Clinical factors predicting objective response to bevacizumab-based chemotherapies in advanced and recurrent epithelial ovarian cancer.

BACKGROUND: Bevacizumab-based chemotherapies are commonly administered in the treatment of patients diagnosed with epithelial ovarian cancer (EOC). The primary aim of this study was to assess the factors that predict the objective response to bevacizumab-based therapies in cases of advanced and recurrent EOC. METHODS: The retrospective data of 264 patients with EOC from the current study were collected between 2009 and 2022 at our clinic. Survival analyses were conducted utilizing the Kaplan-Meier method and the log-rank test. Binary logistic regression analysis was employed to assess the factors predicting the objective response. RESULTS: A predominant subset of patients (83%) presented with serous adenocarcinoma, exhibiting a high-grade differentiation at 87%. The vast majority (80%) of the cohort experienced disease recurrence. Three-fourths of the cases received bevacizumab in combination with platinum-based doublet chemotherapy. In the multivariate analysis, clinical factors such as a disease recurrence (P=0.031), upfront tumor debulking surgery before bevacizumab (P=0.009), doublet chemotherapy (P=0.003), and the presence of malignant pleural effusion (P=0.024) emerged as significant determinants influencing the Objective Response Rate (ORR) in patients undergoing bevacizumab-based therapy. The ORR was 67.5% (N.=178), comprising 15.2% complete responses (N.=40) and 52.1% partial responses (N.=138). The median Progression-Free Survival (PFS) and Overall Survival (OS) were estimated at 10.2 months (95% CI, 8.60-11.9) and 20.1 months (95% CI, 16.0-24.2), respectively. CONCLUSIONS: The responses to bevacizumab-based chemotherapies could be predict by the presence of malignant pleural effusion, disease recurrence, upfront tumor debulking surgery and doublet regimen of chemotherapy.

Postoperative reproductive outcomes in patients with endometriosis-associated infertility: A single-centre retrospective study.

OBJECTIVES: Endometriosis is a chronic inflammatory disease known to contribute to infertility. Laparoscopic excision of endometriotic lesions represents a standard treatment modality for symptomatic women. Our study aims to assess the potential benefits of laparoscopic excision of endometriosis in patients experiencing infertility associated with the condition, as well as to define the clinical factors that may impact the cumulative pregnancy rate. DESIGN: In this retrospective analysis, a total of 102 patients with endometriosis-related infertility were enrolled. MATERIALS, SETTING, METHODS: All participants underwent reproductive surgery and were then categorized into two groups: those who conceived were assigned to Group A, while those who did not were assigned to Group B. The correlation between clinical factors and pregnancy rate was assessed using the log rank test, and both univariate and multivariate analyses were conducted utilizing the Cox regression model. Results The median age of the patients was 33.5 years, with a median follow-up duration of 70 months. Throughout the study period, 71 patients (69.6%) conceived (Group A), while the remaining 31 patients (30.4%) did not conceive (Group B), irrespective of the use of Assisted-Reproduction Technologies. The Cox regression model revealed that factors such as the duration of infertility, presence of deep infiltrating endometriosis, bowel endometriosis, rASRM stages, pelvic adhesions, and recurrent disease negatively impacted postoperative conception rates. Conversely, complete excision and coagulation of endometriotic lesions, as well as ablation of ovarian endometriomas, emerged as independent positive predictive factors for postoperative clinical pregnancy. LIMITATIONS: The retrospective design of the study, as well as a small number of patients. CONCLUSIONS: Complete excision of endometriosis during reproductive surgery may yield a positive effect and optimize the likelihood of pregnancy in patients with endometriosis-related infertility.

Concepts of lines of therapy in cancer treatment: findings from an expert interview-based study.

OBJECTIVE: The concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis. RESULTS: Most interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).

Prognostic impact of metabolic syndrome in patients with primary endometrial cancer: a retrospective bicentric study.

