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The International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging system was modified in 2018, introducing new stage IB subdivisions and new lymph node status considerations in stage IIIC. We compared cervical cancer survival outcomes according to the 2014 and 2018 FIGO staging systems. We selected 10% of cervical cancer cases (2010–2015) from the Korean national cancer registry (2010–2015) through a systematic sampling method. We collected information using a collaborative stage data collection system and evaluated the results according to both staging systems. The log-rank test was used to analyze overall survival differences. No significant difference in survival was observed between 2018 subdivisions IB1/IB2/IB3 (P = 0.069), whereas a considerable difference was observed between these subdivisions according to histological subtypes. In the 2018 FIGO staging system, stage IIIC had better survival than stage IIIA/IIIB (P < 0.001). We observed considerable heterogeneity in 2018 stage IIIC related to the corresponding stages of the 2014 staging system (stages IA1–IIIB). The size of the primary cervical mass was related to survival (P < 0.001). In conclusion, using lymph node status to define stage IIIC captured a broad range of prognoses. The inclusion of primary tumor size considerations may improve the staging accuracy of advanced cervical cancer.

Although most patients with epithelial ovarian cancer respond to frontline platinum-based chemotherapy, around 70% will relapse within 3 years. The phase 3 JAVELIN Ovarian 100 trial compared avelumab (anti-PD-L1 monoclonal antibody) in combination with chemotherapy followed by avelumab maintenance, or chemotherapy followed by avelumab maintenance, versus chemotherapy alone in patients with treatment-naive epithelial ovarian cancer. JAVELIN Ovarian 100 was a global, open-label, three-arm, parallel, randomised, phase 3 trial run at 159 hospitals and cancer treatment centres in 25 countries. Eligible women were aged 18 years and older with stage III–IV epithelial ovarian, fallopian tube, or peritoneal cancer (following debulking surgery, or candidates for neoadjuvant chemotherapy), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to receive chemotherapy (six cycles; carboplatin dosed at an area under the serum-concentration-time curve of 5 or 6 intravenously every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks or 80 mg/m2 once a week [investigators' choice]) followed by avelumab maintenance (10 mg/kg intravenously every 2 weeks; avelumab maintenance group); chemotherapy plus avelumab (10 mg/kg intravenously every 3 weeks) followed by avelumab maintenance (avelumab combination group); or chemotherapy followed by observation (control group). Randomisation was in permuted blocks of size six and stratified by paclitaxel regimen and resection status. Patients and investigators were masked to assignment to the two chemotherapy groups without avelumab at the time of randomisation until completion of the chemotherapy phase. The primary endpoint was progression-free survival assessed by blinded independent central review in all randomly assigned patients (analysed by intention to treat). Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02718417. The trial was fully enrolled and terminated at interim analysis due to futility, and efficacy is no longer being assessed. Between May 19, 2016 and Jan 23, 2018, 998 patients were randomly assigned (avelumab maintenance n=332, avelumab combination n=331, and control n=335). At the planned interim analysis (data cutoff Sept 7, 2018), prespecified futility boundaries were crossed for the progression-free survival analysis, and the trial was stopped as recommended by the independent data monitoring committee and endorsed by the protocol steering committee. Median follow-up for progression-free survival for all patients was 10·8 months (IQR 7·1–14·9); 11·1 months (7·0–15·3) for the avelumab maintenance group, 11·0 months (7·4–14·5) for the avelumab combination group, and 10·2 months (6·7–14·0) for the control group. Median progression-free survival was 16·8 months (95% CI 13·5–not estimable [NE]) with avelumab maintenance, 18·1 months (14·8–NE) with avelumab combination treatment, and NE (18·2 months–NE) with control treatment. The stratified hazard ratio for progression-free survival was 1·43 (95% CI 1·05–1·95; one-sided p=0·99) with the avelumab maintenance regimen and 1·14 (0·83–1·56; one-sided p=0·79) with the avelumab combination regimen, versus control treatment. The most common grade 3–4 adverse events were anaemia (69 [21%] patients in the avelumab maintenance group, 63 [19%] in the avelumab combination group, and 53 [16%] in the control group), neutropenia (91 [28%], 99 [30%], and 88 [26%]), and neutrophil count decrease (49 [15%], 45 [14%], and 59 [18%]). Serious adverse events of any grade occurred in 92 (28%) patients in the avelumab maintenance group, 118 (36%) in the avelumab combination group, and 64 (19%) in the control group. Treatment-related deaths occurred in one (<1%) patient in the avelumab maintenance group (due to atrial fibrillation) and one (<1%) patient in the avelumab combination group (due to disease progression). Although no new safety signals were observed, results do not support the use of avelumab in the frontline treatment setting. Alternative treatment regimens are needed to improve outcomes in patients with advanced epithelial ovarian cancer. Pfizer and Merck KGaA, Darmstadt, Germany.

Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376. Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5–8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3–4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported. Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing. National OncoVenture.

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.

