Browsing Over 45 Presentations
29P - Plasma tumor-derived small extracellular vesicles microRNAs plus CA-125 objectively detect residual disease risk after surgical debulking in advanced ovarian cancer
- Jie Tang (Changsha, China)
- Jie Tang (Changsha, China)
Abstract
Background
No residual disease after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models such as CA-125, CT, PET-CT, or laparoscopy.
Methods
In this multiphase cohort study, 348 pre-treatment plasma and postsurgical tissue consecutive samples, and 272 patients were collected from four clinical centers. Circulating sEVs miRNAs profile associated with residual disease was revealed by RNA sequencing in AOC patients. MiRNAs expression was measured via TaqMan quantitative real-time PCR. The prediction model was established via the least absolute shrinkage and selection operator (LASSO), and logistic regression analysis based on the discovery-validation set. Plasma and tissue sEVs were captured by the magnetic bead sorting system (MACS) using cell-type-specific proteins as markers (EpCAM, FAP, CD45, CD235a, CD31).
Results
After analyzing a comprehensive plasma sEVs miRNAs profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA (miR-320a-3p, miR-378a-3p, miR-1307-3p, let-7d-3p) and CA-125 (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (model vs CA-125, NRI=0.471, P<0.001; IDI=0.538, P<0.001; model vs 4-miRNA panel, NRI=0.122, P=0.001; IDI=0.185, P=0.003). Tumor cells-derived sEVs captured on EpCAM+ magnetic beads were the major vehicles affecting circulating sEVs 4-miRNA expressions. Moreover, the model index scores were significant differences between AOC and other confusable diseases (e.g., advanced colorectal cancer).
Conclusions
A reliable and stable model of circulating tumor-derived sEVs 4-miRNA plus CA-125 was established for preoperatively anticipating the high-risk AOC patients of residual disease to optimize clinical therapy.
Legal entity responsible for the study
J. Tang.
Funding
This work was supported by Grants from the General Project of Natural Science Foundation of Hunan Province (No. 2020JJ4051); Promotion Project of Health Suitability Program in Health Department of Hunan Province (No. WZ2020-15); Science and Technology Innovation Program of Hunan Province (No. 2020SK51101); Hunan Cancer Hospital Climbing Fund (No. ZX2020004); Capacity Building Project of Central Subsidy Medical and Health Institutions (No. 20201127-1001); Key Specialty Construction Project in Hunan Province (No. 20210826-1004); General Project in Health Department of Hunan Province (No. 202205015388).
Disclosure
The author has declared no conflicts of interest.
30P - Molecular biomarkers by next generation sequencing predicting oncological outcomes in ovarian cancer patients
- Shira Peleg Hasson (Tel Aviv, Israel)
- Shira Peleg Hasson (Tel Aviv, Israel)
- Dov Hershkovitz (Tel Aviv, Israel)
- Eliya Shachar (Tel Aviv, Israel)
- Mirika Brezis (Tel Aviv, Israel)
- Ido Wolf (Tel Aviv, Israel)
- Tamar Safra (Tel Aviv, Israel)
Abstract
Background
Ovarian cancer (OC) is the most common cause of gynecologic cancer mortality worldwide. Next generation sequencing (NGS) provides molecular biomarkers which can potentially predict oncological outcomes. We performed a retrospective study to examine progonostic biomarkes for ovarian cancer patients treated in our institution.
Methods
We retrospectively evaluated demographic and clinical information of OC patients referred for NGS molecular testing between 2011-2020 at the Tel-Aviv Medical Center. Cox models were used to analyze the clinical impact of molecular biomarkers including LOH and TMB by assessing overall survival (OS) and progression free survival (PFS).
Results
Of 1026 consecutive patients reviewed, 946 were included in the analysis: 108 (11.4%) were referred to NGS and 838 (88.6%) served as control. Patient baseline parameters were similar between the groups. High loss of heterozygosity (LOH) was associated with longer mOS (99.0 vs. 48.2 months, p=0.004). Sixty-six patients had information on TMB status: 75.8% (50/66) had low TMB status (<5) and 24.2% (16/66) had intermediate TMB status (5-15). None had a high TMB status. Analysis of TMB using the Breslow test showed that patients with TMB ≥4 had a statistically significant longer OS compared with patients with TMB<4 (92.8 months [95%CI, 47.1-138.6] vs. 52.77 months [95% CI, 26.4-79.2], p=0.026).
