Irina Tsibulak

Global practice patterns of sentinel lymph node biopsy in endometrial cancer: a survey from the European Network of Young Gynecologic Oncologists (ENYGO)

This survey aimed to evaluate trends in sentinel lymph node (SLN) biopsy for endometrial cancer among members of the European Society of Gynecologic Oncology (ESGO) and the International Gynecologic Cancer Society (IGCS). We conducted an online cross-sectional survey among gynecologic oncologists over 40 years of age consisting of 30 questions. It was distributed to ESGO and IGCS members via Survey Monkey and Qualtrics between September and December 2022. Surveys were excluded in the analysis if >50% of questions were incomplete. Statistical analysis, performed with SPSS version 27.0. A total of 302 (70.2%) of 430 participants completed the survey, with 159 (52.6%) affiliated with ESGO and 143 (47.4%) with IGCS. The majority were male 206 (68.2%), and 170 (56.3%) were based in Europe. Most respondents (n = 261, 86.4%) were certified gynecologic oncologists. Indocyanine green was the most common tracer used (n = 234, 77.5%), with higher rates of blue dye injections among IGCS respondents (p = .002). The predominant injection volume was 4 cm This study showed significant variations in SLN biopsy practices for endometrial cancer, underscoring the need for global standardization through harmonized guidelines, consistent training, and international collaboration to improve staging accuracy and patient outcomes.

Biopsy‐proven residual cervical cancer at the end of combined chemoradiation predicts poor outcome—Retrospective single‐center cohort study

Abstract 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.

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial

The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy. Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival. Other variables included age, race, performance status, body mass index, stage, histologic type and grade, diagnostic procedure, lymphovascular space invasion before surgery and on final pathology, lymph node status, residual disease, and lesions >2 cm on final pathology. A total of 338 patients underwent simple hysterectomy. Of those, 281 (83%) were performed by minimally invasive surgery and 57 (17%) by open surgery. With a median follow-up of 4.5 years, a total of 12 (4.3%) recurrences were observed in 281 patients having simple hysterectomy by minimally invasive surgery versus 3 in 57 (5.3%) having open surgery (p = .73 from Fisher exact test). Although not randomized, the 2 groups were comparable except for histology and residual disease in the hysterectomy specimen. Patients with minimally invasive surgery had more adenocarcinoma and less adenosquamous compared to open surgery (35.9% versus 22.9% and 3.6% versus 14%, respectively; p = .005). Significantly fewer patients treated by minimally invasive surgery had residual disease in the hysterectomy specimen compared to open surgery (43.1 versus 57.9%; p = .04). No statistically significant difference between minimally invasive and open surgery in pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, or overall survival was found. Our data indicate no statistical evidence that minimally invasive surgery is associated with poorer clinical outcomes for patients meeting the SHAPE criteria who underwent simple hysterectomy. Because the surgical approach was not a randomization factor, a large prospective trial is needed to confirm our results before a routine simple hysterectomy by minimally invasive surgery can be recommended.

Tumor biology and impact on timing of surgery in advanced epithelial ovarian cancer

Recent advances in epithelial ovarian cancer research have led to a shift in treatment strategy from the traditional 'organ-centric' to a personalized tumor biology-based approach. Nevertheless, we are still far behind an individualized approach for cytoreductive surgery in advanced ovarian cancer; the gold standard of primary treatment in combination with systemic agents. The impact of tumor biology on treatment sequence is still understudied. It is obvious, that response to platinum-based therapy is crucial for the success of neoadjuvant chemotherapy. While high-grade serous and endometrioid tumors are commonly characterized by an excellent response, other subtypes are considered poor responders or even resistant to platinum. Undoubtedly, neoadjuvant chemotherapy may filter poor responders, but to date, we still do not have appropriate alternatives to platinum-based chemotherapy in the neoadjuvant and first-line setting and 'adjusting' systemic treatment in cases of poor response to neoadjuvant chemotherapy remains elusive. Primary cytoreduction is still considered the gold standard for fit patients with operable tumor dissemination patterns, especially for those ovarian cancer subtypes that show poor response to platinum. Of note, even in high-grade serous ovarian cancer, approximately 20% of tumors are platinum resistant and the benefit of neoadjuvant chemotherapy in this subgroup is limited. Interestingly, these tumors are associated with the mesenchymal molecular subtype, which in turn correlates with high risk for residual disease after cytoreductive surgery and is characterized by the worst survival outcome among high-grade ovarian cancers. This leads to the question, how to best tailor surgical radicality at the onset of patients' presentation to avoid associated morbidity and with a moderate benefit. Here, we give an overview of recent advances of interaction between tumor biology and surgery in ovarian cancer.

