Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting.

Background/Objectives: Fertility-sparing surgery (FSS) is a standard practice for managing early stage cervical cancer, yet significant variation exists in clinical approaches worldwide. Our objective was to ascertain current practices and preferences for cerclage use among expert centers globally regarding FSS in patients with early stage cervical cancer. Methods: We conducted a cross-sectional survey from May to July 2023 involving expert centers identified through their scientific contributions and participation in international workgroups and conferences.. The survey, comprising 27 questions, evaluated existing practices in FSS. Results: Out of the centers surveyed, 21 (36.2%) gynecologic oncologists responded. For tumors 2 cm, 47.6% utilized neoadjuvant chemotherapy before trachelectomy. Others did not offer FSS or performed an abdominal radical trachelectomy. Over time, there has been a shift towards less radical surgeries for tumors <2 cm and increased use of neoadjuvant chemotherapy for larger tumors. Some abandoned the minimally invasive surgical approach. Nearly all experts (90.5%) placed a cerclage immediately following trachelectomy. Conclusions: The majority of experts opt for radical trachelectomy in early stage cervical cancer, with immediate cerclage placement being a common practice. However, considerable international variations highlight the urgent need for standardized guidelines and further research to optimize treatment strategies, balancing oncological safety with fertility outcomes.

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capability. In other intra-abdominal surgical specialties, CPET outcomes are predictive of operative morbidity. However, in ovarian cancer surgery, its predictive value remains unknown. In this study, we evaluated the association between CPET performance and surgical morbidity in ovarian cancer patients. Secondly, we assessed the association between CPET performance and other surgical outcomes (i.e., hospital stay, readmission and residual disease). This was a retrospective cohort study of patients undergoing primary surgery for ovarian cancer between 2020 and 2023. CPET performance included peak oxygen uptake (VO₂ max), ventilatory efficiency (VE/VO₂) and anaerobic threshold. Outcomes were operative morbidity and included intra- and postoperative complications (Clavien–Dindo), hospital stay, readmission within 30 days and residual disease. A total of 142 patients were included. A lower VO₂ peak and a higher VE/VCO₂ were both associated with the occurrence of postoperative complications, and a poorer anaerobic threshold was associated with more transfusions. VE/VCO₂ remained significantly associated after multivariate analysis (p = 0.035). None of the CPET outcomes were associated with length of stay, readmission or residual disease. In conclusion, VE/VCO₂ was significantly associated with an increased risk of all-cause postoperative complications in ovarian cancer patients undergoing primary surgery.

The primary aim of the present study was to investigate the prognostic impact (defined as disease-free—DFS and overall survival—OS) of the ultrasound scan tumor parameters, patients’ anthropometric parameters, and their combination in early-stage cervical cancer. The secondary aim was to assess the relation between ultrasound characteristics and pathological parametrial infiltration. This is a retrospective, single-center, observational cohort study. Consecutive patients with clinical FIGO 2018 stage IA1–IB2 and IIA1 cervical cancer who underwent preoperative ultrasound examination and radical surgery between 02/2012 and 06/2019 were included. Patients who underwent neo-adjuvant treatment, fertility sparing surgery, and pre-operative conization were excluded. Data from 164 patients were analyzed. Body mass index (BMI) ≤20 Kg/m² (p < 0.001) and ultrasound tumor volume (p = 0.038) were related to a higher risk of recurrence. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI were significantly related to a higher risk of recurrence (p = 0.011, p = 0.031, and p = 0.017, respectively). The only anthropometric characteristic related to a higher risk of death was BMI ≤20 Kg/m² (p = 0.021). In the multivariate analysis, the ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter (with 37 as the cut-off) was significantly associated with pathological microscopic parametrial infiltration (p = 0.018). In conclusion, a low BMI was the most significant anthropometric biomarker impairing DFS and OS in patients with apparent early-stage cervical cancer. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI significantly affected DFS but not OS. The ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter was related to parametrial infiltration. These novel prognostic parameters may be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer.