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Simple Summary: Neoadjuvant chemotherapy (NAC) induced a dynamic change in the TIME that increased the level of immune infiltration, leading to a high number of CD8 T cells with enhanced immune activity. However, increased immune infiltration and immune activity did not present any survival benefit, probably due to concomitant immunosuppression associated with an increase in the proportion of Foxp3+ regulatory T cells. Our results could provide therapeutic strategies to improve the survival benefit from immunotherapies in an NAC setting. The dynamic changes in the tumor immune microenvironment (TIME) triggered by neoadjuvant chemotherapy (NAC) have not been clearly defined in advanced-stage ovarian cancer. We analyzed the immunologic changes induced by NAC to correlate them with clinical outcomes. We compared the changes in the immune infiltration of high-grade serous carcinoma biopsies before and after NAC via immunohistochemistry (147 paired samples) and whole transcriptome sequencing (35 paired samples). Immunohistochemistry showed significantly increased PD-L1 levels and TIL levels after NAC. Whole transcriptome sequencing revealed that the stromal score, immune score, and cytolytic activity score significantly increased after NAC. An increased tumor-infiltrating lymphocyte (TIL) level in response to NAC was associated with shorter progression-free survival compared with decreased TIL level after NAC. In tumors with increased TIL levels after NAC, the relative fraction of CD8 T cells and regulatory T cells significantly increased with immunohistochemistry. Post-NAC tumors were enriched in gene sets associated with immune signaling pathways, such as regulatory T cell and JAK/STAT signaling pathways. NAC induced dynamic changes in the TIME that increased TIL levels, but their high abundance did not impart any survival benefit. Our data may provide therapeutic strategies to improve the survival benefit from immunotherapies in ovarian cancer. [ABSTRACT FROM AUTHOR]

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high‐grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre‐NAC and post‐NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next‐generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post‐NAC residual tumors. We also examined whether post‐NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy‐resistant component of tumors. Among 102 post‐NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K–AKT–mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression‐free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K–AKT–mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni‐corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker‐driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC. What's new? Patients with high‐grade serous ovarian cancer (HGSOC) with residual disease after neoadjuvant chemotherapy may be affected by tumors that harbor cells with intrinsic resistance to therapy. The present study confirms this suspicion, showing that about 40 percent of HGSOC patients with residual disease have mutations in homologous recombination repair (HRR) genes, thereby fueling drug resistance. More than 90 percent of patients studied exhibited alterations in at least one of six clinically relevant pathways or functional groups. In particular, HRR‐deficient tumors showed a significant increase in PI3K‐AKT‐mTOR pathway alterations, which were further linked to poor overall survival in HGSOC. [ABSTRACT FROM AUTHOR]

Background: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS).Methods: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated.Results: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients.Conclusion: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients. [ABSTRACT FROM AUTHOR]

Abstract Aims We evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC). Methods The data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL. Results Among 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98). Conclusion Among patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified. [ABSTRACT FROM AUTHOR]

Various kinetic parameters of serum CA-125 have been reported to have better correlation with outcomes for patients treated with neoadjuvant chemotherapy (NAC). This study aimed to compare the available kinetic parameters of serum CA-125 in an external cohort of advanced-stage ovarian cancer. Using the cancer registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed 210 patients with advanced-stage ovarian cancer, treated with NAC followed by interval debulking surgery. We compared area under the receiver-operating characteristics curves (AUCs), false negative rate, and negative predictive value (NPV) using 10 different models for optimal cytoreduction and platinum resistance. In addition, we compared incremental AUC for progression-free survival (PFS) and overall survival (OS). No gross residual tumor was observed in 37.0% and residual tumors <1 cm in 82.2% of patients. No model using CA-125 kinetic parameters had an AUC higher than >0.6 for predicting optimal cytoreduction. After adjusting for age, BMI, disease stage, and histologic subtypes, all models had an AUC >0.70 for predicting platinum resistance. However, no model had a high enough NPV (highest value = 82.0%) to avoid chemotherapy futility. For survival outcomes, no model had an incremental AUC >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic parameters showed high accuracy in predicting optimal cytoreduction, platinum resistance, or survival in patients receiving NAC. For advanced-stage ovarian cancer treated with NAC, there is a need to discover reliable biomarkers to better stratify patient response groups for optimal treatment decision-making. [ABSTRACT FROM AUTHOR]

