Advanced Ovarian Cancer Patients Research Articles

Application of Dynamic and Static Light Scattering for Size and Shape Characterization of Small Extracellular Nanoparticles in Plasma and Ascites of Ovarian Cancer Patients.

In parallel to medical treatment of ovarian cancer, methods for the early detection of cancer tumors are being sought. In this contribution, the use of non-invasive static (SLS) and dynamic light scattering (DLS) for the characterization of extracellular nanoparticles (ENPs) in body fluids of advanced serous ovarian cancer (OC) and benign gynecological pathology (BP) patients is demonstrated and critically evaluated. Samples of plasma and ascites (OC patients) or plasma, peritoneal fluid, and peritoneal washing (BP patients) were analyzed. The hydrodynamic radius (Rh) and the radius of gyration (Rg) of ENPs were calculated from the angular dependency of LS intensity for two ENP subpopulations. Rh and Rg of the predominant ENP population of OC patients were in the range 20–30 nm (diameter 40–60 nm). In thawed samples, larger particles (Rh mostly above 100 nm) were detected as well. The shape parameter ρ of both particle populations was around 1, which is typical for spherical particles with mass concentrated on the rim, as in vesicles. The Rh and Rg of ENPs in BP patients were larger than in OC patients, with ρ ≈ 1.1–2, implying a more elongated/distorted shape. These results show that SLS and DLS are promising methods for the analysis of morphological features of ENPs and have the potential to discriminate between OC and BP patients. However, further development of the methodology is required.

Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study

BackgroundOnly 8–23% of advanced epithelial ovarian cancer patients survive for 10 years or longer. Given the need for targeted interventions to improve survival, we interviewed this relatively rare survivor population to gain personalized insights into the reasons for their survival. The aim of this study was to characterize subjective attributions of survival and specific coping mechanisms long-term survivors of ovarian cancer.MethodsTwenty-two semi-structured, qualitative interviews assessing survival attributions and coping strategies were conducted from April to November 2014. Data were analyzed in a multistep process using ATLAS.ti.8: codes were identified during review of the transcripts and refined with literature review; the frequency of codes and code co-occurrence was calculated, and codes were grouped into themes. Resulting themes were checked by a national leader of an ovarian cancer advocacy organization and compared against available literature.ResultsThematic analysis found that participants credited their long-term survival to a variety of factors including medical, social, religious/spiritual, and lifestyle/personal characteristics. Some participants rejected these same attributions, concluding that the reason for survival was due to luck or unknowable. Several of Carver et al.’s theoretical dimensions of coping were evident in our sample: planning, positive reinterpretation, social support, religion and acceptance whereas three relatively new strategies were uncovered: conserving emotional energy, value-based activity coping, and self-care.ConclusionsLong-term survivors’ perspectives were largely consistent with those of newly diagnosed ovarian cancer patients and ovarian cancer survivors of shorter duration. However, the long-term survivors were also willing to reject conventional attributions for survival and recognized the importance of disciplined self-preservational coping strategies.

Primary Debulking Via Robotic-Assisted Laparoscopy for Stage IIIc Poorly Differentiated Endometrioid Adenocarcinoma of the Ovary.

