Patient-derived tumor organoids for personalized medicine in a patient with rare hepatocellular carcinoma with neuroendocrine differentiation: a case report

  • Commun Med (Lond). 2022 Jul 1:2:80. doi: 10.1038/s43856-022-00150-3.
Marie-Anne Meier  #  1  2 ,  Sandro Nuciforo  #  1 ,  Mairene Coto-Llerena  #  1  3 ,  John Gallon  1 ,  Matthias S Matter  3 ,  Caner Ercan  3 ,  Jürg Vosbeck  3 ,  Luigi M Terracciano  4  5 ,  Savas D Soysal  2 ,  Daniel Boll  6 ,  Otto Kollmar  2 ,  Raphaël Delaloye  7 ,  Salvatore Piscuoglio  1  3 ,  Markus H Heim  1  2
Affiliations
  • 1. Department of Biomedicine, University Hospital and University of Basel, CH-4031 Basel, Switzerland.
  • 2. Clarunis University Center for Gastrointestinal and Liver Diseases, CH-4002 Basel, Switzerland.
  • 3. Institute of Medical Genetics and Pathology, University Hospital Basel, CH-4031 Basel, Switzerland.
  • 4. Department of Anatomic Pathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • 5. Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy.
  • 6. Radiology and Nuclear Medicine, University Hospital Basel, CH-4031 Basel, Switzerland.
  • 7. Department of Oncology, University Hospital Basel, CH-4031 Basel, Switzerland.
  • # Contributed equally.
PMID: 35789568 DOI: 10.1038/s43856-022-00150-3
Abstract

Background: Hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED) is a very rare subtype of primary liver Cancer. Treatment allocation in these patients therefore remains a challenge.

Methods: We report the case of a 74-year-old man with a HCC-NED. The tumor was surgically removed in curative intent. Histopathological work-up revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin and chromogranin. Three months after resection, multifocal recurrence of the HCC-NED was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro.

Results: Based on the results of the in vitro drug screening, etoposide and carboplatin are used as first line palliative combination treatment. With genomic analysis revealing a NTRK1-mutation of unknown significance (kinase domain) and tumor organoids found to be sensitive to entrectinib, a pan-TRK inhibitor, the patient was treated with entrectinib as second line therapy. After only two weeks, treatment is discontinued due to deterioration of the patient's general condition.

Conclusion: The rapid establishment of patient-derived tumor organoids allows in vitro drug testing and thereby personalized treatment choices, however clinical translation remains a challenge. To the best of our knowledge, this report provides a first proof-of-principle for using organoids for personalized medicine in this rare subtype of primary liver Cancer.

Keywords
Hepatocellular carcinoma.
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