Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers.

Simple summary: Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III-IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved. Background: Low-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence. Methods: We retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan-Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula. Results: A total of 92 patients were included (median age was 47 years, IQR 35-64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1-10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1-10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1-10 mm (HR = 2.30, 95% CI 1.30-4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92-7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52-6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS. Conclusions: Optimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Haptoglobin phenotype and epithelial ovarian cancer.

BACKGROUND: Haptoglobin (H) is a glycoprotein that regulates the immune response. Serum haptoglobin levels are significantly higher in patients with advanced epithelial ovarian cancer (EOC) with poor survival. Different isoforms of haptoglobin have been found in the serum of patients with EOC. We studied the genetic susceptibility and outcome of patients with EOC correlated to H phenotypes. MATERIALS AND METHODS: Analyses of the H phenotypes were performed on sera from patients stored at -70°C. A modified method based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of sera was used, followed by western blotting. RESULTS: Seventy-nine consecutive patients with EOC and 63 healthy women were enrolled. Their mean (± S.D.) age was 58.9 ± 12.46 years. Overall survival was 66 months (95% confidence interval=37.7-94.2). Similar distribution of haptoglobin phenotypes was observed in EOC and in healthy women. No significant correlation was found between haptoglobin phenotype, overall survival and time-to-progression. Fewer G3 tumors were found in patients with H2-2 compared with those with H1-2 (84.2% and 90.6%, respectively, p<0.04). No significant correlation was found between H phenotype and tumor markers or number of relapses. CONCLUSION: Although ours is a preliminary study based on a small population with scant significant findings, we hypothesize that patients with EOC with haptoglobin 2-2, might have a better prognosis because they present fewer G3 tumors and they may present a stronger immune response than patients with 1-1 and 1-2 phenotypes. Larger studies should be performed to assess the predictive value of haptoglobin phenotype in patients with EOC.

Clinical significance of microinvasion in borderline ovarian tumors and its impact on surgical management.

OBJECTIVE: The aims of this study were to evaluate the rate of recurrences in borderline ovarian tumors (BOTs) with microinvasion and to evaluate the possibility to enlarge fertility-sparing surgery in this group of patients. METHODS: Between 1985 and 2010, 209 patients with BOTs were retrospectively divided into 2 groups: group 1 consisted of 28 women with microinvasive BOTs; group 2 consisted of 181 with BOTs without microinvasion. All of the patients were submitted to surgical treatment: in group 1, 10 patients underwent cystectomy (CYS), 11 patients underwent monolateral salpingo-oophorectomy (MSO), and 7 patients underwent bilateral oophorectomy with or without total hysterectomy (BSO); in group 2, 34 patients underwent CYS, 58 patients underwent MSO, and 89 patients underwent BSO. Specific prognostic factors such as stage, surgical approach, intraoperative spillage, histology, exophytic tumor growth, and endosalpingiosis were analyzed. Tumor recurrence rate and overall and disease-free survivals were evaluated. RESULTS: After a mean follow-up of 53 months, relapses occurred in 21.4% of the cases in group 1 and in 12.7% of the cases in group 2 (P = 0.21). The prognostic factors had no significant differences in the 2 groups. Relapses after CYS, MSO, and BSO were observed in 30%, 27.3%, and 0%, respectively, in group 1 and in 29.4%, 12.1%, and 6.7%, respectively, in group 2. Progression-free survival was significantly longer in BOTs compared to microinvasive BOTs (P = 0.041), but overall survival did not differ. CONCLUSIONS: Although exploratory, our data suggest that BOTs with microinvasion present earlier relapses, but overall incidence of relapses and overall survival do not differ significantly from BOTs without microinvasion. Fertility-sparing surgery is feasible in this group of patients, but strict follow-up has to be suggested.

Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors.

INTRODUCTION: Data in literature about the use of adjuvant treatment to reduce acute adverse effects of radiotherapy on the pelvis are scant, with the exception of a few reports on the topical use of estrogen, which promotes proliferation of epithelium. MATERIALS AND METHODS: In this prospective trial, α-tocopherol acetate was topically administered to patients affected by endometrial and cervical cancer and undergoing radiation treatment to avoid acute vaginal complications. RESULTS: Vaginal application of α-tocopherol reduced vaginal toxicity and pain, although vaginal secretion was not significantly different in the 2 groups studied. The histological scoring system showed a significant reduction of inflammation, no difference in fibrosis, and an increase of acanthosis. CONCLUSIONS: The use of α-tocopherol as adjuvant treatment to reduce the acute adverse effects of radiotherapy on the vagina should be considered.

Performance of a panel of maternal serum markers in predicting preeclampsia at 11-15 weeks' gestation.

OBJECTIVE: We evaluated whether a discriminant model of prediction based on quantitative distribution of a panel of biomolecules in maternal serum can discriminate normal pregnancies from those who will develop preeclampsia (PE) prior to onset of clinical symptoms at 11-15 weeks' gestation. METHODS: Case control study encompassing 56 women destined to develop PE cases matched 1:3 for gestational age with 168 controls. After multiple of median (MoM) conversion of all available markers, comprising total Activin A (t-activin A), P-selectin, and vascular endothelial growth factor receptor (VEGFR) the combined likelihood ratios generated for each marker were used to calculate, for each patient enrolled in the study, the odds of being affected given a positive results (OAPR) of developing PE. For all the analyses performed, the type II error was < 20% with a type I error fixed at 5%. RESULTS: Data were expressed in MoM of controls. P-selectin was identified as the marker with the best discriminant ability between controls and PE, followed by (t-activin A). No significant differences in VEGFR were observed between cases and controls. By using a 3% prevalence of PE (or, about 1:33) we found that the median OAPR of developing PE for the 56 cases was 1:9 or 10% (1:1-1:417). The median OAPR of PE for controls was 1:40 or 2.5% (range, 1:6-1:4205). Detection rate of the statistical model, with a 5% false-positive rate was 59%. CONCLUSION: This analysis revealed that maternal serum markers assessed at the first and second trimester of pregnancy in asymptomatic patients can improve the early detection of cases at higher risk of developing PE.