<h3>Study Objective</h3> It has been demonstrated that minimally invasive surgery (MIS) is feasible and effective for interval cytoreduction after neoadjuvant chemotherapy for advanced ovarian cancer patients. MIS is also widely used to assess resectability in the setting of newly diagnosed advanced ovarian cancer. However, the role of MIS in the primary debulking of advanced ovarian cancer is less clear. Here, we present a case of a patient with stage IIIC high-grade endometrioid ovarian cancer, which was optimally debulked to no gross residual(R0) via robotic-assisted laparoscopy. <h3>Design</h3> This is a presentation of a patient who underwent primary ovarian cancer debulking via robotic-assisted laparoscopy. <h3>Setting</h3> The patient was taken to the operating for a planned robotic left ovarian oophorectomy, myomectomy and resection of endometriosis. Diagnostic laparoscopy revealed peritoneal tumor implants consistent with advanced ovarian cancer. The frozen section confirmed epithelial ovarian cancer. <h3>Patients or Participants</h3> This case involves a 37-yo patient who was found to have advanced ovarian cancer at the time of a planned robotic surgery for a complex left ovarian cyst and resection of fibroids and endometriosis. <h3>Interventions</h3> The patient underwent robotic-assisted total hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, resection of pelvic peritoneal, rectosigmoid, and diaphragmatic tumor nodules, pelvic and paraaortic lymph node dissection as well as pelvic washing. Final pathology showed stage IIIC poorly differentiated endometrioid adenocarcinoma of the ovary. <h3>Measurements and Main Results</h3> Complete gross resection (R0) was achieved. The estimated blood loss was 50 cc. The operative time was 3 hours and 10 mins. She was discharged on postoperative day 1. Her postoperative course was uncomplicated. Adjuvant chemotherapy with IV carboplatin and paclitaxel was initiated three weeks after surgery. <h3>Conclusion</h3> MIS is a feasible option for primary debulking in select cases of advanced ovarian cancer.

Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients.

This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. Ovarian, fallopian tube or primary peritoneal cancer patients with stage III-IV disease received neoadjuvant chemotherapy (NAC) every 3weeks consisting of paclitaxel (80mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0mg/mL × min.) on day 1; and bevacizumab (15mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. Twenty-four patients were included in this study. The median age was 55.5years (37-80years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7-92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

Surgical approach of the left upper quadrant for ovarian cancer in 10 steps

Complete cytoreductive surgery without residual tumor is one of the most important prognostic factors in advanced ovarian cancer patients.[1][1] During cytoreductive procedures, it is not unusual to require multiple digestive...

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Non-Surgical Management of Malignant Bowel Obstruction in Advanced Ovarian Cancer patients: A Systematic Review and Meta-Analysis.

Background:Malignant bowel obstruction is a common cause of morbidity and mortality in patients with advanced ovarian cancer. Many patients aren’t suitable for, or decline, surgical decompression. The outcomes for this frail group of patients are not well characterized.Aim:To evaluate survival outcomes of ovarian cancer patients who undergo non-surgical management of malignant bowel obstruction.Design:Systematic review and meta-analysis.Data Sources:Online literature search of Pubmed, Embase and Medline libraries up until December 2020. Searching abstracts of scientific meetings, reference lists of included studies and contacting experts in the field.Selection Criteria:Studies that investigated non-surgical management of confirmed bowel obstruction in advanced ovarian cancer patients were included. All levels of evidence including RCTs, cohort studies and case-series if they included greater than 5 patients.Data Collection and Analysis:The studies were independently chosen by two reviewers who extracted and analyzed the data separately through OpenMeta Analyst software. Study quality was assessed using the JADAD score and the Newcastle Ottawa Score.Results:24 studies met the eligibility criteria for the systematic review and 9 for the meta-analysis. Median survival of patients managed non-surgically for bowel obstruction was 44 days (95% CI 38-49 days, I 2 = 0%, P = 0.128).Conclusion:The quality of studies was relatively low, however the evidence shows that non-surgical management of bowel obstruction results in a short life expectancy but with controlled symptoms. Where quality of life is the main concern, this may be a feasible and effective strategy.

Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.

