bluuebunny/crossref_metadata_2025_split huggingface dataset:
How long have we got? The accuracy of physicians’ estimates and scenarios for survival time in 898 women with recurrent ovarian cancer (ROC).
Authors: Roncolato Felicia , O'Connell Rachel , Joly Florence , Lanceley Anne , Hilpert Felix , Okamoto Aikou , Aotani Eriko , Pignata Sandro , Donnellan Paul P. , Oza Amit M. , Avall-Lundqvist Elisabeth , Berek Jonathan S. , Sehouli Jalid , Ledermann Jonathan A. , Berton-Rigaud Dominique , Kiely Belinda Emma , Friedlander Michael , Stockler Martin R. ,   ANZGOG and GCIG Symptom Benefit Group
Published: May 2019

5549 Background: Predicting, formulating, and communicating prognosis in women with ROC is difficult. Best-case, worst-case, and typical scenarios for survival time based on simple multiples of an individual’s expected survival time (EST) estimated by their oncologist have proven accurate and useful in a range of advanced cancers. We sought the accuracy and prognostic significance of such estimates in the GCIG Symptom Benefit Study: a multinational, prospective cohort study of women with ROC (platinum resistant and potentially platinum sensitive ROC who have had more than 2 lines of chemotherapy). Methods: Oncologists estimated EST at baseline for each woman they recruited to the GCIG Symptom Benefit Study in 11 countries. We hypothesised a priori that oncologists’ estimates of EST would be unbiased (equal proportions [approximately 50%] of women living longer versus shorter than their EST), imprecise ( < 33% living within 0.75 to 1.33 times their EST), and provide accurate scenarios for survival time (approximately 10% dying within ¼ of their EST, 10% living longer than 3 times their EST, and 50% living from half to double their EST). We also hypothesised that oncologists’ estimates of EST would be independently significant predictors of survival in a multivariable Cox model adjusting for prognostic factors established in previous studies. Results: Oncologists’ individualised estimates of EST in 898 women with ROC were unbiased (55% of women lived longer than their EST) and imprecise (23% lived within 0.75 to 1.33 times their EST). Scenarios for survival time based on oncologists’ estimates of EST were remarkably accurate: 7% of women died within ¼ of their EST, 13% lived longer than 3 times their EST, and 53% lived from half to double their EST. The median EST was 12 months (range 3-70), and median observed was 12.7 months. Oncologists’ estimates of EST were independently significant predictors of overall survival (HR 0.96, CI 0.94-0.98, p < 0.0001) in Cox models accounting for previously established prognostic factors. Conclusions: Oncologists’ estimates of EST were unbiased, imprecise, and independently significant predictors of survival time. Best-case, worst-case and typical scenarios based on simple multiples of EST were remarkably accurate, and provide a useful approach for predicting, formulating, and explaining prognosis in women with recurrent ovarian cancer. Clinical trial information: ACTRN: 12607000603415.
Patient preferences for maintenance PARP therapy in ovarian cancer treatment.
Authors: Havrilesky Laura Jean , Lim Stephanie , Yang Jui-Chen , Lorenzo Amelia , Ehrisman Jessie A , Secord Angeles Alvarez , Johnson Reed , Reed Shelby D. 
Published: May 2019

5558 Background: Maintenance therapy with PARP inhibitors has become prevalent in treating ovarian cancer. However, the preferences of women with ovarian cancer regarding the risks, side effects and benefits afforded by maintenance therapies are largely unstudied. Methods: A discrete choice experiment was designed to elicit the preferences of women with ovarian cancer regarding 6 attributes (levels presented in parentheses) relevant to the decision for maintenance PARP inhibitor therapy versus surveillance: (1) overall survival (36, 38, 42 months); (2) progression-free survival (15, 17, 21 months); (3) nausea (none, mild, moderate); (4) fatigue (none, mild, moderate); (5) probability of death from myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) (0%, 1%, 5%, 10%); and (6) monthly out-of-pocket cost ($0, $50, $500, $1,000). Educational material was provided, with embedded questions to test respondents’ understanding. Participants chose between 2 variable clinical scenarios and a constant scenario representing a treatment break, with multiple iterations. Random-parameters logit regression was applied to model participants’ choices as a function of attribute levels. Results: Of 150 women with ovarian cancer recruited, 95 were eligible and completed the survey. The mean age was 62, 48% had recurrent ovarian cancer, and 13% were currently taking a PARP. Participants always significantly preferred better clinical outcomes to worse (except between 0% and 1% risk of MDS/AML), preferred low out-of-pocket cost, and disliked the idea of a treatment break. Participants valued overall survival most (average importance weight 25 out of 100 total), followed by monthly out-of-pocket cost (24), risk of death from MDS/AML (18), nausea (15), PFS (10) and fatigue (8). On average, participants would tolerate a 2% additional risk of MDS/AML in exchange for 2 additional months of PFS and 7% additional risk of MDS/AML in exchange for 6 additional months of PFS. Conclusions: Women with ovarian cancer are willing to accept the side effects of PARP maintenance therapy and a higher than clinically observed risk of MDS/AML in exchange for clinically observed levels of improvement in PFS.
Survival and clinical outcomes of ovarian cancer patients enrolled in phase I clinical trials.
Authors: Corr Bradley , Moroney Marisa , Sheeder Jeanelle , Sawyer Brandon , Eckhardt S. Gail , Behbakht Kian , Diamond Jennifer Robinson 
Published: May 2019