Conclusions
We identified LOH and TMB ≥4 as strong prognostic biomarkers among OC patients. Prospective studies evaluating larger cohorts are necessary to generate a more extensive evaluation of additional prognostic and predictive biomarkers.
Legal entity responsible for the study
The authors.
Funding
Roche Israel.
Disclosure
All authors have declared no conflicts of interest.
31P - Survival outcomes in BRCA pathogenetic mutated, variant of unknown significance, and wild type ovarian cancer patients treated with PARP inhibitors
- Lucia Musacchio (Rome, Italy)
- Lucia Musacchio (Rome, Italy)
- Claudia Marchetti (Rome, Italy)
- Serena Maria Boccia (Rome, Italy)
- Chiara Cassani (Pavia, Italy)
- Jole Ventriglia (Naples, Italy)
- Vanda Salutari (Rome, Italy)
- Floriana Camarda (Rome, Italy)
- Viola Ghizzoni (Rome, Italy)
- Elena Giudice (Rome, Italy)
- Maria Vittoria Carbone (Rome, Italy)
- Sandro Pignata (Naples, Italy)
- GIOVANNI Scambia (Rome, Italy)
- Domenica Lorusso (Rome, Italy)
Abstract
Background
Correlation between BRCA 1 / 2 pathogenetic mutations and response to Poly (ADP-Ribose) Polymerase inhibitors (PARPi) has been fully investigated and amply recognized in ovarian cancer (OC) patients. Moreover, data about clinical implication of variant of unknown significance (VUS) are lacking. The aim of this study was to evaluate differences in survival outcomes in BRCA 1 / 2 pathogenetic mutated, VUS and wild type (WT) relapsed OC patients treated with PARPi.
Methods
In this retrospective case control study OC patients, whose BRCA 1 / 2 genetic tests were available and receiving PARPi as maintenance at the time of first relapse between 2014 and 2021, were included. Patients were divided into three groups according to BRCA mutational status (BRCA 1 / 2 pathogenetic mutated, VUS and WT). Clinical characteristics at baseline and at the time of relapse before PARPi therapy were evaluated and progression free survival (PFS), defined as the time between date of last platinum and date of progression during PARPi or last follow-up, were assessed in each study group.
Results
Out of 67 patients identified, 24 (35.8%), 20 (29.9%) and 23 (34.3%) presented with BRCA 1 / 2 mutation, VUS and BRCA WT, respectively. In the overall population, most patients were diagnosed at an advanced stage, with 82.1% (n=55) at stage III and 8.9% (n=6) at stage IV. Median age at the time of first recurrence before PARPi was 58 years (Interquartile Range 55-61). Patients received Olaparib, Niraparib and Rucaparib as maintenance at the time of fist relapse after complete or partial response to platinum-based chemotherapy and no statistically significant differences were found in previous Platinum Free Interval (PFI) among the analyzed groups. Median PFS of BRCA 1 / 2 pathogenetic mutated patients was significantly longer than patients BRCA WT or VUS (Not Reached versus 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between BRCA WT and BRCA VUS (p = 0.50).
Conclusions
Our study suggests that BRCA VUS carriers present survival outcomes comparable with BRCA 1 / 2 wild type patients and with shorter PFS than women harboring BRCA 1 / 2 pathogenetic mutations.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Marchetti: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Clovis Oncology; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: PharmaMar. V. Salutari: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: AstraZeneca. S. Pignata: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Pfizer. G. Scambia: Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Other: Clovis Oncology; Financial Interests, Personal, Other: Tesaro; Financial Interests, Personal, Other: Johnson & Johnson. D. Lorusso: Financial Interests, Institutional, Sponsor/Funding: Clovis; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Genmab; Other, Personal, Member of the Board of Directors: GCIG. All other authors have declared no conflicts of interest.