PURPOSE: Endometrial cancer (EC) is the most common gynaecological cancer. Its incidence has been rising over the years with ageing and increased obesity of the high-income countries' populations. Metabolic syndrome (MetS) has been suggested to be associated with EC. The aim of this study was to assess whether MetS has a significant impact on oncological outcome in patients with EC. METHODS: This retrospective study included patients treated for EC between January 2010 and December 2020 in two referral oncological centers. Obesity, arterial hypertension (AH) and diabetes mellitus (DM) were criteria for the definition of MetS. The impact of MetS on progression free survival (PFS) and overall survival (OS) was assessed with log-rank test and Cox regression analyses. RESULTS: Among the 415 patients with a median age of 64, 38 (9.2%) fulfilled the criteria for MetS. The median follow-up time was 43 months. Patients suffering from MetS did not show any significant differences regarding PFS (36.0 vs. 40.0 months, HR: 1.49, 95% CI 0.79-2.80 P = 0.210) and OS (38.0 vs. 43.0 months, HR: 1.66, 95% CI 0.97-2.87, P = 0.063) compared to patients without MetS. Patients with obesity alone had a significantly shorter median PFS compared to patients without obesity (34.5 vs. 44.0 months, P = 0.029). AH and DM separately had no significant impact on PFS or OS (p > 0.05). CONCLUSION: In our analysis, MetS in patients with EC was not associated with impaired oncological outcome. However, our findings show that obesity itself is an important comorbidity associated with significantly reduced PFS.

The clinical relevance of fractional curettage in the diagnostic management of primary endometrial cancer.

OBJECTIVE: Hysteroscopy and fractional curettage are commonly utilized techniques for the diagnosis of postmenopausal abnormal uterine bleeding (AUB) and histopathological verification of primary endometrial cancer (EC). This study delves into the clinical significance of procuring preoperative endocervical tissue in conjunction with corpus fractions through fractional curettage. DESIGN: This retrospective study encompassed a cohort of 84 patients diagnosed with T1-stage endometrial cancer (EC) and 55 patients diagnosed with T2-stage EC, who underwent primary treatment between the years 2011 and 2021 at the University Hospital Frankfurt or Jung-Stilling Hospital Siegen. MATERIALS, SETTING, METHODS: Among the postoperative T2-stage EC patients, a stratification was performed based on preoperative endocervical curettage (ECC) results obtained through fractional curettage. Categorical and continuous variables were compared utilizing the Pearson-Chi-square test, while for multivariate analyses and regression modeling, the Kaplan-Meier method and Cox regression models were respectively employed. RESULTS: The median age of patients with pT2-stage EC was 64 years (range: 38 to 85). A predominant majority of these patients exhibited the endometrioid subtype of EC (90.9%). Upon conducting comparative analysis between groups, a notably higher frequency of laparotomies was observed (p=0.002) among patients in whom preoperatively detected positive endocervical curettage (ECC) was evident. The detection performance of fractional curettage in identifying positive ECC yielded a sensitivity of 70.9% and a specificity of 73.8%. In multivariate analysis, age at diagnosis (p=0.022), positive ECC observed during fractional curettage (p=0.036), and the FIGO stage (p=0.036) emerged as prognostic determinant for progression-free survival (PFS). Independent prognostic factors for overall survival (OS) were age at diagnosis (p=0.003), positive ECC (p=0.008), histological grading (p=0.016), and the FIGO stage (p=0.022). A significant difference in OS was evident between patients characterized by preoperative negative ECC and those displaying positive ECC (81.8 vs. 59.5 months, p=0.019). LIMITATIONS: The retrospective design of the study, as well as a small number of patients. CONCLUSIONS: Preoperative determination of endocervical involvement of primary T2-stage EC could be a prognostic indicator in decision-making to treat EC. The conduct of prospective trials is necessary to definitively establish the routine application and associated benefits of fractional curettage in the context of primary endometrial cancer.

Management of Patients with Hypersensitivity to Platinum Salts and Taxane in Gynecological Cancers: A Cross-Sectional Study by the European Network of Young Gynaecologic Oncologists (ENYGO).

Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey, and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n = 103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Premedication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1-2 HSRs to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3-4 HSRs to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSRs in gynecologic cancer. Our study showed that HSRs in gynecologic cancer are common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSRs in gynecologic cancer was highlighted.

Best original research presented at the 24th European Congress on Gynaecological Oncology-Best of ESGO 2023.

