Ovarian Patients Research Articles

Hospital challenges faced by frail patients with ovarian cancer and the adverse outcomes: A nationwide study.

5572 Background: Ovarian cancer is a leading cause of gynecological cancer-related deaths and one of the most common causes of cancer-related fatalities among women. Frailty has been identified as a predictor of unfavorable outcomes for cancer patients, but there is limited research on its impact on individuals with ovarian cancer. We examined the effects of Frailty in hospitalized ovarian cancer patients and the associated outcomes. Methods: National Inpatient Sample (NIS) 2020 was used to identify the patients with a primary diagnosis of ovarian cancer (local/regional and advanced metastatic) and was stratified into patients with and without Frailty. The primary outcome was mortality, and secondary outcomes included length of stay, the total cost of hospitalization, and other in-hospital adverse outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for confounding variables. Results: A total of 19790 patients were hospitalized with a primary diagnosis of Ovarian cancer, among which 3215 (16.24%) patients had the concurrent diagnosis of Frailty. The mean age of patients with and without Frailty was 65.76 (+/-13.10) and 60 (+/-14.45),p<0.001, respectively. After adjusting for confounding variables, Frailty was associated with an increased risk of mortality in patients with ovarian cancer (OR=3.01(1.83-4.95); p<0.001). Patients with Frailty were also at risk of increased length of stay (+3.80 Days (3.09-4.50; p<0.001) and total cost of hospitalization (+ $ 34662 (22973-46351); p<0.001). Frail patients also had an increased likelihood of Acute respiratory failure (OR=1.72 (1.22-2.42); p=0.002), Acute kidney injury (OR=2.40 (1.88-3.05); p<0.001), Sepsis (OR=4.97 (3.19-7.75); p<0.001), ICU admission (OR=2.23 (1.44-3.45); p<0.001), Pneumonia (OR=2.63 (1.69-4.10); p<0.001), total parenteral nutrition (OR=14.20 (7.80-25.83); p<0.001) and Intubation (OR=2.11 (1.21-3.69); p=0.008). However, there was no difference in the risk of noninvasive mechanical ventilation (OR=2.07 (0.95-4.52); p=0.48) or enteral feeding (OR=32.73 (0.63-1696); p=0.08). Conclusions: Frailty in ovarian cancer patients is considered an independent predictor of mortality. It is also associated with increased healthcare resource utilization and adverse in-hospital outcomes.[Table: see text]

Deciphering the correlation between Chr3q26.2 amplification through homologous recombination deficiency and improved survival in ovarian cancer under platinum-based adjuvant therapy.

e17537 Background: Discriminant copy number alterations (CNAs) have been linked to aberrant DNA repair mechanisms. This study aimed to identify CNA-based biomarkers, alongside homologous recombination deficiency (HRD) scores for ovarian cancer patients receiving platinum (Pt)-based chemotherapy, especially in BRCA1/2 wild-type or HRD-low patients. Methods: Fourteen most prevalent and significant focal CNA regions (seven amplification and seven deletion) were examined to investigate their correlations with HRD scores via SHAP values of an XGBoost model and the effectiveness of Pt-based adjuvant chemotherapy in a cohort of high-grade serous ovarian cancer (HGSC) patients (TCGA cohort, N=576), and the results were validated in a separate Chinese ovarian cancer cohort (test cohort, N=457). An in-house developed next-generation sequencing HRD pipeline (GeneseeqPrime HRD) was used to determine HRD scores. Histological subtypes, molecular features, and potential molecular mechanisms associated with the identified biomarkers were further explored. Results: Of 14 high-level CNA regions identified by GISTIC in the TCGA cohort, Chromosome 3q26.2 amplification [ Chr3(q26.2) Amp, a prevalence of 30.7%] was associated with increased HRD scores in both BRCA1/2-altered ( p=0.01) and wild-type HGSCs ( p=0.03). Consistently, in the test cohort, higher HRD scores ( p<0.01) and elevated chromosome instability scores ( p<0.01) were observed in Chr3(q26.2) amplified samples. Among 406 patients administrated with Pt-based adjuvant chemotherapy in the TCGA cohort, those with Chr3(q26.2) Amp exhibited a relatively high sensitivity rate ( p=0.09) and significantly superior disease-free survival after adjusting for HRD score, patient age, tumor stage, and residual disease [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.48–0.88] when compared to those without, representing Chr3(q26.2) Amp as an independent predictive biomarker. Similar results were obtained in 78 patients using Pt-based adjuvant chemotherapy in the test cohort (HR: 0.68, 95% CI: 0.40–1.15). Moreover, Chr3(q26.2) Amp was more prevalent in HGSCs harboring BRCA1/2 or TP53 aberrations than other histological subtypes driven by PIK3CA, PTEN or KRAS mutations ( p<0.01). In comparison to HGSCs without Chr3(q26.2) Amp, Chr3(q26.2) amplified HGSCs exhibited higher Ragnum hypoxia scores ( p<0.01) and a total of four overexpressed proteins, including p62 ( p<0.01), PIK3CA ( p<0.01), CCNB1 ( p<0.01) and TSC1 ( p<0.01), indicative of suppressed homologous recombination repair pathway and cycle cell arrest. Conclusions: Chr3(q26.2) Amp emerges as a promising biomarker for Pt-based adjuvant chemotherapy in ovarian cancer, potentially reflecting a hypoxia-induced etiology through suppressed homologous recombination repair pathway.

