Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study.

BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce. OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC. PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence. RESULTS: In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots. CONCLUSIONS: No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

Developing a comprehensive molecular subgrouping model for cervical cancer using machine learning.

This study developed a molecular classification model for cervical cancer using machine learning, integrating prognosis related biomarkers with clinical features. Analyzing 281 specimens, 27 biomarkers were identified, associated with recurrence and treatment response. The model identified four molecular subgroups: group 1 (OALO) with Overexpression of ATP5H and LOw risk; group 2 (LASIM) with low expression of ATP5H and SCP, indicating InterMediate risk; group 3 (LASNIM) characterized by Low expression of ATP5H, SCP, and NANOG, also at InterMediate risk; and group 4 (LASONH), with Low expression of ATP5H, and SCP, Over expression of NANOG, indicating High risk, and potentially aggressive disease. This classification correlated with clinical outcomes such as tumor stage, lymph node metastasis, and response to treatment, demonstrating that combining molecular and clinical factors could significantly enhance the prediction of recurrence and aid in personalized treatment strategies for cervical cancer.

Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women.

BACKGROUND: Distinguishing ovarian cancer from other gynecological malignancies is crucial for patient survival yet hindered by non-specific symptoms and limited understanding of ovarian cancer pathogenesis. Accumulating evidence suggests a link between ovarian cancer and deregulated lipid metabolism. Most studies have small sample sizes, especially for early-stage cases, and lack racial/ethnic diversity, necessitating more inclusive research for improved ovarian cancer diagnosis and prevention. METHODS: Here, we profiled the serum lipidome of 208 ovarian cancer, including 93 early-stage patients with ovarian cancer and 117 nonovarian cancer (other gynecological malignancies) patients of Korean descent. Serum samples were analyzed with a high-coverage liquid chromatography high-resolution mass spectrometry platform, and lipidome alterations were investigated via statistical and machine learning (ML) approaches. RESULTS: We found that lipidome alterations unique to ovarian cancer were present in Korean women as early as when the cancer is localized, and those changes increase in magnitude as the diseases progresses. Analysis of relative lipid abundances revealed specific patterns for various lipid classes, with most classes showing decreased abundance in ovarian cancer in comparison with other gynecological diseases. ML methods selected a panel of 17 lipids that discriminated ovarian cancer from nonovarian cancer cases with an AUC value of 0.85 for an independent test set. CONCLUSIONS: This study provides a systemic analysis of lipidome alterations in human ovarian cancer, specifically in Korean women. IMPACT: Here, we show the potential of circulating lipids in distinguishing ovarian cancer from nonovarian cancer conditions.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.