Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues.

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.

The impact of oophorectomy on survival from breast cancer in patients with CHEK2 mutations.

BACKGROUND: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation. METHODS: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast cancer or for benign conditions. Dates of death were obtained from the Polish Vital Statistics Registry. Causes of death were determined by medical record review. Predictors of survival were determined using the Cox proportional hazards model. RESULTS: In all, 839 patients with a CHEK2 mutation were matched to 839 patients without a mutation. The mean follow-up was 12.0 years. The 15-year survival for CHEK2 carriers was 76.6% and the 15-year survival for non-carrier control patients was 78.8% (adjusted HR = 1.06; 95% CI: 0.84-1.34; P = 0.61). Among CHEK2 carriers, the 15-year survival for women who had an oophorectomy was 86.3% and for women who did not have an oophorectomy was 72.1% (adjusted HR = 0.59; 95% CI: 0.38-0.90; P = 0.02). Among controls, the 15-year survival for patients who had an oophorectomy was 84.5% and for women who did not have an oophorectomy was 77.6% (adjusted HR = 1.03; 95% CI: 0.66-1.61; P = 0.90). CONCLUSION: Among women with breast cancer and a CHEK2 mutation, oophorectomy is associated with a reduced risk of death from breast cancer.

Hypoxia-Mediated Decrease of Ovarian Cancer Cells Reaction to Treatment: Significance for Chemo- and Immunotherapies.

Hypoxia, a common factor ruling the microenvironment composition, leads to tumor progression. In this hypoxic context, cytokines and cells cooperate to favor cancer development and metastasis. Tumor hypoxia is heterogeneously distributed. Oxygen gradients depend on the vicinity, functionality of blood vessels, and oxygen ability to diffuse into surrounding tissues. Thus, the vasculature state modulates the microenvironment of the tumor cells. Cells sense and react to small variations in oxygen tension, which explains the lack of tumor cells' unicity in their reaction to drugs. Ovarian cancers are highly hypoxia-dependent, ascites worsening the access to oxygen, in their reactions to both chemotherapy and new immunotherapy. Consequently, hypoxia affects the results of immunotherapy, and is thus, crucial for the design of treatments. Controlling key immunosuppressive factors and receptors, as well as immune checkpoint molecule expression on tumor, immune and stromal cells, hypoxia induces immunosuppression. Consequently, new approaches to alleviate hypoxia in the tumor microenvironment bring promises for ovarian cancer immunotherapeutic strategies. This review focuses on the effects of hypoxia in the microenvironment and its consequences on tumor treatments. This opens the way to innovative combined treatments to the advantage of immunotherapy outcome in ovarian cancers.

External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model.

BACKGROUND: We conducted a study to validate the influence of the systemic immune-inflammation index (SII) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to verify whether the implementation of the SII in place of neutrophil and platelet counts within the International Metastatic Renal Cell Carcinoma Consortium (IMDC) model might increase its prognostic accuracy. PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with mRCC, who were treated with first-line tyrosine kinase inhibitors from 2008 to 2016 in two major oncology centres in Poland. We stratified patients into low SII (< 730) and high SII (≥ 730) groups according to a recent literature report. We used multivariable Cox proportional hazards regressions (CPHRs) to assess the impact of the SII on OS and concordance, global 'goodness-of-fit', calibration and reclassification measures to quantify a potential prognostic benefit from the modification of the IMDC model. RESULTS: Overall, 502 patients (294 with low and 208 with high SII) were included. Median OS was 36.7 months [95% confidence interval (CI) 30.4-41.5 months] and 17.0 months (95% CI 12.5-19.6 months) in the low and high SII groups, respectively. The SII status was significant in CPHRs with the hazard ratio ranging from 1.38 to 1.68. All prognostic accuracy measures favored the SII-modified-IMDC model over the original IMDC model. CONCLUSIONS: Using an external dataset, we showed that high SII was an independent factor for poor OS. The addition of the SII to the IMDC model in place of neutrophil and platelet counts increased the model's prognostic performance.