32P - BRCA1/2 mutations in epithelial ovarian cancer: treatment response and survival analisys in an Spanish tertiary university hospital
- Isabel Miras Rodriguez (Seville, Spain)
- Isabel Miras Rodriguez (Seville, Spain)
- Elisa Calvo García (Seville, Spain)
- Purificacion Estevez Garcia (Seville, Spain)
Abstract
Background
The presence of germline or somatic BRCA1/2 mutation (gBRCA1/2 or sBRCA1/2) on epithelial ovarian cancer (EOC) patients (pts) improves progression-free survival (PFS) and overall survival (OS). BRCAm is the only validated molecular biomarker both prognostic and predictive of platinum and PARPi response. Identification of these pts is already mandatory to optimize treatment strategies and the need for genetic counselling. We aimed to describe our BRCAm EOC population to analyse tumor response and survival outcomes.
Methods
This was an observational, retrospective study with 194 pts diagnosed with advanced EOC (FIGO stage III-IV) in our institution from 01/2015 to 01/2021. The presence of BRCA1/2 mutation was determined using next generation sequencing (NGS).
Results
The most common histology was high-grade serous carcinoma in 86’6%. Median age was 59 years (25-87). BRCA status was WT/mut/unk: 71’1%/19’1%/9’8% (17/37 BRCA1, 20/37 BRCA2). On BRCAm population, 40’5% pts had a family history of EOC or breast cancer (BC) (2/35 pts had a previous BC, 100% BRCA1m). 37’8% had a primary debulking surgery (PDS) (8/13 R0) and 40’5% had an interval debulking surgery (IDS) (14/15 R0). Median OS in pts with PDS was 64 months (mo) (43 mo on WT population) vs 30 mo in pts who were not candidates for surgery (7/37 pts with FIGO stage IV; 13 mo on WT population) (p<0.04). Carboplatin/paclitaxel was the most frequently prescribed CT (70’3%, 10/26 pts neoadjuvant) as first line followed by PARPi in 8 pts (pts newly diagnosed). 15/37 pts progressed to first line (0/15 pts treated with PARPi) and 73% showed a platinum-sensitive disease (9/11 received maintenance PARPi, 3/9 of them relapsed after 12 mo of treatment). First-line PFS was 19 mo. The median follow up was 26 mo. 5/37 pts died due to clinical impairment or relapsed.
Conclusions
Early identification of BRCAm EOC pts is essential in order to optimize treatment sequence, and identify women who can receive PARPi therapy which is established as the standard of care for this population.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Estévez García: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis. All other authors have declared no conflicts of interest.
33P - The Development of Infrastructure for Mainstream Ovarian Cancer Genetic Testing (DEMO)
- Ionut G. Funingana (Cambridge, United Kingdom)
- Ionut G. Funingana (Cambridge, United Kingdom)
- Elaine Leung (Birmingham, United Kingdom)
- Marie-Lyne Alcaraz (Cambridge, United Kingdom)
- Lisa Bird (Birmingham, United Kingdom)
- Joo Ern Ang (Cambridge, United Kingdom)
- Christine Parkinson (Cambridge, Ca, United Kingdom)
- Merche Jimenez-Linan (Cambridge, United Kingdom)
- Sue Freeman (Cambridge, United Kingdom)
- Catherine Spencer (West Bromwich, United Kingdom)
- Julie Winning (Birmingham, United Kingdom)
- Raji Ganesan (Birmingham, United Kingdom)
- Sarah Williams (Birmingham, United Kingdom)
- Kai Ren Ong (Birmingham, United Kingdom)
- Parveen Abedin (Birmingham, United Kingdom)
- Sudha Sundar (Birmingham, United Kingdom)
- Janos Balega (Birmingham, United Kingdom)
- James D. Brenton (Cambridge, United Kingdom)
Abstract
Background
In patients with ovarian cancer effective testing for homologous recombination deficiency (HRD) is crucial to guide the use of PARP inhibitors, with or without bevacizumab. However, variations in uptake of testing and the quality and quantity of specimens are major barriers to the implementation of rapid universal molecular profiling. There are no national standards for diagnostic biopsies to ensure their suitability for molecular diagnostics. The aims of this study are to identify and mitigate the causes of demographic (including ethnicity) and clinical pathway variation for molecular testing in patients diagnosed with ovarian cancer.