Clinical impact of BRCA2 mRNA expression in high-grade serous ovarian cancer: validation using the TCGA cohort

Austria-based real-world data on bevacizumab in newly diagnosed epithelial ovarian cancer

Summary Background Front-line maintenance therapy with bevacizumab demonstrates high efficacy and safety in epithelial ovarian cancer, as already shown in large phase III trials; however, the corresponding study populations are often not fully representative of patients in clinical routine. In this Austria-based multicenter study, we aimed to explore the real-world outcomes of bevacizumab use in front-line treatment of ovarian cancer, including patients with comorbidities and poor performance status. Patients This study is an open label single arm multicenter noninterventional trial and included patients with newly diagnosed advanced epithelial ovarian cancer, who were treated with platinum-based chemotherapy and were candidates for receiving bevacizumab according to the product label. Data collection started in the third quarter of 2012 and ended in the third quarter of 2018. Results In this study 50 patients were included and 575 adverse events were reported for 90% of the patients. The majority of the adverse events were mild (47%) or moderate (37%). The most common adverse events were hypertension (60%), anemia (48%), leukopenia (42%), thrombocytopenia (36%), neutropenia (36%) and proteinuria (26%). A relation to bevacizumab was documented only for 10.3% of all adverse events. In almost 50% of all adverse events, no intervention was needed and bevacizumab treatment had to be interrupted only in 3.3% of all adverse events. The median progression-free survival was 1.3 years (95% CI 1.1–1.8). Conclusion The routine use of front-line bevacizumab for advanced ovarian cancer is associated with high efficacy comparable with that obtained in randomized phase III clinical trials; however, hypertension and proteinuria were reported significantly more often in our Austria-based real-world population.

Global survey on training and practice in sentinel lymph node mapping for endometrial and cervical cancer among early-career gynecologic oncologists

This survey was designed to evaluate exposure to sentinel mapping for cervical and endometrial cancers in addition to the quality and availability of surgical training in sentinel procedures around the world. Furthermore, we aimed to identify obstacles in surgical training in the sentinel procedure to support the adoption of this technique in clinical practice. A 52-item survey was developed and computed using Qualtrics XM and SurveyMonkey software. The target population were members of the European Society of Gynaecological Oncology and the International Gynecological Cancer Society aged ≤40 years. The study invitation was disseminated within both organizations' database. The survey hyperlink was active between September and December 2022. Respondents using the same Internet Protocol address were excluded to avoid duplication of responses. Responses to <50% questions were excluded. Overall, 238 respondents joined the survey, and 182 (76.5%) provided answers that met the inclusion criteria. Sentinel mapping was implemented for a longer period and used more frequently in endometrial than in cervical carcinoma; 55% of the responders were initially trained in systematic lymph node dissection, and 22% were not yet trained in any lymph node staging. The main challenges in applying sentinel procedure for early-career gynecologic oncologists were no access to hands-on training (n = 22, 12.1%) and no clinical routine in performing systematic pelvic (n = 15, 8.2%) and para-aortic (n = 35, 19.2%) lymph node dissection in case of failed mapping. Although sentinel lymph node biopsy is integrated in cervical and endometrial cancer guidelines, a significant number of institutions do not implement this procedure in clinical routine, and 22% of early-career gynecologic oncologists are not trained in any type of surgical lymph node staging. Support for sentinel mapping in national guidelines and guided training opportunities are needed to apply this method globally.