bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness of surgery versus external beam radiation with/without brachytherapy in intermediate and high-risk localized prostate cancer.
Authors: Yin Ming , Monk Paul , Mortazavi Amir , Joshi Monika , Folefac Edmund , Clinton Steven K.
Published: May 2019

e16602

Background: Radical prostatectomy (RP) and definitive radiation with androgen deprivation therapy (ADT) are both standard of care options for intermediate and high-risk localized prostate cancer (PCa). It remains controversial if the two modalities produce equivalent outcomes because the PROTECT trial (2016) and three recent retrospective studies (2018) drew inconsistent conclusions. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried from 2004 to 2015 for localized PCa (TxN0M0) who received upfront surgery or who were recommended for surgery but instead received external beam radiation (EBRT) with or without brachytherapy boost to control selection bias. The Kaplan-Meier method was used to generate overall survival (OS) curves and the Cox regression analysis was performed to compare survival outcomes. Results: A total of 175,349 patients were eligible with a median age of 62 years old (age range: 26 to 99). 167,234 patients had upfront surgery and 8,115 patients had upfront radiotherapy, including 7,099 EBRT and 1,016 EBRT with brachytherapy. Overall, upfront surgery was associated with a better OS, compared with patients who received radiotherapy (all patients: adjusted HR [adjHR], 0.79; 95% CI, 0.74–0.83, P < 0.001). The survival benefit is more pronounced in patients of intermediate-risk group (adjHR, 0.61; 95% CI, 0.57–0.66, P < 0.001; N = 112,816), and remains significant in patients of high-risk group (adjHR, 0.91; 95% CI, 0.84–0.98, P = 0.02; N = 62,533). However, in elderly high-risk PCa patients (age ≥ 70), surgery was associated with a significantly inferior OS, compared with radiotherapy (adjHR, 1.16; 95% CI, 1.06–1.28, P = 0.002). Conclusions: Compared with upfront radiation therapy, definitive surgery was associated with overall survival benefit in intermediate- and high-risk localized PCa, except patients with old age and high-risk features, who should be considered for radiation therapy.
Single agent of apatinib in patients with recurrent or refractory cervical cancer: A real-world multicenter retrospective study.
Authors: Li Ning , Wang Ziyi , Wang Jing , Wu Lingying
Published: May 2019

e17011

Background: Few effective treatment strategy has been established for patients with recurrent or refractory cervical cancer. The present study evaluates the efficacy and safety of apatinib single agent in Chinese patients with recurrent or refractory cervical cancer. Methods: Records of patients with cervical cancer treated from October 1, 2016 to December 31, 2017 in Cancer Hospital, Chinese Academy of Medical Sciences and Hunan Cancer Hospital were reviewed. Patients who met the following criteria were included: 1) patients had pathologically confirmed cervical cancer; 2) patients who experienced progression within 6 months or during previous treatment; 3) patients were given 250 mg apatinib daily for the present recurrence; 4) medical records were complete for evaluation of efficacy and toxicity. Tumor response was determined according to RECIST 1.1. The toxicity was determined according to CTCAE 4.0. SPSS 20.0 was adopted for statistic analysis. The primary endpoint was progression-free survival (PFS). Results: Twenty-nine patients were enrolled in our retrospective study. The clinical characteristics were shown in table 1. Thirteen patients (44.8%) had persistent disease and the other 16 patients (55.2%) had recurrent disease less than 6 months after the last treatment. Up to February 1, 2018, the median follow-up time was 8 months. Five (17.2%) patients achieved partial response, and 11 (37.9%) achieved stable disease, representing a disease control rate of 55.1%. The median PFS was 4 months (1-16 months). Nine patients were still on medication. The reasons of discontinued intervention were disease progression (80.0%, 16/20), toxicity (10.0%, 2/20) and other events unrelated with apatinib (10.0%, 2/20). Common adverse events were hypertension (G1, 65.5%), mucositis (G1, 55.2%), hand-foot syndrome (G1-2, 44.8%) and proteinuria (G1-2, 20.7%). Grade 3 proteinuria occurred in 1 patient (3.4%,). Conclusions: Apatinib single agent might be an effective and tolerable choice for patients with recurrent or refractory cervical cancer. Further study is warranted.[Table: see text]
Uterine corpus invasion as a risk factor in patients with early-stage cervical carcinoma receiving radical surgery.
Authors: Li Yifan , Li Ning , Wu Lingying
Published: May 2019

e17012

Background: To explore whether pathologically verified uterine corpus invasion (UCI) is a risk factor for patients with early-stage (IB1-IIA2) cervical carcinoma receiving radical surgery. Methods: A mathed-case comparison of early-stage cervical carcinoma patients with pathologically verified UCI to patients without UCI on a 1:1 ratio was conducted. High risk factors (lymph node metastasis, paremetrial invasion, vaginal margin invasion) and intermediate risk factors (lymphovascular space invasion (LVSI) and deep stromal invasion) were completely matched between UCI and non-UCI groups. Kaplan-Meier and Log-rank test were applied for univariate analysis, and COX proportional hazard regression models were used for multivariate analysis. Results: 1320 consecutive patients with cervical carcinoma received surgery in our centerfrom Jan. 1st2009 to Dec 31st2014. 79 (5.98%) cases with UCI were identified. Median follow-up time was 43 months. There were 22 cases with recurrence. In UCI group, the recurrence rate was 20.3% (16/79), and in non-UCI group the recurrence rate was 7.6% (6/79). On univariate analysis, SCC, neoadjuvant chemotherapy (NACT), lymph node metastasis, parametrial invasion, LVSI, deep stromal invasion, vaginal invasion and UCI were significantly associated with disease free survival (DFS). After multivariate analysis, UCI ( p= 0.02, RR3.832, 95% CI1.235-11.893)and lymph node metastasis ( p= 0.042, RR 2.890, 95% CI1.038-8.045) were still independent risk factors for deceased DFS. Conclusions: Pathologically verified uterine corpus invasion might be an independent risk factor for decreased DFS in patients with early-stage cervical carcinoma receiving radical surgery.
Survival differences based on tumor size among stage 1B cervical cancer patients in Louisiana using revised FIGO staging system.
Authors: Nair Navya , Zhang Lu , Kuan-Celarier Anna , Wu Xiao-cheng , Jernigan Amelia
Published: May 2019