High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer and is characterized by a high rate of relapse after platinum-based chemotherapy. Herein, we present a comprehensive analysis of 111 Korean HGSOC samples using next-generation sequencing technology to elucidate their transcriptomic landscapes. Our investigation revealed the existence of four distinct transcriptional subtypes of ovarian cancer: immunoreactive, mesenchymal, proliferative, and differentiated, which is comparable to those of TCGA HGSOC transcriptional subgroups. Each subtype exhibited unique correlation networks and their immune cell composition was computationally determined. Notably, the immunoreactive cluster displayed the highest immune score, even in the context of pan solid-cancer types, accompanied by heightened expression of CD4 + and CD8 + T cells ( P   < 0.05), along with notable associations with neutrophil degranulation and antigen presentation pathways (FDR < 0.01). Conversely, the differentiated cluster demonstrated immunodepleted characteristics, featuring an elevated proportion of overexpressed cancer-germline antigens. We also identified several cancer-germline HGSOC antigens that could be further investigated as potential targets for immunological intervention in cancer.

In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response ( P  = 0.043 and P  < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence. Even in patients who are initially sensitive, patients treated with platinum-based therapies often go on to relapse and have limited treatment options. Here, the authors report the efficacy and safety of a phase II trial investigating olaparib, pembrolizumab and bevacizumab as maintenance therapy in platinum-sensitive recurrent ovarian cancer.

To identify the effect of fascial closure using barbed sutures on the incidence of incisional hernia in patients undergoing elective midline laparotomy for gynecological diseases. In this multicenter, non-blind randomized controlled trial conducted from February to December 2021, patients with a BMI < 35 kg/m2 and aged >18 years, scheduled for midline laparotomy, were randomly assigned to receive either barbed (experimental) or non-barbed sutures (control) for fascial closure. The primary outcome was the cumulative incidence rate of incisional hernia up to 1-year post-surgery. Secondary outcomes included incisional hernia up to 2-years post-surgery, wound complications, and postoperative pain assessed by Brief Pain Inventory-Korean scores, and Numeric Rating Scale. Out of 174 patients (experimental, 86; control, 88), 36 were excluded due to dropout or loss to follow-up, leaving 138 patients (experimental, 67; control, 71) included in the analysis. The groups were balanced in terms of cancer surgeries, mean wound length, and mean surgery time. The cumulative incidence rates of incisional hernia up to 1-year (0.0% vs. 1.4%; p > 0.999) and 2-years (0.0% vs. 3.4%, p = 0.496) post-surgery did not differ significantly between the experimental and control groups. Additionally, no significant differences were observed in the incidence of wound dehiscence 4 weeks post-surgery, cumulative incidences of wound dehiscence and wound infection up to 4 weeks post-surgery, or postoperative pain scores between the groups. Fascial closure using barbed sutures resulted in no cases of incisional hernia up to 2-years post-surgery, but did not demonstrate a significant reduction in incisional hernia rates compared with the non-barbed suture. ClinicalTrials.gov NCT04643197.

Background Recent advancements in large language models (LLMs) have led to increasing exploration of their clinical applications, particularly in enhancing decision-making and patient management. This study aimed to evaluate the feasibility of LLMs, specifically the non-reasoning Generative Pretrained Transformer (GPT)-4o and reasoning o3-mini-high, in supporting emergency care of patients with gynecologic cancer. Methods In this retrospective, single-center study, 15 real-world emergency cases in gynecologic oncology were selected. Two gynecologic oncology fellows, two obstetrics and gynecology residents, GPT-4o, and o3-mini-high assessed each case through four steps: providing differential diagnoses and suggesting relevant examinations; interpreting findings, establishing diagnoses, and proposing treatment; prescribing medical orders; and generating patient education materials (LLMs only). Responses were scored for relevance and speed. Paired tests with bootstrapping were used to estimate mean differences (MDs) and 95% confidence intervals (CIs). Results Both LLMs completed the tasks significantly faster than physicians, with an average time reduction of approximately 300 s per model ( P  < 0.001). GPT-4o achieved higher total scores than physicians (MD, 3.55; 95% CI, 2.98–4.10; P  < 0.001) and maintained superiority when speed metrics were excluded (MD, 1.27; 95% CI, 0.80–1.79; P  < 0.001). o3-mini-high also outperformed physicians in total scores (MD, 3.05; 95% CI, 1.98–3.88; P  < 0.001), but not with speed metrics. Satisfaction scores for LLM-generated management were 1.9/2.0 for GPT-4o and 1.8/2.0 for o3-mini-high. Conclusions Both GPT-4o and o3-mini-high are feasible tools for emergency care of patients with gynecologic cancer. GPT-4o may provide advantages, reflecting the pattern-based structure of emergency care in this domain. LLM selection should be based on the domain-specific medical knowledge required rather than on the reasoning status or model version. Further prospective multicenter studies are warranted to confirm our findings as well as clinical effectiveness of LLMs in gynecologic cancer emergency care.

[This corrects the article DOI: 10.1371/journal.pone.0294647.].

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.