Association of enrollment in Medicare Advantage plans versus fee-for-service in patients with a late-stage diagnosis of gynecologic cancer.

11140 Background: In the United States, uterine cancer is the most common gynecologic (GYN) cancer; and ovarian cancer causes more deaths each year than any other GYN cancer. There are currently no recommended population-wide screening tests for ovarian or uterine cancer, which are heavily concentrated in older women. Medicare is the primary health insurer for 97% of Americans aged 65 years and older. This study is the first to examine the association between Medicare enrollment plan – Medicare Advantage (MA) versus fee-for-service (FFS) – and stage at diagnosis among older women newly diagnosed with ovarian or uterine cancer. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER) registries and Medicare enrollment data, we identified 101,193 women aged 65 years and older with newly diagnosed ovarian or uterine cancer between 2007-2019. We categorized patients into two groups: 1) those continuously enrolled in Medicare MA for six months prior to their diagnosis, through the diagnosis month, and the month following diagnosis; 2) those continuously enrolled in Medicare FFS within the same eight-month window. Late-stage was defined as “Distant” stage (with “Local” and “Regional” stages representing an earlier-stage diagnosis) using the SEER Summary Stage variable. The association between Medicare enrollment plan and stage was examined through multivariable logistic regression modeling that adjusted for sociodemographic characteristics. The influence of each predictor on the difference in the probability of late stage was summarized as an adjusted marginal effect (ME). Results: Among uterine cancer patients, 37% had MA insurance. Compared with Medicare FFS enrollees, the adjusted percentage of late-stage diagnosis was 0.6 percentage points (ppt) lower for MA enrollees (95% CI = -1.1-(-0.1); P<0.05). Notably, patients were more likely to have a late-stage uterine diagnosis if they were: non-Hispanic Black or Hispanic (vs. non-Hispanic White); age 75 and older (vs. between 65 -74); and residing in a lower SES neighborhood. Among ovarian cancer patients, 34% had MA insurance. We found no significant difference between Medicare MA and FFS enrollees in ovarian cancer stage at diagnosis. Of note, Non-Hispanic Black patients were significantly more likely to be diagnosed with late-stage disease compared to Non-Hispanic White, and likewise for patients aged 75 and older (vs. between 65-74). Conclusions: Among Medicare beneficiaries (age 65+) diagnosed with uterine cancer, those enrolled in an MA plan were significantly less likely to be diagnosed at a later stage. In similar analyses for ovarian cancer, there was no such MA - FFS difference in the probability of late-stage. As enrollment in Medicare Advantage plans continues to grow, it becomes increasingly important to identify whether there are significant outcome differences between MA and FFS plans.

