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Cancer of the ovaries are the second most common group of gynaecologic cancers, and account for about 5% of all women's cancers. There are two main types; (i) epithelial tumours (carcinomas) which account for 90% of ovarian cancers, and (ii) non-epithelial tumours (eg. Stroma cell and germ cell tumours of the ovary). The epithelial ovarian cancers are usually found in women aged over 40, while the non-epithelial tumours are more common in girls and young women. Epithelial ovarian cancer has few early symptoms, a risk factor is having a family history of the disease. Taking the contraceptive pill is known to be protective against ovarian cancer.
In 2010, 7,011 women in the UK were diagnosed with ovarian cancer (Source: Cancer Research UK).
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MeSH term: Ovarian Neoplasms
US National Library of Medicine
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Showing publications with corresponding authors from the UK (Source: PubMed).
Risk factors for anastomotic leakage after colorectal resection in ovarian cancer surgery: A multi-centre study.
Gynecol Oncol. 2019; 153(3):549-554 [PubMed] Related Publications
BACKGROUND: In advanced ovarian cancer surgery, there is rather limited published evidence, drawn from a small sample, providing information about risk factors for anastomotic leak.
METHODS: Eight hospitals participated in this retrospective study. Data on 695 patients operated for ovarian cancer with primary anastomosis were included (January 2010-June 2018). Twelve pre-/intraoperative variables were analysed as potential independent risk factors for anastomotic leak. A predictive model was created to stablish the risk of anastomotic leak for a given patient.
RESULTS: The anastomotic leak rate was 6.6% (46/695; range 1.7%-12.5%). A total of 457 patients were included in the final multivariate analysis. The following variables were found to be independently associated with anastomotic leakage: age at surgery (OR 1.046, 95% CI 1.013-1.080, p = 0.005), serum albumin level (OR 0.621, 95% CI 0.407-0.948, p = 0.027), one or more additional small bowel resections (OR 3.544, 95% CI 1.228-10.23, p = 0.019), manual anastomosis (OR 8.356, 95% CI 1.777-39.301, p = 0.007) and distance of the anastomosis from the anal verge (OR 0.839, 95% CI 0.726-0.971, p = 0.018).
CONCLUSIONS: Due to the low incidence of AL in ovarian cancer patients, a restrictive stoma policy based on the presence of risk factors should be the actual recommendation. Hand-sewn anastomosis should be avoided.
BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma.
Int J Gynecol Cancer. 2018; 28(3):472-478 [PubMed] Related Publications
METHODS: A tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent. Coexpression of BRCA1 and MAD2 was evaluated, and patient survival analyses were undertaken.
RESULTS: Coexpression of BRCA1 and MAD2 was assessed in 94 EOC samples, and survival analysis was performed on 65 high-grade serous carcinomas (HGSCs). There was a significant positive correlation between BRCA1 and MAD2 expression in this patient cohort (
CONCLUSION: BRCA1 and MAD2 expressions are strongly correlated in EOC, but BRCA1 expression remains the stronger prognostic factor in HGSC.
Bowel resection rate but not bowel related morbidity is decreased after interval debulking surgery compared to primary surgery in patents with stage IIIC-IV ovarian cancer.
J Gynecol Oncol. 2019; 30(2):e25 [PubMed] Free Access to Full Article Related Publications
METHODS: From the Oxford Advanced OC database, we retrieved all patients who underwent surgery between January 2009 and July 2016 and included all patients who underwent RSR. We compared the rates of overall related and not-related morbidity and bowel diversion in patients undergone RSR during PDS vs. IDS.
RESULTS: Three hundred and seventy-one patients underwent surgery: 126 in PDS group and 245 in IDS group. Fifty-two patients in the PDS group (41.3%) and 65 patients in IDS group (26.5%) underwent RSR (p<0.001). Overall not related morbidity rate was 37.5% and 28.6%, p=0.625. Bowel specific complications affected 16.3% vs. 11.1% of the patients (p=0.577). IDS group had higher rate of bowel diversion compared with PDS (46.0% vs. 26.5%, p=0.048).
