bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Sonographic and histopathologic characteristics of MMR-deficient endometrial cancer.
Authors: Smith Daniel Arnold , Paspulati Raj M , Azar Nami R , Laukamp Kai , Kikano Elias , Avril Stefanie , Ramaiya Nikhil H. 
Published: May 2019

e17111 Background: Mismatch repair (MMR) deficiency has emerged as a key biomarker in endometrial cancer with roles in prognosis and guiding therapy. However, the differences of sonographic features between MMR-deficient and MMR-proficient endometrial cancers at initial presentation have not been established. Methods: Transvaginal ultrasound studies of 103 endometrial cancers (60 MMR-deficient, 43 MMR-proficient) at initial presentation were retrospectively analyzed by two experienced radiologists. Histopathologic findings and sonographic features of endometrial morphology recorded according to IETA terminology were compared using Likelihood Ratio Chi-Square and Mann–Whitney U tests. Results: The MMR-deficient group comprised of 90% and the MMR-proficient group of 100% endometrioid subtypes. The following sonographic features were statistically different between MMR-deficient (age 45-95) and MMR-proficient (age 45-83) groups: uniform endometrial echogenicity/pattern, non-uniform endometrial echogenicity/pattern, endometrial midline morphology, presence of a bright edge, and endomyometrial junction morphology. Ultrasound findings of endometrial thickness, synechiae, intracavitary fluid, color Doppler score, and vascular pattern were not significantly different. Statistically significant differences in pathology features included FIGO grade, myometrial invasion, and lymphovascular invasion, while FIGO stage showed no difference. Conclusions: MMR-deficient endometrial cancer is characterized by several statistically different ultrasound and histopathologic features on initial presentation compared to MMR-proficient endometrial cancer.[Table: see text]
Transcriptomic characterization of endometrial cancer in order to find new therapeutic targets.
Authors: Parra-Grande Monica , Ore-Arce Martin , Llorca Cristina , Poveda Andres 
Published: May 2019

e17113 Background: There are unmet needs for targeted therapy in Endometrial Cancer (EC). The integrated genomic characterization of EC provided insights into disease biology. Our primary objective is to identify potential actionable pathways to target therapeutically in EC according to the microsatellite status (microsatellite instability high = MSI-H, and microsatellite stable/microsatellite instability low = MSS/MSI-L). Methods: 375 RNAs from the genomic profile of EC within the TCGA database were used to perform RNA-seq analysis. We analyzed RNA-sequencing data with edgeR package to filter and normalize the data, followed by the limma package with its Voom method, linear modeling and empirical Bayes moderation to asses differential expression. Reactome FI Cytoscape app was used to perform pathway and network-based data analysis. Results: According to the microsatellite status, two groups were identified: Group 1 = MSI-H (127 patients) and Group 2 = MSS/MSI-L (248 patients). Significant expression differences were found in 2141 genes. In the Group 1 we identified 1194 genes overexpressed and 947 genes overexpressed in the Group 2. Group 1 includes genes associated with cell proliferation. Group 2 includes genes associated with genomic instability and apoptosis evasion (table 1). Conclusions: In EC patients, Cyclin-dependent kinase (CDK) pathways could be a potential therapeutic target, especially in patients with MSI-H tumors. Further studies are necessary in order to evaluate the activity of CDKs inhibitors in this population.[Table: see text]
Quality of care and survival of women with uterine cancer by Hispanic origin: An NCDB analysis.
Authors: Gamble Charlotte , Huang Yongmei , Tergas Ana Isabel , Ruiz Maria Paula , Hou June YiJuan , Collado Fady , St. Clair Caryn , Wright Jason Dennis 
Published: May 2019

e17120 Background: In cancer research in the US, Hispanic patients are often analyzed as a homogeneous group despite significant diversity within this ethnic classification. Our objective was to assess the impact of place of origin on quality of care and overall survival for Hispanic women with uterine cancer living in the US. Methods: The National Cancer Database (NCDB) was used to identify all patients with uterine cancer from 2004-2015. Hispanic origin was classified based on NCDB subgroups: Mexican, Puerto Rican, Cuban, South or Central American, and Dominican Republic. Multivariable models were used to assess the adjusted relative risk (aRR) of receiving quality of care indicators. Thirty-day mortality and overall 5-year survival were calculated using multivariable log-Poisson and Cox proportional Hazard models. Results: A total of 5,411 Hispanic women and 288,111 non-Hispanic women were identified. Of Hispanic women, Mexican patients comprised the largest subgroup (n = 2,512), and increased from 34.5% to 49.7% over the study period. South or Central American (n = 1,217) and Dominican (n = 218) patients also increased modestly, while the volume of Puerto Rican patients remained unchanged (n = 877), and Cuban patients decreased from 23.3% to 5.6% (n = 587). Compared to non-Hispanic women, there were no significant differences in the rates of use of minimally invasive surgery, chemotherapy in early stage high risk disease, lymph node dissection, or 30-day readmission among the Hispanic subpopulations. Rates of chemotherapy for advanced stage disease were modestly increased for Dominican (aRR 1.37, 95%CI (1.23-1.54)) and South or Central American (aRR 1.16, 95%CI (1.05,1.29)) groups. Dominican patients had a statistically significant reduction in overall mortality at five years for stage III and IV disease with aHR 0.38, 95%CI (0.16-0.90) and aHR 0.28, 95%CI (0.09, 0.87), respectively. For all other Hispanic subgroups, there were no differences in stage-specific survival. Conclusions: The diversity within the Hispanic cohort of women with uterine cancer in NCDB is changing. Overall quality indicators and survival outcomes are comparable between each Hispanic origin group, with the exception of advanced stage Dominican women who are more likely to receive chemotherapy, and have superior survival outcomes.
Does systemic treatment add value to stereotactic body radiation therapy for locoregional control in head and neck squamous cell carcinoma patients?
Authors: Tufano Andrea M , Newman James , Gogineni Emile , Karten Jessie L , Paul Doru , Ghaly Maged , Seetharamu Nagashree 
Published: May 2019