e17017

Background: In the recently revised 2018 FIGO cervical cancer staging, stage IB is sub-classified into 3 classes based on tumor size. We aim to determine if larger tumor size confers worse survival outcomes in women with stage IB cervical cancer in Louisiana. Methods: Women with stage IB cervical cancer diagnosed between 2010 and 2016 were identified from the Louisiana Tumor Registry. Patients with positive pelvic or para-aortic lymph nodes and those with less than 30 days follow up were excluded. Subjects were classified into three groups based on tumor size: stage IB1 ( < 2cm), stage IB2 (≥ 2cm and < 4cm), and stage IB3 (≥ 4cm). Cox proportional hazards were used to estimate differences in overall (OS) and cause-specific survival (CSS). Covariates included age, race, insurance, census tract-poverty level, and marital status. Results: 198 patients were included with a median follow up time of 43.8 months. Mean age of patients in this cohort was 46.8 years. The subjects were well distributed between the groups: 79 (39.4%) stage IB1, 60 (30.3%) stage IB2, and 60 (30.3%) stage IB3. White women comprised a larger percentage of earlier stage tumors (79.5% 1B1 vs 68.3% 1B2 vs 53.3% 1B3, p < 0.01); Black women were overrepresented in later stage disease (45.0% IB3, 28.3% IB2, 20.5% IB1, p < 0.01). There were no significant differences between the three groups in age, insurance status, poverty level, or marital status. After adjusting for covariates, patients with stage 1B3 disease had worse survival than those with stage 1B1 disease in both OS [HR 6.01 (1.96,18.50)] and CSS [HR 24.31 (2.97,199.00)]. Patients with stage 1B2 disease had worse survival than those with 1B1 disease but this did not reach statistical significance: OS HR 1.88 (0.52,6.74); CSS HR 6.79 (0.77, 59.99). Kaplan-Meier curves of OS and CSS show significant survival differences between the three groups (p < 0.0001) with best outcomes in stage 1B1 and worst in stage 1B3 patients. Conclusions: This analysis of contemporary stage IB cervical cancer patients in Louisiana confirms that tumor size > 4cm confers worse clinical prognosis. Black women are overrepresented advanced stage IB disease. While patients with tumors 2-4cm did worse than those with tumors < 2cm, this did not reach statistical significance. This could be due to the limited sample size of our cohort.
ARID1A interacts with nonmuscle myosin IIA to regulate cancer cell motility.
Authors: Osagie Oloruntoba Ismail , Li Zhigui , Mi Shijun , Aguilan Jennifer T , Huang Gloria S.
Published: May 2019

e17036

Background: ARID1A (BAF250A), a member of the SWI/SNF chromatin remodeling complex, is one of the most frequently mutated genes in human cancer. Here we report the discovery of a novel protein-protein interaction between ARID1A and the actin-binding motor protein, non-muscle myosin IIA (NM IIA) encoded by the myosin heavy chain 9 ( MYH9). Methods: The ARID1A immunoprecipitated protein complex was separated by gel electrophoresis followed by analysis of the peptide digested gel bands by C18-Reversed Phase chromatography using an Ultimate 3000 RSLCnano System (Thermo Scientific) equipped with an Acclaim PepMap C18 column (Thermo Scientific) and connected to a TriVersa NanoMate nanoelectrospray source (Advion) and a linear ion trap LTQ-XL mass spectrometer (Thermo Scientific). Protein identification was performed by Mascot search engine v. 2.5.1 (Matrix Science) against NCBI Homo sapiens database. Scaffold software v. 4.5.1 (Proteome Software Inc.) was used to validate the MS/MS peptide and protein identification based on 99% protein and 95% peptide probabilities. Immunoprecipitation and immunoblotting were done to evaluate the protein-protein interaction in ARID1A-wild type cell lines. Isogenic engineered cell lines, ES2 shRNA-control or shRNA- ARID1A stable transfection , and HCT116 control or ARID1A knockout by CRISPR-Cas9 (Horizon Discovery) were used to evaluate the effect of ARID1A loss on NM IIA expression and phosphorylation, and on cell migration by in vitro scratch assay with time lapse imaging. Results: Scaffold analysis of peptide spectra identified NM IIA with > 99% probability in the ARID1A immunopurified protein complex. In the ARID1A wildtype cell lines ES2 and KLE, endogenous NM IIA co-immunoprecipitated with ARID1A and vice versa. ES2 sh ARID1A cells had decreased total and phosphorylated NM IIA expression, and impaired cell migration compared to control cells. Similarly, HCT116 ARID1A homozygous knockout cells had impaired cell migration compared with HCT116 control cells. Conclusions: We report for the first time that ARID1A interacts with NM IIA to regulate cancer cell motility. Further investigation is ongoing to elucidate the significance of this newly identified function of ARID1A.
Multiple genetic alterations to predict the clinical outcome for bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.
Authors: Du Nan , Gao Jie , Li Fang , Liu Zihao , Chen Huoming , Liao Guoqing , Meng Jichang , Zhao Hui , Huang Mengli , Wang Qing , Cai Shangli
Published: May 2019

