Marcin Bobiński

Advances in Systemic Therapy for Ovarian Cancer Over the Past Decade: A Clinical and Molecular Perspective

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality, with high rates of recurrence and chemoresistance. Advances in understanding the molecular biology of EOC, particularly BRCA mutations and homologous recombination deficiency (HRD), have led to more targeted therapies. This review provides an updated summary of systemic treatments for EOC, with an emphasis on personalized therapy approaches and emerging therapeutic strategies. This review synthesizes current research and clinical trials investigating molecular pathways in EOC, particularly focusing on HRD, BRCA status, and their impact on treatment selection, including the use of PARP inhibitors, chemotherapy, and immunotherapy. Recent studies demonstrate that PARP inhibitors, particularly in patients with BRCA mutations or HRD-positive tumors, have resulted in improved progression-free survival. Ongoing trials combining PARP inhibitors with immunotherapy and angiogenesis inhibitors show promise in extending treatment efficacy and overcoming resistance mechanisms. Despite these advances, recurrence remains common among patients with advanced ovarian cancer. The integration of genetic and molecular insights into systemic treatment is crucial in advancing the management of EOC. While targeted therapies have significantly improved patient outcomes, further research is necessary to optimize treatment strategies and address therapeutic resistance, particularly in patients with non-BRCA-mutated EOC. The future of EOC treatment lies in refining personalized therapies and improving predictive biomarkers for better patient selection.

Health care organization for gynecologic oncology patients fleeing Ukraine: Insights from the European Network of Young Gyne Oncologists survey during the first six months of the military conflict

The Russian invasion of Ukraine in February 2022 caused a mass displacement of over 6 million people, including many women requiring urgent medical care, such as those with gynecologic malignancies. The disruption of cancer treatment in conflict zones poses critical challenges because timely oncologic care is vital for patient survival. This study, conducted by the European Network of Young Gynecologic Oncologists, aimed to assess the health care responses provided to Ukrainian gynecologic oncology patients across European countries during the first 6 months of the conflict. A cross-sectional survey was distributed to European Network of Young Gynecologic Oncologists members between July and August 2022, gathering insights from health care providers about their experiences in managing Ukrainian gynecologic oncology patients. The survey explored the medical needs of displaced patients, challenges encountered, and the resources available. Descriptive statistics were used for data analysis. During the study period, approximately 400 gynecologic oncology patients fleeing Ukraine received care in 38 European health care centers represented by the respondents (N = 50). Surgical interventions (54%), chemotherapy (40%), and specialist consultations (32%) were identified as the most common medical needs. The key barriers to care included language difficulties (44%), lack of previous medical documentation (40%), and inconsistencies in treatment protocols between centers. Psychological support was notably insufficient, with 36% of respondents reporting a lack of adequate resources for addressing mental health needs. The study identifies critical barriers to the continuity of gynecologic oncology care for displaced patients during humanitarian crises. Addressing language barriers, ensuring access to patient medical histories, and providing psychological support are essential to improve care for refugees. The findings underscore the importance for international collaboration and the development of robust frameworks for delivering oncologic care during crises.

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights.

Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.