bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLABRA, frontline approach for BRCA testing in ovarian cancer (OC) treatment naïve population: A Latin America (LA) epidemiologic study.
Authors: Goncalves Susana Beatriz , Giornelli Gonzalo , Pereira Marcelo Horacio , Gallardo-Rincon Dolores , Estevez-Diz Maria Del Pilar 
Published: May 2019

e17050 Background: The majority of OC cases are sporadic, but it is estimated that in 17%, germline mutations in BRCA1 or BRCA2 genes can be identified. BRCA mutated OC has distinct clinical characteristics, increased sensitivity to platinum and non-platinum agents, and to DNA damage repair (DDR) targeting agents like PARP inhibitors. Additionally, somatic BRCA mutations could be identified in tumor tissue. The prevalence of germline BRCA mutations (gBRCAm) and somatic mutations (sBRCAm) has been not been characterized in Latin-american population, which is a paradigm of poly-ethnicity, where prevalence of germline, but especially somatic BRCA mutations in OC, has not been studied. Furthermore, tumor testing as first step may be a new option in BRCA testing algorithm that could avoid the necessity for double testing (gBRCA, then sBRCA testing), in case of gBRCAm negative result. Methods: FLABRA is a cross-sectional, multi-center, study designed to determine the prevalence of sBRCAm in newly diagnosed OC patients versus gBRCAm, and to describe different treatment approaches at front line in LA, as well as current OC genetic counselling. We enrolled 400 consecutive patients from 40 institutions in Argentina, Brazil, Colombia, Mexico, Peru and Panama, diagnosed with OC. Tumor blocks were tested for sBRCA (Myriad Tumor BRACAnalysis CDx™). In sBRCA positive patients, blood samples were analyzed to confirm if the mutation was germline or somatic in origin. In gBRCAm, genetic counseling was advised. Medical records were reviewed for data relevant to medical history, surgery results, treatment approach and genetic counseling. Results: We present the preliminary results with 291 patients already tested. For this first subset of patients, 85/291 (29%) had BRCA mutations identified in their tumors. Preliminary results confirm that starting with tumor testing enlarges the population eligible for PARP inhibitors, by identifying additional patients with somatic mutations only detectable in the tumor. Although preliminary, our data confirms the possibility of identifying additional patients with sBRCA mutations by testing in tumor, with a more cost-effective approach, avoiding a second round of gBRCA testing in patients with BRCA negative results in tumor. Conclusions: In this preliminary analysis we found that somatic BRCA mutations account for a significant proportion from total BRCA mutations within LA population studied.
The association of marital status, socioeconomic status, and race on the survival of ovarian cancer patients.
Authors: Gardner Austin Blake , Sanders Brooke , Mann Amandeep Kaur , Liao Cheng-I , Kapp Daniel Stuart , Chan John K. 
Published: May 2019

