ObjectiveTo evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT).MethodsA retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification system based on scoring the identified prognostic factors were assessed.ResultsYolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. FIGO stage III-IV (RR 3.253, P = 0.029) and normalization of tumor markers (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥ 5 cycles of chemotherapy. FIGO stage I – II and stage III–IV were scored as 0 and 2, respectively. AFP normalization ≤ 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1 – 2, and ≥ 3 were stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk group (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not RFS (P > 0.05).ConclusionDistinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

Serous surface papillary borderline ovarian tumor (SSPBOT) is a distinct subtype of serous borderline ovarian tumor characterized by solid tissue deposition confined to the ovarian surface. Because SSPBOT is rare, there are few published reports on the ultrasonographic features of this condition. In this retrospective study, we investigated 12 cases of SSPBOT. Ultrasound imaging of SSPBOT showed grossly normal ovaries that were encased partially or wholly by tumor deposits that were confined to the surface, with clear demarcation between normal ovarian tissue and surrounding tumors. Color Doppler imaging demonstrated the 'fireworks sign' in all cases of SSPBOT, corresponding to an intratumoral vascular bundle originating from the ovarian vessels and supplying hierarchical branching blood flow to the surrounding tumor. No patient with ovarian high-grade serous carcinoma showed these morphological and Doppler features. In our series, the fireworks sign appeared to be a characteristic feature of SSPBOT that could facilitate correct identification of this tumor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Introduction/Background In the randomised, double-blind, placebo-controlled phase 3 NORA trial (NCT03705156) among patients with platinum-sensitive recurrent ovarian cancer (PSROC), niraparib maintenance therapy using an individualised starting dose (ISD) demonstrated a significant improvement in progression-free survival at the primary analysis and a favourable trend in overall survival (OS) at an interim analysis, irrespective of germline BRCA mutation (gBRCAm) status. In contrast, an inconsistent OS trend was observed among patients without gBRCAm across similar trials of poly(ADP-ribose) polymerase inhibitors (PARPis) in the same setting. This analysis aimed to present the final OS data of NORA. Methodology Eligible patients who were adults with PSROC and responded to their last platinum-based chemotherapy were randomised (2:1) to receive niraparib or placebo once daily. Following a protocol amendment, an ISD was used: 200 mg for those with bodyweight <77 kg and/or platelet count <150×103/µL and 300 mg otherwise. NORA was not powered for OS analysis. This planned, descriptive, final OS analysis was conducted after ≥50% of OS events occurred in the intention-to-treat population. Results Totally, 265 patients were randomised (177 niraparib; 88 placebo) and 249 (94.0%) received an ISD. Baseline characteristics were well balanced between the two groups. By the data cut-off (14 August 2023), median follow-up for OS was 57.9 months (IQR, 54.8–61.6). Notably, 41 (46.6%) placebo-treated patients received subsequent PARPi therapy. With 138 (52.1%) OS events reported, median OS (95% CI) in the overall population was 51.5 months (41.4–58.9) with niraparib and 47.6 months (33.3-not evaluable) with placebo (HR, 0.86; 95% CI, 0.60–1.23). A consistent OS trend was observed in both patients with and without gBRCAm (table 1). No new safety signal was identified for niraparib. Conclusion Niraparib maintenance therapy using ISD demonstrated a favourable OS trend versus placebo in patients with PSROC, regardless of gBRCAm status. Disclosures Charlie Zhang, Jianmei Hou, Zhao Huang, Juan Dong are employees of Zai Lab. They have stocks of Zai Lab. Mansoor R. Mirza has received the grants/research support from GSK, AstraZeneca, Ultimovacs, Apexigen, Deciphera. Mansoor R. Mirza received the honoraria or consultation fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zai Lab, is the stock shareholder of Karyopharml. Mansoor R. Mirza has some Non-Financial Interests: Advisory role (Ultimovacs, Apexigen). Member of Board of Directors: Karyopharm

KRAS is widely mutated in human cancers, resulting in unchecked tumor proliferation and metastasis, which makes identifying KRAS-targeting therapies a priority. Herein, we observe that mutant KRAS specifically promotes the formation of the ERK2-p53 complex in stomach/colorectal tumor cells. Disruption of this complex by applying MEK1/2 and ERK2 inhibitors elicits strong apoptotic responses in a p53-dependent manner, validated by genome-wide knockout screening. Mechanistically, p53 physically associates with phosphorylated ERK2 through a hydrophobic interaction in the presence of mutant KRAS, which suppresses p53 activation by preventing the recruitment of p300/CBP; trametinib disrupts the ERK2-p53 complex by reducing ERK2 phosphorylation, allowing the acetylation of p53 protein by recruiting p300/CBP; acetylated p53 activates PUMA transcription and thereby kills KRAS-mutant tumors. Our study shows an important role for the ERK2-p53 complex and provides a potential therapeutic strategy for treating KRAS-mutant cancer.

Circular RNAs (circRNAs) are regarded as a novel class of widespread endogenous non-coding RNAs, which may play important roles in tumorigenesis by regulating gene expression. Nevertheless, the characterization of circRNAs in epithelial ovarian cancer (EOC) remains largely unknown. This study aimed to investigate circRNA expression profiles in EOC. A total of 54 EOC specimens and 54 normal ovarian tissues (controls) were collected. circRNA-sequencing based circRNA expression profiles were identified in 4 EOC specimens and compared with 4 normal ovarian tissues. circRNA-sequencing data were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the 54 EOC specimens and 54 normal ovarian tissues. The association between differentially expressed circRNAs and various clinicopathological features of EOC was determined using a non-parametric test. Univariate analysis was performed using the log-rank test. A total of 4,388 circRNAs (2,556 upand 1,832 downregulated; fold change of ≥2 and P<0.05) were identified to be differentially expressed in the EOC specimens compared with the normal ovarian tissues. Of these, the levels of 6 circRNAs (circBNC2, circEXOC6B, circFAM13B, circN4BP2L2, circRHOBTB3 and circCELSR1) were confirmed by RT-qPCR. Our data further indicated that these 6 circRNAs were associated with various clinicopathological features of EOC. More importantly, we found that circEXOC6B and circN4BP2L2 may act as novel prognostic biomarkers in patients with EOC. On the whole, the results of this study indicate that differentially expressed circRNAs may participate in the pathogenesis of EOC and may thus have potential for use as novel diagnostic and prognostic biomarkers for EOC. Future experiments with larger sample sizes are required to verify the current findings and illuminate the regulatory mechanisms of action of circRNAs in the tumorigenesis of EOC.