Methods
DEMO is a multi-centre quality improvement study based on a Plan-Do-Study-Act approach. The three components include 1) the establishment of a patient advisory group to explore the variations in uptake and co-produce multimedia, multilingual patient information package to support informed decision making; 2) use of improvement methodology to analyse existing diagnostic pathways and 3) the development of a multidisciplinary consensus guideline to increase the reliability of current biopsy pathways for molecular diagnostics.
Results
A retrospective combined audit from Cambridge and Birmingham of 75 patients over 8 months in 2021 showed high failure rates for somatic molecular testing (tumoural BRCA or HRD testing). Failure rates of 25% (3/12) and 35% (11/31) failed when samples from image-guided biopsies and after chemotherapy were used, respectively. Low uptake of mainstreamed genetic testing in Cancer Centers with high ethnic diversity (∼15% of women diagnosed with ovarian cancer are in the ethnic minorities groups at Birmingham City Hospital) can be related to a gap in understanding the importance of tumour testing in the wider multidisciplinary team and to language and culture barriers.
Conclusions
Failure to address the systemic problems of the biopsy pathway will perpetuate substandard treatments and clinical trial opportunities for women receiving neoadjuvant chemotherapy. Provision of easily accessible video information to initiate patient dialogue and decision making could address the information gap to support informed decision making in women whose English is not their first language.
Legal entity responsible for the study
The authors.
Funding
Ovarian Cancer Action.
Disclosure
S. Sundar: Financial Interests, Personal, Invited Speaker for conference: AstraZeneca; Financial Interests, Personal, Invited Speaker for conference: MSD; Financial Interests, Personal, Invited Speaker at workshop: GSK; Non-Financial Interests, Personal, Leadership Role, President of the British Gynaecological Cancer Society: BGCS. J.D. Brenton: Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Tailor Bio; Financial Interests, Personal, Stocks/Shares: Tailor Bio; Financial Interests, Institutional, Invited Speaker: Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Aprea AB; Non-Financial Interests, Personal, Member: Association of Cancer Physicians. All other authors have declared no conflicts of interest.
34P - Immunocytochemical determination of EpCAM protein expression in ascitic fluid cells in the diagnosis of ovarian cancer using the SER1 test system
- Irina A. Kruglova (Niznii Novgorod, Russian Federation)
- Irina A. Kruglova (Niznii Novgorod, Russian Federation)
- Oleg V. Utkin (Nizhny Novgorod, Russian Federation)
- Svyatoslav V. Zinoviev (Nizhny Novgorod, Russian Federation)
Abstract
Background
The most common first symptom of ovarian cancer (OC) is the accumulation of serous fluid in the abdominal cavity. Morphological verification is necessary to resolve the issue of the nature of the process and the purpose of treatment. Cytological examination (CE) of ascitic fluid is a subjective method based on the knowledge and experience of a morphologist. The use of a comprehensive assessment of the CE with subsequent immunocytochemical (ICH) revision is a trend of modern diagnostics, and the use of test systems for the diagnosis of ICH, focused on one patient, will increase the availability of this type of study in the primary polyclinic. The aim of the work is to evaluate the diagnostic informativeness of using the SER 1 test system in the biochip format to determine the expression of EpCAM protein in ascitic fluid cells in the detection of OC.
Methods
70 samples of ascitic fluid obtained from patients with suspected OC who sought planned or emergency medical care at the surgical hospital of Nizhny Novgorod City Hospital No. 35 in 2021 were analyzed. All samples of ascitic fluid were examined cytologically. Using the SER1 test system (RUSSELL LLC, Russia), an ICH study was conducted, the results of which were visualized using a Zeiss Primo Star microscope (Carl Zeiss, Germany). The findings were classified in accordance with the International Cytological Classification of Effusion Fluids (TIS RSFC).