5559 Background: Ovarian cancer patients who enroll in Phase I clinical trials are typically platinum resistant, heavily pretreated patients with a poor prognosis. Historically, clinical benefit of Phase I trials in this patient population has been uncertain. We assessed prognostic factors and survival in women with recurrent, previously treated ovarian cancer who enrolled in Phase I clinical trials. Methods: We performed a retrospective analysis of all ovarian cancer patients who were treated on Phase I clinical trials from 2008 through 2018 at the University of Colorado Cancer Center. Patient characteristics, treatment-related toxicities and survival data were assessed. Descriptive statistics and Cox proportional hazards models were utilized to identify risk factors associated with survival time. Results: A total of 132 individual patients were treated on Phase I clinical trials. Patients had a median age of 59 years (range 33-88) with a median of 5.5 (range 1-13) previous chemotherapy lines. 53/132 (40%) of patients were treated on multiple Phase I trials with a median of 1 (range 0-5) prior Phase 1 clinical trial enrollments. All patients had an ECOG performance status of 0 or 1. Overall response rate (defined as complete or partial response) was 9% and disease control rate (defined as complete or partial response or stable disease as best response) was 33%. Median overall survival (OS) was 11.5 months (95% CI: 9.3-13.7). Two patients died on trial due to progression of disease while no patients died due to treatment-related toxicity. In multivariate analysis, independent risk factors predicting shorter survival were elevated CA-125 (HR 2.8; 95% CI: 1.6-5.2) and albumin < 3.5 g/dL (HR 2.5; 95% CI: 1.65-3.79). BMI > 25 predicted longer survival (HR 0.65; 95% CI: 0.44-0.96). Conclusions: Phase I clinical trials for heavily pretreated ovarian cancer patients are safe by a standard of no patients experiencing toxicity-related deaths in our study. They are clinically efficacious with patients experiencing OS of 11.5 months, which is comparable to existing approved therapies. Elevated CA-125 and low albumin levels predict shorter survival, while BMI > 25 predicts longer survival. Phase I clinical trial options should be considered for all heavily pretreated ovarian cancer patients if available to them.
Effect of estrogen and progesterone receptor expression on progression-free and overall survival outcomes in low-grade serous ovarian cancer.
Authors: Llaurado Fernandez Marta , Dawson Amy , Kim Hannah , Lam Nicole , Bruce Maegan , Russell Holly , Hoenisch Joshua , Provencher Diane M. , Nourmoussavi Melica , Gilks Cyril Blake , Lee Cheng-Han , Kobel Martin , Wong Nelson , Scott Stephanie , Dimattia Gabriel , Mes-Masson Anne-Marie , Carey Mark Stafford 
Published: May 2019