e17037

Background: Bevacizumab(BV) plus chemotherapy is widely used in patients with advanced ovarian cancer(OC). However, there was not predict biomakers to determined the use of BV-based treatment in OC currently.Therefore, exploring the predict biomarkers for BV is imperative. Methods: Tumor issues of advanced OC treated with BV plus chemotherapy were used for next generation sequencing (NGS) with a 150-gene targeted panel. The correlation between Progression-Free Survival (PFS) and genes or clinicopathology features was analyzed by Kaplan-Meier or Cox regression. For multivariate Cox regression, all factors with a p-value < 0.05 in univariate Cox regression were included. The potential predictive genes would be analyzed with VEGF-related signatures by using 374 OC mRNA data from The Cancer Genome Atlas (TCGA).Statistical analysis was performed using GraphPad Prism and SPSS. Results: 62 Chinese advanced OC patients treated with BV-base therapy were enrolled in this study from May 2015 to March 2018.The median PFS of these patients was 5.7 months , while ORR and DCR rate was 14.5% and 96.8%, repecitively.Patients with EGFR or HER2 alterations had poorer PFS compared with wild-type (EGFR,4.2 months vs. 7.4 months,p = 0.019;HER2,3.8 months vs. 7.3 months, p = 0.045), while MYC amplification patients got better PFS than MYC wild-type patients(17.4 months vs. 6.0 months,p = 0.049). However, in multivariate Cox regression anlysis, EGFR and HER2 were significantly correlated with PFS(P < 0.001 and p = 0.016,respectively),and MYC amplification seemed to have a positive trend(p = 0.052).Moreover,patients with HER2 alterations has a poorer OS(p = 0.008).The VEGF-related signatures analysis results indicated EGFR variants may upregulated VEGFA expression to induced resistant of BV,while downregulation of HIF was significantly correlated with MYC amplification,which was beneficial to efficacy of BV.HER2 alterations has not correlated with VEGF pathways,suggesting HER2 was a poor prognosis of OC instead of an negative predictor of BV. Conclusions: NGS is an effective method to reveal the potential predictor for BV plus chemotherapy in advanced ovarian cancer, and the patients with EGFR or HER2 alterations should consider alternative regimens such as anti-EGFR or anti-HER2 target therapy instead of BV-based regimens.
Incorporation of HIPEC into a high volume ovarian cancer program: Initial results and outcomes.
Authors: Leiser Aliza L. , Girda Eugenia , Stephenson Ruth D. , Song Mihae , Buckley de Meritens Alexandre , Rodriguez-Rodriguez Lorna
Published: May 2019

e17040

Background: HIPEC showed a progression free survival when incorporated into interval cytoreductive surgery for ovarian cancer patients in a recent phase lll trial. This has led to a paradigm shift at many institutions and the consideration of HIPEC. The goal of this study is to report on the initiation of this program and change in practice at a high volume cancer center over a period of 1 year. Methods: Reviewed surgical cases from 1/2018 through 1/2019 where patients were thought to have a primary ovarian or fallopian tube cancer. Variables included age, stage, histology, primary or interval debulking surgery, number of neoadjuvant (NAJ) chemotherapy cycles. HIPEC patients were selected out and variables examined included intraoperative procedures, optimal cytoreduction, type of chemotherapy administered, postoperative complications, and ability to receive consolidation chemotherapy. Results: 35 cases where ovarian cancer known or suspected preoperatively. 23 patients had primary surgery consisting of tah/bso/surgical staging/tumor debulking. 0/23 of these patients were offered HIPEC chemotherapy as an upfront strategy. 12 patients received neoadjuvant chemotherapy for recurrent (2) or advanced (10) disease. 11/12 of these patients proceeded to an interval surgery. 6/11 (54%) were planned for HIPEC. This was aborted in 1/6 because of thrombocytopenia. 5/6 patients went on to receive HIPEC. They received 3-6 cycles of NAJ chemotherapy, platinum and taxane. 3/5 also received preoperative Avastin. All had R0 resection. 1 patient had a bowel resection. Either carboplatin or cisplatin was used for HIPEC over 90 minutes. 2/5 patients had postoperative G2-3 cytopenias. 3/5 patients were able to receive consolidation chemotherapy, 2 of them within six weeks of surgery and with Avastin containing regimens. Conclusions: In a large volume center initiating a HIPEC ovarian cancer program in less than one years’ time, HIPEC was offered to 50% of patients undergoing interval debulking for Stage III or IV serous ovarian cancer after NAJ chemotherapy and in rare cases for patients with recurrent cancer planned for cytoreduction. Patients may go on to receive postoperative chemotherapy but may have prolonged cytopenias and consolidation therapy delays. HIPEC was not incorporated into an upfront surgical strategy.[Table: see text]
Prognostic implications of lymph node metastasis in advanced ovarian cancer: Analysis of the National Cancer Database 2006 to 2014.
Authors: Elgamal Mohamed , Saha Sukamal , Cherry Meghan , Saharan Vishesh , Buttar Robin , Wiese David , Dutt Neelum , Singh Trevor , Eilender David S. , Grewal Sandeep Singh , Arora Madan L.
Published: May 2019