e17056 Background: To evaluate the influence of marital status, socioeconomic status, and race on the survival of ovarian cancer patients. Methods: Data were obtained from the SEER database from 2010 to 2015. Analyses were performed with Kaplan–Meier and multivariate Cox proportional hazard models. Results: Of 19,772 patients with ovarian cancer (median age: 60), 82.8%, 7.1%, 9.4%, and 0.7% were White, Black, Asian, and Native American, respectively. 54.5%, 21.7%, 11.5%, and 12.3% were married, single, divorced, and widowed. Married patients were older than single patients but younger than divorced and widowed patients (59 vs. 54 vs. 61 vs. 75 years; p < 0.001). 55.5%, 30.7%, 64.1%, and 38.8% of White, Black, Asian, and Native American patients were married (p < 0.001). 90.6% of married patients were insured compared to 71.8% single, 78% divorced, and 86.1% widowed (p < 0.001). Patients who were married presented at earlier clinical stages (I-II) and lower tumor grades (I-II) compared to widowed and divorced patients (p < 0.001). Married patients were more likely to receive chemotherapy compared to single, divorced, and widowed patients (79.1% vs. 71.3% vs. 76.7% vs. 67.6%; p < 0.001). The 5-year disease-specific survival (DSS) of the overall group was 60.1%. Married patients had similar DSS compared to single patients at 62.3% vs. 65.0%, but improved survival vs 53.7% divorced and 46.6% widowed (p < 0.001). In multivariate analysis, patients with stage II-IV or grade III-IV disease, older age (HR: 1.002, 95% CI: 1.001 to 1.003, p < 0.01), Medicaid (HR:1.16, 95% CI: 1.11-1.22 p < 0.0001) or no insurance (HR:1.20, 95% CI: 1.11-1.30, p < 0.0001) had worse prognosis. Married patients had improved survival relative to widowed patients (widowed HR = 1.08; 95% CI: 1.03-1.14; p < 0.01). Race did not influence DSS when controlling for surgery, chemotherapy, and radiation. Conclusions: Married patients were younger, had less advanced diseases relative to divorced and widowed patients, and were more likely to receive adjuvant chemotherapy compared to unmarried patients. Marital status is an independent predictor for survival relative to widowed status. DSS among races was not significant.
Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery.
Authors: Vincent Laura , Jankowski Clémentine , Ouldamer Lobna , Ballester Marcos , Bendifallah Sofiane , Bolze Pierre-Adrien , Akladios Cherif , Costaz Hélène , Lavoué Vincent , Uzan Catherine , Collinet Pierre , Touboul Cyril , Huchon Cyrille , Bricou Alexandre , Dridi Sabrina , Padeano Marie-Martine , Fraisse Jean , Bengrine Leila , Arnould Laurent , Coutant Charles 
Published: May 2019

e17060 Background: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer treated by neo-adjuvant chemotherapy(NAC) followed by interval debulking surgery. Methods: Data of 483 patients from FRANCOGYN database, were retrospectively included in 11 French expert centers between January 2000 and December 2016. Interval cytoreductive surgery was realized in all patients after 2 or 3 or 4 or more than 4 courses of NAC. Completeness of Cancer Resection score led to define residual disease after surgery. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. Results: The median overall survival was 52 months, after a median follow up of 30 months. 73.5% patients had no residual disease after surgery. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or lombo-aortic lymphadenectomy (p= 0.002), residual disease after surgery ( p< 0.001), positive cytology after NAC ( p< 0.001), omental disease after NAC ( p= 0.002), no pathologic complete response (pCR) ( p= 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p= 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p= 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. Conclusions: Residual disease after surgery and positive cytology after NAC are significantly associated with decreased overall survival of FIGO stage IIIc or IVa ovarian cancer. Therefore, complete cytoreductive surgery is ovarian cancer main prognostic factor.
Mutational landscape of ovarian cancers (OC) identified by prospective clinical sequencing in a nationwide cancer network.
Authors: Schink Julian , Alvarez Ricardo H. , Elvin Julia Andrea , Moran Amber , Rollins Rebecca , Geisler John P. , Chura Justin , McIntosh David , Godbee Natalie , Tan Bradford A. , Markman Maurie 
Published: May 2019

e17067 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of OC assayed in a nationwide cancer network. Methods: 449 Pts with advanced OC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant (CR) GA were defined as associated with targeted therapies or mechanism-driven clinical trials. Treatment histories for the 449 patients were obtained with IRB-approved retrospective review. Results: Median age was 56 years (range, 23-83), 71% were Caucasian. GA were identified in 94% (420/449) of OC, of which 283 (63%) had a clinically relevant genomic alteration (CRGA). 24.0% in HRD ( BRCA1/2, ATM, PALB2, BRIP1). CRGA in other potentially targetable pathways were identified: 48.0% MEK pathway ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) CRGA, 33.5% PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7), and 10.6% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). All OC tested were microsatellite stable and only one patient had a tumor mutational burden > 20 muts/Mb. 21% (59/283) of OC patients were ordered a genomically-matched treatment, 58% (37/64) were agents that were FDA approved in a different tumor type, and 17% (11/64) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. For the off label non-study population the median PFS was 19 weeks, and the median OS was 34 weeks. Conclusions: In a large series of OC assayed with CGP, 21% of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.
Factors associated with one-year mortality after debulking surgery in older women with ovarian cancer.
Authors: Filippova Olga T. , Tew William P. , O'Cearbhaill Roisin Eilish , Sonoda Yukio , Long-Roche Kara C. , Zivanovic Oliver , Gardner Ginger J. , Chi Dennis , Shahrokni Armin 
Published: May 2019

