Skip to main content

CASE REPORT article

Front. Oncol.
Sec. Pediatric Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1408729
This article is part of the Research Topic Novel Molecular Targets and Therapies for Pediatric Extracranial Solid Tumors View all 4 articles

Heterogeneous SSTR2 target expression and a novel KIAA1549::BRAF fusion clone in a progressive metastatic lesion following 177 Lutetium-DOTATATE molecular radiotherapy in neuroblastoma: A Case Report

Provisionally accepted
Se Whee Sammy Park Se Whee Sammy Park 1*Susanne Fransson Susanne Fransson 2Fredrik Sundquist Fredrik Sundquist 1,3Joachim Nilsson Joachim Nilsson 1,3Per Grybäck Per Grybäck 1,3Sandra Wessman Sandra Wessman 1,3Jacob Strömgren Jacob Strömgren 3Anna Djos Anna Djos 2Henrik Fagman Henrik Fagman 4Helene Sjögren Helene Sjögren 5Kleopatra Georgantzi Kleopatra Georgantzi 1,3Nikolas Herold Nikolas Herold 1,3Per Kogner Per Kogner 1,3Dan Granberg Dan Granberg 3Mark N. Gaze Mark N. Gaze 6Tommy Martinsson Tommy Martinsson 2Kasper Karlsson Kasper Karlsson 1Jakob J. Stenman Jakob J. Stenman 1,3
  • 1 Karolinska Institutet (KI), Solna, Sweden
  • 2 University of Gothenburg, Gothenburg, Västergötland, Sweden
  • 3 Karolinska University Hospital, Huddinge, Stockholm, Sweden
  • 4 University Library, University of Mannheim, Mannheim, Baden-Württemberg, Germany
  • 5 Sahlgrenska University Hospital, Gothenburg, Sweden
  • 6 University College London Hospitals NHS Foundation Trust, London, United Kingdom

The final, formatted version of the article will be published soon.

    In this case report, we present the treatment outcomes of the first patient enrolled in the LuDO-N Trial. The patient is a 21-month-old female diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. The patient initially underwent first line therapy according to SIOPEN HRNBL-1 but was switched to second line treatments due to disease progression and she was finally screened for enrollment in the LuDO-N trial due to refractory disease. Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue Lutetium-177 octreotate ( 177 Lu-DOTATATE), which was well-tolerated. Dosimetry analysis revealed a heterogeneous uptake across tumor lesions, resulting in a significant absorbed dose of 54 Gy in the primary tumor, but only 2 Gy at one of the metastatic sites in the distal femur. While initial treatment response showed disease stabilization, the distal femoral metastasis continued to progress, leading to the eventual death of the patient. Tissue analysis of the biopsies collected throughout the course of the disease revealed heterogeneous drug target expression of somatostatin receptor 2 (SSTR2) across and within tumor lesions. Furthermore, genomic profiling revealed a novel KIAA1549::BRAF fusion oncogene amplification in the distal femoral metastasis at recurrence that might be related with resistance to radiation, possibly through the downregulation of SSTR2. This case report demonstrates a mixed response to molecular radiotherapy (MRT) with 177 Lu-DOTATATE. The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes which will be important for advancing treatment strategies based on MRT for children with high-risk NB.

    Keywords: LuDO-N Clinical Trial, molecular radiotherapy, Neuroblastoma, tumor heterogeneity, case report

    Received: 28 Mar 2024; Accepted: 20 Jun 2024.

    Copyright: © 2024 Park, Fransson, Sundquist, Nilsson, Grybäck, Wessman, Strömgren, Djos, Fagman, Sjögren, Georgantzi, Herold, Kogner, Granberg, Gaze, Martinsson, Karlsson and Stenman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Se Whee Sammy Park, Karolinska Institutet (KI), Solna, Sweden

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.