5560 Background: Research on ER/PR receptor function in low-grade serous ovarian cancer (LGSC) and the determinants of response to treatment are lacking. A recent study (Sehouli et al.,2018) described ER/PR immunohistochemistry (IHC) cut-points that distinguished PFS. Thus, we report on a group of patients with ER/PR expression by IHC in tumor samples of patients with LGSC and used this information to evaluate survival outcomes. Methods: Clinical information and FFPE sections were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR). Tissue microarray (TMA) sections were stained for ER/PR using standard IHC techniques (MK). 50 stage 3 and 5 stage 4 patients were analyzed. ER/PR expression was scored using a simple scoring system ( < 1% cells staining, 1-50%, and ≥ 50%) and Allred scoring. We compared Kaplan-Meier (KM) survival (PFS and OS) curves using Log rank testing and Cox regression was used to model predictive/prognostic factors. A p-value of 0.05 was considered significant. Results: The mean age of the population was 49.5 years (SD;13.7). Ninety percent of patients were treated by surgery followed by platinum-based chemotherapy (PBC). Simple scoring did not discriminate outcomes as well for ER levels. PR Allred score ( < 2, vs 2- < 6 vs ≥6) clearly discriminated KM curves for PFS (p = 0.036) and OS (p = 0.01). For Allred ER score ( < 7 vs.7- < 8 vs 8) did not distinguish PFS (p = 0.4) but notably most patients received PBC after surgery. ER Allred score significantly distinguished OS (p = 0.008). Significant factors on Cox regression for PFS were residuum (p = 0.008;95%CI:1.2-3.1) and PR (p = 0.05;95%CI:0.39-0.99), whereas for OS ER(p = 0.01:95%CI:0.2-0.8) and residuum (p = 0.04;95%CI:1-2.8). Conclusions: ER/PR expression by Allred scoring was associated with PFS and OS. Patients will benefit from much needed research on ER/PR prediction/prognosis in LGSC. This work can inform clinical trials selection/stratification and patient selection for endocrine treatment.
Real life efficacy and safety data of bevacizumab-based front line treatment in advance or metastatic ovarian cancer patients: Focus on patients with malignant ascites—A phase IV study.
Authors: Nikolaou Michail , Ziras Nikolaos , Athanasiadis Ilias , Ardavanis Alexandros , Vaslamatzis Michael , Kentepozidis Nikolaos K. , Makrantonakis Paris , Christopoulou Athina , Michalaki Vasiliki , Polyzos Aristidis , Emmanouilides Christos E. , Vardakis Nikolaos , Kotsakis Athanasios , Georgoulias Vassilis 
Published: May 2019

5562 Background: The standard of care for Epithelial Ovarian cancer (EOC) is the combination of a taxane plus a platinum compound (TC) whereas the addition of bevacizumab (bev) to this regimen (TC-bev) has been shown to improve the PFS. Patients (pts) with ascites have more aggressive disease and less overall survival. The aim of the study was to evaluate the safety of the TC/bev regimen in the real life clinical practice. Methods: A multi-center observational study, approved by the ethics committees of the participating centers, including 314 pts with stage III/IV EOC, was conducted (11.2011-06.2014) in Greece. Two independent cohorts, with similar clinico-pathologic characteristics, were treated with front-line TC (n = 109) or TC/bev (n = 205) according to the physician’s choice. 83 (40.5%) and 40 (36.7%) in the TC/bev and TC groups presented with ascites. Results: Disease control was achieved in 90.7% and in 78.9% of patients treated with TC/bev and TC, respectively (p = 0.003). Pts with ascites treated with TC/bev experienced a better overall response rate (ORR) (68.7% Vs 55%) and less progression disease (PD) compared to patients receiving TC (13.2% Vs 30.8%). The median PFS in all pts was 21.5mo and 12.4mo (p < 0.001) and median PFS in ascites pts was 18.1mo and 10.3mo in the TC/bev and TC cohort , respectively (p < 0.001). The median OS was not reached in the TC/bev group and it was 36.9mo in the TC group, ( p = 0.059) while in the ascites pts also has not reached and it is 22.5m, respectively ( p = 0.023). The 3 year survival rate in all pts was 59.4% and 50.4% and in ascites pts was 55.3% and 30% in the TC/bev and TC respectively. Neutropenia was the most common grade 3/4 adverse event in 16.6% and 9.1% in TC/bev- and TC- treated patients ( p = 0.072) with no other adverse events > 5%. Conclusions: These real life data demonstrate that the combination of TC/bev represents an active and well tolerated regimen offering survival benefit in patients with stage III/IV EOC and especially in patients with ascites. Additional larger prospective studies are required to confirm these observations. Clinical trial information: NCT01982500.
Everolimus plus letrozole treatment of recurrent gynecologic cancers.
Authors: Miller Kenneth David , Min Frederick , Barter James , Hughes Corilynn , Kalnitskaya Lyudmila , Bell-Farrell Wanda , Lalagari Sujana , Solis Alexis , Phelps Jeanne , Wade Christine , Tangrea Michael , Feldman Marvin J. 
Published: May 2019