CONCLUSION: NACT was associated to an overall reduced rate of RSR compared to IDS. No differences in overall related and not-related complications in patients requiring RSR were seen between the 2 groups. Patients in the IDS group had a significantly higher rate of bowel diversion.
Targeted surgical prevention of epithelial ovarian cancer is cost effective and saves money in BRCA mutation carrying family members of women with epithelial ovarian cancer. A Canadian model.
Gynecol Oncol. 2019; 153(1):87-91 [PubMed] Related Publications
METHODS: A patient level simulation was developed comparing outcomes between two groups, using Canadian data. Group 1: no mutation testing with treatment if EOC developed. Group 2: cascade testing (index patient BRCA tested and the first and second-degree relatives tested if index patient or first-degree relative respectively were positive) with RRS in carriers. End points were Incremental Cost-Effectiveness Ratio (ICER) and budget impact.
RESULTS: 2786 women with EOC (1 year incidence) had 766 first and 207 second-degree female relatives. BRCA mutations were present in 390 index cases, 366 first and 49 second-degree relatives. With 100% RRS uptake, 59 EOC were prevented and testing dominated no testing (more effective and less costly; ICER -$8919). The total cost saving over 50 years was $2,904,486 (cost saving of $9,660,381 in treatment costs versus increased cost from cascade testing/RRS of $6,755,895). At a threshold of $100,000 per QALY, prevention was cost effective in all modelled scenarios.
CONCLUSIONS: Targeted prevention in BRCA mutation carriers not only prevents EOC but is cost-effective compared to treating EOC if it develops.
Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial.
Gynecol Oncol. 2019; 152(3):560-567 [PubMed] Related Publications
METHODS: The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (gBRCAmut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Adverse events (AEs) of special interest were based on the known safety profile of poly(ADP-ribose) polymerase inhibitors.
RESULTS: Patients aged ≥70 years in the gBRCAmut cohort receiving niraparib (n = 14) had not yet reached a median PFS compared with a median PFS of 3.7 months for the same age group in the placebo arm (hazard ratio [HR], 0.09 [95% confidence interval (CI), 0.01 to 0.73]). Non-gBRCAmut patients aged ≥70 years receiving niraparib (n = 47) had a median PFS of 11.3 months compared with 3.8 months in the placebo arm (HR, 0.35 [95% CI, 0.18 to 0.71]). Median duration of follow-up in the niraparib arm was 17.3 months in patients ≥70 years and 17.2 months in patients <70 years. Frequency, severity of AEs, and dose reductions in the niraparib arm were similar in patients aged <70 and ≥ 70 years population. The most common grade ≥ 3 AEs in patients ≥70 years were hematologic: thrombocytopenia event (34.4%), anemia event (13.1%), and neutropenia event (16.4%).
CONCLUSIONS: For patients ≥70 years of age receiving niraparib as maintenance treatment in the ENGOT-OV16/NOVA trial, PFS benefits and incidence of any grade or serious treatment-emergent AEs were comparable to results in the younger population. Use of niraparib should be considered in this population.
Black and Minority Ethnic women's decision-making for risk reduction strategies after BRCA testing: Use of context and knowledge.
Eur J Med Genet. 2019; 62(5):376-384 [PubMed] Related Publications
A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants.
Int J Cancer. 2019; 144(9):2192-2205 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification.
J Gynecol Oncol. 2019; 30(1):e13 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
METHODS: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I-II EEA. ER and PR negativity were determined when <1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network.
RESULTS: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21-12.52) and overall survival (OS; HR=7.59; 95% CI=2.55-22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60-10.14) and OS (HR=5.56; 95% CI=1.37-22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28-23.89) and stage II-IV (n=129; HR=5.77; 95% CI=1.57-21.27). No association was found between ER/PR loss and TCGA classification.
CONCLUSION: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I-II EEA patients.
GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): A novel CTNNB1 rearrangement.
Genes Chromosomes Cancer. 2019; 58(3):155-163 [PubMed] Related Publications
Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.
N Engl J Med. 2018; 379(26):2495-2505 [PubMed] Related Publications
METHODS: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both ( BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival.
RESULTS: Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib.
CONCLUSIONS: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; SOLO1 ClinicalTrials.gov number, NCT01844986 .).
