role in treating children with rare primary malignant liver tumors, treatment options are few when it is unsuccessful. In response, a handful of physicians have turned to transarterial radioembolization with yttrium-90 (TARE-Y90), which is well-known as a safe and effective minimally invasive interventional radiology treatment for adults with unresectable hepatocellular carcinoma (HCC).
TARE-Y90 radioembolization includes the injection of millions of glass or resin beads containing the isotope directly into the arteries that deliver blood to tumors. The transarterial chemoembolization (TACE) alternative has a longer time to progression, shrinks tumors faster for liver transplantation, lowers the risk of postembolization syndrome, and requires a shorter hospital stay and fewer treatments for patients.
TARE-Y90 in the pediatric setting has not been studied extensively, but a growing body of case-based data supporting its safety and efficacy in children is being compiled. Physicians at Nemours Children's Health, Wilmington, DE, began using TARE-Y90 as an upfront, curative therapy in 2017. It is one of a very small number of hospitals nationwide that offer the treatment for children with liver cancer.
The program is led by Allison Aguado, MD, one of the few pediatric interventional radiologists in the U.S. trained in the special precautions children require. For example, adjusting the dose based on the size of the child's tumor volume is necessary, as is modifying the dosimetry of TARE-Y90 following lung segmentation used to calculate lung weight, which is essential in monitoring the amount of radiation entering the lungs.
Growing Interest
In 2021, Aguado was invited by the Society of Interventional Radiology to present on ongoing research at Nemours at its annual conference, including findings from two small studies in which they used TARE-Y90 to treat children with liver cancer. The first research paper published was a retrospective review of 10 children with histologically confirmed primary liver malignancy given TARE-Y90 as salvage therapy (Pediatr Blood Cancer 2018; https://doi.org/10.1002/pbc.27510).
The median age at treatment was 5.5 years, ranging between 2 and 18 years. Median patient survival from initial diagnosis was 12.5 months with a range of 10-28 months, and median patient survival after TARE-Y90 was 4 months with a range of 2-20 months. Retreatment was well-tolerated in three of 10 patients, with those patients demonstrating the longest survival times, ranging between 7 and 20 months, with one patient transplanted 6 weeks after receiving TARE-Y90.
Based on RECIST 1.1 criteria of all target lesions, eight of nine patients had stable disease, and one of nine had progressive disease. Additionally, using mRECIST criteria, which requires postcontrast arterial phase imaging, two of seven patients had a partial response, four of seven had stable disease, and one of seven had progressive disease. Researchers concluded that TARE-Y90 of unresectable primary liver malignancy "is both technically feasible and demonstrates an anticancer effect" in addition to retreatment being well-tolerated. TARE-Y90 should be "considered as adjunctive therapy in pediatric patients with unresectable hepatic malignancies," reported the authors who emphasized the need for more research on the topic.
The second study and research paper shared results from children with primary liver malignancies treated using TARE-Y90 with curative intent at Nemours (Pediatr Blood Cancer 2020; https://doi.org/10.1002/pbc.28421). According to Aguado, et al, two children with hepatoblastoma and suboptimal responses to initial chemotherapy who received therapy with TARE-Y90 had significant response, leading to resection and remission. Three additional patients were subsequently treated at Nemours with TARE-Y90, all of whom were downstaged to liver resection, reinforcing TARE-Y90 as a bridge to surgery and transplantation.
Meanwhile, an ongoing and actively recruiting clinical trial led by Aguado, et al, is designed to determine the impact of TARE-Y90 on quality of life; progression-free survival at 2 years and 5 years, respectively; tumor response; resection rate; transplant rate; and histological and biological response (NCT04315883). Recently, Aguado shared additional insight with the Oncology Times into the research and TARE-Y90 treatment program she leads at Nemours.
Oncology Times: What inspired you to investigate this research question?
Aguado: "Primary pediatric liver malignancies are rare, accounting for just 1-2 percent of childhood cancers. However, outcomes for patients with unresectable tumors after chemotherapy are dismal, with limited options and guarded outcomes. Novel therapies are needed to provide alternative options to bridge patients to liver resection or transplant or for palliation."
Oncology Times: What are important takeaways from your studies?
Aguado: "Limited data demonstrate safety and feasibility of TARE-Y90 in children for both palliation and as a component of curative therapy. Two studies describe TARE-Y90 used successfully in children as part of therapy with curative intent, which led to hepatic resection in two patients with hepatoblastoma and two patients with HCC."
Oncology Times: Were there any unexpected or surprising results?
Aguado: "Preliminary data show that, in addition to tumor control, hypertrophy of future liver remnant was demonstrated in five children with hepatoblastoma, which facilitated conventional liver resection."
Oncology Times: Is there anything about the results that others might get wrong?
Aguado: "While early results of TARE-Y90 used in the frontline armamentarium of curative therapy are encouraging, surgery remains the foundation of cure for pediatric liver tumors."
Oncology Times: What are potential clinical implications?
Aguado: "TARE-Y90 may offer an alternative therapy to decrease liver tumor size and allow for surgical resection or liver transplant. Earlier integration with combination therapies may be helpful and offer an important option and strategy that ultimately may improve survival and result in less chemotherapy delivered, decrease rates of liver transplant, and present potentially curative options for refractory and recurrent patients. More research is required to determine the efficacy of TARE-Y90 in children and to define the clinical scenarios where benefit is likely to be optimized."
Chuck Holt is a contributing writer.