Bevacizumab (BV) plus chemotherapy is broadly used in advanced ovarian cancer (OC). However, the efficacy of BV-based regimens for advanced OC patients is not satisfactory. Therefore, it is urgent to explore the predictive genetic biomarkers for BV.Tumor tissues from advanced OC patients receiving BV-based regimens were analyzed with a 150-gene targeted panel for next generation sequencing. The associations between gene alterations or clinicopathology features and progression-free survival (PFS) were analyzed by Kaplan–Meier curves or Cox regression. The association of the genetic alteration in potential predictive genes and expressions of 11 vascular endothelial growth factor-related genes were analyzed in The Cancer Genome Atlas cohort using 292 OC cases.Sixty two Chinese advanced OC patients treated with BV-based therapy were included. The median PFS of was 6.9 months, and objective response rate was 14.5%. In multivariate Cox regression analysis, the status of endothelial growth factor receptor (EGFR) (hazard ratio = 6.39, 95% confidence interval [CI] 2.25–18.13, P < .001) and human epidermal growth factor receptor 2 (HER2) (hazard ratio = 3.58, 95% CI 1.27–10.08, P = .016) were significantly correlated with PFS. MYC Proto-Oncogene amplification seemed to have a positive trend (hazard ratio = 0.21, 95% CI 0.05–1.02, P = .052). Moreover, EGFR and HER2 alterations were not prognostic factors of overall survival for OC in The Cancer Genome Atlas OC cohort. The vascular endothelial growth factor-related signature analysis indicated vascular endothelial factor A expression was upregulated with EGFR alterations (P = .034) which may be involved in BV resistance, and HER2 alterations were associated with hypoxia inducible factor 1 subunit alpha overexpression significantly (P = .029).EGFR or HER2 alterations are negative predictors of PFS for OC patient treated with BV plus chemotherapy. Therefore, the clinicians may consider to use alternative regimens such as anti-EGFR or anti-HER2 targeted therapy instead of BV-based regimens on these patients when standard care fail.

733P Bevacizumab (Bev), olaparib (Ola) and durvalumab (Durva) in patients with recurrent advanced ovarian cancer (AOC): The GINECO BOLD study

In high-grade AOC patients, the combination of immunotherapy, PARP inhibitors (PARPi), and antiangiogenic agents, may enhance the efficacy of each treatment. Different chemotherapy-free combinations were previously found to be feasible. A significant activity of the Durva + Ola +/- Bev combination was reported in platinum-sensitive recurrent (PSR) AOC in the MEDIOLA trial. However the efficacy of the triplet in platinum resistant relapse (PRR) has never been assessed.

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial

IntroductionThe use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian...

Primary treatment of advanced ovarian cancer: how does the 'real world' practice?

Aims: This study evaluated primary treatment modalities in advanced ovarian cancer according to sociodemographic characteristics and characterized chemotherapy regimens used. Methods: This was a retrospective study of newly diagnosed advanced ovarian, tubal or peritoneal cancer patients at two hospitals from 2011 to 2016. Results: Of 175 women, 41% received neoadjuvant chemotherapy and 59% received primarycytoreductive surgery. Within the neoadjuvant chemotherapy group, 23% did not have a surgical consultation prior to initiating treatment. Women receiving neoadjuvant chemotherapy lived closer to an academic center and more frequently received carboplatin/paclitaxel every 3weeks. Cytoreductive surgery patients more frequently received intraperitoneal chemotherapy. Conclusion: The authors identified disparities in age, insurance, distance from treatment center and chemotherapy choice in the primary treatment for ovarian cancer.

The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer.

Ovarian cancer is one of the most common gynecological malignancies with highest mortality rate among all gynecological malignant tumors. Advanced ovarian cancer patients can obtain a survival benefit from chemotherapy, including platinum drugs and paclitaxel. In more recent years, the administration of poly-ADP ribose polymerase inhibitor to patients with BRCA mutations has significantly improved the progression-free survival of ovarian cancer patients. Nevertheless, primary drug resistance or the acquisition of drug resistance eventually leads to treatment failure and poor outcomes for ovarian cancer patients. The mechanism underlying drug resistance in ovarian cancer is complex and has not been fully elucidated. Interestingly, different non-coding RNAs (ncRNAs), such as circular RNAs, long non-coding RNAs and microRNAs, play a critical role in the development of ovarian cancer. Accumulating evidence has indicated that ncRNAs have important regulatory roles in ovarian cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically highlight the emerging roles and the regulatory mechanisms by which ncRNAs affect ovarian cancer chemoresistance. Additionally, we suggest that ncRNAs can be considered as potential diagnostic and prognostic biomarkers as well as novel therapeutic targets for ovarian cancer.

