Genomic profiling of the residual disease of advanced high‐grade serous ovarian cancer after neoadjuvant chemotherapy

Autor: Sora Kim, Soonmyung Paik, Su Bin Jo, Dachan Kim, Hanna Lee, Yu‐Jin Jung, Jung Eun Shim, So Hee Kim, Su‐Jin Bae, Jung Yun Lee, Hyun Soo Kim, Yong Jae Lee
Rok vydání: 2019
Předmět:
Adult
Oncology
Cancer Research
medicine.medical_specialty
Neoplasm
Residual
Genomic profiling
Biopsy
Ovariectomy
medicine.medical_treatment
Disease
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Serous ovarian cancer
Humans
Aged
Retrospective Studies
Ovarian Neoplasms
Chemotherapy
business.industry
TOR Serine-Threonine Kinases
Cell Cycle
Ovary
Cytoreduction Surgical Procedures
Genomics
Middle Aged
Cell cycle
medicine.disease
Survival Analysis
Neoadjuvant Therapy
Progression-Free Survival
Cystadenocarcinoma
Serous
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Mutation
Disease Progression
Immunohistochemistry
Female
Ovarian cancer
business
Proto-Oncogene Proteins c-akt
Adjuvant
Signal Transduction
Zdroj: International Journal of Cancer. 146:1851-1861
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.32729
Popis: The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.
Databáze: OpenAIRE
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