5567 Background: Hormonal therapy has limited activity in gynecologic (Gyn) cancer treatment. mTOR inhibitors plus aromatase inhibitors (AI's) improve the response rate and response duration in breast cancer patients. We studied this combination in heavily pre-treated women having estrogen receptor positive (ER+) Gyn cancers. Methods: This phase II study combines everolimus and letrozole for ER+ Gyn cancers with disease progression following primary and salvage chemotherapy. 19 patients participated (Ovary-10, Endometrium-7, and Primary Peritoneal Cancer-2). The mean age was 64, prior lines of therapy ranged from 2-7, and median time from diagnosis to study entry was 67 months (m) (range 10-348m). Results: There were no complete responders, but 7 of 19 (37%) patients treated had clinical benefit, with 1 PR and 6 with stable disease. In responding patients, the earliest time to best response was 2m and the median time to progression was 5m (range 5-40+m). The mean number of treatment cycles was 11. Toxicities: The most common adverse events were: hyperglycemia, rash, stomatitis, fatigue, and anemia. 7 patients required dose reductions, and 2 discontinued study drugs due to pneumonitis. The therapy was generally well tolerated in both women < 65 and > 65 years old. Toxicities were less common with reduced everolimus doses. Conclusions: Recurrent Gyn cancers become refractory to chemotherapy. We tested the combination of everolimus plus letrozole in heavily pretreated patients with ER + recurrent disease. 1 patient had a PR and 6 had stable disease with a range of 5-40+m. This oral regimen was generally well tolerated and allowed time without IV chemotherapy, while providing clinical benefit to patients with refractory ER+ Gyn cancers.
Elucidation of PARP inhibitor activity in BRCAwt recurrent ovarian cancer by hrr mutational gene profile analysis.
Authors: Mirza Mansoor Raza , Feng Bin , Shan Ming , Sun Kaiming , Yalcin Ilkar , Coleman Kevin , Thress Kenneth S. , Hazard Sebastien , Wang Jing Y. , Matulonis Ursula A. 
Published: May 2019

5568 Background: Niraparib is an oral, selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved for maintenance treatment of BRCA mutated ( BRCAmut) and BRCA wild-type ( BRCAwt) recurrent ovarian cancer patients (pts) who are in response to platinum-based chemotherapy. In the non-germline BRCA mutated (non-g BRCAmut) cohort of the ENGOT-OV16/NOVA trial, clinical benefit with niraparib vs placebo was seen in pts regardless of their Myriad myChoice HRD test status ( BRCAmut and homologous recombination deficiency [HRD] score), with a hazard ratio (HR) of 0.38 in HRD-positive (HRDpos) and 0.58 in HRD-negative (HRDneg) pts. To determine if treatment benefit in HRDneg pts may result from mutations in other homologous recombination repair ( HRR) genes, we examined the relationship between progression-free survival and other HRR gene mutations in the NOVA non-gBRCAmut cohort. Methods: A retrospective, exploratory biomarker analysis was conducted using all available tumor samples from 331 pts enrolled in the NOVA non-g BRCAmut cohort. Mutation status of HRR genes was evaluated using a 43-gene NGS assay (Myriad Genetics), including BRCA1/2 and 16 additional HRR genes. Results: In this exploratory analysis of the NOVA non-g BRCAmut cohort, niraparib demonstrated clinical benefit in pts with somatic BRCA mutation (HR, 0.27) and in BRCAwt pts (HR, 0.47). In addition, BRCAwt pts with other HRR gene mutations also derived benefit from niraparib (HR, 0.31), as did BRCAwt/ HRRwt pts (HR, 0.49). When BRCAwt/ HRRwt pts were categorized by HRD score, clinical benefit was also observed in both HRDpos and HRDneg pts, with HRs of 0.33 and 0.60, respectively. These results suggest that, although these biomarkers have good positive predictive value, they are not good negative predictors for niraparib benefit in this indication. Conclusions: This retrospective, exploratory analysis of the ENGOT-OV16/NOVA non-g BRCAmut cohort suggests that although pts with somatic BRCA mutation and other HRR mutations benefit from niraparib treatment, clinical benefit is also seen in HRDneg pts without HRR mutations, perhaps related to other genomic, epigenetic, or functional alterations within ovarian tumors yet to be defined.
Correlation of surgeon radiology assessment with laparoscopic scoring in patients with advanced-stage ovarian cancer.
Authors: Fleming Nicole D. , Westin Shannon Neville , Meyer Larissa , Rauh-Hain Jose Alejandro , Shafer Aaron , Onstad Michaela , Cobb Lauren Patterson , Bevers Michael W. , Burzawa Jennifer K. , Zand Behrouz , Fellman Bryan M. , Jazaeri Amir A. , Levenback Charles F. , Coleman Robert L. , Soliman Pamela T. , Sood Anil K 
Published: May 2019