Background: The survival of patients with ovarian cancer has improved because of surgery and chemotherapy. This study aimed to estimate the changes in survival rates among Korean women with ovarian cancer prior to the introduction of targeted therapy for ovarian cancer.Methods: Data were obtained from the Korea Central Cancer Registry regarding patients who were diagnosed with epithelial ovarian cancer between 1995 and 2014. The relative survival rates were calculated for 5-year periods using the Ederer II method. Cox proportional hazard models were created to assess the associations of demographic and clinicopathological factors with ovarian cancer survival.Results: During the study period, 22,880 women were diagnosed with epithelial ovarian cancer. The 5-year relative survival rate improved from 57.2% during 1995-1999 to 63.8% during 2010-2014 (P < 0.001). Survival outcomes improved between 1995 and 1999 and 2010-2014 for the serous and endometrioid carcinoma subtypes (P < 0.001). However, no improvements were observed for the mucinous and clear cell carcinoma subtypes (P = 0.189 and P = 0.293, respectively). Multivariate analysis revealed that younger age, early stage, recent diagnosis, primary surgical treatment, and non-serous histological subtype were favorable prognostic factors.Conclusion: Survival outcomes have improved for serous and endometrioid epithelial ovarian cancer in the last 20 years. However, no improvement was observed for patients with mucinous and clear cell carcinoma subtypes. [ABSTRACT FROM AUTHOR]

Background: There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. Methods: We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Results: Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1–3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). Conclusion: IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the perioperative outcomes and prognostic impact of the consecutive steps of imaging, frailty assessment, and diagnostic laparoscopy (DLS) in patients with advanced epithelial ovarian cancer (EOC).Methods: Patients diagnosed with EOC during 2012-2015 were analyzed retrospectively. Surgical and survival outcomes were compared between three treatment groups: patients without high tumor dissemination (HTD) who underwent primary debulking surgery (PDS group); patients with HTD who underwent DLS (DLS group); and patients with HTD diagnosed by cytological confirmation of malignancy followed by neoadjuvant chemotherapy (NACT group).Results: Of 181 patients, 85, 38, and 58 underwent PDS, DLS, and NACT, respectively. Among the 38 consecutive patients who initially underwent DLS, 6 were considered suitable for PDS; the remaining 32 were eligible for NACT followed by interval debulking surgery. The median operative times of debulking surgery in the PDS, DLS, and NACT groups were 365 min (interquartile range [IQR]: 216.5-476.5 min), 266.2 min (IQR: 160.3-193.5 min), and 339.0 min (IQR: 205-425 min; P = 0.042), respectively, with respective median estimated blood loss volumes of 962.2 mL (IQR: 300-1037.5 mL), 267.1 mL (IQR: 150-450 mL), and 861.7 mL (IQR: 150-1200 mL; P = 0.023). The DLS group had significantly reduced transfusion requirements and intensive care unit admission rates (P = 0.006). The Kaplan-Meier survival analysis indicated significantly poor PFS in the NACT group. However, there was no significant difference in OS among the three groups.Conclusions: The consecutive steps of imaging, frailty assessment, and DLS might facilitate rapid assessments of peritoneal disease extent and resectability; this novel algorithm might also be used to individualize treatment. [ABSTRACT FROM AUTHOR]

