Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case seriesResearch in context
Allison F. O’Neill,
Alanna J. Church,
Angela Feraco,
Jennifer Spidle,
Catherine B. Wall,
Heung Bae Kim,
Scott Elisofon,
Khashayar Vakili,
Max Pimkin,
Neekesh V. Dharia,
Nathan R. Shelman,
Antonio R. Perez-Atayde,
Carlos Rodriguez-Galindo
Affiliations
Allison F. O’Neill
Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA; Corresponding author. Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Alanna J. Church
Boston Children’s Hospital and Harvard Medical School, Department of Pathology, Boston, MA, USA
Angela Feraco
Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA
Jennifer Spidle
Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA
Catherine B. Wall
Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA
Heung Bae Kim
Boston Children’s Hospital and Harvard Medical School, Department of Surgery, Boston, MA, USA
Scott Elisofon
Boston Children’s Hospital and Harvard Medical School, Department of Hepatology, Boston, MA, USA
Khashayar Vakili
Boston Children’s Hospital and Harvard Medical School, Department of Surgery, Boston, MA, USA
Max Pimkin
Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA
Neekesh V. Dharia
Genentech, South San Francisco, CA, USA
Nathan R. Shelman
University of Kentucky, Department of Pathology, Lexington, KY, USA
Antonio R. Perez-Atayde
Boston Children’s Hospital and Harvard Medical School, Department of Pathology, Boston, MA, USA
Carlos Rodriguez-Galindo
St. Jude Children’s Research Hospital, Departments of Global Pediatric Medicine and Oncology, Memphis, TN, USA
Summary: Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Methods: Six paediatric patients (median age:16 years, range: 12–17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).