e17069 Background: The objective of this study was to assess the factors associated with one-year mortality following cytoreductive surgery among women ≥65 years with epithelial ovarian cancer (EOC). Methods: Since 2011, patients aged 65 and older with advanced EOC, who underwent cytoreductive surgery within two months of initial visit, and had at least one year of follow up were included. Mortality data was retrieved from social security death index. Independent variables of interest were age, American Society of Anesthesiologist Physical Status (ASA-PS) classification, preoperative albumin, Memorial Sloan Kettering Frailty Index (MSK-FI), procedure time, intraoperative blood loss, 30-day minor and major adverse events, 30-day readmission and emergency room visits, stage, rate of suboptimal surgery, and receipt of neoadjuvant chemotherapy (NACT). Univariate analysis was performed to assess relationship between these variables and one-year mortality. Results: In total, 263 women (median age 70, range 65-88), of whom 26% had stage IV disease and 5% suboptimal surgery, were included. One-year mortality was 6.5% (n = 17), with six patients dying within six months. On univariate analysis, patients who died within the first year differed from those who were alive at one year in terms of length of stay (13 vs 9 days, p = 0.01), pre-operative albumin (3.8 vs 4.1, p = 0.01), major adverse events (29.4% vs. 12.2%, p = 0.04), and receipt of NACT (33.3% vs. 14.7%, p = 0.05). Patients who died within one year had an insignificant difference in MSK-FI (1.4 vs. 0.8, p = 0.08), and pre-operative hemoglobin (11.4 vs. 12.1, p = 0.06), as well as no difference in in age, ASA-PS, stage, procedure time, blood loss, minor adverse events, readmission and emergency room visits. Patients with suboptimal surgery did not have significantly higher one-year mortality rates, compared to those with optimal resection (11.8% vs. 4.5%, p = 0.5). Conclusions: Cytoreductive surgery in the selected group of older women is safe. In this cohort, age and ASA PS were not among factors associated with one year mortality. More robust risk stratification for this cohort is needed.
CD49d (high) T cells in the ovarian cancer microenvironment are a potential target for the optimization of immune checkpoint therapy in ovarian cancer.
Authors: De May Henning , Desai Sharina Palencia , Kinjyo Ichiko , Harris Jaryse , Adams Sarah Foster 
Published: May 2019

