Ryusuke Murakami1, Noriomi Matsumura2, Hirofumi Michimae3, Hiroshi Tanabe4, Mayu Yunokawa5, Haruko Iwase6, Motoi Sasagawa7, Toshiaki Nakamura8, Osamu Tokuyama9, Masashi Takano10, Toru Sugiyama11, Takashi Sawasaki12, Seiji Isonishi4, Kazuhiro Takehara13, Hidekatsu Nakai14, Aikou Okamoto4, Masaki Mandai15, Ikuo Konishi16. 1. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan. Electronic address: noriomi@kuhp.kyoto-u.ac.jp. 3. Kitasato University, School of Pharmacy, Department of Clinical Medicine (Biostatistics), Tokyo, Japan. 4. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan. 5. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Kanagawa, Japan. 7. Department of Gynecology, Niigata Cancer Center Hospital, Niigata, Japan. 8. Department of Obstetrics and Gynecology, Kagoshima City Hospital, Kagoshima, Japan. 9. Department of Gynecology, Osaka City General Hospital, Osaka, Japan. 10. Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan. 11. Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, Japan. 12. Department of Obstetrics and Gynecology, National Hospital Organization, Kure Medical Center, Hiroshima, Japan. 13. Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Japan. 14. Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan. 15. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan. 16. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Abstract
OBJECTIVE: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment. METHODS: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype. RESULTS: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared. CONCLUSIONS: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.
RCT Entities:
OBJECTIVE: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment. METHODS: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype. RESULTS: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared. CONCLUSIONS: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.
Authors: Audra N Iness; Lisa Rubinsak; Steven J Meas; Jessica Chaoul; Sadia Sayeed; Raghavendra Pillappa; Sarah M Temkin; Mikhail G Dozmorov; Larisa Litovchick Journal: Front Oncol Date: 2021-03-04 Impact factor: 6.244
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