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BackgroundFew studies analyzed the prognostic role of systemic inflammatory markers in early-stage ovarian cancer. The primary endpoint of the present study was to assess the prognostic impact of baseline inflammatory markers in early-stage ovarian cancer. The secondary endpoints were to compare the disease-free survival (DFS) of inflammatory markers with standard risk factors and to correlate these with BRCA mutational status.MethodsRetrospective, single-center, observational study. Patients with FIGO-stage I–II and IIIA1 epithelial ovarian cancer undergoing primary surgery between 10/2012 and 12/2019 were included. Inflammatory markers were evaluated on the results of the complete blood count and coagulation tests, performed before ovarian cancer surgery. The Receiver Operating Characteristic curve was used to determine the optimal cut-off value of different baseline inflammatory biomarkers for the DFS analysis. ResultsThree hundred fifty-nine patients were included in the study period. Baseline neutrophil–lymphocyte ratio (NLR) ≥ 3 and systemic immune inflammation index (SII, defined as platelet x neutrophil–lymphocyte ratio) ≥ 1000 were associated with worse 3 year DFS and baseline SII ≥ 1000 was associated with worse 3 year OS. BRCA-mutated patients with SII ≥ 1000 and with NLR ≥ 3 had significantly worse DFS compared to SII < 1000 and with NLR < 3. FIGO stage > I was the only independent risk factor for higher risk of recurrence.ConclusionSII ≥ 1000 and NLR ≥ 3 were associated with worse 3 year DFS and SII ≥ 1000 was associated with worse 3 year OS. The subgroups of BRCA-mutated patients with higher inflammation markers (SII ≥ 1000 and NLR ≥ 3) were associated with worse DFS. These findings might be helpful to design personalized treatment and more intensive surveillance.

ObjectiveTo evaluate a relation between BRCA1/2 status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery.MethodsData were retrospectively collected on patients with unresectable disease undergoing three or four cycles of neoadjuvant chemotherapy and interval debulking surgery at the Gynecologic Oncology Unit of the Catholic University of the Sacred Heart from January 2016 to December 2020. All patients were assessed for BRCA1/2 somatic mutation at diagnosis. The omental specimens obtained at the interval surgery were evaluated according to Bohm’s Chemotherapy Response Score System.ResultsA total of 172 patients were included in the analysis, 69 (40%) patients were BRCA1/2 mutation carriers and 103 (60%) patients were wild type. In the wild-type group (BRCAwt), 73 (70.9%) patients had a Chemotherapy Response Score of 1 or 2 and 30 (29.1%) patients had a score of 3. In the BRCA1/2 carriers group (BRCAmut), 39 (56.5%) patients had a score of 1 or 2 and 30 (43.5%) patients had a score of 3. Among the BRCAwt group, those with a Chemotherapy Response Score of 3 had a prolonged median progression-free survival (22 vs 15 months, p=0.003). Among the BRCAmut carriers group, no differences were found (30 vs 27 months, p=0.55). No difference in overall survival was observed in either the BRCAmut carriers population (p=0.23) or the BRCAwt population (60 vs 44 months, p=0.06).ConclusionsPatients with BRCA1/2mut seem to achieve a score of 1, 2 or 3 with the same frequency. In contrast, patients with BRCAwt seem to have a score of 1 or 2 more frequently than a score of 3. In patients with BRCA1/2mut, this score may not be an indicator of chemosensitivity.

Neoadjuvant chemotherapy with interval debulking surgery represents an alternative treatment for advanced ovarian cancer. Currently, there are few data about the use of poly adenosine diphosphate-ribose polymerase inhibitors in the neoadjuvant setting. To evaluate whether the administration of olaparib in combination with standard chemotherapy in the neoadjuvant setting can improve tumor response. The addition of a poly adenosine diphosphate-ribose polymerase inhibitor to standard chemotherapy will achieve a higher response rate in BRCA mutated patients compared with standard chemotherapy This is a multicenter, phase II, single arm, open label trial. Eligible patients will receive three cycles of weekly carboplatin plus paclitaxel, and intermittent olaparib administration. Responding patients will undergo an interval debulking surgery with pathological evaluation of response to chemotherapy. Patients must have histologically confirmed International Federation of Gynecology and Obstetrics stages III–IV primary ovarian, peritoneal, or fallopian tube cancers, high grade serous or endometrioid histology, not suitable for primary cytoreductive surgery with a documented BRCA1 or BRCA2 germline and/or somatic mutation. Rate of complete pathological response after three cycles of the experimental chemotherapy regimen. A total of 35 patients will be enrolled in the study. Expected complete 42 accrual in January 2022, with presentation of results by June 2022. NCT04261465