Effect of circulating tumor cells (CTC) and CTC clusters with PD-L1 dynamic biomarker on cellular burden in patients with ovarian cancer.

e17566 Background: In the precision oncology era, monitoring response to the treatments using circulating blood-based biomarkers e.g. circulating tumor DNA (ctDNA) and Circulating Tumor Cells (CTCs) are being rapidly evaluated and established. The leading cause of ovarian cancer patient mortality is owing to the delayed diagnosis, inability of patient selection for targeted therapies, including the use of immune checkpoint blockade (ICB) agents. The treatment of ovarian cancer usually involves a combination of surgery and chemotherapy. However, post operative resection and therapy with curative intent often fails in accounting the Minimal Cellular Disease (MCD). The dissemination of Circulating Tumor Cells (CTC) remains a dogma of Minimal Residual Disease (MRD) that diffuse and cause micro-metastasis through their epithelial to mesenchymal transitions (EMT) and ‘bio-mechanistic activation’ in blood circulation. Simultaneous detection of over-expression of Programmed Cell Death-Ligand 1 (PD-L1) on CTCs as a dynamic biomarker may be expedient for assessing patients for immune checkpoint inhibitor (ICT) therapy. Methods: In retrospective analysis of real-world data, 75 ovarian cancer patient’s peripheral blood was analyzed for the presence of CTCs with and without the expression of PD-L1 and CTC clusters. CTC were positively detected using OncoDiscover platform approved by CDSCO in 1.5 ml peripheral blood. The platform is multifunctional magneto nanosystem mediated by anti-epithelial cellular adhesion molecule (EpCAM) antibody. CTCs were identified as positive if they were EpCAM +ve, CK+ve, PD-L1 +ve, DAPI +ve and CD45-ve. PD-L1 expression on the CTCs was analyzed based on the linear intensity gradients of the fluorescence signals using image acquisition on an automated Zeiss Microscope. Results: At baseline sample analysis, 86 % (n=65) of the patients showed ≥ 1CTCs per 1.5 ml of blood. The CTC distribution in this study ranged from 1-9 CTCs. Whereas, 46.15 % (n=30) patients with CTCs showed the expression of PD-L1. Noteworthy, the highest number of CTCs were observed ~ 26.7 % (n=23) in age group 41-50. Interestingly, 8 % (n=6) of total patients showed the presence of CTC clusters. The presence of CTCs with expression of PD-L1 and CTC clusters did not correlate with factors like staging, follow ups, metastasis, and DFS status. Conclusions: We observed presence of MCD and MRD in CRC patients, in spite of curative intent in ovarian cancers. Detection of CTCs, CTC clusters with over-expression of PD-L1- as a real time dynamic biomarker may be useful for assessing the patients for early metastasis, regression, and selecting patient suitable for immune checkpoint inhibitor (ICT) therapy when the tissue is inadequate or unavailable for better outcome.

Weekly BH009 in patients with squamous cell carcinoma of the head and neck (SCCHN) and ovarian cancer: Interim phase I results.

