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Pediatric liver cancer may lead to brain metastases

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May 30, 2018

Fibrolamellar hepatocellular carcinoma, a rare childhood liver cancer, metastasized to the brain, prompting researchers to recommend surveillance neuroimaging for patients with advanced disease, according to published findings.

“Current treatment for fibrolamellar hepatocellular carcinoma focuses on gross total resection, as systemic therapy remains unstandardized,” Sanford M. Simon, PhD, professor at the Laboratory of Cellular Biophysics at The Rockefeller University, and colleagues wrote. “However, fibrolamellar hepatocellular carcinoma is frequently diagnosed at an advanced stage, and the majority relapse within 1 year despite resection. ... Reports of two patients with brain metastasis exist in the literature but neither provides neuroimaging, pathologic or molecular analysis of the lesions.”

The researchers described three cases of confirmed brain metastasis in the disease, all of which occurred in 18-year-old women. For all three patients, cranial scans occurred only after the women had developed symptoms of brain tumors, including severe headaches and changes in mental status. All patients also had lung metastases.

The first woman, identified as Patient 1, presented with a symptomatic abdominal mass and received surgery for a primary liver tumor. A year later, she received a liver transplant after disease recurrence. When clinicians performed Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets on her brain metastasis, they discovered BCOR, HGF and ROS1 somatic alterations. The patient died 3 months after a left frontotemporal craniotomy and removal of the mass.

Patient 2 presented with a year-long history of abdominal pain, at which point caregivers used imaging to discover a large left hepatic mass with scattered lesions on the rest of the liver, as well as an enlarged peripancreatic lymph node. She underwent resection for brain metastasis, and received palliative radiation to metastases in the pelvis and lower abdomen, as well as erlotinib (Tarceva; Genentech, Astellas Oncology). At the time of publication of the study, Patient 2 remained alive without any intracranial recurrence. She remained on erlotinib therapy for extracranial metastasis.

Patient 3 demonstrated recurrent emesis and lethargy. She was found to have hyperammonemia, a right hepatic mass, a pulmonary nodule and extensive deep vein thrombosis in her left leg. After treatment for the DVT, she underwent surgery for lung metastasis and the primary liver tumor. She received multiple types of chemotherapy, including imetelstat (GRN163L, Geron), tivantinib (ARQ197, Arqule), cisplatin, gemcitabine, necitumumab (Portrazza, Eli Lilly), sorafenib (Nexavar, Bayer), denosumab (Prolia/Xgeva, Amgen), everolimus, letrozole and leuprolide. These drugs produced “inadequate response,” Simon and colleagues wrote.

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After neuroimaging revealed she had brain metastases, the patient underwent resection of the dominant lesion. She received stereotactic radiation for the remaining intracranial lesions. One year after surgery, Patient 3 had more than 10 foci of intracranial metastases and had developed a metastasis to the acetabulum. The patient, although alive, was no longer receiving therapy at time of publication.

“Currently, no prescribed recommendations exist for surveillance neuroimaging [among] patients with fibrolamellar hepatocellular carcinoma,” Simon and colleagues wrote. “Given the frequency of advanced stage at diagnosis, the lack of effective systemic therapies and low PFS among resected patients, we believe that the at-risk cohort of patients for brain metastases is nontrivial. ... For those without intracranial metastasis at the time of diagnosis, there is currently no data to support the interval for surveillance neuroimaging, but it is our recommendation that it be incorporated into the assessment of extracranial disease.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.