bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: An institutional experience.
Authors: Jain Kavitha , Chaturvedi Arun , Misra Sanjeev , Kumar Vijay , Gupta Sameer , Lakshmanan Manikandan , Garg Sudeep 
Published: May 2019

e17044 Background: Epithelial ovarian cancer is the second most common gynecological malignancy among Indian women. Primary debulking surgery remains the standard of care in advanced operable ovarian cancer patients, but is associated with morbidity. Neoadjuvant chemotherapy followed by delayed primary cytoreductive surgery maybe a better treatment strategy in advanced ovarian cancer. We present our experience of neoadjuvant chemotherapy in advanced ovarian cancer with special emphasis on treatment outcomes. Methods: A retrospective analysis of advanced epithelial ovarian carcinoma (Stage IIIc and IV) patients treated at the Department of Surgical Oncology at King George’s Medical University, Lucknow between 2012 and 2017 was done. Results: A total of 151 patients with advanced ovarian carcinoma were treated during this period. Median age at diagnosis was 46 years. Among these patients, 137 underwent surgery, of which 59.1% were optimally cytoreduced. Papillary serous adenocarcinoma was the most common histological subtype (76.1%). Recurrence was seen in 79.3% patients, with a median time to recurrence 17 months (range 6.5 - 39 months). They were managed with second line chemotherapy and surgery. Median overall survival in this study for optimally cytoreduced stage III patients was 39 months and 18 months for optimally cytoreduced stage IV patients. Median progression free survival for stage III was 12 months and stage IV was 6 months. Conclusions: Neoadjuvant chemotherapy facilitates surgery in advanced ovarian cancer and helps in assessing chemotherapy responsiveness. It provides an opportunity to modify systemic treatment if there no response to therapy or disease progression.
Bovine milk-derived exosomes mediated delivery of resibufogenin and its effect on platinum-resistant ovarian carcinoma.
Authors: Zhou Guannan , Ding Jingxin 
Published: May 2019

e17065 Background: Platinum-resistant ovarian carcinoma presents poor prognosis owing to its chemotherapeutic resistance. Resibufogenin is a kind of traditional Chinese medicine with potential anti-cancer ability. Exosomes are naturally occurring membrane particles that mediate intercellular communication by delivering molecular information between cells. The purpose of the current study was to evaluate the effect of bovine-milk-derived exosomes as carriers of resibufogenin to Platinum-resistant ovarian carcinoma and investigate the mechanism. Methods: Exosomes were isolated from bovine-milk using differential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and western blot. Drug screening among 172 traditional Chinese medicines to find out resibufogenin. The exosomes were loaded with resibufogenin and the effectiveness of exosome-mediated drug was assessed with viability assay, transwell assay and flow cytometry assay. The distribution of exosome-delivered resibufogenin in cells was inspected by confocal microscopy. Xenograft mouse models were constructed to clarify the treatment response in vivo. mRNA sequencing assay, qPCR assay, immunohistochemistry assay and western blotting assay were used to detect and verify the targeted pathways. Results: Our main finding that resibufogenin inhibits the proliferation, migration and invasion in platinum-resistant ovarian carcinoma. Bovine-milk-derived exosomes delivered resibufogenin into platinum-resistant ovarian carcinoma and enhanced the cytotoxicity of resibufogenin. In vivo experiment demonstrated that resibufogenin suppressed the growth of xenograft tumors, with lower ki-67 expression and higher tunel expression. The mRNA sequencing assay, qPCR assay, immunohistochemistry assay and western blotting assay showed that the PI3K/AKT and Regulation of actin cytoskeleton signaling pathways account for the results above. Conclusions: Bovine-milk-derived exosomes can be used as effective carriers of resibufogenin to platinum-resistant ovarian carcinoma. Bovine-milk-derived exosomes-loading resibufogenin inhibits platinum-resistant ovarian carcinoma growth and migration in vitro and in vivo through PI3K/AKT and Regulation of actin cytoskeleton signaling pathway.
Prognostic value of monocyte to lymphocyte ratio (MLR) in epithelial ovarian cancer (EOC).
Authors: Cucurull Marc , Felip Eudald , Garcia Juan Jose , Erasun Carlos , Angelats Laura , Teruel Iris , Martinez-Román Sergi , Hernández Joaquin , Esteve Anna , España Sofia , Romeo Margarita 
Published: May 2019