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

PURPOSE: The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). METHODS: Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. RESULTS: Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100µl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100µl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100µl (AUC:0.77, P=0.0136) was noticed. CONCLUSIONS: Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease.

Clinical features and outcomes of germline mutation BRCA1-linked versus sporadic ovarian cancer patients.

BACKGROUND: The role of germline mutations in BRCA1 and BRCA2 genes in the risk of the development of ovarian cancer is clinically well established. BRCA1/2 testing seems to have increasing role in clinical management in patients with advanced ovarian cancer who require treatment with poly(ADP-ribose) polymerase inhibitors. METHODS: Between 2002 - 2008, 125 consecutive patients with ovarian cancer were categorized as having three founder mutations in the BRCA1 gene in Poland as: 5382insC [exon 20], 4153delA [exon 11.17], and 300 T > G [exon 5]. PFS (progression free survival) and OS (overall survival) were determined by Kaplan-Meier analysis with log rank test, univariate comparisons, and multivariate regression analysis using Cox proportional hazards model. RESULTS: Of the 125 patients, the founder mutations of BRCA1 were reported in 17 patients (13.6 %). The median OS was longer for BRCA mutated patients (not reached vs 35.6 months, p = 0.041). PFS was similar for both kinds of ovarian cancer. In multivariate analysis, age ≥70 years, suboptimal surgery, and BRCA1 wild type were poor prognostic factors. The BRCA1 mutation reduced the likelihood of death in ovarian cancer by 86 % (HR 0.14; CI: 0.032-0.650, p = 0.012). CONCLUSION: In conclusion, we found better overall survival for ovarian cancer patients with BRCA1 germline mutations in comparison with patients without these mutations (sporadic) ovarian cancer. Thus, BRCA1 germline mutations appear to be an independent prognostic factor for ovarian cancer.

Mitomycin C and high-dose 5-fluorouracil with folinic acid as a therapeutic option for heavily pretreated patients with metastatic colorectal cancer: prospective phase II trial.

BACKGROUND: Standard treatment for patients with unresectable colorectal cancer metastases includes chemotherapy regimens based on irinotecan, oxaliplatin, fluoropyrimidines, anti-vascular endothelial growth factor therapy, and anti-EGFR. Additional therapeutic options are needed for patients with good performance status who have disease progression during or after standard therapies. METHODS: A nonrandomized phase II study was modeled as a two-stage Chen design. Eligible patients had a diagnosis of metastatic colorectal cancer (mCRC) with progression after prior cytotoxic regimens based on oxaliplatin and irinotecan. Treatment consisted of mitomycin C in combination with high-dose 5-fluorouracil (5-FU) and folinic acid (the MLF regimen; mitomycin C as an intravenous bolus of 6 mg/m² i.v. on days 1 and 22 every 7 weeks; folinic acid at 250 mg/m² in combination with 5-FU at 2,600 mg/m² as a continuous intravenous infusion (24 hours) weekly for 6 of every 7 weeks. RESULTS: The median age of the 74 eligible patients was 62 years (range: 47-79 years). In these heavily pretreated patients with mCRC, the MLF regimen was the fourth or fifth line in more than 60% of the patients. Two patients (3.2%) achieved a partial response, and 33 (53.2%) achieved a best response of stable disease, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Median progression-free survival was 4.9 months. The median overall survival was 9.7 months. The most common nonhematologic side effects included mucositis (24.4% for all grades, and 9.5% with grade 3/4), diarrhea (15.0% for all grades, 13.6% with grade 3/4), fatigue (44.7% for all grades, 13.6% with grade 3/4), nausea (12.3% for all grades, 6.8% with grade 3/4), and peripheral neuropathy (17.6% for all grades, 2.7% with grade 3/4). Among the most frequent hematological toxicities were neutropenia (27.1% for all grades, 14.9% with grade 3/4), thrombocytopenia (18.9% for all grades, 8.1% with grade 3/4), and anemia (13.6% for all grades, 4.1% with grade 3/4). Dose reductions due to adverse events were necessary in 29 of 74 patients (37.6%), and discontinuation of therapy due to toxicity was necessary for 14 of 74 patients (18.2%). CONCLUSION: Our study shows the MLF regimen can be administered safely to patients with heavily pretreated mCRC. Median progression-free and overall survival compares favorably with other options used or approved in this setting. A randomized trial in this setting should be considered.