e17075 Background: Despite the correlation between tumor infiltrating lymphocytes and long-term survival, immune-based therapies have underperformed for the treatment of ovarian cancer. This is attributed to an immune suppressive intraperitoneal microenvironment. With evidence that T cell dysfunction in the ovarian tumor environment is not reflected peripherally, we hypothesized that anatomically restricted T cell subsets play a role in local disease regulation. High expression of integrin α4 (CD49d) is selectively seen on peritoneal T cells in patients and healthy mice. Here we tested whether CD49d(high) CD8 T cells also contribute to anti-tumor immunity in ovarian cancer models. Methods: Using a syngeneic immune competent model of high grade serous ovarian cancer (ID8ova), we evaluated the phenotype of CD49d(high) T cells at varying stages of intraperitoneal disease by flow cytometry. Antigen specificity was tested using a SIINFEKL/H-2Kb NIH tetramer assay. Results: CD49d is highly expressed by peritoneal CD8 T cells but not by splenocytes in tumor-bearing mice (29.8% vs. 3.3% of CD8 cells respectively). Supporting a role in anti-tumor immunity, 92% of tumor antigen-specific CD8 T cells in the peritoneal cavity expressed high CD49d. While the proportion of peritoneal CD8 cells that express high CD49d is similar in healthy and tumor-bearing mice, CD49d(high)CD8 cells upregulate the expression of co-inhibitory receptors with tumor progression. At late stages of the disease, PD-1, TIM3, and LAG3 are exclusively expressed by peritoneal CD49d(high) cells (range 94.7 +/- 3.05%). Consistent with our prior data, PD1+TIM3+LAG3+ CD8 T cells were not present in the spleen, confirming the anatomic specificity of this lymphocyte subset. Conclusions: These findings add to the accumulating evidence that tumor immunity is locally regulated and identify an IP specific subset of CD8 T cells that could be selectively targeted with immune checkpoint blockade. We predict that strategies directing immune therapy to the peritoneal tumor microenvironment will enhance treatment efficacy and limit off-target toxicities in women with ovarian cancer.
Hypermetabolic activity by FDG-PET after immunogenic chemotherapy and multi-peptide immunotherapy in ovarian cancer.
Authors: Marquez-Manriquez Juan Pablo , Lucero-Diaz Pedro Alejandro , Durazo Alberto , Matute-Briseno Jose Antonio , Gallardo-Rincon Dolores , Perez-Astorga Mario ALBERTO , Gutierrez-Marquez Michelle ANTONIA , Camacho-Hernandez Alejandro 
Published: May 2019

e17079 Background: There are several reports of increased of SUV in the lymph nodes of cancer patients after immune manipulation such as the administration of vaccines and checkpoint inhibitors. However the clinical importance of these phenomena is poorly understood. The administration of two immunogenic drugs and eight peptides in HGSOC induced atypical bright zones in multiple lymph nodes and, in areas with microscopic disease where potentially we can have cancer stem cells (CSC’s). Methods: We enrolled N = 10 HGSOC after the local IRB ethic committee approval. All the patients had 3 recurrences with mPFS = 8 months of the third relapse. The last FDG-PET scan was used as basal image for the study. Blood was collected for cellular and humoral immunology analysis such as Granzyme B ELISPOT and ELISA. Tissue was used for IHC analysis for the evaluation of CD8, FOXP3, Th1, and proteins related with CSC’s. The patients received 50 mg of oxaliplatin and 30 mg of doxorubicin total dose every week four times simultaneously with multi peptide immunotherapy. A second FDG-PET scan was performed after the termination of the treatment. Results: After the treatment 100% of the patients showed intense atypical bright uptake areas in lymph nodes and in the peritoneum. There was a correlation between the brightness intensity (SUV), and the Granzyme B production (p = 0.001). We found multiple bright small lesions in the peritoneum that were not visible before treatment. We demonstrated the presence of proteins related with CSC’s in the original tumor tissue and an antibody immune response against EGFR (P = 0.005), Ape-1 (p = 0.003) and Bcl-2 (p = 0.05). Conclusions: Immunotherapy may produce hypermetabolic activity that could lead to overtreatment when evaluated by FDG-PET in HGSOC. Vaccination may activate lymph nodes and anti-cancer immune interventions may also activate CD8 and Th1 cells able to accumulate in CSC’s clusters and increased notably the SUV, which may lead to false relapse interpretation by the radiologists and oncologists.
Association between time to first subsequent therapy (TFST) and overall survival (OS) in previously untreated patients with ovarian cancer (OC): A SEER Medicare database analysis.
Authors: Desai Kaushal , Muston Dominic , Adeboyeje Gboyega , Monberg Matthew J. 
Published: May 2019