Results
During CE, data were obtained: non-diagnostic material (ND) - 11.4%, absence of malignant cells (NFM) - 44.3%, presence of cells with atypia of unclear significance (AUS) - 10%, suspicion of cancer (SFM) - 20%, malignant nature of cells (MAL) - 14.3%. An additional ICC study of EpCAM protein expression on SER 1 test systems changed the results within the categories: NFM - 58.6%, AUS - 0%, SFM - 2.8%, MAL - 27.2%.
Conclusions
A comprehensive assessment of the CE of effusion fluids, supplemented by ICH staining, increases the detectability of malignant tumor cells by 1.9 times, reducing the number of conclusions in the AUS,SFM categories. The use of the SER1 test system introduces ICH research into the practice of primary hospitals that do not belong to the oncology profile and contributes to the earlier diagnosis of OC.
Legal entity responsible for the study
The authors.
Funding
Russell Llc, Russian Federation.
Disclosure
All authors have declared no conflicts of interest.
35P - Racial Disparities in Diagnosis, Histological Type,Treatment and Survival in Ovarian Cancer Patients in the US from 1992 to 2018: SEER-based Analysis.
- Eman I. Zin Eldin (Menoufia, Egypt)
- Eman I. Zin Eldin (Menoufia, Egypt)
Abstract
Background
Ovarian malignancies are the 7th diagnosed malignancy and the 8th cause of death in females worldwide. Ovarian cancer includes a great heterogeneous group of neoplasms that differs in histological type, pathological stage, risk factors, prognosis, and treatment. Racial disparities in incidence, treatment, and mortality in cancers exist globally. With Surveillance, Epidemiology, and End Results (SEER) program in place, detection of these disparities would be feasible. herein racial disparities in ovarian cancer are analyzed.
Methods
Using SEER*Stat 8.3.9 program and then Case listing session and extracting data from Incidence - SEER Research Data, 13 Registries, Nov 2020 Sub (1992-2018). Patients with malignant behavior and known age diagnosed between 1992 to 2018 and site recode ICD-O-3 WHO 2008(ovary) were included; patients with incomplete data were excluded. Descriptive analysis and Kaplan Miere survival are done using IBM SPSS Statistics 25.
Results
46854 patients were included in the analysis, Non-Hispanic (NH) white race was 69.9% of them followed by the Hispanic group represents 11.8%. There was a great association between races and histology; eta was 0.06, Most predominant histological type was non-invasive low-grade serous carcinoma by 22.9%,20.7%,18.9% in NH white, Hispanic, NH black respectively. 2nd most predominant was Serous tubal intraepithelial carcinoma in NH American Indian/Alaska Native and NH Asian or Pacific Islander by 24.0% and 18.8% respectively. Kaplan Meier analysis revealed the best median survival time of 78 months (95%CI 70.89:85.12, SE 3.63) in NH Asian or Pacific Islander group, followed by Hispanic (All Races) with 56 months (95%CI 52.09:59.91, SE 1.99). The worst survival time was noticed in Non-Hispanic Black with a median survival time of 27 months (95%CI 24.95:29.05 SE 1.04). Log Rank p-value =0.001. Regarding Racial association with staging; eta was 0.04 and distant stage was predominant in all races 68.0%,68.7%,57.7%,67.1%,62.6% for NH White, NH Black, NH Asian or Pacific Islander, NH American Indian/Alaska Native, Hispanic (All Races) respectively.