e17545 Background: BH009 is a novel polysorbate 80-free formulation of docetaxel that will eliminate hypersensitivity reactions associated with polysorbate 80. BH009 has completed a bioavailability study compared to Taxotere and was found to have a better safety profile to Taxotere with the potential for higher doses. As a result, we conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), and the safety profile of a weekly BH009 regimen in the treatment of patients with advanced SCCHN and Ovarian cancer. Methods: This phase I study assessed safety of BH009 in patients with advanced SCCHN and Ovarian cancer. BH009 was administered at escalating doses (starting dose 40 mg/m2) as a 1-h i.v. infusion for three consecutive weeks every 28 days without dexamethasone premedication. Results: Up to January 2024, 11 patients were treated with BH009 (4 at 40 mg/m2, 7 at 50 mg/m2). 2 patients with SCCHN, and 9 patients with ovarian cancer. 100% of ovarian cancer patients were recurrent platinum-resistant ovarian cancer (PROC) patients. 82% (9/11) of patients had received prior taxanes, of whom 33% (3/9) had received prior docetaxel. There were no DLT observed in 40 mg/m2 dose groups, and one DLT was observed in the 50 mg/m2 group (grade 3 febrile neutropenia). The MTD for BH009 is expected to exceed 50 mg/m2, which would be higher than that of Taxotere under the same dosing regimen (≥50mg/m2 vs 42mg/m2*), and the overall tolerability was better than Taxotere. In this study, treatment-related adverse events (TRAEs) occurred in 100% (11/11) patients. The most common grade 3/4 TRAEs were Leukopenia (36%, n=4), Anaemia (36%, n=4), and Neutropenia (55%, n=6). Non-hematologic toxicities were generally mild with no grade 4 toxicity observed. No AEs that led to death were related to BH009. Up to January 2024, the DCR is 50% (3/6) after 2 courses of treatment. The ORR in 6 evaluable patients was 33% (2/6, 1 patient with SCCHN at 40 mg/m2, 1 patient with ovarian cancer at 50 mg/m2). One patient (17%, 1/6) with ovarian cancer at 50 mg/m2 dose group received a complete response to the target lesion and the non-target lesion was partially responded after 2 courses of BH009, and this patient had been previously treated with docetaxel, carboplatin, and bevacizumab. Conclusions: The weekly BH009 for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and the overall tolerability is better than Taxotere. BH009 has the potential to increase the dose of administration and improve the clinical efficacy. Dose escalation is ongoing. Clinical trial information: NCT06232863 . [Table: see text]

Cold prevention of alopecia during chemotherapy: Real clinical practice.

e24132 Background: Alopecia is one of the most common visible adverse effects of anticancer drug therapy. The incidence of grade 2 alopecia can be as high as 90% in patients getting anthracyclines or taxanes. Decreased scalp temperature causes vasoconstriction which limits the flow of chemotherapeutic agents into the scalp and reduces the metabolism of hair follicle cells at the time of maximum concentration of cytotoxic agents in plasma. This leads to a decrease in the antimitotic and antimetabolic effects of chemotherapy. ORBIS II scalp cooling device has been successfully implemented in comprehensive oncology centers. However, the results of large-scale studies are still lacking which delays application of this technology in clinical practice. The aim of our study was to evaluate the efficacy and safety of alopecia cold prophylaxis using ORBIS device in a regional referral center in Russia. Methods: Between 22 June 2022 and 13 December 2023 101 patients (100 women and 1 man) were treated using ORBIS II in the Department of Chemotherapy N1, City Clinical Cancer Hospital N1, Moscow. Various combinations of chemotherapeutic agents depending on cancer type were administered. Breast cancer was the most common type (63), followed by ovarian (15), uterine (9), lung (6) and cervical cancer (3). Other primaries were represented by 1 patient each: pancreatic, rectal, gastric, fallopian tube and colon cancer. Totally 431 scalp cooling procedures were performed including 261 (61%) in breast cancer and 78 (18%) in ovarian cancer patients. Outcomes were evaluated using the CTCAE/CTCAE V5.0 toxicity criteria. We evaluated the development of 1 grade alopecia (hair loss of less than 50% and not requiring a wig) as a positive result. On the contrary, a negative result was registered in patients with grade 2 alopecia, namely hair loss of 50% or more and/or requiring a wig. Results: Grade 1 alopecia was experienced by 61% of patients and the other 39% had grade 2 alopecia. Notably, the highest incidence of grade 2 alopecia was observed in patients who received doxorubicin 60 mg/cm2 + cyclophosphamide 600 mg/cm2 once every 21 days (9.9%). Taxane-based regimens had a 21% incidence of grade 2 alopecia, while platinum-containing regimens had a 11% incidence. No serious adverse events occurred during the application of cold prophylaxis. The procedure was well-tolerated by all patients. Conclusions: The use of a cold helmet is an effective method of preventing chemotherapy-induced alopecia. Our analysis yielded a success rate of 61%, which is comparable to the worldwide data range of 50% to 80%.