e17066 Background: Identifying high-risk early-stage EOC patients (p) is a major issue. Also, controversy about the role of neoadjuvant chemotherapy prior to surgery in advanced EOC is still ongoing. A high MLR is related to poorer outcomes in several cancers, and also in ovarian cancer according to limited retrospective series. We explored the clinical value of MLR in a cohort of EOC p. Methods: We included all EOC p diagnosed in our center, from January 2008 to April 2017, who had undergone radical treatment. Overall survival (OS) was assessed by Kaplan Meyer. Maximally selected rank statistics was used to determine the MLR cut-off value for the greatest OS discrimination. The hazard ratio (HR) of death of MLR was explored by multivariate Cox regression models, adjusted by age at diagnosis, stage I/II versus (vs) III/IV, high grade serous carcinomas (HGSC) vs other, primary surgery vs interval surgery after neoadjuvant chemotherapy (PS, IS), residual disease < 1 vs > 1cm, year of diagnosis, and hemoglobin, neutrophils, platelets and MLR at diagnosis. Results: 124 p were included. Median age at diagnosis was 58.7 years; 55.6% were HGSC;67.7% stage III/IV; 69.3% received PS; 14.3% had residual disease > 1cm. Median OS was 75 months. MLR was the laboratory parameter that more significantly impacted on OS in our model (p = 0.02). Optimal MLR cut-off was 0.38. The MLR > 0.38 group (MLR-hi) had a higher-risk of death (HR = 2.9; 95% IC: 1.3–6.5) with respect to those with MLR < = 0.38 (MLR-lo). Median OS were 100 and 35 months, respectively. In the MLR-lo group, median age at diagnosis was 56.9 years (vs 61.9 in the MLR-hi, p 0.047), 44.8% were HGSC (vs 61.2%, p 0.134), and 49.97% were stages I/II (vs 14.2%, p 0.001). MLR-hi p who had undergone PS or IS had similar OS (p = 0.63). In contrast, among MLR-lo p, PS showed significantly higher OS than IS (p < 0.0001). Conclusions: In our cohort, MLR was an independent prognostic factor in EOC. Its potential role to identify high-risk early-stage p and to predict worse outcomes after PS among advanced-stage p need to be explored in larger cohorts.
Poly adenosine diphosphate ribose polymerase inhibitors maintenance in patients with ovarian cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: WIN Htut Thura , Tun Aung , Sultan Anita , Swarup Sriman , Zaw Myo , Hlaing Pwint Phyu , Myat Yin Mon , Jahan Nusrat , Mogollon-Duffo Francis , Rehman Shabnam , Hardwicke Fred L. , Thein Kyaw Zin 
Published: May 2019

e17081 Background: Ovarian cancer is the deadliest of gynecologic cancers and many recur despite achieving a clinical response to initial platinum-based chemotherapy. The use of poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in ovarian cancer. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2019 were queried. Phase 3 randomized controlled trials (RCT) which employed PARP inhibitors maintenance in ovarian cancer were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to some heterogeneity among studies. Results: Four phase III RCTs with a total of 1792 patients were eligible. The study arm used olaparib or niraparib or rucaparib while the control arm utilized placebo. The randomization ratio was 2:1 in all studies. Participants were sensitive to platinum-based chemotherapy, as newly diagnosed in SOLO-1 trial and had been previously on two such regimens in the other trials, with an objective response. Almost all patients in the SOLO-2 and SOLO-1 trials had a gBRCA mutation, while there were patients with and without the said mutation in the other two studies. The pooled HR for PFS was statistically significant at 0.32 (95% CI: 0.27-0.38; P < 0.0001), including gBRCA cohort (HR, 0.28; 95% CI: 0.24-0.33; P < 0.0001) and non-gBRCA cohort (HR, 0.39; 95% CI: 0.32-0.48; P < 0.0001). Conclusions: Our meta-analysis demonstrated that the use of maintenance therapy with PARP inhibitors significantly improved PFS compared to placebo, regardless of the presence or absence of gBRCA mutation.
A retrospective review on extended carboplatin infusion and incidence of hypersensitivity reaction in gynecologic malignancies in a single institution.
Authors: Park Jennifer , Lee Matthew C. , Kockenmeister Erik , John Veena S. 
Published: May 2019