Conclusions
Our analysis goes along with present literature regarding racial disparities.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
36P - Factors associated with platinum resistance in ovarian cancer patients receiving neoadjuvant chemotherapy
- Qinglei Gao (Wuhan, China)
- Qinglei Gao (Wuhan, China)
- Liu Xingyu (Wuhan, China)
- Hu Ting (Wuhan, China)
- Xiaofei Jiao (Wuhan, China)
- Zhao Yingjun (Wuhan, China)
- Guanchen Ma (Wuhan, China)
- Yabing Huo (Wuhan, China)
- Li Ming (Wuhan, China)
- Zikun Peng (Wuhan, China)
- Jianhua Chi (Wuhan, China)
- Shaoqing Zeng (Wuhan, China)
- Yang Yuyy (Wuhan, China)
Abstract
Background
Currently, researchers have found that neoadjuvant chemotherapy (NACT) which could enhance the stemness of ovarian cancer cells and induce platinum resistance gene mutations is an independent risk factor for platinum resistance. However, there is little data concerning the potential factors contributing to platinum resistance in patients receiving NACT. Herein, we conducted this real-world retrospective study to explore the factors associated with platinum resistance in NACT population.
Methods
Patients with histologically confirmed advanced ovarian cancer (IIIC-IV) who had received NACT at seven hospitals in China were enrolled from May 2004 to June 2020. Univariate and multivariate logistic regressions were performed with odds ratios (ORs) and 2-tailed 95% confidence intervals (CIs) to analyze the impacts of age, type, grade, stage, CA125 level, number of NACT cycles, and postoperative residual disease (R0, no macroscopic residual disease; R1, the maximum diameter of postoperative residual disease ≤ 1cm; R2, the maximum diameter of postoperative residual disease > 1cm) on platinum resistance. Statistical significance was considered at P < 0.05.
Results
A total of 630 patients with stage IIIC-IV ovarian cancer who received NACT were included in the analysis. 316 (50.2%) patients received no more than two cycles of neoadjuvant chemotherapy. Patients with 1 or 2 NACT cycles had a lower rate of platinum resistance recurrence than patients with more than 2 NACT cycles (26.3% vs 35.4%, P = 0.017). In the univariate analyses, Stage IV and more than 2 NACT cycles were risk factors for platinum resistance (OR = 1.44, P = 0.039; OR = 1.54, P = 0.014). Besides, R1 and R2 were also risk factors for platinum resistance (OR = 1.61, P = 0.017; OR = 2.19, P = 0.001). In the multivariate logistic regression analyses, more than 2 NACT cycles was an independent risk factor for platinum resistance (OR = 1.79, P = 0.005). R1 and R2 were also independent risk factors for platinum resistance (OR = 2.00, P = 0.004; OR = 3.17, P < 0.001).
Conclusions
More than 2 cycles of NACT and residual disease were independent risk factors for platinum resistance in advanced ovarian cancer patients receiving neoadjuvant chemotherapy.
Legal entity responsible for the study
Tongji Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
37P - Obesity and ovarian cancer, a controversial risk factor
- Firas Baidoun (Cleveland, OH, United States of America)
- Firas Baidoun (Cleveland, OH, United States of America)
- Jasmin Abdeldayem (Cleveland, OH, United States of America)
- Anas M. Saad (Detroit, MI, United States of America)
- Muhammad T. Sarmini (Cleveland, OH, United States of America)
- Mohamed M. Gad (Cleveland, AL, United States of America)
- Muhamad Alhaj Moustafa (Jacksonville, FL, United States of America)
Abstract
Background
Ovarian cancer is the eighth most common malignancy in females and the third most common gynaecological malignancy in the world. It is the leading cause of gynaecological cancer death in the world. Obesity, which is increasing worldwide, is still a controversial risk factor for ovarian cancer and till now there is no consensus on the obesity role on ovarian cancer. Therefore, we investigated the association between obesity and ovarian cancer using a large inpatient database.
Methods
We used the National Inpatient Sample (NIS) database to review female admissions between 2002 and 2015. Patients were grouped based on the presence or absence of obesity using the appropriate ICD-9 codes. We used a multivariate logistic regression to assess the association between obesity and ovarian cancer.