e17042

Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling is not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from the National Cancer Database (NCDB). Methods: Only Stage III and IV patients (pts) from NCDB 2006–2014 undergoing debulking surg and ChemoRx were included. Group A: pts with debulking surg without bowel resection; Group B: pts with major bowel resection and Group C: pts with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) NeoAdj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. Pearson Chi Square testing was used to evaluate the survival between -ve and +ve LN pts. Results: A total of 13839 Pts were included. There were 5757 Pts (41.59%) with -ve LN status, versus 8082 Pts (68.4%) with +ve LN status. Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6,828 in Group A, 6,413 in Group B and 598 in Group C pts. For all patients in Groups A, B, and C, the 5 yr overall survival was better in LN -ve than LN +ve pts. The overall survival for both LN -ve and LN +ve pts was better in Adjuvant chemoRx in all 3 groups, except for Stage III Group C LN-ve pts, where NeoAdj was better (75% vs 37.5%). Overall survival was also slightly better in Stage III vs Stage IV pts. (Table-1). Conclusions: Even though LN dissection is not routinely done during debulking surgery, overall pts with LN metastasis do worse than LN -ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered, as it may provide important prognostic information. Table-1: 5 yr Survival by LN status [Table: see text]
E-consult: To better inform patient.
Authors: LE Brun Jean-Francois , Babin-Commeny Julie , Martin Francoise Sandrine , Babin Guillaume
Published: May 2019

e17049

Background: All surgeons have a personalized way of consulting, some deliver information exclusively orally, others through free-form diagrams or anatomical charts. Most patients go home with these patterns that are more or less readable with all the uncertainty of what they really understood or assimilated. Methods: To meet the expectations of patients, we made a computer application to help the surgeon during the consultation.During the consultation, gynecologist surgeons from Center F BACLESSE explained, with the help of the e-consult application, the pathology, surgical intervention, postoperative consequences and potential drug treatments to a cohort of 61 patients admitted for consultation. At the end of the consultation, all the patients received a PDF sheet or an email containing the diagrams constructed in collaboration with the surgeon. Using a questionnaire, we evaluated the satisfaction of the patients. Results: The computer tool was popular with the majority of patients. Regarding the information on the surgical procedure, 86% of the patients judged them as very good, 80% judged the information on adjuvant treatment (radiotherapy, chemotherapy, hormone therapy) as very good and 89% were very satisfied with the information given by the doctor. For the computer tool, 81% of patients found the illustrations very clear, 79% found that the application is a very good help to understanding and 89% found that the interaction with the doctor is sufficient. During the consultation, 100% of the patients were able to ask the desired questions, and 97% think that this computer tool completes the information. For the submitted document, 100% of the patients found it very clear and 100% found that it meets the expectations of the patients. Discussion: E-consult is a unique app created to improve the quality of information delivered to patients during the consultation. The doctor can prove that the information was delivered to the patient, through the development of a PDF during the consultation. A video demonstration is available with the following link: Play the video . Conclusions: e-health is becoming more and more important in medicine. Patients are becoming more connected. E-consult improves the quality of the information received in a simple and personalized way, it is the first application, available at will, designed to improve the understanding of patients. This application integrates with each step in the patient care path.
Accuracy of primary laparoscopic staging in patients with early ovarian malignancies: A retrospective multicenter study.
Authors: Radosa Julia Caroline , Mertke Pauline , Radosa Christoph Georg , Brucker Sara , Taran Florin Andrei , Kommoss Stefan , Ulrich Uwe , Hackethal Andreas , Deeken Martin , Radosa Marc P , Juhasz-BÃ¶ss Ingolf , Solomayer Erich-Franz
Published: May 2019

e17052

Background: Early ovarian malignancies (eOM) are often diagnosed incidentally in the course of diagnostic minimal invasive surgery or laparoscopy for preoperative suspected benign indications. To what extent initial minimal-invasive staging matches final FIGO stage following definite surgery is controversially discussed and current literature on this question is sparse. The aim of this study was to assess accuracy of laparoscopic staging of eOM with regard to final FIGO stage. Methods: We retrospectively identified all patients treated for eOM between 01/2000 and 10/2018. Participating sites were Gynecologic comprehensive cancer centers with great expertise in minimal invasive surgery. Inclusion criteria were no preoperative suspicion of advanced malignancy, initial staging laparoscopy, completion of surgical treatment via laparotomy and complete follow-up data. Clinical data and outcomes were abstracted from the medical record. Rate of upstaging and distinct causes were assessed and initial and definite FIGO stage and 3-year disease free (DFS) and overall survival (OS) were compared with regard to the incidence of upstaging. Results: 107 patients with eOM were included in the final analysis. In 72 (67 %) patients primary laparoscopic staging was concordant with final staging. 35 (33 %) cases were upstaged after the second operation. Regarding the cause for upstaging 4 (11 %) were upstaged because of infiltration of the contralateral ovarian capsule, 16 (46 %) because of peritoneal infiltrates and in 15 (43 %) patients an iatrogenic rupture of the ovarian tumor occurred during laparotomy. 21 (60 %) cases were upstaged within FIGO stage I and 14 (40 %) cases from stage I to II. Comparison of 3-year DFS and OS showed no differences regarding upstaging. Conclusions: In this population of patients with eOM, staging laparoscopy performed by specialized laparoscopic oncologic surgeons showed a sufficient accuracy with no case of upstaging to advanced FIGO stages. Regarding oncologic safety laparoscopic staging showed no impact on 3-year DFS and OS.
Telomere length and its implication as prognostic marker in ovarian cancer patients.
Authors: Atallah David M. , Antoun Stephanie , Moubarak Malak , EL Kassis Nadine , Chahine Georges Y. , Hilal George
Published: May 2019