Impact of right upper quadrant cytoreductive techniques with extensive liver mobilization on postoperative hepatic function and risk of liver failure in patients with advanced ovarian cancer.
Gynecol Oncol. 2018; 151(3):466-470 [PubMed] Related Publications
METHODS: We retrospectively reviewed all patients with OC who underwent liver resection, mobilization and/or diaphragmatic-stripping between 01/2013 and 12/2016. Postoperative liver enzyme function (LFTs), assessed by alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (Bil), was correlated with postoperative complications.
RESULTS: 132 patients were identified. 81 patients (61%) underwent upfront, 25(19%) interval and 26(20%) secondary cytoreduction. The surgical procedures were right diaphragmatic peritoneal stripping (81/132;61%), full-thickness resection (42/132;32%), liver-capsule resection (85/132;64%), porta-hepatis tumor resection (11/132;8%) and partial hepatectomy (5/132;4%). 74%(98/132) of patients increased their LFTs postoperatively with a peak at 24-hours. Highest ALT median was 1.7-fold of upper normal limit (UNL), with the highest ALT value rising up to 28-fold UNL on the 1st postoperative day (PoD)(range 6-1792 IU/L). Median value of highest ALP was within normal, with the highest ALP value rising up to 4-fold UNL on PoD 5(range 22-512 IU/L). Median value of highest Bilirubin level was also within normal, with highest Bilirubin level rising up to 6-fold UNL on PoD 5(range: 2-120 μmol/L). Mean LFT-normalization time was 7 days (range: 3-14 days). No significant morbidity was directly linked to LFT deterioration, apart from one case (0.8%) of fatal fulminant hepatic-failure.
CONCLUSION: RUQ-cytoreduction is almost always associated with a transient LFT-increase, with no significant clinical implications and spontaneous normalization within the first postoperative week. Due to the existing risk of fulminant liver failure, albeit rare and difficult to predict, postoperatively elevated LFTs should be monitored, until normalization. Large prospective studies are required to assess the predictive value of LFTs and other risk factors for postoperative hepatic failure in patients with OC undergoing extensive RUQ-cytoreduction.
Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.
Nat Commun. 2018; 9(1):3970 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility.
Genet Med. 2019; 21(4):913-922 [PubMed] Related Publications
METHODS: Germline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing.
RESULTS: Thirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case.
CONCLUSION: Within our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.
Prognostic implications of histological tumor regression (Böhm's score) in patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian carcinoma.
Gynecol Oncol. 2018; 151(2):264-268 [PubMed] Related Publications
METHODS: This was a retrospective cohort study of patients who received NACT between 2010 and 2015. The 3 point histopathological regression score of Böhm was used to classify chemotherapy response. Survival outcomes between the 3 different subgroups was analysed and compared with standard clinico-pathological variables using the Cox proportional hazards model and log-rank test.
RESULTS: Study cohort comprised 111 patients. Chemotherapy response score (CRS) 3 was observed in 47 (42.4%) and CRS 1and CRS 2 in 22 (19.8%) and 42 (37.8%) women respectively. Women with CRS score of 1 and 2 combined showed a three-fold increased risk of progression on both univariate and multivariate assessment (HR 3.54; C.I 2.19-5.72, p < 0.001). The median overall survival for patients with CRS 1 was 34 months, CRS 2 was 30 months and 47 months for CRS 3. CRS 1 and 2 combined was the only variable that held significance in prediction of reduced overall survival on multivariate assessment (HR 3.26, C.I 1.91-5.54, p 0.0006). CRS 1 and 2 were also associated with 5.15-fold increased risk of relapse within 6 months of completion of chemotherapy (Odds ratio OR 5.15, C.I 0.07-0.47, p - 0.002).
CONCLUSION: CRS is an independent prognosticator of survival and reliable predictor of relapse within 6 months in advanced high grade serous tubal and ovarian carcinoma patients receiving NACT.
Gonadotropins and Their Analogs: Current and Potential Clinical Applications.
Endocr Rev. 2018; 39(6):911-937 [PubMed] Related Publications
Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility.
PLoS One. 2018; 13(7):e0197561 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Mechanism of cytokinesis failure in ovarian cystadenomas with defective BRCA1 and P53 pathways.
