Prognostic significance of PIK3CA mutation in stage IIB to IVA cervical cancers treated by concurrent chemoradiotherapy with weekly cisplatin
| Autor: | Chenyang Xu, Azusa Akiyama, Shuling Liu, Ayumi Shikama, Manabu Sakurai, Hiroyuki Ochi, Hiroyuki Yoshikawa, Shuang Zhang, Takeo Minaguchi, Toyomi Satoh, Bouchra Lachkar, Nobutaka Tasaka, Sari Nakao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult medicine.medical_specialty cervical cancer Class I Phosphatidylinositol 3-Kinases Observational Study cisplatin Uterine Cervical Neoplasms Antineoplastic Agents Drug Administration Schedule chemoradiotherapy 03 medical and health sciences 0302 clinical medicine Radioresistance Internal medicine Weekly cisplatin medicine Stage iib Humans neoplasms PI3K/AKT/mTOR pathway Aged Neoplasm Staging Retrospective Studies Cisplatin Cervical cancer business.industry Standard treatment Carcinoma General Medicine PIK3CA Middle Aged medicine.disease Prognosis Concurrent chemoradiotherapy Survival Rate 030104 developmental biology Treatment Outcome 030220 oncology & carcinogenesis Mutation Female business medicine.drug Research Article |
| Zdroj: | Medicine |
| ISSN: | 0025-7974 |
| Popis: | The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Although the activated PI3-kinase/Akt pathway is known to be involved in both cisplatin-resistance and radioresistance, to date, only a few studies have reported significant associations between PIK3CA gene mutational status and outcome by CCRT in the disease. The aim of this study was to clarify the prognostic significance of PIK3CA mutational status in cervical cancers treated by CCRT. We analyzed PIK3CA mutation in 59 patients with stage IIB to IVA cervical carcinomas primarily treated by CCRT with weekly cisplatin using formalin-fixed paraffin-embedded biopsy specimens before treatment. Fifty-seven of 59 patients (97%) had locally advanced cancers with stage IIIA to IVA. Clinicopathologic data and patient survival were retrospectively compared according to PIK3CA mutational status. PIK3CA mutation was found in 7 of 59 patients (12%). No significant differences in clinicopathologic characteristics were observed according to PIK3CA mutational status. Patients with wild-type PIK3CA showed significantly improved cancer-specific survival as compared with mutated patients (P = .044). Subsequent survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.3–11.8; P = .017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2–11.0; P = .024). Together with previous published findings, the current study further supports the clinical significance of PIK3CA mutation in cervical cancer. Our observations suggest that molecular inhibitors targeting the PI3-kinase/Akt pathway may improve the outcome by CCRT in cervical cancers harboring PIK3CA mutation, providing significant implications for novel treatment strategy based on precision medicine in the disease. |
| Databáze: | OpenAIRE |
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