Ethnic and clinical differences in gBRCA and HRD mutated breast and ovarian cancers and their response to PARP inhibitors.

e13102 Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]

Sleep disturbance and fatigue in patients with ovarian cancer during chemotherapy and surgery compared to PARPi maintenance therapy.

e23248 Background: Sleep disturbance and fatigue are prevalent among advanced ovarian cancer (OC) patients and are associated with poor health outcomes. It is unclear how sleep disturbance and fatigue vary across treatment timelines. This study evaluated how patients rate their sleep disturbance and fatigue levels at different points in their treatment trajectory. Methods: 200 U.S. patients with stage III/IV OC diagnosed in 2020-2023 were enrolled. Survey items asked patients to retrospectively assess their sleep disturbance and fatigue levels prior to diagnosis, during treatment, and presently. Sleep disturbance and fatigue were measured using a custom set of Patient-Reported Outcomes Measurement Information System (PROMIS) items based on previous findings. Most were receiving maintenance therapy (44%) or other treatments (34%), and 23% completed treatment. Nearly all participants received surgery (93%) and chemotherapy (97%). 44% of patients had received PARP inhibitor (PARPi) therapy, 18% received immunotherapy, and < 10% received other therapies. Repeated sample t-tests compared symptom burdens. Results: Participants ranked sleep disturbance as most intense during chemotherapy (52%), followed by surgery (33%), hormone therapy (32%), and PARPi (15%). Most participants ranked fatigue as most intense during chemotherapy (67%), followed by hormone therapy (31%), surgery (20%), and PARPi therapy (17%). Paired t-tests show that among participants who received only surgery, chemotherapy and PARPi therapy, sleep disturbance was perceived to be significantly more intense during chemotherapy than when receiving PARPi, t(55) = -2.83, p = .006) and in the 2 weeks after surgery than PARPi therapy, (t(55) = -2.08, p = .043) ( Table). Fatigue was significantly more intense during chemotherapy than when receiving PARPi, (t(55) = -6.21, p < .001) and following surgery than PARPi (t(54) = -4.16, p < .001). Conclusions: OC patients experience intense sleep disturbance and fatigue and perceive levels differently depending on treatment. Chemotherapy was rated the worst for both sleep disturbance and fatigue compared to PARPi and other therapies. Targeted screening and psychosocial support can address these symptoms throughout treatment, especially after chemotherapy. [Table: see text]

Analysis of glycemia during olaparib therapy in patients with ovarian cancer.

e17559 Background: Olaparib (poly(ADP-ribose) polymerase inhibitor) is a relatively new anticancer drug and some of its metabolic side effects, such as its effect on blood glucose, are not yet well defined. The aim of the study was a retrospective analysis to investigate olaparib-induced changes in glucose levels in patients with ovarian cancer (OC). Methods: The study was conducted on 32 OC patients with normoglycemia (3.9–5.5 mmol/l) confirmed before olaparib treatment. The fasting glucose (FG) levels were estimated after I (one month), II (two months), and III (three months) courses of olaparib treatment. The severity of hyperglycemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: During treatment with olaparib, grade 1 hyperglycemia was found in 18 patients (56.2%), therefore hemoglobin A1C level measurement was recommended. The number of patients with impaired fasting glucose (5.6–6.9 mmol/l), characteristic of a pre-diabetic state, was 17 (53.1%), while glycemia indicative of diabetes (≥7.0 mmol/l) were found in 1 patient (3.1%). The statistically significant increase in glycemia was observed after I course of treatment (p< 0.0001), then after the second (p=0.0003), and III course (p=0.0025). Conclusions: During olaparib therapy, hyperglycemia was observed in 56.2% of the analyzed OC patients, implying the need for glycemic monitoring during monthly routine check-ups to implement effective behavioral and therapeutic management.

Identification and validation of immunity- and disulfidptosis-related genes signature for predicting prognosis in ovarian cancer