e17102 Background: Carboplatin has been the standard treatment for advanced gynecologic malignancies in the first line setting as well as treatment of relapsed disease. Carboplatin induced hypersensitivity reaction (HSR) is observed more frequently in a second line setting and symptoms can range from rash to life threatening symptoms such as anaphylaxis, which could preclude further treatment. A retrospective study by O’Cearbhaill showed HSR rate with extended infusion protocol to be 3.4%. However, two subsequent prospective studies by Lax and O’Cearbhaill did not find that extended infusion reduced the risk or severity of HSR. We reviewed the incidence of HSR with three hour extended-infusion carboplatin at our institution. Methods: Our practice at the Monter Cancer Center changed from standard 1 hour carboplatin retreatment infusion to extended-infusion in 2011. We reviewed charts of 162 patients from 2011 to present who received a three hour extended infusion of carboplatin. All patients received prophylactic H1 and H2 blockers along with steroids. HSR was determined in two ways: 1) Identifying patients who reported clinical symptoms of HSR. 2) Identifying which patients had received diphenhydramine, hydrocortisone and/or epinephrine as indicated for an infusion reaction. Results: 162 patients were identified: 83 with ovarian cancer, 44 with uterine cancer, and 16 with fallopian tube cancer, 10 with primary peritoneal cancer, and 9 with cervical/vulvar cancer. Most had relapsed disease and were previously treated for stage IV (35%), or stage III (47%) with platinum doublet chemotherapy at least six months prior. Only 1 out of 162 (0.6%) had a grade 1 reaction with hives and was treated with dexamethasone and diphenhydramine. She was previously treated with carboplatin 17 months prior. Her current HSR occurred during her fifth cycle of retreatment. She was not re challenged with the drug and elected not to undergo desensitization. Conclusions: Hypersensitivity reactions develop in about 12-33% of women retreated with carboplatin peaking at eight cycles (Lax et al.). The mechanism behind HSR is unclear but considered to be from repeated exposure to free platinum metal concentration. Incidence of HSR at our institution was lowest ever-reported at 0.6%, suggesting that our extended infusion protocol with the appropriate premedication is appropriate for carboplatin-retreat patients. Further prospective studies to evaluate this regimen is warranted.
Real-world duration of maintenance therapy in 2nd-line and later ovarian cancer (OC).
Authors: Garofalo David , Aydin Ebru , Labrador Monica , Webster Jennifer , Donaldson Joseph , Varughese Prateesh , Smith Helen , Hagan Melissa , Malik Ash , Scott Jeffrey A. 
Published: May 2019

e17103 Background: Recurrent OC patients 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 compare the time to next treatment of available maintenance treatment options in recurrent OC. Methods: This analysis utilized the Integra Data Exchange (DTX) database, a deidentified data source from community oncology practice systems (EMR, claims). This retrospective study included 3,629 OC patients with at least two visits between 7/16/16 and 4/16/18. 1,767 patients started at least one 2nd line or later line of therapy and 577 of these patients had at least one line of maintenance treatment. Maintenance options were monotherapy PARP inhibitors, Bevacizumab, or non-platinum-chemotherapy. Patients who did not receive maintenance were categorized as observation. Time to next treatment (start of maintenance to start of next line of therapy) was compared through ANOVA and paired T-test analyses. Results: A statistically significant difference was seen in time to next treatment between PARPi (n = 151) and bevacizumab maintenance (n = 212) (p = < 0.0125) and between PARPi and cytotoxic maintenance (n = 163) (p = < 0.0001). Bevacizumab and PARPi maintenance had significantly longer duration when compared to observation (n = 1,626) (p = < 0.0001). Cytotoxic maintenance duration was not significantly different than observation (p = 0.93). Conclusions: Our real world analysis found that there was a statistically significant increase in time to subsequent lines of therapy when certain maintenance treatment (PARPi, Bevacizumab) is utilized following 2nd line and later treatment in OC. Further, between available maintenance options, PARPi had the longest time to next treatment when compared to other maintenance options.[Table: see text]
Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?
Authors: Kahn Ryan , Gordhandas Sushmita , Maddy Brandon Paul , Baltich Nelson Becky , Askin Gulce , Christos Paul J. , Caputo Thomas A. , Chapman-Davis Eloise , Holcomb Kevin , Frey Melissa Kristen 
Published: May 2019

