{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:22Z","timestamp":1787027902406,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival. Objectives: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer. Materials and methods: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II\u2013IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52\u2013129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan\u2013Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy. Results: The Kaplan\u2013Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005). Conclusions: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.<\/jats:p>","DOI":"10.3390\/curroncol28050313","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T22:34:01Z","timestamp":1632263641000},"page":"3668-3682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-6159","authenticated-orcid":false,"given":"Stanislav","family":"Slavchev","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University \u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"},{"name":"Obstetrics and Gynecology Clinic, St. Anna University Hospital, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavor","family":"Kornovski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University \u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"},{"name":"Obstetrics and Gynecology Clinic, St. Anna University Hospital, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-382X","authenticated-orcid":false,"given":"Angel","family":"Yordanov","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonka","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University \u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"},{"name":"Obstetrics and Gynecology Clinic, St. Anna University Hospital, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-3095","authenticated-orcid":false,"given":"Stoyan","family":"Kostov","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University \u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"},{"name":"Obstetrics and Gynecology Clinic, St. Anna University Hospital, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-6398","authenticated-orcid":false,"given":"Svetoslava","family":"Slavcheva","sequence":"additional","affiliation":[{"name":"ES Cardiology, First Department of Internal Diseases, Faculty of Medicine, Medical University \u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_3","unstructured":"World Health Organization (2021, April 24). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Amini, M., Zayeri, F., and Salehi, M. (2021). Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: Results from global burden of disease study 2017. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-10429-0"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/bmj.38678.389583.7C","article-title":"Excess risk of fatal coronary heart disease associated with diabetes in men and women: Meta-analysis of 37 prospective cohort studies","volume":"332","author":"Huxley","year":"2005","journal-title":"Br. Med. J."},{"key":"ref_6","unstructured":"(2021, April 24). Cardiovascular Disease Statistics in Eurostat, Statistic Explained. Available online: https:\/\/ec.europa.eu\/eurostat\/statisticsexplained\/index.php?title=Cardiovascular_diseases_statistics."},{"key":"ref_7","unstructured":"(2021, April 24). Cancer Research UK. Available online: https:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/statistics-by-cancer-type\/ovarian-cancer\/survival#ref-2full."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","first-page":"CD007565","article-title":"Optimal primary surgical treatment for advanced epithelial ovarian cancer","volume":"2011","author":"Elattar","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.20892\/j.issn.2095-3941.2016.0024","article-title":"Genetic and molecular changes in ovarian cancer","volume":"13","author":"Hollis","year":"2016","journal-title":"Cancer Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.critrevonc.2005.04.008","article-title":"Prognostic impact of increasing age and co-morbidity in cancer patients: A population-based approach","volume":"55","author":"Houterman","year":"2005","journal-title":"Crit. Rev. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1525-1438.2007.01036.x","article-title":"Comorbidity and ovarian cancer survival in Denmark, 1995\u20132005: A population-based cohort study","volume":"18","author":"Tetsche","year":"2008","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ygyno.2021.03.008","article-title":"Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer","volume":"161","author":"Mallen","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11720","DOI":"10.1038\/srep11720","article-title":"Comorbidity and survival among women with ovarian cancer: Evidence from prospective studies","volume":"5","author":"Jiao","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ygyno.2012.12.039","article-title":"Comorbidity is an independent prognostic factor for the survival of ovarian cancer: A Danish register-based cohort study from a clinical database","volume":"129","author":"Sperling","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1080\/0284186X.2018.1440085","article-title":"Confounders other than comorbidity explain survival differences in Danish and Swedish ovarian cancer patients\u2014A comparative cohort study","volume":"57","author":"Noer","year":"2018","journal-title":"Acta Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10552-017-0867-1","article-title":"History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: Evidence from the ovarian cancer association consortium","volume":"28","author":"Minlikeeva","year":"2017","journal-title":"Cancer Causes Control."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Akhavan, S., Ghahghaei-Nezamabadi, A., Modaresgilani, M., Mousavi, A.S., Sepidarkish, M., Tehranian, A., and Rezayof, E. (2018). Impact of diabetes mellitus on epithelial ovarian cancer survival. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5162-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1097\/IGC.0b013e31824b403d","article-title":"Does Significant Medical Comorbidity Negate the Benefit of Up-front Cytoreduction in Advanced Ovarian Cancer?","volume":"22","author":"Ferriss","year":"2012","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00423-020-01895-y","article-title":"Predictors of overall survival following extended radical resections for locally advanced and recurrent pelvic malignancies","volume":"405","author":"Kong","year":"2020","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1158\/1055-9965.EPI-13-0625","article-title":"Impact of Cardiovascular Comorbidity on Ovarian Cancer Mortality","volume":"22","author":"Shinn","year":"2013","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/(SICI)1097-0142(20000201)88:3<653::AID-CNCR24>3.0.CO;2-1","article-title":"Cancer and comorbidity: Redefining chronic diseases","volume":"88","author":"Ogle","year":"2000","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.atherosclerosis.2017.06.001","article-title":"Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention","volume":"263","author":"Masoudkabir","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/00004347-199907000-00019","article-title":"Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament","volume":"18","author":"Scully","year":"1999","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/CIRCULATIONAHA.115.020406","article-title":"Shared Risk Factors in Cardiovascular Disease and Cancer","volume":"133","author":"Koene","year":"2016","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ygyno.2010.12.329","article-title":"The impact of diabetes on survival in women with ovarian cancer","volume":"121","author":"Bakhru","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Savant, S.S., Sriramkumar, S., and O\u2019Hagan, H.M. (2018). The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer. Cancers, 10.","DOI":"10.3390\/cancers10080251"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.critrevonc.2016.06.006","article-title":"Metformin use and gynecological cancers: A novel treatment option emerging from drug repositioning","volume":"105","author":"Gadducci","year":"2016","journal-title":"Crit. Rev. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ygyno.2012.07.115","article-title":"Metformin targets ovarian cancer stem cells in vitro and in vivo","volume":"127","author":"Shank","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.ygyno.2017.05.009","article-title":"Statin treatment is associated with survival in a nationally representative population of elderly women with epithelial ovarian cancer","volume":"146","author":"Vogel","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1097\/AOG.0000000000004173","article-title":"Updates and New Options in Advanced Epithelial Ovarian Cancer Treatment","volume":"137","author":"Kurnit","year":"2021","journal-title":"Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/HCO.0000000000000619","article-title":"Risk factors for chemotherapy-related cardiac toxicity","volume":"34","author":"Polonsky","year":"2019","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1093\/annonc\/mdr408","article-title":"Longitudinal changes in cardiac function after cisplatin-based chemotherapy for testicular cancer","volume":"22","author":"Altena","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1200\/JCO.1991.9.9.1704","article-title":"Cardiac disturbances during the administration of taxol","volume":"9","author":"Rowinsky","year":"1991","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1093\/eurheartj\/ehn384","article-title":"Bevacizumab treatment for cancer patients with cardiovascular disease: A double edged sword?","volume":"29","author":"Pereg","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_36","first-page":"A16315","article-title":"Olaparib, a Clinically Used Poly(adp-ribose) Polymerase Inhibitor, Protects against Oxidant-Induced Cardiac Myocyte Death in vitro and Improves Cardiac Contractility during Early Phase after Heart Transplantation in an in vivo Rat Model","volume":"136","author":"Marcatti","year":"2017","journal-title":"Circulation"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:02:56Z","timestamp":1760166176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,21]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["curroncol28050313"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28050313","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,21]]}}}