Survivin expression as a prognostic factor in patients with epithelial ovarian cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The aim of this study was to evaluate association of expression of survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients with advanced ovarian cancer (AOC). METHODS: We retrospectively evaluated 60 consecutive patients with AOC (International Federation of Gynecology and Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin was assessed immunohistochemically. The median of expression total score survivin equals 2 was adopted to dichotomize the group. The positive and negative expression of p53 was used to dichotomize the group. RESULTS: The expression of survivin in tumor tissue taken before and after NAC was a significant difference in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P = 0.0003), and total score (P = 0.0001). There was a significant difference in p53 expression in tumor tissue before and after NAC in the percentage of stained nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a prognostic factor in patients with AOC treated with NAC (P = 0.0484). The expression of survivin and p53 was not a predictive factor. Independent adverse predictor factors were as follows: lack of optimal interval debulking surgery and the lack of an objective response (the respective hazard ratio was 3.93 [95% confidence interval, 2.07-7.46; P < 0.0001] and 2.36 [95% confidence interval,1.25-4.47; P = 0.0080]). The suboptimal range of interval debulking surgery, resistance to platinum, and the lack of paclitaxel in the NAC were adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence interval, 1.17-5.83], 2.72 [95% confidence interval, 1.07-6.89], and 2.56 [95% confidence interval, 1.06-6.18]; P < 0.05]). CONCLUSIONS: High expression of survivin could be a prognostic factor in patients treated with NAC for AOC.

[Screening for ovarian cancer in BRCA1/BRCA2 mutations carriers]. / Badania przesiewowe w kierunku raka jajnika u nosicielek mutacji genów BRCA1/BRCA2.

Worldwide screening for early detection of ovarian cancer in both, the general population and the group of women at high risk for ovarian cancer including BRCA genes mutations carriers, has proven to be ineffective. The recommended screening methods, including a pelvic examination, transvaginal ultrasound, and CA125 performed biannually continue to fail due to their relatively low sensitivity specificity and positive predictive value tests, as well as the fact that cancer is still detected in advanced stages (FIGO III/IV). However proteomic techniques and the ongoing search for more sensitive and specific biomarkers to increase effectiveness of screening tests for ovarian cancer bring new hope. We reviewed the current literature on screening for ovarian cancer in BRCA genes mutations carriers.

Cabozantinib in the Routine Management of Renal Cell Carcinoma: A Systematic Literature Review of Real-World Evidence.