e17055

Background: Telomeres are DNA structures protecting the linear ends of eukaryotic chromosomes against degradation and fusion, thereby maintaining genome stability. Telomerase is an enzyme that stabilizes the length of linear chromosomes by de novo synthesizing telomeric repeats during incomplete DNA replication, thus ensuring immortalization. This enzyme is expressed in 80% of cancers, including ovarian carcinoma. The human telomerase reverse transcriptase has been investigated as a detection marker for cancers in early stages, and a prognosis marker in late stages disease. The aim of this study is to investigate telomere length as a marker for survival and recurrence in ovarian carcinoma. Methods: 37 ovarian cancer biopsies have been isolated from Lebanese patients. The biopsies were subjected to DNA extraction, and then telomere length was assayed in cancer cells following the method elaborated by R. Cawthon (2002). The results obtained were expressed as ratios (36B4 is a single copy gene) Ct Telomere/Ct 36B4. Clinical data of each patient have been retrieved, including survival, recurrence, lymph node ratio, age, weight. Results: The results obtained revealed a direct relation between telomere length and survival. In fact, patients with shorter survival rates (less than 1 year) exhibited 30% longer telomeres compared with patients with longer survival rates (3 to 5 years). Moreover, recurrence rates increased with longer telomeres. Higher ratios (35%) were detected in patients with early recurrence (less than 1 year) compared to patients with late or absent recurrence. However, no direct effect between telomere length and the other parameters was spotted. Conclusions: telomere length could be used as a prognostic marker in patients with ovarian cancer by predicting better survival and lower recurrence in case of shorter telomeres. This will be of a great value when making therapeutic decisions in a heterogeneous and aggressive disease as ovarian cancer.
Effects of bevacizmab, eribulin and oxaliplatin in relapsed patients with platinum-resistant and refractory ovarian carcinomas: A preliminary case series with biomarker evaluation.
Authors: Suminokura Jin , Kouta Hiroko , Kudoh Kazuya , Horikoshi Miyuki , Yoshikawa Tomoyuki , Matsuura Hiroko , Miyamoto Morikazu , Takano Masashi , Kikuchi Yoshihiro
Published: May 2019

e17059

Background: Eribulin is a candidate for paclitaxel-refractory breast cancers, and Bevacizmab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A combination therapy using weekly administration of B with eribulin and oxaliplatin (EriOX) in relapsed patients with platinum-resistant and refactory ovarian carcinomas (PR-ROC) was evaluated retrospectively, and the association with response and serum biomarkers was investigated. Methods: Medical charts of the patients who met the criteria shown below were identified: (a) histologically confirmed epithelial ovarian cancer (b) diagnosed as platinum-resistant ovarian cancer (c) treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m2), and oxaliplatin (30mg/m2), three weeks on and one week off, q4weeks (d) written informed consent. Biomarker analyses including serum VEGF, BNP, p53, and IL-6 were also conducted. Results: A total of 34 patients were treated with weekly-B-EriOX. Median age of the patients was 58.5 years (range: 35-76), and median number of previous regimen was 4(range: 2-9). Overall, two patients (6%) had a complete response (CR), 8 patients (24%) had a partial remission (PR) and 16 patients (47%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 29% and 76%, respectively. Median progression-free survival was 4 months (range: 1-27+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (11%). Non-hematological AE greater than grade 2 was observed in one case: hypo albuminemia and edema, which were manageable and tolerable. The patients with elevation of serum mutated p53 protein and IL-6 had poorer prognosis. Conclusions: Weekly B and EriOX administration showed a remarkable response for patients with PR-ROC. Elevation of serum mutated p53 protein and IL-6 could be biomarkers for this regimen. These results warrant further prospective studies with additional biomarker analyses.
Clinical characteristics of clear cell ovarian cancer: A retrospective multicenter experience of 308 patients in South Korea.
Authors: Lee Hee Yeon , Hong Ji Hyung , Byun Jae Ho , Kim Hee Jun , Baek Sun Kyung , Kim Jin Young , Kim Ki Hyang , Yun Jina , Kim Jung A , Park Kwonoh , Lee Hyo Jin , Lee Jung Lim , Won Young-Woong , Kim Il-Hwan , Bae Woo Kyun , Sun Der Sheng , Lee Suee , Lee Min-Young , Lee Guk Jin , Hong Sook Hee
Published: May 2019