e17119 Background: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer (EC) to identify those with underlying Lynch syndrome (LS). However, since its implementation in 2013, the effectiveness of this screening method on identifying individuals with LS across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), MLH1 methylation, and microsatellite instability (MSI) analysis among EC patients. Methods: We conducted a complete systematic search of online databases PubMed, Embase, Medline, and Cochrane Library between 1990-2018. A DerSimonian–Laird random-effects model meta-analysis was utilized to estimate the weighted prevalence of LS diagnoses. Results: The comprehensive search produced 3,427 publications. 29 peer-review studies met the inclusion criteria. 6,649 EC patients were identified, 206 (3%) were confirmed to have LS following positive universal tumor molecular screening.5,917 patients underwent tumor IHC, 28% had abnormal staining. 3,140 patients underwent MSI analysis, 31% had MSI instability. Among EC patients with deficient IHC staining or positive MSI analysis, the weighted prevalence of LS was 15% and 19% respectively. 1159 patients exhibited loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation negative, 32 demonstrated a germline MLH1 mutation (2.8% of all MLH1 absent staining; 22.4% of all MLH1 methylation negative). 43% of EC patients diagnosed with LS via tumor typing would have been missed by family history-based screening alone. Conclusions: Despite widespread implementation of universal tumor testing in EC, data regarding results have previously been limited. For the first time, this study provides large-scale predictive values that will help practitioners evaluate abnormal results in the context of LS and aid in patient counseling. [Table: see text]
Differential vaginal wall dosing in high-dose rate brachytherapy for endometrial cancer: The potential for superior coverage of at-risk areas while preserving organs at risk—An analysis of simulated data.
Authors: Sinha Dhiraj , Alleyne-Mike Kellie , De_four Sherisse , Ratan Naveen , Ramesh Shashidhar 
Published: May 2019

e17121 Background: The treatment of curable endometrial cancer (EC)involves surgery with adjuvant radiotherapy. Histology of EC is a major determining factor for intracavitary brachytherapy (ICRT) treatment volume in early stage EC. Many guidelines recommend ICRT treatment of an extended volume up to the whole length of the vaginal stump (VS) for cases of high risk histologies (HRH) wherein a differential dosing of proximal and distal VS has the potential to achieve targeted therapeutic doses to at risk areas without compromise to critical structures.We present a simulated novel way to treat the VS by ICRT in cases of EC with HRH. Analysis of the simulated and approved plans allow us to compare the doses to organs at risk (OAR’s). Methods: Seventy-five cases from July 2017-August 2018 were reviewed and twenty-five (25) met the criteria for inclusion in this study. All these cases received External Beam Radiation Therapy (EBRT) dose of 50.4Gy/28. The ICRT simulation CT data-set was subsequently used to generate the study plan which was then compared to the actual treatment plan. In order to treat the whole VS but spare OARs a club-shaped design was proposed. This technique involved treating the upper 1/3 with a prescription point at 0.5cm lateral to the applicator surface and the lower 2/3 with a prescription point at the applicator surface. The length of the VS was defined from the tip of the applicator to 2cm superior to the introitus. The D2cc values for the contoured bladder and rectum were extracted from the treatment plan and used along with the D2cc values from the EBRT treatment to calculate OAR EQD2. QUANTEC Constraints used were (ICRU 83): EQD2 bladder: 90Gy; EQD2 rectum: 75Gy. Once calculated, the results were analyzed and the percent deviation between the proposed plan and the constraints as well as the approved plan were determined. Results: Twelve (12) of twenty-five (25) cases were HRH cases. The club-shaped design to treat the whole VS didn't further compromise the OAR (EQD2: 22% below constraints) or the rectum (EQD2: 1% below constraints). There was only a 2% difference between the final constraints in both treatment techniques. Conclusions: This technique to treat the full VS length can be used without adversely affecting OAR toxicities with superior coverage to at risk areas while maintaining dose constraints to OAR. Results, however, are limited by the small sample size.
Incidence of comorbidities on death certificate data in women with gynecological cancers.
Authors: McLaughlin Mary Elizabeth , Suneja Gita , Chino Junzo P. 
Published: May 2019