Real-world cabozantinib use has increased since its approval to treat patients with advanced renal cell carcinoma (RCC) in 2016. We reviewed cabozantinib use in real-world clinical practice and compared outcomes with pivotal cabozantinib randomized control trials (RCTs). This PRISMA-standard systematic literature review evaluated real-world effectiveness and tolerability of cabozantinib in patients with RCC (PROSPERO registration: CRD42021245854). Systematic MEDLINE, Embase, and Cochrane database searches were conducted on November 2, 2022. Eligible publications included ≥ 20 patients with RCC receiving cabozantinib. After double-screening for eligibility, standardized data were abstracted, qualitatively summarized, and assessed for risk of bias using the Newcastle-Ottawa Scale. Of 353 screened publications, 41 were included, representing approximately 11,000 real-world patients. Most publications reported cabozantinib monotherapy cohort studies (40/41) of retrospective (39/41) and multicenter (32/41) design; most included patients from North America and/or Europe (30/41). Baseline characteristics were demographically similar between real-world and pivotal RCT populations, but real-world populations showed greater variation in prevalence of prior nephrectomy, multiple-site/brain metastasis, and nonclear-cell RCC histology. Cabozantinib activity was reported across real-world treatment lines and tumor types. Overall survival, progression-free survival, and objective response rate values from pivotal RCTs were within the ranges reported for equivalent outcomes across real-world studies. Common real-world grade ≥ 3 adverse events were consistent with those in pivotal RCTs (fatigue, palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension), but less frequent. No new tolerability concerns were identified. Real-world RCC survival outcomes for cabozantinib monotherapy were broadly consistent with pivotal RCTs, despite greater heterogeneity in real-world populations.

Treatment patterns, health care utilization, and costs of ovarian cancer in Central and Eastern Europe using a Delphi panel based on a retrospective chart review.

OBJECTIVE: Despite the considerable disease burden of ovarian cancer, there were no cost studies in Central and Eastern Europe. This study aimed to describe treatment patterns, health care utilization, and costs associated with treating ovarian cancer in Hungary, Poland, Serbia, and Slovakia. METHOD: Overall clinical practice for management of epithelial ovarian cancer was investigated through a 3-round Delphi panel. Experts completed a survey based on the chart review (n = 1542). The survey was developed based on clinical guidelines and the International Federation of Gynecology and Obstetrics Annual Report. Means, ranges, and outlier values were discussed with the experts during a telephone interview. Finally, consensus estimates were obtained in face-to-face workshops. Based on these results, overall cost of ovarian cancer was estimated using a Markov model. RESULTS: The patients included in the chart review were followed up from presurgical diagnosis and in each phase of treatment, that is, surgical staging and primary surgery, chemotherapy and chemotherapy monitoring, follow-up, and palliative care. The 5-year overall cost per patient was €14,100 to €16,300 in Hungary, €14,600 to €15,800 in Poland, €7600 to €8100 in Serbia, and €12,400 to €14,500 in Slovakia. The main components were chemotherapy-associated costs (68%-74% of the total cost), followed by cost of primary treatment with surgery (15%-21%) and palliative care (3%-10%). CONCLUSIONS: Patients with ovarian cancer consume considerable health care resources and incur substantial costs in Central and Eastern Europe. These findings may prove useful for clinicians and decision makers in understanding the economic implications of managing ovarian cancer in Central and Eastern Europe and the need for innovative therapies.

Severe neurological symptoms in a patient with advanced renal cell carcinoma treated with sunitinib.

Neurological symptoms are uncommon in patients administered sunitinib therapy; however, a few cases of dramatic neurotoxicity attributable to the development of reversible posterior leukoencephalopathy syndrome have been reported. Here, we report a case of a 71-year old woman with severe neurological symptoms occurring during sunitinib therapy for metastatic renal cell carcinoma. The clinical symptoms were typical for reversible posterior leukoencephalopathy syndrome, but there were no accompanying neuroimaging abnormalities. A Naranjo probability score of 3 indicates the adverse drug reaction was possible, but we discuss other potential causes of this event.

The Effect of Acetylsalicylic Acid, as a Representative Non-Steroidal Anti-Inflammatory Drug, on the Activity of Myeloperoxidase.

BACKGROUND: Acetylsalicylic acid (ASA or aspirin) is one of the world's most widely used non-steroidal anti-inflammatory drug (NSAID). Numerous studies have shown that the long-term use of aspirin may contribute to longer survival among patients with various types of cancer, including ovarian cancer. AIM: The aim of this study was to investigate the effect of ASA on myeloperoxidase (MPO), which is found at an elevated level in women with ovarian cancer, among others. METHODS: The influence of different concentrations of ASA on the chlorinating and peroxidase activity of MPO was analysed. The relationship between the concentration of ASA and the degree of inhibition of MPO activity was determined based on the results. CONCLUSIONS: Aspirin has a significant effect on MPO activity. The use of 50 mM ASA resulted in the enzyme activity being inhibited by more than 90%.