e17062

Background: Clear cell ovarian cancer is rare, accounts for about 3-10% of epithelial ovarian carcinoma, and is known to be associated with endometriosis. This tumor type has poor prognosis due to inherent chemoresistance. We investigated clinical characteristics and prognostic factors of clear cell ovarian cancer in South Korea. Methods: We reviewed the medical records of 308 patients with clear cell histology ovarian cancer who underwent debulking surgery from 21 institutions in South Korea between 1995 and 2015. Results: Mean age was 51 years (range, 25-81) and 194 patients (63.7%) had stage I disease, 34 (11.1%) had stage II, 66 (21.6%) had stage III, and 11 (3.6%) had stage IV. 107 patients (34.9%) had endometriosis. 9 patients (2.9%) received neoadjuvant chemotherapy, 248 (80.5%) received postoperative chemotherapy, and among them, 238 (96%) received taxane-platinum chemotherapy. 275 patients (89.3%) achieved optimal debulking. 112 patients (37%) had recurrence, 182 (59.1%) was disease-free, and 12 (3.9%) lost follow up. Median value of CA-125 was 72.34 U/ml (range, 1.9-8930), 45.7 in stage I, 98.9 in stage II, 192.1 in stage III, and 634.8 in stage IV. 1-year, and 3-year rate of disease-free survival (DFS) was 70%, and 63%, respectively. 1-yr DFS rate was 90% in stage Ia and Ib, 88% in stage Ic and II, and 60% in stage III and IV. According to the same stage grouping, 3-year DFS rate was 82%, 70%, and 40%, respectively. Overall survival (OS) rate at 1 year was 97%, 99%, and 90%, and 97%, 96%, and 88% at 3 year. Multivariate analysis revealed optimal debulking (HR 6.62, p < 0.001) as a significant prognostic factor for DFS. Among the 94 patients with early stage (Ia and Ib), 17 patients (18.1%) received adjuvant chemotherapy, and there was no significant difference in DFS according to adjuvant chemotherapy (log rank p = 0.57). Conclusions: In patients with clear cell ovarian cancer, optimal debulking surgery was associated with improved DFS. And the role of adjuvant chemotherapy in early stage clear cell ovarian cancer is elusive and needs further study.
Increasing potency and safety of anticancer drugs through sortilin receptor-mediated cancer therapy: A new targeted approach for the treatment of ovarian cancer.
Authors: Annabi Borhane , Demeule Michel , Currie Jean-Christophe , Larocque Alain , Charfi Cyndia , Béliveau Richard
Published: May 2019

e17068

Background: The development of personalized therapies against ovarian cancer remains highly challenging in current modern oncology. One strategy to achieve greater selectivity and better anticancer drug delivery into cancer cells is to conjugate cytotoxic agents to specific peptide ligands that selectively target receptors abundantly and/or exclusively expressed on these cells. Increased expression of Sortilin, a scavenging receptor, has been clinically observed in invasive ovarian cancer biopsies, and correlated with tumor grades. In light of this, we developed a peptide conjugation platform and a new Sortilin receptor-mediated vectorization strategy to increase cell targeting selectivity and cell delivery efficacy of anticancer agents. Methods: As a proof-of-concept, Doxorubicin was conjugated to a Sortilin binding peptide (KA-peptide). In vitro, intracellular delivery of the Doxorubicin-KA-peptide conjugate (DoxKA) was assessed in ES-2 and SKOV-3 ovarian cancer cell line models using flow cytometry and fluorescent microscopy. Sortilin gene silencing was performed with specific siRNA. DoxKA efficacy and safety were evaluated in vivo using ES-2 (CD1 nude mice) and SKOV-3 (athymic mice) subcutaneous xenograft models. Results: Uptake of DoxKA was observed in both Sortilin-positive ovarian cancer cell lines tested and was reduced when Sortilin expression was specifically silenced or upon competition with the Sortilin ligands Neurotensin and Progranulin. Results indicate that the uptake of DoxKA occurs via Sortilin-mediated endocytosis in contrast to simple diffusion for Doxorubicin. DoxKA was found to bypass the P-glycoprotein (P-gp) efflux pump in MDCK-MDR1 cells overexpressing P-gp as the uptake of DoxKA was unaffected by the P-gp inhibitor Cyclosporin A. In vivo, DoxKA showed lower potential side effects than Doxorubicin alone did, with decreased accumulation in healthy tissues such as heart and ovary. DoxKA caused a more potent inhibition of human ovarian tumor xenografts growth in mice and was better tolerated (absence of leukopenia and neutropenia) than the unconjugated Doxorubicin at an equivalent dose. Conclusions: These results strongly support the future clinical use of this platform to generate novel personalized therapeutics with specific targeting of Sortilin-positive tumors in the next stage of development in phase 1 clinical trial.
How do we bridge the gap? persistent differences in the preoperative experience for patients with gynecologic cancer treated at a public hospital.
Authors: Gerber Deanna , Khouri Olivia R , Frey Melissa Kristen , Boyd Leslie R. , Curtin John Patrick
Published: May 2019

e17074

Background: Disparities in the treatment of patients (pts) with gynecologic cancer (ca) are well-documented. In 2016, we published our experience with structural barriers present preoperatively at a public and private hospital (H) treated by the same team of gyn oncologists. Since then, there have been system-wide changes to address inequalities in the preoperative (preop) work-up. Our goal was to evaluate if the streamlined preop work up at the public H was sufficient to close the gap in management. Methods: A retrospective review was conducted for pts who had surgery for a gyn ca at a public and private H between 7/1/15 and 7/1/16. This was analyzed and compared to the previously studied cohort reviewed from 7/1/13 to 7/1/14. Results: We included 251 pts for analysis (public H 47; private 204). There was no difference in age, type of ca, or stage between H. The public H pts had a longer wait from diagnosis to surgery (55 vs 39d; P < .001) as well as surgical booking to surgery (25 vs 19d; P < .001). When compared to the pts treated at the public H from 7/13-14, there was a significant improvement in wait time from diagnosis to surgery (55 vs 66 days; P < .001), diagnosis to surgical booking (21 vs 28 days; p = 0.008) as well as booking to surgery (25 vs 26; P < .001). There was no difference in the number of preop visits between the 2 groups at the public H. Conclusions: Since implementation of new preop guidelines at the public H, the wait times from diagnosis of ca to both booking and surgery have decreased. While this represents progress, there remain discrepancies when compared to the private H. There remains room for improvement in the preop experience for the pts treated at the public H. [Table: see text]
An optimized homologous recombination deficiency (HRD) algorithm ASGAD for predicting PARP inhibitor response in ovarian cancer patient.
Authors: Jiao Yang , Chen Dong Ju , Liu Bo , Meng Pei , Sun Lei , Cai Yu Hang , Shi Tai Ping
Published: May 2019

