Se Whee Sammy Park, Susanne Fransson, Fredrik Sundquist, Joachim N. Nilsson, Per Grybäck, Sandra Wessman, Jacob Strömgren, Anna Djos, Henrik Fagman, Helene Sjögren, Kleopatra Georgantzi, Nikolas Herold, Per Kogner, Dan Granberg, Mark N. Gaze, Tommy Martinsson, Kasper Karlsson, Jakob J. E. Stenman
{"title":"神经母细胞瘤 177Lutetium-DOTATATE 分子放疗后进展性转移病灶中的 SSTR2 目标异质性表达和新型 KIAA1549::BRAF 融合克隆:病例报告","authors":"Se Whee Sammy Park, Susanne Fransson, Fredrik Sundquist, Joachim N. Nilsson, Per Grybäck, Sandra Wessman, Jacob Strömgren, Anna Djos, Henrik Fagman, Helene Sjögren, Kleopatra Georgantzi, Nikolas Herold, Per Kogner, Dan Granberg, Mark N. Gaze, Tommy Martinsson, Kasper Karlsson, Jakob J. E. Stenman","doi":"10.3389/fonc.2024.1408729","DOIUrl":null,"url":null,"abstract":"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 (<jats:sup>177</jats:sup>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 <jats:italic>KIAA1549</jats:italic>::<jats:italic>BRAF</jats:italic> 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 <jats:sup>177</jats:sup>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.","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heterogeneous SSTR2 target expression and a novel KIAA1549::BRAF fusion clone in a progressive metastatic lesion following 177Lutetium-DOTATATE molecular radiotherapy in neuroblastoma: a case report\",\"authors\":\"Se Whee Sammy Park, Susanne Fransson, Fredrik Sundquist, Joachim N. Nilsson, Per Grybäck, Sandra Wessman, Jacob Strömgren, Anna Djos, Henrik Fagman, Helene Sjögren, Kleopatra Georgantzi, Nikolas Herold, Per Kogner, Dan Granberg, Mark N. Gaze, Tommy Martinsson, Kasper Karlsson, Jakob J. E. Stenman\",\"doi\":\"10.3389/fonc.2024.1408729\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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 (<jats:sup>177</jats:sup>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 <jats:italic>KIAA1549</jats:italic>::<jats:italic>BRAF</jats:italic> 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 <jats:sup>177</jats:sup>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.\",\"PeriodicalId\":12482,\"journal\":{\"name\":\"Frontiers in Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fonc.2024.1408729\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fonc.2024.1408729","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Heterogeneous SSTR2 target expression and a novel KIAA1549::BRAF fusion clone in a progressive metastatic lesion following 177Lutetium-DOTATATE molecular radiotherapy in neuroblastoma: a case report
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 (177Lu-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 177Lu-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.
期刊介绍:
Cancer Imaging and Diagnosis is dedicated to the publication of results from clinical and research studies applied to cancer diagnosis and treatment. The section aims to publish studies from the entire field of cancer imaging: results from routine use of clinical imaging in both radiology and nuclear medicine, results from clinical trials, experimental molecular imaging in humans and small animals, research on new contrast agents in CT, MRI, ultrasound, publication of new technical applications and processing algorithms to improve the standardization of quantitative imaging and image guided interventions for the diagnosis and treatment of cancer.