Stephan Polterauer

Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents.

The systemic immune-inflammation index (SII) is an independent prognostic parameter of survival in patients with invasive vulvar cancer

To assess the prognostic value of the systemic immune-inflammation index (SII) in patients with vulvar cancer. Data of 130 consecutive patients who underwent primary surgical resection for vulvar cancer at the Medical University of Vienna between 1999 and 2018 was retrospectively analyzed. The SII was defined as platelets × neutrophils/lymphocytes as previously described. Its prognostic value on disease-specific survival (DSS) and overall survival (OS) was evaluated by univariate log-rank tests and multivariable cox regression models. Prediction accuracy was assessed by receiver operating characteristics curves and Youden's J statistics. A Hosmer-Lemeshow test was performed to confirm the model's goodness of fit. A pre-therapeutic high serum SII (>866.4) was associated with advanced International Federation of Gynecology and Obstetrics (FIGO)-stage. In univariate survival analysis, a high SII was associated with both DSS (p<0.001) and OS (p=0.001). A multivariate cox regression model confirmed the prognostic value of SII regarding DSS (p<0.001) and OS (p=0.014) independently from patients' age and FIGO stage. Pretherapeutic SII may serve as a promising predictor for survival in patients with vulvar cancer. After clinical validation, the SII may be used to improve both pre-treatment patient risk stratification and patient counseling.

Cost-utility-analysis of molecular-integrated-profile for women with (high)intermediate risk endometrial cancer - PORTEC-4a an international, randomised, phase 3 trial.

The international PORTEC-4a trial demonstrated that individualised adjuvant treatment for women with (high)intermediate risk endometrial cancer (HIR-EC), guided by a molecular-integrated-risk-profile, achieves similar high local tumour control, while nearly half of patients were spared adjuvant treatment. Although determination of the molecular-integrated-profile increases diagnostics costs due to additional immunohistochemistry and DNA-sequencing, these costs may be offset by savings on other care and improved patient outcomes. Women with early-stage HIR-EC eligible for the PORTEC-4a trial, were randomised (2:1) to either adjuvant treatment according to their molecular-integrated-profile or standard vaginal brachytherapy (VBT). EC-related costs were evaluated from a healthcare perspective over a three-year follow-up period. Costs were related to quality-adjusted-life-years (QALYs) using the EORTC-QLU-C10D instrument. T-test compared mean QALYs and costs, with multiple imputation for missing data. All 564 patients were included in the cost-utility-analysis; 367 in molecular-profile arm and 197 in standard arm. QALYs were comparable (p = 0.58). Total healthcare costs were somewhat, but not significantly, lower in molecular-profile arm compared to standard arm (€11,898 vs €13,047, p = 0.11). Costs spent up until recurrence were significantly lower in molecular-profile arm (€9,995 vs €11,926, p < 0.01), while there was no significant difference in treatment for recurrence (€1,903 vs €1,121, p = 0.17). At a willingness-to-pay threshold of €20,000/QALY, the strategy as proposed by PORTEC-4a was 89% likely to be cost-effective. Individualised adjuvant treatment based on a molecular-integrated-profile was more cost-effective than standard VBT for patients with HIR-EC. These results further support the implementation of the molecular-integrated-profile in routine clinical practice.