e17077

Background: Homologous recombination deficiency (HRD) results less efficient and error-prone DNA double strand break (DSB) repair, thus causes genomic in stability and impacts on cancer susceptibility to Poly‐(ADP‐Ribose)‐Polymerase (PARP) inhibitors. Evaluating HRD level in gynecologic cancer patients is becoming far more important and influential, so far, there is no standard method to be used in clinical. Methods: Here, we optimized an HRD score algorithm, termed as ASGAD, which combines three classic factors, including loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI), large-scale state transition score (LST), along with tumor ploidy to predict PARP inhibitor response in ovarian cancer patient. Results: Traditional global optimization strategy for purity and ploidy calculation is usually sensitive to initial values and may lead to incorrect convergences. Here we designed a two-step optimization manner to avoid this problem. Firstly, a density-based clustering algorithm was applied on BAF and CN, and the genotype was assigned to the most legible cluster. Then the rectified BAF and CN was calculated and used to find the maximum likelihood genotype of each segment. The segmentation processed was also improved by applying a series of statistical test to merge similar adjacent segments. The accuracy of allele-specific copy-number detection is significantly improved vie this algorithm, deriving stable and reliable HRD scores especially on aneuploid and hyperploid tumor cases. In this study, we assessed ASGAD algorithm in almost 150 ovarian cancer patient samples, who had treated with platinum effectively. BRCA1/2 deficient was defined as either one deleterious mutation in BRCA1/2, with LOH in the wild type copy or two deleterious mutations in the same gene. The results showed that the 19/23 BRCA1/2 deficient samples are also HRD-high, giving the sensitivity of 82.61%. Besides, we identify 58 HRD-high samples with intact BRCA1/2, who might benefit from PARP inhibitors, by the ASGAD algorithm. Interestingly, we analyzed 4 HRD-high samples by using whole-exome sequencing (WES), and found other HR genes mutations in these samples, including PARP4, FANCM, MSH2, MSH6, ATR, POLD1. Conclusions: The expanded use of PARP inhibitors in HRD tumors using the ASGAD algorithm requires more validation.
The effects of Wnt inhibition on tumor progression and the tumor microenvironment in a syngeneic mouse model of ovarian cancer.
Authors: Goldsberry Whitney , Doo David W , Meza-Perez Selene , Katre Ashwini A. , Norian Lyse , Randall Troy , Arend Rebecca Christian
Published: May 2019

e17078

Background: Alterations in the Wnt/β-catenin pathway have been associated with tumor progression in multiple cancers. Gene expression profiling in ovarian cancer has correlated Wnt upregulation to patterns of immune evasion in the tumor microenvironment (TME). We investigated effects of in vitro Wnt inhibition in a murine ovarian cancer cell line with p53 knocked out as a model to mimic human ovarian carcinoma. Methods: We used a small molecule inhibitor, CGX-1321, in C57Bl6 mice, an immunocompetent mouse model, injected intraperitoneally with either ID8 cells, a murine ovarian cancer cell line, or ID8-p53-/- cells. Mouse omentums were collected and weighed for evaluation of tumor growth. Representative histology slides were stained for H&E. Western blots for β-catenin baseline levels were performed on the cell lines. TopFlash Assays with WNT3A stimulation were used for analysis of cell line nuclear β-catenin levels. Flow cytometry was performed on mouse omentums for TME evaluation. Results: Treatment with CGX-1321 decreased tumor size via omentum weight with both cell lines, p = 0.0098 with ID8 cells and p = 0.0855 with ID8-p53-/- cells. H&E slides revealed a decreased tumor progression. Western blots confirmed a difference in baseline β-catenin levels between these two cell lines. However, TopFlash assays showed a response to stimulation. Changes in the TME between treated samples with ID8-p53-/- cells did now show significant differences via flow cytometry. Conclusions: In the syngeneic mouse model with a murine ovarian cancer cell line, with p53 knocked out, tumor size and proliferation were decreased with treatment with Wnt inhibition. Surprisingly, the TME changes were inconclusive via flow cytometry. Perhaps these cells do not rely upon the Wnt/ β-catenin pathway as heavily, as seen in changes to baseline β-catenin levels, or perhaps tumors progress quicker and the critical time point of TME change is being overlooked. More investigation needs to be performed to further elucidate these differences.
Clinicopathologic features and prognostic analysis of stage I ovarian clear cell cancer.
Authors: Wang Tian Tian , Li Ning , Wu Lingying
Published: May 2019