The Polish Society of Gynecological Oncology Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma (2023).

BACKGROUND: Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines. AIM: to summarize the current evidence for diagnosis, treatment, and follow-up of endometrial carcinoma and to provide evidence-based recommendations for clinical practice. METHODS: The guidelines have been developed according to standards set by the guideline evaluation tool AGREE II (Appraisal of Guidelines for Research and Evaluation). The strength of scientific evidence has been defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification. The grades of recommendation have been based on the strength of evidence and the level of consensus of the PSGO development group. CONCLUSION: Based on current evidence, both the implementation of the molecular classification of endometrial cancer patients at the beginning of the treatment sequence and the extension of the final postoperative pathological report of additional biomarkers are needed to optimize and improve treatment results as well as to pave the route for future clinical trials on targeted therapies.

Real-life data of abiraterone acetate and enzalutamide treatment in post-chemotherapy metastatic castration-resistant prostate cancer in Poland.

Background: Abiraterone acetate (ABI) and Enzalutamide (ENZA) are second-generation hormone drugs that show breakthrough activity in post-chemotherapy, metastatic castration-resistant prostate cancer (mCRPC). The leading oncological and urological guidelines indicate both drugs with the same strong recommendation. There is a lack of randomized trials which compare the efficacy of ABI and ENZA. The current study aimed to compare the effectiveness of the drugs with an analysis of prognostic factors related to those drugs. Patients and methods: The study included 420 patients with docetaxel (DXL) pretreated mCRPC from seven Polish cancer centers. Patients were treated according to inclusion and exclusion criteria in the Polish national drug program (1000 mg ABI and 10 mg prednisone, n=76.2%; ENZA, 160 mg; n=23.8%). The study retrospectively analyzed the overall survival (OS), time to treatment failure (TTF), PSA 50% decline rate (PSA 50%) and selected clinic-pathological data. Results: In the study group, the median OS was 17 months (95% CI: 15.6-18.3). The median OS (26.1 vs. 15.7 mo.; p<0.001), TTF (14.2 vs. 7.6 mo.; p<0.001) and PSA 50% (87.5 vs. 56%; p<0.001) were higher in ENZA than in ABI treatment. Multivariate analysis shows that ENZA treatment and PSA nadir <17.35 ng/mL during or after DXL treatment were related to longer TTF. ENZA treatment, DXL dose ≥750 mg, PSA nadir <17.35 ng/mL during or after DXL treatment was related to longer OS. Conclusions: ENZA treatment may be related to more favorable oncological outcomes than ABI treatment in the studied Polish population of patients. A 50% decline in PSA is an indicator of longer TTF and OS. Due to the non-randomized and retrospective nature of the analysis, the current results require prospective validation.

[Surgical treatment in ovarian cancer prevention in carriers of the BRCA1/BRCA2 mutation]. / Postepowanie chirurgiczne w profilaktyce raka jajnika u nosicielek mutacji genów BRCA1/BRCA2.

Ovarian cancer remains to be a real challenge in spite of considerable progress in many areas of modern medicine. The use of genetic testing for detecting mutations of the BRCA genes has been offering clinical scrutiny between mutated versions of the BRCA genes and higher risk of both breast and ovarian cancer A population survey is a method of choice to find out more efficient screening management in order to identify cancer patients who further will be treated effectively early A review of literature on surgical PBSO (prophylactic bilateral salpingooophorectomy) in the BRCA genes mutations carriers with focus on preventive results against morbidity of ovarian cancer has been presented in the article.

Malignant tumors in patients with end stage renal failure undergoing renal replacement therapy.