European Society of Gynaecological Oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery

The European Society of Gynaecological Oncology (ESGO) developed and established for the first time in 2016, and updated in 2020, quality indicators for advanced ovarian cancer surgery to audit and...

Test me now or, test me later: prospective study of molecular testing in ovarian cancer

Objectives: Advances in molecular tumor profiling through Next-Generation Sequencing (NGS) has led to an increase in available therapeutic options for patients with gynecologic malignancies beyond standard chemotherapy. Specifically, the addition of Poly-(ADP-ribose) Polymerase inhibitors (PARPi) has signaled a paradigm shift in the management of ovarian cancer. The objective of this prospective study was to evaluate how the timing of NGS has affected the implementation of PARPi within a patient's treatment timeline between 2016 and 2019 at a single institution. Methods: Ovarian cancer patients were enrolled in a prospective Personalized Medicine Initiative (PMI) from January 2016 to December 2019 at a single institution. Archival tissue from each patient was sent for NGS testing. Initially, the project included only patients with recurrent or progressive ovarian cancer. This was expanded in a stepwise fashion to now include newly diagnosed high-grade, advanced stage ovarian cancer patients. Primarily, descriptive statistics were used to analyze the data. Results: Of the 308 patients, 251 (81%) had stage III or IV disease; 216 (70%) had high grade serous histology. NGS successfully identified 197 (64%) patients with at least one genetic alteration directed towards an FDA-approved or standard of care therapy. 27 (39%) received a PARPi due to wtBRCA, 25 (36%) for sBRCA, 8 (11%) for gBRCA, and 6 (8%) for LOH+/BRCAwt. The average time between initial diagnosis and NGS decreased from approximately 46 months in 2016-2017 to 30 months in 2018-2019. Likewise, the average number of lines of therapy completed before NGS decreased from 3 in 2016-2017 to 1 in 2018-2019. Furthermore, we found that the time between NGS and PARPi implementation decreased from an average of 12 to 5 months from 2016 to 2019, respectively. Conclusions: Increasingly, early implementation of NGS in the management of ovarian cancers has allowed for more patients to be placed on targeted therapies, including PARPi, for which they otherwise would not be eligible. After 2019, the majority of patients received NGS prior to their second line of treatment. This data suggests early NGS permits PARPi to be used at an earlier time point within a patient's treatment course. Currently, we are testing all newly diagnosed high-grade, advanced stage ovarian cancer patients at as soon as tissue is available to help guide further treatment decisions. In addition, this study demonstrates NGS has a clinically compatible turnaround time, which may guide clinical management of patients with ovarian cancer. Further follow-up studies need to evaluate the impact of earlier PARPi implementation on patient survival.

Evolving trends in ovarian cancer treatment in the US between 2011 and 2019: less surgery and more biologics?