Results
We reviewed 50,469,770 admissions of which 4,365,971 (8.7%) were obese. Both groups had a similar median age (54 years) but obese patients were more likely to be black (20% vs. 14%, P<.001), have polycystic ovarian syndrome (PCOS) (0.5% vs 0.1%, P<.001), endometriosis (0.9% vs. 0.7%, P<.001) and be smokers (12% vs 9%, P<.001). Family history of ovarian cancer was similar in both groups. After adjusting for age, BRCA1/BRCA2 mutations, family history, lynch syndrome, smoking, IUD, endometriosis, PCOS, infertility, oral contraceptive pills, and hormone replacement therapy, obese patients were significantly less likely to have ovarian cancer (OR=0.821, 95%CI[0.808-0.835], P< .001) compared with patients without obesity. To further assess the association between obesity and ovarian cancer in pre-menopause vs post-menopause, we did a subgroup analysis based on age, the same trend was observed in both patients younger and older than 50 years.
Conclusions
In our large database study, we found that obesity was associated with lower rate of ovarian cancer and that association was seen in both young and older patients. However, the timeliness of obesity in relation to ovarian cancer cannot be determined through the NIS database and thus further prospective epidemiological studies are warranted.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
38P - Impact of 1-year COVID-19 pandemic in patients with ovarian carcinoma treated with chemotherapy based on a GLOBAL DATA NETWORK
- Luis M. Manso Sanchez (Madrid, Spain)
- Luis M. Manso Sanchez (Madrid, Spain)
- Ainhoa Madariaga Urrutia (Madrid, Spain)
- Gema Hernández-Ibarburu (Madrid, Spain)
- Rodrigo Sanchez Bayona (Madrid, Spain)
- Pablo Tolosa Ortega (Madrid, Va, Spain)
- Laura Lema Roso (Madrid, Spain)
- Manuel Alva (Madrid, Spain)
- Andrea Modrego (Madrid, Spain)
- Pablo Serrano (Madrid, Spain)
- Luis Paz-Ares (Madrid, Spain)
Abstract
Background
The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Patients with ovarian cancer (OC) have been affected by a delay in diagnosis, surgery, and chemotherapy treatment (Jacome LS et al. Cancer Manag Res. 2021).
Methods
Here we have obtained a comprehensive overview of the impact of COVID-19 in patients with OC on a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCOs) all over the world. Descriptive statistics were used, and survival analyses were conducted using the Kaplan-Meier method.
Results
Through propensity score matched analyses of 74 global HCOs from 14 countries[AM1] we found that the number of new diagnoses of OC was reduced between the period from March 2020 to March 2021 (n=10.453) compared to 1-year prior to the COVID-19 pandemic (n=11.449), RR 0.91 [95%CI 0.88–0.9], p< 0.0001. SARS-CoV-2 infection in patients with OC treated with chemotherapy (n=710) was associated with worse overall survival than in patients without chemotherapy (n=1.770), HR 0.33 [95%CI 0.23-0.48], p< 0.0001.The risk of inpatient hospitalisation due to COVID-19 infection was higher in patients receiving chemotherapy vs no chemotherapy, RR 0.50 [95%CI 0.43-0.59], p < 0.0001. Overall, there was a very low rate of invasive mechanical ventilation utilization, with no differences in its use detected between those patients undergoing chemotherapy (n=24) and those who did not (n=18), RR 0.75 [95%CI 0.41-1.37), p=0.347.
Conclusions
This study highlights the necessity of extending preventive measures worldwide to protect vulnerable OC patients from SARSCoV-2 infection and promote intensive vaccination strategies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
39P - Longitudinal Increases in Albumin-Adjusted Serum Calcium Predict Ovarian Cancer
- Gary Schwartz (Grand Forks, ND, ND, United States of America)
- Gary Schwartz (Grand Forks, ND, ND, United States of America)
- Dennis Lutz (Grand Forks, United States of America)
- Maria Bell (Sioux Falls, United States of America)
- Marilyn Klug (Grand Forks, ND, United States of America)
Abstract
Background
Screening methods for ovarian cancer are urgently needed. Previously, we showed that women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin (Schwartz et al, 2020, Gynecol Oncol 2020:159:264-269). These changes could be useful in screening. We asked, prior to their diagnosis, are women with ovarian cancer more likely to show a positive slope in their in albumin-adjusted serum calcium (a-asc)?
