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

IF 3.5 3区 医学 Q2 ONCOLOGY Frontiers in Oncology Pub Date : 2024-09-11 DOI:10.3389/fonc.2024.1408729
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
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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. 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引用次数: 0

摘要

在本病例报告中,我们介绍了首例加入 LuDO-N 试验的患者的治疗结果。患者是一名21个月大的女孩,被诊断为高危神经母细胞瘤(NB)和广泛的骨骼转移。患者最初接受了SIOPEN HRNBL-1的一线治疗,但因疾病进展而转为二线治疗,最后因疾病难治而被筛选加入LuDO-N试验。患者入组后接受了两轮放射性标记的体生长抑素类似物辛辣酸镥-177(177Lu-DOTATATE)治疗,耐受性良好。剂量测定分析表明,肿瘤病灶的吸收不均匀,原发肿瘤的吸收剂量高达 54 Gy,但股骨远端一个转移部位的吸收剂量仅为 2 Gy。虽然最初的治疗反应显示病情趋于稳定,但股骨远端转移瘤仍在继续发展,最终导致患者死亡。对整个病程中收集的活检组织进行分析后发现,在肿瘤病灶之间和内部,体生长抑素受体2(SSTR2)的药物靶点表达存在异质性。此外,基因组图谱分析显示,复发的股骨远端转移瘤中存在一种新的KIAA1549::BRAF融合癌基因扩增,可能通过下调SSTR2与放射抗性有关。本病例报告显示了对177Lu-DOTATATE分子放射治疗(MRT)的混合反应。观察到的不同肿瘤病灶之间 SSTR2 表达的差异表明,异质性靶点表达可能是该患者治疗失败的原因。在LuDO-N试验中开展的进一步调查将更全面地了解SSTR2表达水平与治疗结果之间的相关性,这对于推进基于MRT的高危NB儿童治疗策略非常重要。
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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.
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来源期刊
Frontiers in Oncology
Frontiers in Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
6.20
自引率
10.60%
发文量
6641
审稿时长
14 weeks
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.
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