Int J Cancer. 2018; 143(11):2932-2942 [PubMed] Article available free on PMC after 01/12/2019 Related Publications
Diaphragm disease in advanced ovarian cancer: Predictability of pre-operative imaging and safety of surgical intervention.
Eur J Obstet Gynecol Reprod Biol. 2018; 226:47-53 [PubMed] Related Publications
STUDY DESIGN: A retrospective review of all cases of AOC with metastatic diaphragm disease surgically treated at the Pan-Birmingham Gynaecological Cancer Centre, UK between 1st August 2007 and 29th February 2016.
RESULTS: A total of 536 women underwent surgery for primary AOC. Diaphragm disease was evident intra-operatively in 215/536 (40.1%) and 85/536 women (15.9%) underwent a procedure involving their diaphragm. Of these 85 cases, 38 peritoneal strippings (38/85, 44.7%), 31 partial diaphragmatic resections (31/85, 35.6%) and 16 electro-surgical ablations (16/85, 18.9%) were performed. There were no significant differences in post-operative complications between the three different diaphragmatic surgical groups. Of those patients who underwent peritoneal stripping or partial diaphragm resection, 12% were upstaged to stage 4A by virtue of pleural invasion. The positive predictive value for pre-operative radiological identification of diaphragmatic disease was 78.6%. CT imaging failed to detect diaphragmatic involvement despite obvious diaphragm disease during surgery in 29.4% of cases, giving a low negative predictive value of 64.8%. The sensitivity and specificity for CT imaging in detecting diaphragm disease was 44.3% and 93.8%, respectively.
CONCLUSIONS: Diaphragmatic disease is often discovered in AOC. However, pre-operative assessment with CT imaging is not reliable in accurately detecting diaphragm involvement. Therefore, all patients with AOC should be regarded as in potential need for diaphragm surgery and their operation undertaken in cancer centres with adequate expertise in upper abdominal surgery. If there is a suspicion of diaphragm muscle invasion during diaphragmatic peritonectomy, the muscle should be partially resected. This will lead to potential upstaging of disease to stage 4A and therefore, to suitability for targeted therapy. In our Centre, the surgical removal of diaphragmatic disease did not significantly increase surgical morbidity.
Radiolabeled Antibodies Against Müllerian-Inhibiting Substance Receptor, Type II: New Tools for a Theranostic Approach in Ovarian Cancer.
J Nucl Med. 2018; 59(8):1234-1242 [PubMed] Related Publications
Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the EPIC Cohort.
Cancer Epidemiol Biomarkers Prev. 2018; 27(7):790-804 [PubMed] Article available free on PMC after 01/12/2019 Related Publications
Ovarian Cancer Prevention and Screening.
Obstet Gynecol. 2018; 131(5):909-927 [PubMed] Related Publications
The effect of FASN inhibition on the growth and metabolism of a cisplatin-resistant ovarian carcinoma model.
Int J Cancer. 2018; 143(4):992-1002 [PubMed] Article available free on PMC after 01/12/2019 Related Publications
Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer.
J Clin Oncol. 2018; 36(13):1300-1307 [PubMed] Related Publications
Concomitant Laparoscopic and Thoracoscopic Resection of Recurrent High-Grade Ovarian Cancer.
J Minim Invasive Gynecol. 2018 Nov - Dec; 25(7):1148 [PubMed] Related Publications
DESIGN: An instructive video showing the combined thoracic and abdominal surgical procedure.
SETTING: Department of Gynecological Oncology, Churchill Hospital, Oxford University, UK.
PATIENTS: A 64-year-old woman undergoing endoscopic treatment for a third recurrence of ovarian cancer after a full surgical staging in 2007. The disease-free interval from the last recurrence was 31 months.
INTERVENTION: The operation was performed by a multidisciplinary team of thoracic and gynecologic oncologist surgeons. Surgery started with thoracoscopic resection of a right enlarged paracardiac lymph node of 24 mm and a small wedge of the right lung, which was attached to the lymph node. At laparoscopy, 2 nodules of 3 and 5 mm were excised from the mesosigmoid and 1 nodule of 20 mm was resected from the right hemidiaphragm.