Background The GOG-218 and ICON-7 studies recently showed that adding bevacizumab to first-line therapy for patients with advanced ovarian cancer increased progression-free survival. However, the high cost and long treatment duration prevents the incorporation of bevacizumab in practice. The aim of this study was to explore and quantify patients' preferences for adding bevacizumab to first-line therapy. Methods A discrete choice experiment (DCE) and trade-off question were designed and distributed to 102 ovarian cancer patients. Participants were asked to choose between two hypothetical first-line therapies that differed in terms of effectiveness, safety, and the financial burden. A trade-off technique varying the cost of bevacizumab was used to quantify a willingness-to-pay threshold for selecting bevacizumab. Results All attributes of the DCE had a statistically significant impact on respondents' preferences and the financial burden was the most important attribute. The results of the trade-off question showed that more than half of patients would prefer to add bevacizumab to standard chemotherapy when the cost of the drug was reduced to 17% (1/6) of the baseline cost. Conclusion Patients' preferences for bevacizumab in the adjuvant treatment of ovarian cancer depend primarily on drug costs. Our results suggest that the current cost of bevacizumab is sufficiently high that the majority of ovarian cancer patients are not willing to pay to accept a small increase in progression-free survival. [ABSTRACT FROM AUTHOR]

In 1999, the National Cancer Institute issued a clinical advisory strongly touting the advantage of cisplatin-based chemoradiation (CCRT) for cervical cancer patients requiring radiation for their treatment. This study aimed to compare survival outcomes of cervical squamous cell carcinoma and adenocarcinoma before and after the advent of CCRT. Data were obtained from the Korea National Cancer Incidence Database for patients who were diagnosed with cervical cancers between 1993 and 2012. We compared survival according to histologic subtypes in cervical cancer patients diagnosed before (1993–1997), during (1998–2002), and after (2003–2012) the introduction of CCRT. A total of 80,766 patients were identified, including 64,531 (79.9%) women with squamous cell carcinomas and 7,265 (9.0%) with adenocarcinoma. With the introduction of CCRT, survival trends gradually increased in patients of both histologic subtypes with regional tumors. However, survival was significantly higher in squamous cell carcinoma than in adenocarcinoma patients regardless of treatment modalities (surgery alone, P < 0.001; surgery followed by CCRT, P < 0.001; or primary CCRT, P = 0.003). Multivariate analysis showed that adenocarcinoma was an independent negative prognostic factor for survival regardless of the time period (before CCRT, hazard ratio (HR) = 1.49; 95% confidence interval (CI), 1.37–1.62; after introduction of CCRT, HR = 1.40; 95% CI, 1.30–1.50). Although the survival of adenocarcinoma has improved after the introduction of CCRT, adenocarcinoma is still associated with worse overall survival compared to squamous cell carcinoma in the era of CCRT. [ABSTRACT FROM AUTHOR]

The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62–0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63–0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26–0.43; OS; HR, 0.37; 95% CI, 0.22–0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54–0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56–0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19–0.81) over PD-L1 negative population. ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes. • ICIs and platinum-based chemotherapy are primary options for advanced or recurrent EC, and prolong PFS and OS. • A substantial PFS benefit was observed in patients with Caucasian race, endometrioid histology, and PD-L1 positivity. • Personalized treatments are vital in ICI therapy, considering factors like MMR status, ethnicity, and PD-L1 expression. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of 268 epithelial ovarian cancer patients who had received three or four cycles of NAC and undergone optimal resections through IDS. The Kaplan–Meier method and Cox regression analysis were used to assess the effects of disease burden (peritoneal cancer index (PCI)), degree of complexity of surgery (surgical complexity score/s (SCS)), and extent of residual disease. In no residual disease (R0) patients, those with intermediate/high SCS had shorter progression-free survival (PFS; p = 0.001) and overall survival (OS; p = 0.001) than patients with low SCS. An analysis of a subset of patients with R0 and low PCIs showed those with intermediate/high SCS had worse PFS and OS than patients with low SCS (p = 0.049) and OS (p = 0.037). In multivariate analysis, patients with R0 as a result of intermediate/high SCS fared worse than patients whose R0 was achieved by low SCS (PFS hazard ratio (HR) 1.80, 95% CI 1.05–3.10; OS HR 5.59, 95% CI 1.70–18.39). High PCIs at the time of IDS, high SCS, and residual disease signal poor prognoses for patients treated with NAC. [ABSTRACT FROM AUTHOR]