<h3>Objectives:</h3> The surgical and medical treatment landscape of upfront ovarian cancer patients is rapidly evolving. Using real-world population data, we assessed trends in the timing of surgery, initiation of chemotherapy and use of novel biologics in upfront therapy of advanced stage ovarian cancer. <h3>Methods:</h3> Using a real-world electronic health database (Flatiron), we identified all advanced stage ovarian cancer patients diagnosed between 1/1/2011 and 12/31/2019. Flatiron is a longitudinal, demographically and geographically diverse database, which contains health records from more than 280 cancer clinics and 2 million cancer patients in the United States. We calculated descriptive statistics describing patient demographics (age and race), clinico-pathological characteristics (stage and histology), and treatment patterns (utilization of neoadjuvant therapy and bevacizumab). We measured trends over time by comparing averages in three time intervals: 2011-2013, 2014-2016, and 2017-2019. Chi-square tests were used to assess the statistical significance of observed differences and measured trends. <h3>Results:</h3> Of 2,747 patients (median age: 67 years, IQR: 58-75), Whites, Hispanics, Blacks, and Asians, and other/unknown race represented 71%, 7%, 6%, 2% and 14%, respectively. The majority (65%) had stage III and remainder (35%) stage IV cancers. 59% had ECOG scores 0-1. Serous, endometrioid, clear, mucinous and other/unknown histology consisted of 74%, 2%, 2%, 1% and 20% of cancers. Over the last 9 years, 15% were treated with bevacizumab within 6 months of diagnosis. The average time from diagnosis to initiation of therapy was 70 days. Comparing data from 2011-2013, 2014-2016, and 2017-2019, the use of neoadjuvant chemotherapy increased from 18.6% to 31.3% to 36.3% (p<0.001) with a corresponding decrease in upfront surgery followed by chemotherapy (64.3% to 50.7% to 41%). Of note, 20% of patients in 2019 did not receive any surgery. In addition, the incorporation of bevacizumab to chemotherapy increased from 7% to 11% to 24% (p<0.001) in the study periods. More specifically, the use of this biologic increased from 7% to 8% to 28% (p<0.001) in neoadjuvant patients; from 7% to 9% to 20% (p<0.001) in primary surgery patients and from 8% to 18% to 26% (p<0.001) in the no surgery group. Much of this increase occurred following FDA approval of bevacizumab in 2018, with utilization growing from 26% to 46% and 19% to 32% between 2018 and 2019 in the neoadjuvant and primary surgery groups. <h3>Conclusions:</h3> Our real-world analysis shows that the adoption of neoadjuvant chemotherapy in advanced stage ovarian cancer patients has increased to more than one-third of patients, and that nearly half received bevacizumab in 2019. Further research is warranted to study the outcomes of the large fraction (>20%) of patients that did not undergo surgery.

Olaparib in combination with bevacizumab compared to bevacizumab monotherapy for the first-line maintenance treatment of advanced ovarian cancer: a cost-effectiveness analysis

<h3>Objectives:</h3> The addition of maintenance olaparib to bevacizumab (OLAP+BEV) demonstrated significant progression-free survival (PFS) benefit vs BEV alone in the randomized trial PAOLA-1 in advanced ovarian cancer patients with homologous recombination deficiency (HRD)-positive tumors. We aim to quantify the health and economic impact by evaluating the US cost-effectiveness of OLAP+BEV relative to BEV as a maintenance treatment for women with advanced ovarian cancer who had partial or complete response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status <h3>Methods:</h3> Our economic model was a cohort-level four state partitioned survival model with a lifetime horizon. States were progression-free, post first progression, post second progression, and death, modelled using first PFS (PFS1), second PFS (PFS2) and overall survival (OS) outcomes from the PAOLA-1 trial. This approach captured multiple progressions, and the differing health state utility after each progression. PFS1 was modelled through parametric mixture survival modeling to a landmark survival point at 5 years, beyond which, patients who have not progressed are assumed to experience all-cause mortality as the general population. PFS2 and OS were modelled by fitting standard parametric models, and time on treatment data was used directly from PAOLA-1, with a treatment cap of 24 months for OLAP and 15 months for BEV. The cost of HRD testing was calculated as unit cost divided by prevalence and was included as a one-time cost for OLAP+BEV arm. US-based health state utility values were analyzed by applying the methods developed by Pickard. The analyses were conducted from a US healthcare payer perspective, with an annual discount rate of 3%. We also explored the robustness of results using deterministic (DSA) and probabilistic sensitivity analysis. <h3>Results:</h3> At year 5, 45.1% and 16.9% patients remained PFS from OLAP+BEV and BEV arm, respectively. The results showed that compared with bevacizumab alone, OLAP+BEV led to a gain in quality-adjusted life years (2.89 QALYs gain) and life years (3.43 Lys gain) but resulted in higher costs, leading to a deterministic incremental cost-effectiveness ratio (ICER) of $75,276 per QALY. OLAP+BEV had an 87.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. DSA identified efficacy (PFS and OS parameters), subsequent treatment and utility values as key model drivers. <h3>Conclusions:</h3> OLAP+BEV is associated with LY and QALY gain, and is cost effective for US payers relative to BEV monotherapy for the treatment of women with advanced, HRD-positive ovarian cancer

