Borut Kobal

Circulating serum sVCAM-1 concentration in advanced ovarian cancer patients: correlation with concentration in ascites

Abstract Background. Vascular cell adhesion molecule-1 (VCAM-1) is associated with ovarian cancer progression but the origin of its soluble form (sVCAM-1) in serum is not well investigated. The purpose of this study was to elucidate whether the concentration of sVCAM-1 in serum correlates with the concentration in ascites, that represents local tumour environment, and with systemic inflammation, various clinicopathological characteristics, and patient outcome. Patients and methods. Thirty-six patients with advanced ovarian cancer were included in the study. Serum for sVCAM-1 analysis was obtained prior to surgery. Ascites samples were collected at the beginning of the operation. Clinical data were collected from patients’ medical records. sVCAM-1 in samples was analysed by flow cytometric bead-based assay. The mean follow-up period was 11 months (range 0-23) from the time of surgery. Results. Serum sVCAM-1 concentrations are positively correlated to ascites sVCAM-1 concentrations. There was a weakly positive correlation of serum sVCAM-1 with tumour size and no correlation with inflammatory tumour markers, FIGO stage or grade. Higher concentrations of sVCAM-1 were associated with poor disease outcome (death from ovarian cancer) in almost all cases before chemotherapy was started. Conclusions. This is the first study demonstrating that serum concentrations of sVCAM-1 in advanced ovarian cancer patients correlate with sVCAM-1 concentrations in ascites, thus expressing the biologic potential of malignant disease to metastasis, rather than systemic inflammation. Higher serum and ascites sVCAM-1 concentrations might have predictive potential for different biologic behaviour.

The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

Primary debulking surgery versus primary neoadjuvant chemotherapy for high grade advanced stage ovarian cancer: comparison of survivals

Abstract Background The aim of the study was to analyze the overall survival (OS) and progression free survival (PFS) of patients with high grade and advanced stage epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a single gynecologic oncology institute. We compared primary debulking surgery (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT + IDS) stratifying data based on residual disease with the intent to identify the rationale for therapeutic option decision and the role of laparoscopic evaluation of resectability for that intention. Patients and methods This is observational retrospective study on consecutive patients with diagnosis of high grade and International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC referred to our center between January 2008 and May 2012. We selected only patients with a follow-up of at least 60 months. Primary endpoint was to compare PDS versus NACT + IDS in term of progression free survival (PFS) and overall survival (OS). Secondary endpoints were PFS and OS stratifying data according to residual disease after surgery in patients receiving PDS versus NACT + IDS. Finally, through Cox hazards models, we tested the prognostic value of different variables (patient age at diagnosis, residual disease after debulking, American Society of Anesthesiologists (ASA) stage, number of adjuvant-chemotherapy cycles) for predicting OS. Results A total number of 157 patients were included in data analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we found no significant differences in term of OS (41.3 versus 34.5 months, respectively) and PFS (17.3 versus 18.3 months, respectively). According to residual disease we found no significant differences in term of OS between NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0 or residual disease = 1, as well as no significant differences in PFS were found comparing NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0; contrarily, median PFS resulted significantly lower in PDS patients receiving optimal debulking (residual disease = 1) in comparison to NACT + IDS patients receiving complete debulking (residual disease = 0). PDS arm was affected by a significant higher rate of severe post-operative complications (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly associated with complete debulking. Conclusions We confirm previous findings concerning the non-superiority of NACT + IDS compared to PDS for the treatment of EOC, even if NACT + IDS treatment was associated with significant lower rate of post-operative complications. On the other hand, selecting patients for NACT + IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does not worse the OS compared to the patients not completely debulked with PDS.

Evaluation of prognostic factors for advanced ovarian cancer treatment with an emphasis on optimal primary cytoreduction

Background: Initial surgical debulking followed by a systemic chemotherapy is the standard treatment sequence for advanced ovarian cancer (AOC) treatment. The purpose of this article is to evaluate prognostic factors that impact the success of AOC treatment. Methods: All patients with AOC (FIGO stage III and IV) who were surgically treated at the Division of Gynaecology, University Medical Centre of Ljubljana, in the period from 2003 to 2008 and further received cytotoxic chemotherapy at the Institute of Oncology in Ljubljana were included in this retrospective study. Women with advanced borderline ovarian cancer and patients who initially received neoadjuvant chemotherapy and those whose adjuvant chemotherapy was not platinum-based were excluded from the analysis. Results: A total of 159 women were enrolled in the study, while data were analyzed for 116 patients. Their median age was 59 years (23–80 years) and did not have a significant influence on the treatment outcome. Clear-cell histological type of AOC was an important risk factor for a disease-free interval (DFI) (HR = 2.41, CI 95 % 0.9–5.9; p = 0.08) and overall survival (OS) (HR 4.045; 95.0 % CI 1.5–10.6; p = 0.003). Postoperative residual tumour larger than 2 cm represented a statistically independent risk factor for poor OS. Residual tumour in the upper abdomen did not represent a statistically significant risk factor either for DFI (HR = 1.93; CI 95 % 0.9–4.06; p = 0.08) or for OS (HR = 1.47; 95.0 % CI 0.5–3.8; p = 0.491). Median follow up time was 29.5 months, median DFI 18 months (95 % CI 16– 20) and median OS 32 months (95 % CI 22–42). 74 (63.8 %) patients died. Conclusion: Clear-cell histological type of AOC and residual tumour larger than 2 cm are the most important risk factors for early progress of the disease and poor OS. Hence improvement of surgical treatment is crucial for better treatment outcomes for patients with AOC. The latter can be achieved by an interdisciplinary surgical approach.