BackgroundOvarian cancer (OC) ranks as the fifth most prevalent neoplasm in women and exhibits an unfavorable prognosis. To improve the OC patient's prognosis, a pioneering risk signature was formulated by amalgamating disulfidptosis-related genes. MethodsA comparative analysis of OC tissues and normal tissues was carried out, and differentially expressed disulfidptosis-related genes (DRGs) were found using the criteria of |log2 (fold change) | > 0.585 and adjusted P-value <0.05. Subsequently, the TCGA training set was utilized to create a prognostic risk signature, which was validated by employing both the TCGA testing set and the GEO dataset. Moreover, the immune cell infiltration, mutational load, response to chemotherapy, and response to immunotherapy were analyzed. To further validate these findings, QRT-PCR analysis was conducted on ovarian tumor cell lines. ResultsA risk signature was created using fourteen differentially expressed genes (DEGs) associated with disulfidptosis, enabling the classification of ovarian cancer (OC) patients into high-risk group (HRG) and low-risk group (LRG). The HRG exhibited a lower overall survival (OS) compared to the LRG. In addition, the risk score remained an independent predictor even after incorporating clinical factors. Furthermore, the LRG displayed lower stromal, immune, and estimated scores compared to the HRG, suggesting a possible connection between the risk signature, immune cell infiltration, and mutational load. Finally, the QRT-PCR experiments revealed that eight genes were upregulated in the human OC cell line SKOV3 compared with the human normal OC line IOSE80, while six genes were down-regulated. ConclusionsA fourteen-biomarker signature composed of disulfidptosis-related genes could serve as a valuable risk stratification tool in OC, facilitating the identification of patients who may benefit from individualized treatment and follow-up management.

Implementation of video assisted point-of-care germline genetic education and testing for patients with peri-diagnostic pancreatic cancer.

e22530 Background: Germline genetic testing is universally recommended for patients with exocrine pancreatic cancer (PC). Pretest consultation with a genetics professional is recommended to ensure patients are informed about risks, benefits, and limitations of testing. This is a resource intensive process and is associated with a suboptimal testing rate (~30%). Prior work demonstrates that video-assisted pre-test education does not increase patient anxiety compared to traditional pre-test genetic counseling in peridiagnostic ovarian cancer patients. In this report, we assess the feasibility of using a similar video assisted, streamlined genetic education and testing approach in peridiagnostic PC patients. Methods: As part of a pilot quality improvement initiative, patients with a diagnosis of exocrine PC seen in a single academic practice were offered streamlined, video-assisted genetic education followed by germline testing. Patient eligibility for this pilot included: new diagnosis or radiographic suspicion of PC; English language proficiency; and no prior germline testing. After this approach was presented by the medical oncology team, eligible patients viewed a 9-minute educational video describing the goals, pros, and cons of germline genetic testing. After watching the video, patients were given the option to proceed with testing that day. Patients with pathogenic mutations were referred for formal post-test genetic counseling, and patients with variants of uncertain significance (VUSs) were referred on a case-by-case basis. Following IRB approval, we conducted a retrospective review of the experience of all patients presenting to this pilot site from April-Dec 2023. Results: During the study period, 56 new patients with exocrine PC presented to the pilot site. 50 patients were eligible for participating in the pilot program. All patients, except one who declined on the basis of transferring care, consented to testing (49/50; 98%). Median patient age was 71, 49% were female. Race distribution was: White (30), Asian (6), Black (4), Other (2), Declined (7). Median time from patient diagnosis to testing was 11 days. One patient had a germline ATM mutation, and this patient was seen for formal posttest counseling 18 days after testing was initiated. Seven patients had VUSs. Six new patients presenting during the study period were not eligible for this pilot, all due to limited English proficiency. All 6 of these patients underwent genetic testing after translation service assisted counseling by either the primary oncology or cancer genetics team. Conclusions: Video assisted point-of-care genetics education and testing led to nearly universal uptake of genetic testing in peridiagnostic PC patients. This workflow was feasible, timely, and optimized use of genetic counseling resources.

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

59P Real-world effectiveness of niraparib in recurrent ovarian cancer patients in France: Impact of starting dose and timing of the maintenance initiation

59P Real-world effectiveness of niraparib in recurrent ovarian cancer patients in France: Impact of starting dose and timing of the maintenance initiation

Comprehensive molecular profiling of newly diagnosed advanced, high-grade ovarian cancer: Unveiling BRCA1/2 mutations and genomic instability scores to advocate for public insurance coverage of genetic testing—Insights from the Hellenic Society of Medical Oncology (HeSMO) national program.