e17127 Background: Risk factors for the development of gynecological cancers are known to vary; however, the effect on mortality is uncertain. Methods: Using CDC Wonder Database, death certificate data, all women who died of cancer in the United States from 2003-2016 were included if a cancer diagnosis was listed as a primary or contributing cause. Cases were then divided into gynecological (GYN) cancer or not, and thereafter characterized as cervical, ovarian, uterine, or other. Other causes contributing to death (comorbidities were then captured via ICD10 codes listed on death certificates and grouped into similar disease states. Chi-squared and Mann-Whitney U tests were performed for statistical significance. Results: Of 35,324,091 death certificates, 4,177,823 deaths were women with cancer listed as a cause of death. 440,792 were gynecological cancer, with cervical cancer in 62,807; uterine cancer in 134,420; ovarian cancer in 221,119; and other gynecological cancers in 25,946. Women with GYN cancers were more likely to have intestinal obstruction (2.7% vs 0.7%, OR 4.05), ascites (0.7% vs 0.2%, OR 3.30), HIV (0.1% vs 0.05%, OR 1.53), kidney disease (4.7% vs 3.6%, OR 1.33), and thrombo-embolic disorders (4.3% vs 3.5%, OR 1.25) when compared to non-GYN cancers (all p < 0.00001). Uterine cancer was more likely to have diabetes-related comorbidities (6.4% vs 3.8%, OR 1.75), metabolic syndrome (9.5% vs 6.1%, OR 1.60), thrombo-embolic disorders (5.5% vs 3.8%, OR 1.48), ischemic heart disease (5.0% vs 3.6%, OR 1.43), than other GYN cancers (all p < 0.00001). Cervical cancer was more associated with HIV (0.3% vs 0.03%, OR 10.73) and tobacco-related disorders (4.7% vs 1.9%, OR 2.56). Ovarian cancer was more associated with ascites (1.1% vs 0.4%, OR 2.93), intestinal obstruction (3.5% vs 1.8%, OR 2.04), and pleural effusion (1.1% vs 0.6%, OR 1.92) (all p < 0.00001). Conclusions: Comorbidities contributing to death significantly differ amongst gynecological cancers and non-gynecological cancers, which has relevance to strategies that can be differentially employed to reduce mortality. In particular, women with uterine cancer may benefit from reduction in risk of diabetes, ischemic heart disease, and embolic disorders; those with cervical cancer may benefit from smoking cessation and optimal HIV management.
Prognostic models for prediction of overall survival after first-line platinum-based chemotherapy for primary metastatic nasopharyngeal carcinoma.
Authors: Li Wang-Zhong , Liu Guo-Ying , Liang Hu , Lv Shu-Hui , Lv Xing , Guo Xiang , Xia Wei-Xiong , Yanqun Xiang 
Published: May 2019

e17501 Background: Platinum-based chemotherapy remains the main treatment strategy for patients with primary metastatic nasopharyngeal carcinoma (mNPC). However, survival outcomes are heterogeneous. The present study sought to develop clinical predictive models for overall survival (OS) in mNPC. Methods: Institutional database was queried for patients with mNPC who received first-line platinum-based chemotherapy between 2008 and 2015. Eligible patients (n = 460) were split into a training (2008-2013, n = 296) and an internal validation cohort (2014-2015, n = 164) according to the period of diagnosis. Potential prognostic factors for OS were evaluated using univariate and multivariate analyses. The performance of prognostic models was assessed by discrimination and calibration. The clinical usefulness of prognostic models was evaluated by decision curve analysis. Results: We established two nomogram-based prognostic models to predict OS probability, the first (baseline model) based on baseline factors, the second (composite model) incorporating posttreatment plasma Epstein-Barr virus DNA (EBV DNA) and objective response (OR) to first-line chemotherapy. The incorporation of posttreatment plasma EBV DNA and OR to the model improved the predictive accuracy. The C-index of composite model for predicting OS was 0.767 (P < .001), which was statistically higher than the C-index values for baseline model (0.686). The results were confirmed in the internal validation cohort. Conclusions: We developed and validated two prognostic models that can be used before and after completion of first-line chemotherapy, respectively. The proposed models can be used for prognosis prediction and better selection of patient into clinical trials.