The 'Best of ESGO 2023' manuscript comprises a compilation of the best original research presented during the European Society of Gynaecologic Oncology annual congress held in Istanbul between September 28 and October 1, 2023. Out of 1030 submitted abstracts, 33 studies presented during the Best Oral Sessions, Mini Oral Sessions, and Young Investigator Session were selected by the ESGO Abstract Committee and the European Network of Young Gynae Oncologists (ENYGO) authors. There was a strong focus on surgical de-escalation, immunotherapy, maintenance therapy, and molecular profiling in gynecologic oncology. With this manuscript, ENYGO and ESGO aim to disseminate the valuable research results to readers interested in our field.

Pregnancy after laparoscopic surgery for endometriosis: How long should we wait? A retrospective study involving a long-term follow up at a university endometriosis center.

OBJECTIVE: To find the factors that influence the time until pregnancy after laparoscopic intervention and to evaluate the proper time to start assisted reproductive therapy (ART). METHODS: This is a retrospective analysis that includes a prospective evaluation of patients with infertility and with a diagnosis of endometriosis. A subgroup of patients who desired to be pregnant after laparoscopic intervention (102 patients) was followed up for 36-197 months after the surgery. RESULTS: In this study, 71 (69.9%) and 60 (58.8%) of the patients achieved pregnancy and live birth, respectively. In the group of patients who became pregnant, the duration of infertility was significantly lower (2.7 ± 2.1 years vs. 4.7 ± 3.2 years). The median time until pregnancy after laparoscopic intervention was 8 months (the average was 10 months). After 38 months, no pregnancy occurred. CONCLUSION: In the group of patients with endometriosis and infertility, the first 12 months were the optimal time for pregnancy. For women with revised American Society for Reproductive Medicine classification of endometriosis (rASRM) stages I and II, spontaneous pregnancy can probably be delayed for up to 24 months, but in patients with rASRM stages III and IV, ART may be considered after 12 months. The gynecologist must be careful about the timing of further interventions after the operation.

Synergistic Sensitization of High-Grade Serous Ovarian Cancer Cells Lacking Caspase-8 Expression to Chemotherapeutics Using Combinations of Small-Molecule BRD4 and CDK9 Inhibitors.

Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a combination of primary chemotherapy with platinum and taxane agents. Tumor recurrence following first-line chemotherapy with Carboplatin and Paclitaxel is detected in 80% of advanced ovarian cancer patients, with disease relapse occurring within 2 years of initial treatment. Platinum-resistant ovarian cancer is one of the biggest challenges in treating patients. Second-line treatments involve PARP or VEGF inhibitors. Identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have determined that low Caspase-8 expression in ovarian cancer patients leads to poor prognosis. High-Grade Serous Ovarian Cancer (HGSOC) cells lacking Caspase-8 expression showed an altered composition of the RNA Polymerase II-containing transcriptional elongation complex leading to increased transcriptional activity. Caspase-8 knockout cells display increased BRD4 expression and CDK9 activity and reduced sensitivities to Carboplatin and Paclitaxel. Based on our work, we are proposing three potential therapeutic approaches to treat advanced ovarian cancer patients who exhibit low Caspase-8 expression and resistance to Carboplatin and/or Paclitaxel-combinations of (1) Carboplatin with small-molecule BRD4 inhibitors; (2) Paclitaxel with small-molecule BRD4 inhibitors, and (3) small-molecule BRD4 and CDK9 inhibitors. In addition, we are also proposing two predictive markers of chemoresistance-BRD4 and pCDK9.

The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.

Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration- and cell-invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8-deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.

Sequential Targeting of PLK1 and PARP1 Reverses the Resistance to PARP Inhibitors and Enhances Platin-Based Chemotherapy in BRCA-Deficient High-Grade Serous Ovarian Cancer with KRAS Amplification.

Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.

New Insights on the Minimal-Invasive Therapy of Cervical Cancer.