Real world trends in biomarker testing in U.S. advanced ovarian cancer patients

Objectives: Since the first FDA approved indication for PARP inhibitors in the treatment of advanced ovarian cancer (OC), biomarkers have begun to play a growing role in treatment decision making. Germline and tumor molecular BRCA testing and HRD genomic instability are prognostic for the response to, and beneficial effect of, PARP inhibitor in both the recurrent and, particularly the front line, maintenance setting. In light of emerging data and use of PARP inhibitors, the objective of this study was to describe trends in biomarker testing over time in women with advanced OC. Methods: We conducted a retrospective analysis of advanced ovarian cancer patients with commercial or Medicare Advantage claims data in the Optum Research Database. Patients’ index date was set as the earliest diagnosis of OC between 2010 and 2019. Patients with at least one treatment line were followed until death, loss to follow up, or the end of the study period (10/31/2019). Information on germline BRCA tests, tumor BRCA tests, and other biomarker tests were collected from the claims data. Tests were not considered mutually exclusive and patients could receive more than one test. Trends in biomarker testing over time were evaluated using descriptive statistics. Download : Download high-res image (86KB) Download : Download full-size image Results: During the study period, 5,899 eligible patients were identified and a total of 4,641 biomarker tests were performed in 2,996 patients. Of the eligible patients, 2,996 (50.8%) received at least one biomarker test and 2,857 (48.4%) received at least one BRCA test (germline or somatic). Biomarker testing rates increased significantly over time from 24.1% in 2010 to 73.0% in 2019. The majority of biomarker testing conducted was for germline or somatic BRCA1 or BRCA2 mutations, however 882 (19.0%) test claims were for an unlisted molecular pathology procedure, targeted genomic sequence analysis panel, or a commercial comprehensive genomic profiling (CGP) test (15.0%, 2.9% and 1.1% respectively). In addition to the rate of testing increase, BRCA testing moved into earlier lines of therapy over time. In 2010, 12.6% of all patients received a BRCA test before or during the first line of therapy compared to 58.6% by 2019. Conclusions: Consistent with the evolution of PARP inhibitors moving to earlier lines of therapy, the implementation of biomarker testing has increased over time in women with OC. Insurance claims data provide useful information, but may understimate testing for patients diagnosed prior to entering a plan. While we have demonstrated a positive trend in the rate and earlier timing of testing, education is still needed to ensure rates of appropriate and timely testing continues to rise.

Predictors of long-term survivorship after neoadjuvant chemotherapy in advanced ovarian cancer patients

Objectives: Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. Methods: This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. Results: We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p Download : Download high-res image (404KB) Download : Download full-size image Conclusions: Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions.

Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: the MIID-SOC trial

<h3>Objectives:</h3> We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). <h3>Methods:</h3> A total of 50 women with at least a partial response by RECIST 1.1 criteria to NACT were enrolled in a multi-institutional prospective pilot study (<i>MIID-SOC trial- NCT03378128</i>). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by primary surgeon dictated surgical approach, either continue laparoscopically (MIS) or laparotomically. However, if the procedure was to continued MIS, the placement of a hand-assist port for manual palpation was mandated as to emulate a laparotomic approach and all 43 sites were re-evaluated. A total of 2 patients could not be evaluated by laparoscopy because of dense adhesions, 2 patients did not undergo cytoreductive surgery as the laparoscopy deemed the patient unresectable, and 1 patient withdrew consent prior to surgery. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict resectability via the MIS approach. Based on statistical probability of each factor predicting cytoreductive approach, 10 abdominopelvic sites were selected for inclusion in the final model. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis (ROC-AUC) was used to assess the ability of the model to predict the MIS surgical approach. Statistical significance was evaluated using Fisher's exact test. <h3>Results:</h3> A total of 28 patients (61%) underwent MIS cytoreductive surgery. All patients had an optimal cytoreductive surgery (<1 cm residual disease) regardless of approach. The presence of disease on the following abdominopelvic sites were most strongly associated with predicting an MIS surgical approach: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC=0.699. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.9%. The specificity, or ability to identify patients who would be able to undergo an optimal MIS interval cytoreductive surgery was 70.6%. <h3>Conclusions:</h3> In this model, a PIV of <2 was able to identify patients who were likely to undergo an optimal MIS interval cytoreductive surgery. This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Towards a functional model of drug sensitivity in advanced-stage ovarian cancer: clinical correlation of drug sensitivity assays in organoid tissue cultures

Objectives: Though many ovarian cancer patients respond to primary treatment, a significant portion will not respond and are considered ‘platinum resistant/refractory.’ Such patients experience a significantly worse prognosis relative to those who are ‘platinum sensitive.’ Pre-treatment prediction of platinum sensitivity has eluded scientists, which forces clinicians to undergo a ‘trial and error’ method of treatment by which resistant patients are forced to try and fail a futile line of therapy. Patient-derived organoid (PDO) cultures represent a potentially powerful functional model which preserves tumor heterogeneity (Hill et al, 2018). Here, we describe the successful culture of 4 PDOs from patients with advanced stage ovarian carcinoma and their correlation with clinical treatment outcome. Methods: Fresh tissue was obtained from the patients’ debulking surgery. It was digested, and a cell pellet was created. The pellet was washed several times, re-suspended in Matrigel, plated, and grown at 37oC over several days. PDOs were treated with standard doses of carboplatin (1 µM) and paclitaxel (10 nM). The percent of viable cells at 72 hours was measured using the CellTiter-Glo 3D platform (Promega, Madison, WI). The patients’ clinical charts were then reviewed 6 months after the completion of primary chemotherapy to determine clinical platinum sensitivity as defined by clinical parameters. Results: PDOs were successfully obtained from each of the four patients with advanced stage ovarian carcinoma. Three patients had primary disease, and 1 patient was being treated for a recurrence. The patient with recurrent disease received chemotherapy immediately prior to her debulking surgery, and the rest underwent primary debulking surgery with chemotherapy to follow. Three patients had high grade serous histology, and 1 patient had low grade serous histology. Three patients ultimately had platinum resistant disease, and their PDOs all demonstrated >50% cell viability in response to carboplatin and paclitaxel with 2 resistant PDOs demonstrating a remarkable 90% and 95% cell viability. The PDO from the patient with platinum sensitive disease by clinical criteria demonstrated 49% cell viability in response to treatment (Table 1). Download : Download high-res image (123KB) Download : Download full-size image Conclusions: We describe the successful creation of PDOs from fresh tissue obtained from debulking surgery in advanced stage ovarian cancer patients. If we use ≥50% cell viability as our initial, preliminary sensitivity threshold, results from the PDO drug sensitivity assay correlate with clinical platinum sensitivity in this pilot feasibility. We propose to confirm the predictability of drug sensitivity thresholds in future, larger studies using PDOs. Currently, there is no standardized drug sensitivity assay or response parameters defined as predictable for PDOs. Such work will be integral in the formation of a functional model of drug sensitivity, which can be used in the clinic to predict platinum sensitivity without requiring a patient to try and fail futile treatments.