5570 Background: To determine the correlation between surgeon radiology assessment and laparoscopic scoring in patients with newly diagnosed advanced stage ovarian cancer. Methods: Following IRB approval, 14 gynecologic oncologists from a single institution performed a blinded review of radiology imaging from 20 patients with advanced stage ovarian cancer. All patients previously underwent laparoscopic scoring assessment to determine primary resectability at tumor reductive surgery (TRS) using a validated scoring method from April 2013 to December 2017. The patients with predictive index value (PIV) scores < 8 were offered primary surgery and those with a score ≥8 received neoadjuvant chemotherapy (NACT). Surgeons viewed contrasted CT imaging reports and images from all patients in a blinded fashion and recorded PIV scores using the same validated scoring method. Linear mixed models were conducted to calculate the correlation between radiology and laparoscopic score for each surgeon and as a group. Once the model was fit, the inter-class correlation (ICC) and 95% confidence interval was calculated. Results: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Most patients had stage IIIC disease (85%) and median laparoscopic score was 9 (range 0-14). Surgeon faculty rank included Assistant Professor (n = 5), Associate Professor (n = 4), and Professor (n = 5). Median surgeon experience during the study period with laparoscopic assessment was 13 cases (range 1-28) and TRS was 22.5 cases (range 2-48). The kappa inter-rater agreement was -0.017 (95% CI 0.023 to -0.005) indicating low inter-rater agreement between radiology review and actual laparoscopic score. The ICC in this model was 0.06 (0.02-0.21) indicating that surgeons do not score the same across all the images. When using a clinical cutoff of PIV of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI: 0.49-0.73). Number of laparoscopic cases, TRS cases, or faculty rank was not significantly associated with agreement. Conclusions: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. 44% of patients in our study may have been inadequately triaged by radiology review alone, which may have led to suboptimal TRS. Our study highlights the utility of laparoscopic scoring assessment to determine resectability over radiology assessment alone in ovarian cancer.
Real-world data analysis of ovarian cancer (OC) maintenance utilization among maintenance eligible patients.
Authors: Garofalo David , Aydin Ebru , Labrador Monica , Webster Jennifer , Brown Greg , Donaldson Joseph , Gierman Hinco Jasper , Varughese Prateesh , Malik Ash , Scott Jeffrey A. 
Published: May 2019

5579 Background: Approximately 1% of US women will be diagnosed with epithelial OC during their lifetime. OC patients who achieve a response to platinum-based chemotherapy may benefit from maintenance therapy, with the goal of inducing a lasting remission or extending the time interval before progression without any deleterious impact on quality of life1. This analysis, based on real world data sourced from US community oncology practices, was designed to assess the current utilization of maintenance therapy among maintenance eligible patients. Methods: This analysis utilized the Integra Data Exchange (DTX) database, a deidentified data source from community oncology practice systems (EMR, practice management, paid claims). This retrospective study included 3,629 OC patients with at least two visits between 7/16/16 and 4/16/18. 398 patients who completed 2nd line or later platinum-based chemotherapy for 4-9 cycles and/or had a complete/partial response between 1/1/17 and 7/31/18 were included. Potential maintenance therapy options were monotherapy of PARP inhibitors, bevacizumab, and non-platinum-chemotherapy agents. Rate of maintenance therapy after platinum-based treatment was assessed. Results: Our real-world analysis found that 49% of 398 maintenance eligible patients received maintenance therapy at least once following response to 2nd line or later platinum chemotherapy. Among those that received maintenance, 46% received PARPi, 28% bevacizumab, and 26% non-platinum chemotherapy. Further, 56% of women with BRCA mutations received maintenance treatment, compared with 49% of women without BRCA mutations. Conclusions: Though there are several options available, 51% of OC women studied who could potentially benefit from maintenance treatment did not receive maintenance. Only 56% of BRCA mutation carriers were targeted for maintenance in the real world. Among patients that receive maintenance therapy following 2nd line or later platinum chemotherapy 46% received a PARPi based regimen. 1) Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomized controlled trial. Lancet Oncol. 2018 Aug;19(8).