e17090

Background: Ovarian clear cell carcinoma is one kind of Epithelial ovarian carcinoma and is considered high-grade tumor. This retrospective analysis aimed to evaluate the clinical and pathologic features and to determine prognostic variables in patients with stage I ovarian clear cell cancer. Methods: 378 patients with ovarian clear cell cancer were treated in National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, from February 1999 to December 2018. And 214(56.6%) had stage I disease. We retrospectively analyzed the prognostic relevance of different clinicopathological variables in 102 patients underwent surgery treatment, specifically including age, initial symptom, endometriosis, stage, tumor size, serum CA125 and CA199, chemotherapy regimens and treatment course. Results: The median age was 51 years old. 64(62.7%) patients presented with large pelvic mass (median diameter:12.0cm). 82.4% patients had no more than 200U/ml elevation of serological CA125(median: 50.76U/ml). 81.8% patients had no more than 100U/ml elevation of serological CA199(median: 24.8U/ml). The median follow-up time was 40.5 months. The 5-year disease-free survival was 82.8%. All patients were restaged using the 2014 FIGO staging system. 31(30.4%), 17(16.7%), 25(24.5%), 17(16.7%)patients had stage IA, IC1, IC2, IC3, respectively. Univariate analysis showed that tumor size(P = 0.045) and serum CA199(P = 0.025) were related with poor disease-free survival. 5-year disease-free survival (86.9%) of patients with four course chemotherapy was comparable to that (80.2%) with five or more. Patients at stage IC1 or IC2/IC3(rupture before surgery) had the similar outcomes compared with patients at stage IA. And the results of multivariate statistical analysis showed there was no independent, statistically significant prognostic variable. Conclusions: Tumor size and serum CA199 were related with prognosis. Disease-free survival at stage IC1 or IC2/IC3 was comparable to that at stage IA. Five course chemotherapy or more may not improve the 5-year disease-free survival than four.
Clinical outcomes of postoperative intraperitoneal chemotherapy for patients with early-stage high-grade serous ovarian cancer (HGSC) treated at British Columbia cancer agency.
Authors: Lee Joohyun , Tinker Anna
Published: May 2019

e17105

Background: Intraperitoneal (IP) chemotherapy has been shown to prolong overall survival in optimally debulked stage III ovarian cancer in randomized trials. In British Columbia, we extrapolated this benefit of IP chemotherapy to early stage HGSC patients for the last 10 years, as these patients are optimally debulked at surgery but still have a high rate of recurrence. We conducted a retrospective study of clinical outcomes associated with IP/IV chemotherapy compared to IV chemotherapy for optimally debulked stage I HGSC cases. Methods: This was a retrospective cohort study of women with stages IA-IC HGSC who had primary surgery between 2007-2015, and received either IV or IP/IV chemotherapy post-operatively. We compared progression-free survival (PFS) and overall survival (OS) outcomes between these 2 groups. Kaplan-Meier method evaluated chemotherapy delivery route with progression free survival (PFS) and overall survival (OS), using the statistical program R. Results: We identified 99 patients; 80 (81%) received IV chemotherapy and 19 (19%) received IP/IV chemotherapy. Among IP/IV cohort, 2/19 (11%) discontinued IP therapy during treatment due to abdominal pain at IP port site or hypersensitivity reaction to IV paclitaxel. 5-year PFS was 88.4% (74.5-100%) and 69.7% (58.7-82.7%) among the IP/IV and IV cohorts, respectively (p = 0.549). There was a trend for higher 5-year OS for the IP/IV group; however, this did not reach statistical significance (100% vs. 71.4%; p = 0.182). Conclusions: In our study, IP/IV chemotherapy for stage I HGSC patients was associated with a trend for higher 5-year PFS and OS compared to IV chemotherapy. This observation warrants further prospective investigation.
Is microsatellite instability a negative prognostic factor in early stage endometrial cancer patients?
Authors: Lacin Sahin , Tasar Gozde Elif , Usubutun Alp , Arik Zafer , Karakas Yusuf , Yuce Deniz , Salman Mehmet Coskun , Kars Ayse
Published: May 2019

e17107

Background: Endometrial cancer(EC) is a heterogeneous disease with diverse histological features and biological behaviour. Microsatellite instability (MSI) which occurs in cancerous tissue secondary to mismatch repair (MMR) defect of hereditary or somatic origin is a well-known feature further diversifying genetic tumor landscape. In this study, we aim to investigate the relationship between MSI and prognosis in patients with early stage EC. Methods: The patients diagnosed with EC between 2004 and 2017 were retrospectively analysed in the study. The demographic characteristics, disease stage, menopausal status, and clinical and laboratory values were noted. MLH1, MSH2, MSH6 and PMS2 antibodies were used to detect microsatellite status within the tumor tissue samples. Results: The mean age of the 93 patients and menopause was 60.6 ± 9.8 and 49.68 ± 4.5 years , respectively. The median follow-up period was 28 (1-110) months. At the time of diagnosis, number of the patients with stage IA, IB, II, III, and IV were 5, 64, 8, 14, and 2, respectively. Forty three patients were grad 1, 23 patients grad 2, and 27 patients were grade 3. In terms of microsatellite status, 59 patients (63.4%) were microsatellite stable (MSS) and 34 patients (36.6%) were microsatellite instable(MSI). There was no significant association between MSI and tumor stage or grade (X2 = 1.97 p = 0.74 and X2= 3.2, p = 0.19, respectively). There was a significant relationship between peritumoral lymphocyte infiltration rate (pTIL) and MSI. PTIL ratio was higher in tumoral tissues with MSI, whereas pTIL was low in MSS tumor tissues (X2= 28.6, p < 0.0001). Patients with MSI tended to have poorer survival than patients with MSS irrespective of disease stage; mOS rates were 76 and 91 months, respectively (p = 0.086). However, patients with early stage disease and MSI had significantly poorer survial in comparison to patients with similar disease stage and MSS: Overall survival rates for patients with MSI and MSS were 75.8 and 94.7 months, respectively (Log-rank p = 0.048). Conclusions: There is a limited number of studies assessing the association between MSI and clinical outcomes in EC. Our study hints at the presence of potential relationship between MSI and pognosis in patients with MSI. Similar to previous studies performed with various types of tumors we found that EC with MSI attract more immune cells to tumor microenvironments. Interestingly, patients with MSI tended to have poorer prognosis despite augmented immune-cell inftration.