3146 Background: Homologous recombination deficiency (HRD) in ovarian cancer, indicative of impaired DNA repair, contributes to genomic instability (GIS). Beyond mutations in BRCA1/2 genes, GIS is particularly significant for identifying patients who may benefit from PARP inhibitors. Equivalence between Myriad Genetics' myChoice CDx and the standard diagnostic tests OncoScan and Amoy Diagnostics has been published, prompting HeSMO to launch a national program addressing GIS and BRCA 1/2 mutations in newly diagnosed advanced high grade ovarian cancer patients, with the utilization of these more economically advantageous tests, in order to guide effective therapeutic strategies, since official reimbursement is not yet applicable in our country. Methods: Patients with locally advanced or metastatic high-grade stage III/IV ovarian cancer were eligible for the HeSMO program, submitting an FFPE tissue tumor sample. The evaluation focused on HRD detection (positive or negative) and GIS assessment (high or low), combining results from OncoScan and Amoy Diagnostics. Results: Between August 2022 and December 2023, 511 patients from Greece underwent testing. 48.14% (n=246) tested HRD positive, 46.58% (n=238) HRD negative. High GIS score was observed in 44.81% (n=229), low GIS in 49.71% (n=254). Potential pathogenic mutations in BRCA1/2 genes were found in 19.96% (n=102). BRCA1 mutations (13.70%, n=70) included key mutations: c.190T&gt;C p.(Cys64Arg), c.3700_3704delGTAAA p.(Val1234GlnfsTer8), c.4065_4068del p.(Asn1355LysfsTer10). BRCA2 mutations (6.26%, n=32) comprised of c.1129G&gt;T p.(Glu377Ter), c.3650_3659del p.(Arg1217IlefsTer8), c.7150C&gt;T p.(Gln2384Ter). In 27 samples (5.28%) no result was produced. Conclusions: HRD and GIS are vital genomic instability biomarkers in high-grade ovarian cancer. These metrics provide valuable insights into tumor aggressiveness, guiding therapeutic decisions, including the use of PARP inhibitors. In this study of 511 patients from 50 centers across Greece, 48.14% tested positive for HRD, emphasizing PARP inhibitors' significance and suggesting hereditary implications. Our commitment to enhance patient access to reliable diagnostic biomarker testing in Greece is unquestionable. Furthermore, we believe, our results will strengthen our efforts towards official state reimbursement, paving the way for local HRD testing solutions. [Table: see text]

Nationwide real-world usage of blood-based (liquid) biomarker testing in Japan.

e23311 Background: Despite the advances in precision oncology with biomarker testing including CGP (comprehensive genomic profiling), not all patients are able to benefit from tissue-guided treatment decisions, underscoring a significant demand for advancements in liquid-based biomarker testing for such patients. However, the treatment landscape based on the application and integration of liquid biopsy in clinical practice has yet to be fully characterized in Japan. Methods: Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter in Japan, was established by the Ministry of Health, Labour and Welfare (MHLW) with the start of cancer genome medicine since June 2019. The database collects the clinical and genomic data from 68,242 patients who underwent CGP by the end of 2023. This study included all patient records who underwent liquid CGP testing using FoundationOne Liquid test from the C-CAT database up to June 2023. Results: We analyzed data from 7,461 records, where the patients had an average age of 65.1 (±12.0) years; 58.8% were male. A majority (51.3%) exhibited an ECOG performance status of 0, and 66.5% reported a family history of carcinoma. Predominant cancer types included pancreatic (1,825; 24.5%), prostate (1,182; 15.8%) and biliary tract cancers (838; 11.2%). Following review by an MTB (molecular tumor board), new treatments were initiated in 5.8% (434) of cases, with targeted therapy (181; 41.7%) and chemotherapy (174; 40.9%) being the primary interventions. Separately, 9 (2.1%) of new treatments post-MTB occurred as part of clinical trials. Median (IQR) durations from specimen collection to MTB, MTB to treatment initiation, and specimen collection to post-MTB treatment were 28 (24-34), 35 (13-64), and 63 (42-94) days, respectively. The largest proportion of biomarker testing occurred after the start of second line of therapy (1,720; 23.1%) Pancreatic and biliary tract cancer patients tend to have biomarker testing at the earlier line, whereas prostate and ovarian cancer patients tend to have at the later line. Conclusions: Although the positioning of liquid CGP testing may differ among cancer types, it is important for patients to select appropriate tissue- and liquid-based biomarker testing at the right timing. Understanding this descriptive landscape of biomarker tests utilized in real-world settings will aid decision-making for addressing unmet needs (e.g., low accessibility to treatment) in cancer genome medicine and its positioning in improving the standard of cancer care.