MEASUREMENTS AND MAIN RESULTS: The total operative time was 251 minutes, and no intraoperative complication occurred. No conversion to open surgery was necessary. The estimated blood loss was 50 mL. There was no visible residual disease at the end of the surgery. The patient was discharged 4 days after surgery. The final pathology report confirmed the presence of endometrioid adenocarcinoma in all specimens removed. Adjuvant chemotherapy with carboplatin/paclitaxel was started 2 weeks later. At the 60-day follow-up, no complications were recorded. A computed tomographic scan performed after 6 cycles of chemotherapy did not reveal any evidence of relapse.
CONCLUSIONS: The combined endoscopic approach might be feasible in selected patients.
Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation.
Int J Cancer. 2018; 143(3):515-526 [PubMed] Article available free on PMC after 01/12/2019 Related Publications
An Outpatient, Dose-Intense, Intravenous Cisplatin and Oral Etoposide Regimen for the Treatment of Advanced, Platinum-Resistant Ovarian Cancer.
Int J Gynecol Cancer. 2018; 28(3):448-452 [PubMed] Related Publications
METHODS: This was a retrospective study to assess the use of standard (inpatient; treatment time of 12 hours) versus modified (outpatient; treatment time of 4 hours) regimens. The primary outcome included all-grade and grade 3/4 adverse events. Secondary outcomes included clinical benefit response and, median progression-free survival and overall survival.
RESULTS: Between January 2012 and December 2014, 66 women with metastatic ovarian cancer received dose-intense weekly cisplatin and oral etoposide (n = 45 standard, n = 21 modified). The commonest all-grade adverse events were anemia (96% vs 90%, standard and modified, respectively), fatigue (73% vs 67%), neutropenia (71% vs 76%), hypocalcemia (51% vs 43%), and thrombocytopenia (49% vs 57%). There were no statistically significant differences in the incidence or grades of adverse events. The clinical benefit response was 53% in the standard group and 62% in the modified group (P = 0.9). The median progression-free survival was 4.2 and 6.5 months (incidence rate ratio, 1.22; 95% confidence interval, 0.71-2.15; P = 0.29), and median overall survival was 6.6 and 8.4 months (incidence rate ratio, 1.83; 95% confidence interval, 1.04-3.35; P = 0.03), in favor of the modified regimen.
CONCLUSIONS: Our shorter, within-day regimen for delivering dose-intense weekly cisplatin and oral etoposide to treat platinum-resistant metastatic ovarian cancer is safe and efficacious.
Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer.
Eur J Surg Oncol. 2018; 44(6):760-765 [PubMed] Related Publications
METHODS: A retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure.
RESULTS: 231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimal<1 cm (R1) and Suboptimal (R2) was 51.1, 36.1, and 34.3 months respectively. Statistically significant differences in survival were seen in patients achieving R0vR2 (p < 0.019) but not in R0vR1 (p = 0.125) or R1vR2 (p = 0.358). In group 2, the OS for those achieving R0, R1 and R2 was 53.0, 24.7, and 22.1 months respectively. Statistically significant differences were seen between R0vR1 and R0vR2 (p < 0.00001) but not between R1vR2 (p = 0.917). No difference in OS was seen between groups 1 and 2. In patients achieving R1, there was a trend towards decreasing OS with increasing exposure to NACT from 36.1 (95%CI 32.0-40.2)months with 3 cycles to 24.3 (95%CI 14.4-34.2)months with ≥6 cycles.
CONCLUSIONS: Surgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles.
A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.
Comb Chem High Throughput Screen. 2018; 21(1):50-56 [PubMed] Related Publications
METHOD: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them.
RESULTS AND CONCLUSION: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.
Genes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis.
Cancer Res. 2018; 78(6):1383-1391 [PubMed] Related Publications
White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.
Ann Intern Med. 2018; 168(5):326-334 [PubMed] Related Publications
Objective: To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk.
Design: 2 case-control (initial and validation) studies.
Setting: 2 hospitals in Norway (patients) and a population-based study (control participants).
Participants: 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study.
Measurements: All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC).
Results: In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively.
Limitations: Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting.
Conclusion: Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC.
Primary Funding Source: Norwegian Cancer Society.
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