OBJECTIVE: The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion involves both prospective and retrospective data and general and theoretical considerations. We wanted to look at the data available today and review the different opinions, offering an impartial assessment of the ongoing controversy. METHODS: The available literature was reviewed, focusing on articles arguing for and against minimally invasive surgery in cervical cancer. We tried to avoid any fundamental bias, as is often evident in the available reviews on the subject. Literature both before and after the 2018 publication was taken into consideration. RESULTS: As is usual in discussions of concepts, the literature that is now available provides arguments for both sides of this challenging issue, depending on one's standpoint. Science-related writing is not immune to trends. There is a curious shift in opinion seen before and after 2018. One must question whether there was a prejudice in favor of minimally invasive surgery prior to the publication of the NEJM articles and a bias against it afterward. CONCLUSION: Whether further minimally invasive surgery for cervical cancer is invariable is tied to the more pressing question of how this surgery will have to be centralized in the future. Unless these questions are linked, no satisfactory solution can be found.

The Role of DAPK1 in the Cell Cycle Regulation of Cervical Cancer Cells and in Response to Topotecan.

Cervical cancer is one of the most serious health conditions, with nearly 500,000 women developing the disease each year worldwide. At present, the treatment of recurrent cervical cancer remains largely ineffective, and efforts in cancer drug development are currently focused on critical serine/threonine kinases, such as death-associated protein kinase 1 (DAPK1) and polo-like kinase 1 (PLK1). In the current study, we aimed at exploring the cell cycle roles of DAPK1 and PLK1 in cervical cancer cells. To achive this goal, we used multiple methods including western blotting and assays for studying kinase activity, apoptosis, cell cycle, cell proliferation, immunofluorescence and proximity ligation. The present study demonstrated that, in cervical cancer cells, the enzymatic activity of DAPK1 was regulated in a cell cycle-specific manner. NIMA-related kinases, CDKs, PLKs and Aurora kinases regulate the function of centrosomes by orchestrating the separation of chromosomes during cell division. The present study added DAPK1 to this group of protein kinases due to its localization at centrosomes during mitosis. It was shown that DAPK1 was autophosphorylated at Ser308 in the G2 phase and during mitosis. From prophase to metaphase, the colocalization of PLK1 and DAPK1 at centrosomes was observed. Furthermore, the interaction of both these kinases could be demonstrated using proximity ligations assays and immunoprecipitations. DAPK1 was found to be a substrate of PLK1. Topotecan is an effective drug used for the treatment of cervical cancer. Therefore, the current study examined the role of DAPK1 in topotecan-induced cervical cancer cell death, and it was identified that RNA interference-based silencing of DAPK1 decreased the apoptotic effect of topotecan. Thus, these findings suggested that DAPK1 could be a biomarker and a potential target for the response to topotecan during the therapy of patients with cervical cancer.

The Small-Molecule Inhibitor MRIA9 Reveals Novel Insights into the Cell Cycle Roles of SIK2 in Ovarian Cancer Cells.

The activity of the Salt inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK)-related kinase family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in several cancers, including ovarian cancer, where it promotes the proliferation of metastases. Furthermore, as a centrosome kinase, SIK2 has been shown to regulate the G2/M transition, and its depletion sensitizes ovarian cancer to paclitaxel-based chemotherapy. Here, we report the consequences of SIK2 inhibition on mitosis and synergies with paclitaxel in ovarian cancer using a novel and selective inhibitor, MRIA9. We show that MRIA9-induced inhibition of SIK2 blocks the centrosome disjunction, impairs the centrosome alignment, and causes spindle mispositioning during mitosis. Furthermore, the inhibition of SIK2 using MRIA9 increases chromosomal instability, revealing the role of SIK2 in maintaining genomic stability. Finally, MRIA9 treatment enhances the sensitivity to paclitaxel in 3D-spheroids derived from ovarian cancer cell lines and ovarian cancer patients. Our study suggests selective targeting of SIK2 in ovarian cancer as a therapeutic strategy for overcoming paclitaxel resistance.

Pre-operative serum CA125, peritoneal cancer index and intra-operative mapping score as predictors of surgical results in primary epithelial ovarian cancer.