We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single-agent chemotherapy (CT) in patients with platinum-resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations. KGOG 3045 was an open-label, investigator-initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received ≥2 prior lines of therapy were enrolled. Patients with high PD-L1 expression (TPS ≥25%) were assigned to arm A (D + CT), whereas those with low PD-L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT). Overall, 58 patients were enrolled (5, 18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3–4 treatment-related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression-free survival (adjusted HR, 0.435; 95% CI, 0.229–0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT. Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation. • Efficacy and safety of chemotherapy plus durvalumab with or without tremelimumab were studied in PROC without HRR mutation. • Addition of tremelimumab improved progression-free survival on multivariable Cox HR analysis. • Biomarkers were explored with immunohistochemistry and whole-exome and transcriptome sequencing. • Mutation in MUC16 and high EPCAM were associated with favorable response in the overall cohort. • Arm-specific biomarker in tremelimumab group were EPCAM expression and matrix remodeling score. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship of the time interval from the completion of neoadjuvant chemotherapy (NAC) to the initiation of postoperative adjuvant chemotherapy (POAC) with the survival outcomes in patients with ovarian cancer. Methods We retrospectively investigated 220 patients with pathologically confirmed epithelial ovarian cancer who received NAC at Yonsei Cancer Hospital between 2006 and 2016. The time interval was defined as the period from the completion of NAC, spanning interval debulking surgery (IDS), to the initiation of POAC. Results The median time interval was 42 (range 16–178) days; 103 patients (53.1%) received POAC within 42 days after NAC while 91 patients (46.9%) received it after 42 days. There were no significant differences in patient characteristics between these 2 groups. Kaplan-Meier analysis showed that patients with longer time intervals (> 42 days) had poorer progression-free survival and overall survival (P = 0.039 and 0.005, respectively). In the multivariate analysis, patients with longer time intervals had significantly poorer progression-free (hazard ratio, 1.41; 95% confidence interval, 0.98–2.03; not significant) and overall survivals (hazard ratio, 2.03; 95% confidence interval, 1.16–3.54). When the patients were categorized according to time interval quartiles (≤ 37, 38–42, 43–50, and > 50 days), longer time intervals were associated with higher risks of recurrence and death (P for trend: 0.006 and < 0.001, respectively). Conclusion The time interval from the completion of NAC to the initiation of POAC appears to influence survival. Efforts to reduce the time interval might improve the outcomes in ovarian cancer patients undergoing NAC. [ABSTRACT FROM AUTHOR]

With expanded use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi), there is a potential impact of PARPi resistance on platinum resistance. A post-hoc analysis of SOLO2 demonstrated a reduction in response to subsequent platinum-based therapy among patients who received prior olaparib but not placebo. The present multicentre, retrospective, observational study was conducted to determine the effects of olaparib on subsequent therapy for recurrent epithelial ovarian cancer (EOC). Data on EOC patients with BRCA1/2 -mutated tumours who received second-line platinum-based chemotherapy between January 2012 and June 2020, at three South Korean institutions (n = 197) were collected. Patients who received olaparib as maintenance therapy after second-line chemotherapy were assigned to the olaparib group (n = 105), and subjects who did not receive olaparib maintenance therapy were assigned to the control group (n = 92). The primary endpoint was time intervals from the date of second disease progression (PFS1) to the date of third disease progression (PFS2), expressed as PFS2 − PFS1. As expected, PFS1 in the olaparib group was longer than the control group. However, PFS2 – PFS1 in the olaparib group was significantly shorter than that of the control group (median 7.9 vs. 13.6 m; p = 0.0005). Even when the third-line PARPi maintenance (cross-over) patients were excluded from the control group, the response to subsequent therapy in the olaparib group remained poor (median 7.7 vs. 11.5; p = 0.0422). Patients with platinum-sensitive BRCA1/2 mutated tumours who progressed during olaparib maintenance after second-line chemotherapy were less likely to respond to third-line chemotherapy compared to controls who did not receive olaparib, suggesting that resistance to olaparib may contribute to chemotherapy resistance. • Although second-line olaparib significantly improved PFS1, olaparib did not prolong PFS2. • Relapsed patients despite 2 L-olaparib maintenance show poor response to subsequent chemotherapy. • The negative effects were more pronounced in patients with PFS1 > 12 months. [ABSTRACT FROM AUTHOR]

MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

Corrigendum to "Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data" Gynecol. Oncol. [Extracted from the article]