Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer

Author:

Uehara Takashi12ORCID,Matsuzaki Juntaro34,Yoshida Hiroshi5,Ogawa Yuto6,Miura Junichiro6,Fujimiya Hitoshi6,Yamamoto Yusuke3,Kawauchi Junpei7,Takizawa Satoko7,Yonemori Kan8,Sakamoto Hiromi9,Kato Ken10ORCID,Ishikawa Mitsuya1,Ochiya Takahiro11ORCID

Affiliation:

1. Department of Gynecology, National Cancer Center Hospital , Tokyo , Japan

2. Department of Obstetrics and Gynecology, Chiba University Hospital , Chiba , Japan

3. Laboratory and Integrative Oncology, National Cancer Center Research Institute , Tokyo , Japan

4. Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy , Tokyo , Japan

5. Department of Diagnostic Pathology, National Cancer Center Hospital , Tokyo , Japan

6. R&D Department, Dynacom Co., Ltd. , Chiba , Japan

7. New Projects Development Division, Toray Industries, Inc. , Kamakura city, Kanagawa , Japan

8. Department of Breast and Medical Oncology, National Cancer Center Hospital , Tokyo , Japan

9. Department of Biobank and Tissue Resources, National Cancer Center Research Institute , Tokyo , Japan

10. Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital , Tokyo , Japan

11. Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University , Tokyo , Japan

Abstract

Abstract Objective The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. Methods Consecutive patients with clinical stage IIIB–IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. Results Of the 108 patients with stage IIIB–IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. Conclusions Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.

Funder

Development of Diagnostic Technology for Detection of miRNA in Body Fluids

Japan Agency for Medical Research

JSPS KAKENHI

Cancer Research from the Ministry of Health, Labor, and Welfare of Japan

National Cancer Center Research and Development Fund of Japan

National Cancer Center Research and Development Fund

Publisher

Oxford University Press (OUP)

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