OBJECTIVE: Prediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer and their predictive value for post-operative outcome. METHODS: A total of 70 patients with primary epithelial ovarian cancer, who underwent primary cytoreductive surgery at Charité, Berlin between January 2013 and February 2014 were included. In all patients, pre-operative CA125 values, intra-operative peritoneal cancer index, and intra-operative mapping of ovarian cancer were determined. RESULTS: Using a receiver operating characteristic analysis, cut-off values for CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer score could be defined. Patients with pre-operative serum CA125 >600 U/mL had a three times higher risk for residual tumor after primary cytoreductive surgery (p=0.037). A peritoneal cancer index score >20 indicated a nine times increased risk for residual tumor (p=0.003). More than six affected abdominopelvic fields on the intra-operative mapping of ovarian cancer was associated with a 25 times higher risk of residual tumor after primary cytoreductive surgery (p≤0.05). The combination of all three values predicted residual tumor in up to 90% of patients. CONCLUSION: We found that pre-operative CA125 >600 U/mL, peritoneal cancer index >20, and intra-operative mapping of ovarian cancer score >6 could be used as predictors of complete tumor resection. The combination of all these three values predicted the incomplete resection of disease in up to 90% of patients even in experienced centers.

Impact of re-excision of residual adjacent vulvar intraepithelial neoplasia (VIN III) and histological tumour-free margin (hTFM) on survival in primary squamous cell carcinoma of vulva.

BACKGROUND: hTFM in primary vulvar cancer is an important prognostic factor. Ideally, a diameter of > 8 mm should be achieved after primary surgery. The role of VIN III persistence after primary surgery in vulvar cancer is still unclear. The main objective of the current study was to study the role of residual VIN III re-excision and compare differences in disease-free survival among patients with different hTFM and in primary vulvar cancer. METHODS: Forty-two patients with residual adjacent VIN III after primary surgery for vulvar cancer which were operated between 2000 and 2016 in our clinic were enrolled in this retrospective study. Re-excision rates for residual adjacent VIN III were calculated. According to the histological margin patients were divided into three group: < 3, 3-8 and > 8 mm. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models, respectively. RESULTS: The vast majority of patients had pT1b stage (57.1%), grading G2 (71.4%) and lymph node-negative (45.3%) disease at first diagnosis. The re-excision rate was 57.1%. The 5-year disease-free survival (DFS) rates in patients with < 3, 3-8 and > 8 mm hTFM were 50.0, 50.0 and 81.0%, respectively (p = 0.032). The 5-year DFS rates in patients with re-excision and without re-excision for VIN III were 77.3 and 52.9%, respectively (p = 0.060). In univariate analysis was solely hTFM > 8 mm a prognostic factor for DFS (p = 0.017). CONCLUSIONS: hTFM may be a potential prognostic indicator for DFS in vulvar cancer patients. Re-excision for residual adjacent VIN III could not be established as a prognostic factor for DFS after primary surgery in squamous cell cancer of vulva.

Claudin-1 is linked to presence of implants and micropapillary pattern in serous borderline epithelial tumours of the ovary.

AIMS: Expression of Claudin-1 has been associated with prognosis in several cancers. Here we investigated the expression pattern of Claudin-1 in borderline tumours of the ovary (BOT). METHODS: We analysed a cohort of 114 cases of borderline tumour (BOT). Claudin-1 expression was studied by immunohistochemistry using a polyclonal antibody and was compared with clinical and histopathological characteristics. RESULTS: Strong Claudin-1 expression was found in 30 cases (26.3%) independent of histological subtype. Expression was significantly less frequent in International Federation of Gynecology and Obstetrics (FIGO) stage I (p= 0.045), while the presence of microinvasion did not correlate with Claudin-1 expression. In contrast, we detected a highly significant association of Claudin-1 expression with the presence of peritoneal implants (p=0.003) and micropapillary pattern (p=0.047), which are features exclusively seen in serous BOT. Moreover, when we restricted our analysis to the subtype of serous BOT, the association of Claudin-1 expression with peritoneal implants (p<0.001) and micropapillary pattern (p =0.003) remained highly significant. CONCLUSIONS: In conclusion, Claudin-1 expression is associated with the presence of peritoneal implants and micropapillary pattern, which have been shown to be associated with poor prognosis. We speculate that overexpression of Claudin-1 might be linked to the mitogen-activated protein kinase pathway activation in BOT and suggest further studies to define its prognostic and potential therapeutic value.

Clinical Outcome After Completion Surgery in Patients With Ovarian Cancer: The Charite Experience.