In 1975 Matas and co-workers were the first in the world literature to show an increased risk of malignant tumor occurrence in the group of hemodialyzed patients and kidney transplant recipients. The report is an analysis of world literature from the last 35 years in reference to epidemiology as well as the profile of screening tests and diagnostic methods related to malignant tumors in the population with end stage renal disease, especially hemodialyzed patients.

Sorafenib as a third line therapy in patients with epithelial ovarian cancer or primary peritoneal cancer: a phase II study.

PURPOSE: New agents are required for the patients with epithelial ovarian cancer (EOC) who progress after first and second line of the treatment. Tumor vasculature targeted agents are potentially active in EOC. We aimed to assess the activity of sorafenib in patients with recurrent EOC who had received two prior therapies. PATIENTS AND METHODS: A phase II non-randomized, open-label, single-arm study aimed to assess the efficacy, safety and tolerance of sorafenib monotherapy as a third line therapy in patients with EOC or primary peritoneal cancer (PPC). Sorafenib was administered as 400 mg twice daily on days 1-28 of each 4-week cycle. The primary end point of the study was to demonstrate the progression free survival (PFS). RESULTS: Eleven patients were enrolled. The median number of cycles was two. Among the 11 patients eligible for efficacy analysis, no patients experienced a partial response or complete response or stable disease lasting longer than 6 months according to RECIST criteria. Thus, the trial stopped at the end of the first stage of study design. The median PFS was 2.00 months (95% CI, 1,80-3,90). The median OS was 11.78 months (95% CI, 7.66 to 15.39). There were no grade 4 toxicities and few grade 3 toxicities. CONCLUSION: Sorafenib fails to achieve sufficient objective response or sustained disease stabilization as third-line treatment for EOC.

Prognostic Significance of Survivin Expression in Patients with Ovarian Carcinoma: A Meta-Analysis.

BACKGROUND: Survivin belongs to the protein family of inhibitors of apoptosis (IAP) and is a regulator of the cell cycle and apoptosis. The aim of this study was to assess the clinical and prognostic significance of expression survivin in patients with ovarian cancer. METHODS: We systematically searched for articles in PubMed, the American Chemical Society (Publications), Medline, the Royal Society of Chemistry, Scopus and the Web of Science. Patient clinical data, overall survival (OS), disease-free survival (DFS), and survivin expression were extracted from individual studies. We performed statistical analysis using the STATA 16 package. Eighteen publications containing data from 2233 patients with ovarian cancer were included in this meta-analysis. RESULTS: We found an adverse effect of survivin expression on OS (risk ratio (HR): 1.60; 95% confidence interval (CI): 1.33-1.93, p = 0.00) but this was not observed on DFS (HR: 1.06; 95% CI: 0.55-2.05, p = 0.87). The analysis of clinicopathological parameters showed that survivin expression was associated with the histological grades (G1-2 vs. G3) (odds ratio (OR) = 0.53, 95% CI: 0.34-0.83, p = 0.01) and: International Federation Gynecology and Obstetrics (FIGO) stage (I-II vs. III-IV) (OR = 0.22, 95% CI: 0.09-0.55, p = 0.00), but it was not significantly correlated with the histological subtype (OR = 1.14, 95% CI: 0.83-1.58, p = 0.42). CONCLUSIONS: Our meta-analysis suggests that survivin expression may be a marker of poor prognosis in ovarian cancer. Survivin expression was associated with parameters of greater aggressiveness of ovarian cancer. Prospective studies are needed to confirm our results indicating that survivin expression can be used as an ovarian cancer biomarker.

Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer - mass spectrometry analysis.

INTRODUCTION: Due to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III-IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer. MATERIAL AND METHODS: A total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS. RESULTS: Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging (p = 0.001, p = 0.024 and p = 0.005), and grading (p = 0.021, p = 0.021 and p = 0.033). CONCLUSIONS: Plasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.