Summary: Ovarian cancer (OC) management presents a challenging scenario in clinical practice due to its late diagnosis, high recurrence rate, and dismal 5‑year survival rate of 45%—especially in platinum-resistant cases. Antibody–drug conjugates (ADCs) are novel drugs that enable the selective delivery of potent cytotoxic agents directly to tumor cells, thereby maximizing treatment effectiveness while minimizing harm to healthy cells. Recent studies have shown promising results in this regard. Mirvetuximab soravtansine achieved remarkable results in the MIRASOL trial, suggesting it as a potential new standard of care for folate receptor-α-positive platinum-resistant OC treatment. Furthermore, trastuzumab deruxtecan demonstrated promising results in the PanTumor02 trial, showing clinically meaningful efficacy across a broad spectrum of HER2-positive solid tumors. This review article explores the current state of ADCs in ovarian cancer and their potential to improve outcomes in patients with recurrent ovarian cancer, especially in the platinum-resistant setting.

Introduction: Persistent tumor after combined chemoradiation for locally advanced cervical cancer is an established prognostic factor. Detection may include magnetic resonance imaging, positron emission tomography (PET) combined with CT scan, ultrasound, or biopsies; however, no agreement about the best method and time point has been reached. In our institution, a standardized biopsy protocol of at least four punch biopsies is routinely performed at the last brachytherapy with re‐biopsies 6 weeks later in cases not showing histologic complete response (hCR). This study aims to assess the prognostic relevance of these biopsies, especially with respect to the time point of hCR. Material and Methods: This investigation was a retrospective single‐center observational cohort study that included all patients treated for locally advanced or node‐positive cervical cancer with combined chemoradiation at the University Hospital Innsbruck between 2008 and 2023. Patients with a hCR at the end of radiotherapy were classified as primary negative and otherwise as primary positive. Primary positive patients that achieved complete response at a control biopsy 6 weeks later were classified as secondary negative, and the remaining patients with residual tumor as secondary positive. Progression‐free survival (PFS) and overall survival (OS) were compared between all these groups. Results: We included 184 patients in this study, from which 46 (25%) were classified as primary positive. These patients experienced a significantly worse PFS compared to primary negative patients ( p = 0.008, HR = 2.03, 95% CI [1.20, 3.45]). The difference in PFS was also evidenced when comparing primary negative patients to those who had a hCR 6 weeks after radiotherapy (secondary negative) ( p = 0.018, HR = 2.00, 95% CI [1.13, 3.56]). However, in primary positive patients, OS was not significantly reduced ( p = 0.29, HR = 1.45, 95% CI [0.73, 2.86]). Conclusions: Early response evaluation using punch biopsies at the time of the last brachytherapy can identify patients with residual tumor, which exhibit a statistically significant and clinically meaningful risk of disease progression. This risk was not reversed even in the case of a delayed hCR 6 weeks after completion of chemoradiation.

Objective The use of conventional doxorubicin in combination with trabectedin leads to a considerable prolongation of progression-free survival in the treatment of uterine sarcomas but is associated with dose-limiting toxicities. Significant progression-free survival improvement was recently obtained through treatment prolongation with trabectedin single agent. We hypothesize that the therapeutic index of pegylated liposomal doxorubicin combined with trabectedin could be superior to the combination with conventional doxorubicin due to a more favorable toxicity profile. Methods In this retrospective cohort study, the clinical outcome was analyzed in patients with advanced or recurrent uterine sarcomas with measurable disease treated with pegylated liposomal doxorubicin 30 mg/m² plus trabectedin 1.5 mg/m² given every 3 weeks between January 2011 and April 2023 at the University Hospital in Innsbruck. Response evaluation was done every three cycles. Toxicity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria on 107 administered cycles. Results A total of 21 patients were included in the study. In 67% (n=14) of patients, pegylated liposomal doxorubicin plus trabectedin was given as first-line treatment. One patient (5%) achieved a complete response and four (19%) a partial response, resulting in an objective response rate of 24%. Four other patients (19%) had stable disease. The median duration of the response was 14 months (range 3–74). Progression was recorded in 12 patients (57%). Median progression-free survival was 6 months (95% CI 1 to 11 months), while median overall survival was 26 months (95% CI 9 to 43 months). A median of 6 (range 1–11) cycles per patient were administered. Regarding grade ≥3 toxicity, neutropenia was recorded in 29%, thrombocytopenia in 14%, and febrile neutropenia in 19% of patients. Hematologic toxicity was the most frequent reason for dose delays (n=16) and dose reductions (n=5). Conclusion Our study found an overall clinical benefit for the combination of pegylated liposomal doxorubicin plus trabectedin in metastatic uterine sarcomas of 43% and appears to exhibit a favorable toxicity profile which allows prolonged administration of this regimen.

Background/Objectives: This study aimed to demonstrate the higher efficacy of cryotherapy in temperature reduction in the upper compared to the lower extremity when used for prevention of chemotherapy-induced peripheral neuropathy (CIPN). Methods: This study was conducted between May 2020 and January 2023 at the Department of Obstetrics and Gynecology at the Medical University of Innsbruck. The analysis included all patients from the CROPSI study who received cryotherapy on their upper (UEX) and lower extremity (LEX) and had completed all assessments from start to end of chemotherapy as well as follow-up. The assessments included temperature measurements and neurological tests during CT and at follow-up after completion of CT. Results: Of the 97 patients recruited in the study, 50 completed all assessments and were therefore included in this analysis. Cryotherapy was more effective when cooling was applied to the upper extremity compared to the lower. On the upper extremity, cryotherapy achieved a cooling effect of 12.5 °C compared to 9.6 °C on the lower extremity (p < 0.001). Patients scored better in both neurological tests on their upper extremity compared to lower. Regarding side effects, there was no significant difference between upper and lower extremities. No severe side effects were reported for either location. Conclusions: Our study suggests that currently available devices for continuous cooling for cryotherapy are significantly more effective on the upper extremity.

Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across three TP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC. Methods: RNA-sequencing and clinical data of 603 patients from The Cancer Genome Atlas were analyzed. DC subset abundance was assessed for cDC progenitor, conventional DC type 1 (cDC1), conventional DC type 2 (cDC2), plasmacytoid DC (pDC), and mature DC by marker gene signatures. Differences in DC scores across tumors were analyzed using Kruskal–Wallis. Survival analyses were performed using Kaplan–Meier and Cox regression. Spearman’s correlation was used to determine associations between parameters. Results: HGSOC showed the lowest pDC abundance, yet high pDC scores were independently associated with shorter PFS (HR = 1.55, 95% CI: 1.05–2.27; p = 0.027), representing the only DC-subset-related prognostic signal observed across tumor types. pDCs correlated positively with neutrophils and negatively with monocytes, and pDCs, cDC2s, and cDC progenitors correlated inversely with TMB. No consistent link was found between pDC and TP53 mutation classes. However, tumors harboring specific TP53 mutations within established hotspot regions exhibited significantly lower pDC levels (p = 0.015). Conclusions: Our findings reveal distinct DC infiltration patterns and highlight the immunological vulnerability of TP53-mutated HGSOC. pDCs appear to exert a tumor-promoting, immune-evasive role, suggesting that DC function depends on their programming and tumor context. Selective targeting of DC subsets may offer novel therapeutic opportunities in TP53-mutated, low-TMB cancers.

Definitive radiochemotherapy with external beam radiotherapy and brachytherapy is standard for locally advanced cervical cancer (LACC). Advanced techniques