Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles.

Yoshiko Mori,Toshiyoshi Fujiwara,Yosuke Katata,Akihiro Nyuya,Hiroyuki Kishimoto,Yoshiyuki Yamaguchi,Fumitaka Taniguchi,Takeshi Nagasaka,Takashi Kawai,Keisuke Kimura,Junko Haraga,Ryo Inada,Masahiko Nishizaki,Keiichiro Nakamura,Yuzo Umeda,Toshiaki Toshima,Kazuya Yasui

doi:10.18632/oncotarget.24735

Yoshiko Mori, Toshiyoshi Fujiwara + Show 15 more

Open Access

https://doi.org/10.18632/oncotarget.24735

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Journal: Oncotarget	Publication Date: Mar 27, 2018
Citations: 24	License type: cc-by

Affiliation: Okayama University, Kawasaki Medical School

Abstract

We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7–16 months] in BRAF-mutant and 34 months (95% CI: 22–58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21–25 months) in BRAF-mutant and 38 months (95% CI: 24–42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

Highlights

Ovarian metastasis is estimated to account for 5%– 30% of all ovarian malignancies [1,2,3,4,5] and most frequently originates from colorectal cancers (CRC), followed by cancers of the endometrium, stomach, appendix and breast [6]
We first evaluated the clinical prevalence of ovarian metastases from CRCs in 296 female patients in our cohort (Figure 1)
These cases were categorised into three subsets: those with ovarian metastases (n = 19, 6.4%), those with extra-ovarian metastases only (n = 96, 32.4%) and those without recurrence or metastasis (n = 181, 61.1%) (Table 1)

Summary

Introduction

Ovarian metastasis is estimated to account for 5%– 30% of all ovarian malignancies [1,2,3,4,5] and most frequently originates from colorectal cancers (CRC), followed by cancers of the endometrium, stomach, appendix and breast [6]. Remarkable progress has been achieved in the treatment of advanced CRC, after the introduction of effective systemic chemotherapeutic regimens, including oxaliplatin and irinotecan, and molecular-targeted antibodies [12]. These novel agents have enabled better tumour response rates and overall survivals (OS) in patients. Despite these significant improvements, patients with ovarian metastases from CRCs have a worse prognosis than patients with CRCs that metastasised to other sites [13]

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