OBJECTIVE: The aim of this study was to estimate surgical outcome and survival benefit after completion surgery. METHODS: We evaluated 164 patients with epithelial ovarian cancer who underwent incomplete primary cytoreductive surgery or rather received only staging procedures from January 2000 to December 2014 in outside institutions. Patient-related data were registered in prospective database of Tumor Bank Ovarian Cancer. The outcome analyses were performed for early and advanced stages of ovarian cancer separately. RESULTS: The majority of patients were at the time of completion surgery in advanced stages of disease. From overall 111 advanced epithelial ovarian cancer patients, 74 (66.6%) could be operated macroscopically tumor free, minimal residual disease 1 cm or less was achieved in 15.3% of the cases. Mean overall survival for patients without versus those with any tumor residual was 70 months (95% confidence interval, 61.3-81.5) versus 24.7 months (95% confidence interval, 7.1-42.4; P ≤ 0.0001). After applying completion surgery, 47 (28.6%) and 12 (6.7%) patients were upstaged in FIGO (International Federation of Gynecology and Obstetrics) IIIC and IV stages, respectively. Upstaging resulted in therapy changes in 10 patients (19%) with assumed FIGO IA stages. Major operative complications were registered in 28.8% of advanced cases, and 30-day mortality reached 1.8%. CONCLUSIONS: Recent research has shown that the most profound impact on survivorship occurs when women get proper care from surgeons trained in the latest techniques for treating ovarian cancer. Completion surgery maintained that even after initial incomplete cytoreduction outside of the high specialized units, after applying appropriate surgery techniques macroscopically, disease-free situation is achievable and outcomes are comparable with the results of primary debulking surgery.

Lymph Node Involvement Pattern and Survival Differences of FIGO IIIC and FIGO IIIA1 Ovarian Cancer Patients After Primary Complete Tumor Debulking Surgery: A 10-Year Retrospective Analysis of the Tumor Bank Ovarian Cancer Network.

OBJECTIVE: The main goal of the current study was to compare survival differences among subgroups of primary ovarian cancer patients in International Federation of Gynecology and Obstetrics (FIGO) stages IIIC and IIIA1 after complete tumor debulking surgery. METHODS: A total of 218 patients with primary ovarian cancer who received complete cytoreductive surgery were included in the current retrospective analysis of the validated Tumor Bank Ovarian Cancer Network Database, which covers the periods January 2002 until December 2012. According to their tumor spread pattern, patients were divided into three groups: Group A (peritoneum only), Group B (peritoneum and lymph nodes), and Group C (lymph nodes only). Associations between groups and clinicopathological factors were analyzed using standard statistical procedures. RESULTS: The vast majority of patients were classified into Group B. Lymph node involvement was detected in 70.5 % of the cases where peritoneal implants presented ≥2 cm beyond the pelvis (Group A + B). The estimated 5-year overall survival (OS) rates were 47.4 % in Group A, 45.1 % in Group B, and 91.7 % in Group C (p < 0.01). In the subgroup analysis of Group B, both pelvic and para-aortic lymph node involvement was found in 57 % of patients. Patients in Group B who had para-aortic lymph node involvement only had better median progression-free survival (PFS) compared with patients with pelvic lymph node involvement only and pelvic and para-aortic lymph node involvement (28, 16, and 18 months, respectively; p = 0.02). The median OS differed significantly between patients with para-aortic lymph node involvement only versus patients with both pelvic and para-aortic involvement (68.5 vs. 46.7 months; p = 0.02). Three-year PFS was 90.0 % in FIGO IIIA1(i) and 62.6 % in FIGO IIIA1(ii) (hazard ratio 2.30, 95 % confidence interval 0.45-11.58). CONCLUSIONS: Patients with FIGO stage IIIC with lymph node involvement only had the best clinical outcome compared with patients in the same stage with peritoneal involvement only. Furthermore, involvement of both pelvic and para-aortic lymph nodes were of the same infrequency, and involvement of only para-aortic lymph nodes in this stage resulted in a better chance of survival than involvement of pelvic lymph nodes only or both pelvic and para-aortic lymph nodes simultaneously. In accordance with the revised FIGO classification of 2013, our study revealed that FIGO IIIA1(i) is prognostically better compared with FIGO IIIA1(ii).