Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform

The oncologist

article

Hossein Taghizadeh¹  Gerald W. Prager¹  Robert M. Mader¹  Leonhard Müllauer³  Stefanie Aust⁴  Stephan Polterauer⁴  Heinz Kölbl⁴  Veronika Seebacher⁴  Christoph Grimm⁴  Alexander Reinthaller⁴ 

[1] Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna;Comprehensive Cancer Center Vienna;Clinical Institute of Pathology, Medical University of Vienna;Department of Obstetrics and Gynecology, Medical University of Vienna

关键词: Precision medicine;    Gynecologic oncology;    Molecular aberrations;    Molecular profiling;    Immunohistochemistry;    Targeted agents;   

DOI  :  10.1634/theoncologist.2019-0904

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Introduction Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. Patients and Methods In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC). Results In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 ( n = 42, 20%), KRAS ( n = 14, 6.6%), PIK3CA ( n = 11, 5.2%), PIK3R1 ( n = 9, 4.3%), ATR ( n = 8, 3.8%), PTEN ( n = 8, 3.8%), BRCA1 ( n = 6, 2.8%), NF1 ( n = 4, 1.9%), NOTCH1 ( n = 4, 1.9%), and POLE ( n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds ( n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane ( n = 18, 25 %). Conclusion Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. Implications for Practice Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.

【 授权许可】

CC BY|CC BY-NC