ObjectivesThe chemotherapy response score (CRS) has been developed for measuring response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. This study aimed to validate the ability of this three-tier scoring system of pathologic response on omental specimens to determine prognosis in a subgroups of patients who had clinical complete response to neoadjuvant chemotherapy.MethodsThis was a retrospective study, conducted in women receiving interval debulking surgery at the Division of Gynecologic Oncology, between December 2007 and April 2017. Inclusion criteria were: high-grade serous ovarian cancer, FIGO stage IIIC/IV, platinum-based neoadjuvant chemotherapy, and clinical complete response after neoadjuvant chemotherapy (normalization in CA125 levels, disappearance of all target and non-target lesions according to RECIST 1.1). CRS was defined by a single pathology review and classified as previously reported: CRS1, no or minimal tumor response with fibroinflammatory changes limited to a few foci ranging from multifocal or diffuse regression-associated fibroinflammatory changes with viable tumor in sheets, or nodules to extensive regression-associated fibroinflammatory changes with multifocal residual tumor; CRS2, appreciable tumor response with viable tumor readily identifiable; and CRS3, complete absence of tumor or nodules with maximum size of 2 mm. CRS was analyzed according to clinical variables and survival.ResultsA total of 108 patients were eligible for analysis. The average age was 65 (range 36–85) years. A total of 91 (84.3%) patients had stage IIIC disease and 17 (15.7%) patients had stage IV disease. No statistically significant differences were observed in terms of age, FIGO stage, CA125 serum levels, type of chemotherapy schedules, and number of cycles between the three groups. Patients in the CRS3 group had a longer median progression-free survival (25.8 months) compared with CRS2 or CRS 1 (20.3 vs 17.4 months, respectively; p=0.001). Median overall survival was 68.9 months for CRS3, 35.0 months for CRS2, and 45.9 months for CRS1 (p=0.034).ConclusionComplete or near-complete pathologic response assessed in the omental specimens of advanced epithelial ovarian carcinoma patients after neoadjuvant chemotherapy (CRS3) is predictive of prolonged progression-free and overall survival. In particular, this is true in women with a clinical complete response.

Introduction/BackgroundSeveral studies have explored the prognostic role of hormone receptor status in high grade serous ovarian cancer (HGSOC). However, few reports have investigated their expression according to BRCA mutational status. Notably, there is evidences of a strong interaction between BRCA1/2 proteins and steroid hormones system, including higher titres of estradiol and progesterone in BRCA1/BRCA2 mutation carriers. Thus, we sought to explore the hormone receptor pattern and its potential prognostic impact in a well-characterized cohort of HGSOC patients stratified for BRCA status.MethodologyWe assessed ERα, ERβ1, ERβ2, ERβ5, PR (progesterone receptor) and AR (androgen receptor) expression by immunohistochemistry in a single-centre observational retrospective cohort study of 207 HGSOC women, profiled for BRCA-1/2 mutation status with available clinical and molecular features.Results135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut) were observed. No significant differences were detected in hormone receptor expression between the two populations. However, in the subgroup analysis according to menopausal status, a significantly lower ERα expression was found in pre-menopausal BRCA-mut compared to BRCA-wt patients (p=0.02) (figure 1). Regarding survival analysis, none of the examined hormone receptors had a significant prognostic role. However, a higher ERα/ERβ5nuclear ratio differently affected outcome according to BRCA status: positively in BRCA-wt cohort (HR 0.77; CI 0.61–0.96; p=0.019) and negatively in BRCA-mut cohort (HR 1.41; CI 1.06–1.87; p=0.020) (table 1). Finally, higher PR levels were associated with platinum sensitivity in the whole population (p=0.019).Abstract 2022-RA-685-ESGO Figure 1Abstract 2022-RA-685-ESGO Table 1Survival analysis on BRCA-wt vs. BRCA mutated (n=207)ConclusionThis study suggests a potential role of estrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, revealing a possible therapeutic potential of targeting this interaction.

Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA1/2-mut as compared to BRCA-wt patients (p = 0.02). None of the examined hormone receptors has revealed a significant prognostic role in the whole sample, apart from the ratio ERα/ERβ5 nuclear, for which higher values disclosed a positive role on the outcome in BRCA-wt subgroup (HR 0.77; CI 0.61–0.96; p = 0.019). Conversely, it negatively affected overall survival in the presence of BRCA1/2-mut (HR 1.41; CI 1.06–1.87; p = 0.020). Finally, higher PR levels were associated with platinum sensitivity in the whole sample (p = 0.019). Our data, though needing further validation, suggest a potential role of oestrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, thus revealing a possible therapeutic potential for targeting this interaction.

The recent scientific research on ASDEX Upgrade (AUG) has greatly advanced solutions to two issues of Radio Frequency (RF) heating in the Ion Cyclotron Range of Frequencies (ICRF): (a) the coupling of ICRF power to the plasma is significantly improved by density tailoring with local gas puffing; (b) the release of RF-specific impurities is significantly reduced by minimizing the RF near field with 3-strap antennas. This paper summarizes the applied methods and reviews the associated achievements.