Weidenbusch Bushra, Richter Günther H S, Kesper Marie Sophie, Guggemoos Monika, Gall Katja, Prexler Carolin, Kazantsev Ilya, Sipol Alexandra, Lindner Lars, Nathrath Michaela, Witt Olaf, Specht Katja, Beitinger Frigga, Knebel Carolin, Hosie Stuart, von Eisenhardt-Rothe Rüdiger, Weichert Wilko, Luettichau Irene Teichert-von, Burdach Stefan
Department of Pediatrics and Children's Cancer Research Center, Kinderklinik München Schwabing, Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München, Munich, Germany.
CCC München - Comprehensive Cancer Center; and DKTK German Cancer Consortium Munich, Munich, Germany.
Oncotarget. 2018 Apr 17;9(29):20747-20760. doi: 10.18632/oncotarget.25087.
Survival rates of pediatric sarcoma patients stagnated during the last two decades, especially in adolescents and young adults (AYAs). Targeted therapies offer new options in refractory cases. Gene expression profiling provides a robust method to characterize the transcriptome of each patient's tumor and guide the choice of therapy. Twenty patients with refractory pediatric sarcomas (age 8-35 years) were assessed with array profiling: ten had Ewing sarcoma, five osteosarcoma, and five soft tissue sarcoma. Overexpressed genes and deregulated pathways were identified as actionable targets and an individualized combination of targeted therapies was recommended. Disease status, survival, adverse events (AEs), and quality of life (QOL) were assessed in patients receiving targeted therapy (TT) and compared to patients without targeted therapy (non TT). Actionable targets were identified in all analyzed biopsies. Targeted therapy was administered in nine patients, while eleven received no targeted therapy. No significant difference in risk factors between these two groups was detected. Overall survival (OS) and progression free survival (PFS) were significantly higher in the TT group (OS: P=0.0014, PFS: P=0.0011). Median OS was 8.83 versus 4.93 months and median PFS was 6.17 versus 1.6 months in TT versus non TT group, respectively. QOL did not differ at baseline as well as at four week intervals between the two groups. TT patients had less grade 1 AEs (P=0.009). The frequency of grade 2-4 AEs did not differ. Overall, expression based targeted therapy is a feasible and likely beneficial approach in patients with refractory pediatric sarcomas that warrants further study.
在过去二十年中，小儿肉瘤患者的生存率停滞不前，尤其是在青少年和青年（AYA）群体中。靶向治疗为难治性病例提供了新的选择。基因表达谱分析提供了一种可靠的方法来表征每个患者肿瘤的转录组，并指导治疗方案的选择。对20例难治性小儿肉瘤患者（年龄8 - 35岁）进行了阵列分析：其中10例患有尤因肉瘤，5例骨肉瘤，5例软组织肉瘤。将过表达基因和失调通路鉴定为可操作靶点，并推荐了个体化的靶向治疗组合。对接受靶向治疗（TT）的患者评估疾病状态、生存率、不良事件（AE）和生活质量（QOL），并与未接受靶向治疗（非TT）的患者进行比较。在所有分析的活检样本中均鉴定出可操作靶点。9例患者接受了靶向治疗，而11例未接受靶向治疗。两组之间的危险因素无显著差异。TT组的总生存期（OS）和无进展生存期（PFS）显著更高（OS：P = 0.0014，PFS：P = 0.0011）。TT组与非TT组的中位OS分别为8.83个月和4.93个月，中位PFS分别为6.17个月和1.6个月。两组在基线以及四周间隔时的QOL无差异。TT组的1级AE较少（P = 0.009）。2 - 4级AE的发生率无差异。总体而言，基于表达的靶向治疗对于难治性小儿肉瘤患者是一种可行且可能有益的方法，值得进一步研究。