Urinary-based detection of MSL, HE4, and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.

e17567 Background: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified by Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio). In total, this study was based on 1080 biomarker detection runs from 188 serum and 172 urine samples from 192 ovarian cancer patients. Results: While absolute concentrations of MSL and CA125 were higher in serum than in urine, serum HE4 concentrations were considerably lower than urinary HE4 concentrations. Nonetheless, relative intra-patient levels of all three biomarkers strongly correlated between matched serum vs. urinary samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity in predicting surgical outcome and relapse/death among both body fluid types (urinary HE4: AUC=0.854; AUC=0.750, respectively). All clinically relevant findings of urinary MSL, HE4 and CA125 were reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis. Conclusions: We report that the capacity of MSL, HE4 and CA125 for predicting surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.

4P Mutational landscape of ovarian cancer patients (pts) by homologous recombination deficiency (HRD) status

4P Mutational landscape of ovarian cancer patients (pts) by homologous recombination deficiency (HRD) status

57P Prognostic impact of functional domain of BRCA1/2 mutation in platinum-sensitive recurrent epithelial ovarian cancer patients receiving PARP inhibitors

57P Prognostic impact of functional domain of BRCA1/2 mutation in platinum-sensitive recurrent epithelial ovarian cancer patients receiving PARP inhibitors

Identification of tumor-marker gangliosides for early cancer detection: A multi-platform approach.

e17551 Background: Tumor-marker gangliosides (TMGs) have enormous potential for early-stage cancer detection as diagnostic biomarkers despite being relatively understudied in this context. AOA Dx is focused on the analytical development of three separate platforms for the quantitation of TMGs in human serum. The development of these platforms for TMG quantitation may allow for the identification of diagnostic signatures for early-stage cancer detection. Methods: First, we are developing a pipeline of antibody-based assays to target TMGs. To aid in development of multiple immunoassays, we collected specificity and affinity data on commercial and proprietary antibodies targeting TMGs using glycoarrays. We are also currently using two immune-based platforms to target TMGs. We have developed an enzyme-linked immunosorbent assay (ELISA) and we have implemented high-performance thin-layer chromatography (HPTLC) to detect individual and total gangliosides. Additionally, we are applying both targeted and untargeted mass spectrometry to human serum from confirmed cancer diagnoses. Results: The specificity and affinity data from the glycoarrays confirm that our TMG antibodies have negligible cross-reactivity and are suitable for diagnostic platform development. Additionally, our developed ELISA allows for the quantification of TMGs in diverse and complex matrices including human serum and plasma, cell lines, and exosomes. HPTLC also detects individual and total gangliosides in each of these matrices, which allows for high-throughput analysis for TMG quantitation. Finally, the application of both targeted and untargeted mass spectrometry has identified multiple TMGs characterized by unique lipid tails. Notably, MS analysis shows that the serum of melanoma and ovarian cancer patients exhibited significantly increased levels of several ganglioside species compared to age-matched healthy serum, further highlighting the potential of TMGs as a promising avenue for cancer diagnosis. Further experiments will focus on refining all platforms. We will also expand the demographic representation of our human serum sample cohort to confirm the initial findings from our mass spectrometry experiments and continue to use this platform to identify additional TMGs of interest. Conclusions: AOA Dx is advancing the development of a multi-platform approach for the detection of TMGs. Our objective is the identification of a diagnostic disease signature for early-stage cancer detection. The validation of this type of diagnostic panel would allow for expedited diagnosis and treatment of cancers currently diagnosed at late stages, ultimately reducing healthcare costs and increasing survival rates. Future research will aim to validate these biomarkers in independent prospective studies.

Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.