e17095 Background: TFST may be a patient-relevant indicator of efficacy beyond progression in OC, however, the association between TFST and OS is unknown. We analyzed the SEER Medicare database to determine whether OS varied by TFST in previously untreated patients with OC. Methods: From the SEER-Medicare linked database, we identified newly diagnosed OC patients (≥66 years) who initiated first-line chemotherapy between 2009 and 2015. Patients were followed through the end of 2016. TFST was defined as the time from initiation of first-line chemotherapy until the start of subsequent therapy or death. Cox models summarized the overall association between TFST and OS through hazard ratios (HRs), and by TFST strata for patients who had a TFST event. In case hazards were non-proportional, we examined the fit of independent parametric survival curves. Results: In the cohort of 1407 patients, 1005 patients had a TFST event. Median age was 74 years and 34.9% were alive at the time of this analysis. For population with a TFST, the median TFST was 13.1 months and median OS was 30.88 months (HR = 0.29, 95% CI: 0.26, 0.32). Among patients < 75 years, the median TFST was 13.65 months and the median OS was 37.07 months (HR = 0.24, 95% CI: 0.21, 0.28). In the full cohort of 1407 patients, the best-fitting distributions accelerated failure time models under which the (unrestricted) mean TFST and OS were 44.9 and 73.8 months respectively. This indicated that on average TFST was an acceleration of OS by a factor of 39%. Conclusions: In this elderly population of previously untreated OC, longer TFST was associated with longer OS. Limitations of this analysis include censoring of OS and immortal time bias. [Table: see text]
Clinical benefit of bevacizumab in Mexican ovarian cancer patients according to the intention of treatment by the oncologist.
Authors: Gallardo-Rincon Dolores , Bahena-Gonzalez Antonio , Montes-Servín Edgar , Montes-Servín Elizabeth , Michel-Tello David , Toledo-Leyva Alfredo , Alamilla Gabriela , Espinosa-Romero Raquel , Gonzalez-Ibarra Ernesto , Morales-Vasquez Flavia , Cano Blanco Claudia , Coronel-Martinez Jaime A , Cetina-Perez Lucely Del Carmen 
Published: May 2019

e17097 Background: Ovarian cancer (OC) is the first cause of gynecological cancer, and the fifth cause of women cancer-death in US. In Mexico, more than 4,500 new cases of ovarian cancer are diagnosed yearly and it represents the second cause of gynecological cancer mortality. Bevacizumab (BVZ) is an antiangiogenic antibody that has been approved for first-line and recurrence therapy in OC patients. The aim of the study was to evaluate the clinical benefit of BVZ in different lines of treatment in Mexican OC patients. Methods: A total of 94 OC patients treated with BVZ were recruited at the Ovarian Cancer Program of the Instituto Nacional de Cancerología, from February 2012 to September 2018. Clinicopathological characteristics and toxicity was correlated with line of treatment. PFS curves were estimated by the Kaplan–Meier method, while comparisons among groups were analyzed with log-rank or Breslow tests. Results: Most of the patients were stage IIIC (69.1%) with HGSP histology (73.4%). 24 patients (25.5%) received BVZ as first-line treatment before debulking surgery (50% for suboptimal and 45.8% for optimal cytoreduction). 48 patients (51.1%) received BVZ for second-line (72.9% after a platinum-resistant and 27.1% after a platinum-sensitive recurrence) and 22 patients (23.4%) for three or more lines of treatment. Venous thromboembolic events (VTE) were more frequent in multi-treated patients ( P= 0.030). The median PFS was 23.7, 11.7 and 5.8 months for first, second and third or more lines, respectively. Patients with optimal debulking surgery had a better PFS compared with suboptimal and BVZ in first-line patients (24.8 vs 20.9; P= 0.050). Patients with BVZ in second-line who are a platinum-sensitive recurrence had better PFS compared to those with a platinum-resistant disease (15.1 vs 7.6; P= 0.040). Conclusions: OC patients had clinical benefit from treatment with BVZ when used as first-line and first recurrence treatments. The use of BVZ for third or later line treatment has a questionable benefit and is associated with a higher rate of VTE. Also, we highlight that 77% of the patients had the greatest-benefit while 33% had limited-benefit.