Methods
This is a population-based case-control study based in Sioux Falls, SD. Cases were women with epithelial ovarian cancer. Controls are women without a diagnosis of cancer. Patients with a history of cancer and/or parathyroid disease were excluded. Data are from patients’ Comprehensive Metabolic Panels (CMPs). We calculated albumin-adjusted serum calcium (a-asc) and estimated regression equations of each woman’s a-asc from pre-diagnosis to diagnosis. Data were analyzed by multiple regression, ANCOVA and logistic regression.
Results
We studied 124 cases and 98 controls. Cases were significantly older than controls (64.7 12.9 SD, vs. 41.0 16.8 years). For controls, the first and last a-asc was 9.23 mg/dL, for a slope of 0. For cases, the first and last values of a-asc were 9.28 and 9.37 mg/dL, for a slope of 0.04 mg/dl per year (P<0.001). The probability of cancer for a 0.04 mg/dL/year increase in a-asc increased with age until age 70 and showed a significant dose-response. The Odd Ratio (OR) of ovarian cancer for a 65 yr old woman with a 0.06 mg/dL increase/year was ∼3.0; the OR for a 1 mg/dl increase/year was ∼10. This effect was also seen for early stage tumors and persisted after age-adjustment.
Conclusions
In health, serum calcium levels are tightly regulated and the “expected” slope of a-asc is zero. A significant positive slope of a-asc in women with ovarian cancer, if confirmed by future studies, suggests that an increase in the slope a-asc could help identify women with undiagnosed ovarian cancer. Increases in a-asc were often small and could be easily overlooked. However, a computer algorithm could calculate the slope from patients’ annual records. Women with rising a-asc could be candidates for increased medical surveillance (e.g., transvaginal ultrasonography).
Legal entity responsible for the study
The authors.
Funding
This research was funded by grants from the University of North Dakota School of Medicine & Health Sciences, the Great Plains IDeA-CTR and the Coverys Community HealthCare Foundation (to GGS).
Disclosure
All authors have declared no conflicts of interest.
40P - Exome sequencing analysis of primary and recurrent ovarian carcinomas
- Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
- Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
- Anna Sokolenko (Saint-Petersburg, Russian Federation)
- Tatiana Gorodnova (Saint-Petersburg, Russian Federation)
- Alexandr O. Ivantsov (Saint-Petersburg, Russian Federation)
- Ilya Bizin (Saint-Petersburg, Russian Federation)
Abstract
Background
Ovarian carcinomas (OCs) are highly sensitive to platinum-based therapy, however most of OCs eventually relapse. This study aimed to compare genomic profiles in primary vs. recurrent OCs.
Methods
Primary, recurrent and normal tissue triplets obtained from 15 patients were subjected to exome sequencing. The comparison included 1) spectrum of driver mutations [Tamborero et al., 2018; PMID: 29592813]; 2) tumor mutation burden (TMB); 3) HRD score [Telli et al., 2016; PMID: 26957554]; 4) mutational signatures [Degasperi et al., 2020; PMID: 32118208].
Results
All driver mutation present in primary tumors remained in the genome through the treatment course. One or several new driver somatic mutations emerged in 6/15 (40%) recurrent lesions. These alterations involved RB1 and ELAC2 (n = 1), TNC (n = 1), TRIO and IKBKB (n = 1), PAX5 and CDH10 (n = 1), SOX9 (n = 1), ABCB4 and EEF1A1 (n = 1) genes. Recurrent tumors demonstrated small but statistically significant increase of TMB as compared to primary lesions (4.7 vs. 3.9 per megabase, p = 0.01). HRD demonstrated high degree of similarity within primary/recurrent tumor pairs. PLATINUM mutation signature was characteristic for platinum-sensitive relapses, but not for platinum-resistant recurrences or chemonaive tumors (p = 0.02).
Conclusions
HRD score remains stable through the treatment history. PLATINUM mutation signature reflects not only the mere fact of prior exposure to platinum-based therapy, but also the efficacy of this therapeutic regimen.
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation, grant 21-75-30015.
Disclosure
All authors have declared no conflicts of interest.