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.

Autor:	Park SWS; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Fransson S; Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Sundquist F; Department of Urology, Karolinska University Hospital, Stockholm, Sweden.; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Nilsson JN; Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Grybäck P; Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Wessman S; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden., Strömgren J; Department of Pediatric Radiology, Karolinska University Hospital, Stockholm, Sweden., Djos A; Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Fagman H; Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Sjögren H; Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden., Georgantzi K; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden., Herold N; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden., Kogner P; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden., Granberg D; Department of Breast, Endocrine Tumors and Sarcomas, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden., Gaze MN; Department of Oncology, University College London Hospitals National Health Service (NHS) Foundation Trust, London, United Kingdom., Martinsson T; Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Karlsson K; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Stenman JJE; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Surgery, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Sep 11; Vol. 14, pp. 1408729. Date of Electronic Publication: 2024 Sep 11 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1408729
Abstrakt:	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 girl 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. A 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 the initial treatment response showed disease stabilization, the distal femoral metastasis continued to progress, leading to the eventual death of the patient. A 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's 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 to advance treatment strategies based on MRT for children with high-risk NB. Competing Interests: JJES is affiliated with the companies Expression Analytics Oy and Trifma Oy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from the Swedish Childhood Cancer Fund, Swedish Cancer Society, Region Stockholm, and Advanced Accelerator Applications/Novartis (AAA). AAA had the following involvement in the study: financial support of the trial, provision of the investigational medicinal product (IMP) as well as non-IMPs free of charge. (Copyright © 2024 Park, Fransson, Sundquist, Nilsson, Grybäck, Wessman, Strömgren, Djos, Fagman, Sjögren, Georgantzi, Herold, Kogner, Granberg, Gaze, Martinsson, Karlsson and Stenman.)
Databáze:	MEDLINE
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