e17505 Background: Stereotactic body radiotherapy (SBRT) has been shown to provide locoregional control in head and neck squamous cell carcinoma (HNSCC) patients (pts) who are not candidates for curative procedures due to poor performance status, comorbidities, or radiation dose limitations from prior treatment. The addition of chemotherapy (chemo) and/or cetuximab (CET) is hypothesized to improve outcomes compared to SBRT alone, but there is limited data on comparative effectiveness. We compared outcomes of pts treated with SBRT vs. SBRT + chemo and/or CET using retrospective observational data from our institution. Methods: We identified new and recurrent HNSCC pts treated with SBRT +/- systemic therapy from 2012 to 2018. Age, Charlson Comorbidity Index (CCI) and stage were recorded. Primary outcome was locoregional disease control rate based on Modified Response Evaluation Criteria in Solid Tumors on 3-month post-treatment imaging. Secondary outcome was overall survival (OS) at 1 year. Pts were divided into 4 groups: SBRT, SBRT+chemo, SBRT+CET, and SBRT+chemo+CET (cohorts A, B, C and D, respectively). Results: 90 pts with median age of 73 years and median follow-up of 11.5 months were included. 94.4% were stage III or IV, and 68.9% had recurrent disease. The most commonly utilized chemotherapy was carboplatin and paclitaxel. Cohorts A, B, C and D constituted 28.9%, 31.1%, 31.1% and 8.8% respectively. Groups were well matched except for pts in Cohort A being significantly older than those in Cohort B (74.9 vs. 68.4 years; p = 0.01). Average CCI estimated 10-year survival was 8.4%. There was a trend towards improved locoregional control at 3 months in Cohort B vs. A (57.1% vs. 34.6%, p = 0.09), and improved OS at 1 year (46.4% vs. 23.1%; p = 0.07). These trends were not observed in comparisons between other cohorts. Conclusions: Chemo + SBRT may improve disease control as well as 1 year OS in HNSCC pts who do not qualify for curative procedures. Given the younger age of pts receiving chemo, selection bias cannot be excluded. Prospective studies with larger patient cohorts are needed to further evaluate the benefits and toxicities of adding systemic treatment to SBRT in this population.
Comparison of mortality and second primary oropharyngeal malignancies by human papilloma virus (HPV) status in patients (pts) with oropharyngeal squamous cell carcinoma (OPSCC) using an updated Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Holstead Ryan , Rasul Rehana , Golden Anne , Seetharamu Nagashree 
Published: May 2019

e17518 Background: Prognosis and patterns of failure differ between HPV positive (pos) and HPV negative (neg) OPSCC. HPV neg have an increased risk of developing head, neck, and lung SPM due to field cancerization. Second primary OPSCC in HPV pos pts may be due to persistent risk for HPV-mediated carcinogenesis and compromised immune status. The rate and location of SPM in HPV pos pts is not as well described and HPV-specific surveillance guidelines are yet to be determined. Methods: Retrospective cohort study from a custom SEER database of OPSCC diagnosed from 2013-2015 was conducted. Differences in overall survival (OS) and SPM were compared by HPV status using Gray’s test. Cox proportional hazard models were performed, adjusting for age, race, sex, year of diagnosis, tumor grade, stage, and first treatment. Results: 12,895 pts were identified, with a mean age of 61.8 (SD = 9.97) years, mostly male (83.2%), and white (87.3%), with 45.0% HPV pos, 15.3% HPV neg, and 39.7% HPV unknown (unk). Proportion of HPV pos pts increased from 2013-2015 (40.7%-49.2%). HPV pos pts tended to have higher stage and grade of tumor. Most patients were treated with chemotherapy and radiation. Median duration of follow up was 13 (5-22) months. HPV pos had significantly lower unadjusted 2-year mortality compared to neg or unk (13.7% vs. 38.9% vs. 32.8%, p < 0.001). Median OS for HPV pos, HPV neg and HPV unk was 29 months (m), 25.6 m, and 24.45 m respectivey (p < 0.0001). From the multivariable Cox regression, HPV neg pts had 2.25 times the risk (95% CI: 1.99-2.54) of death compared to HPV pos pts. Incidence of OP SPM was similar (0.008-0.011%) in all three HPV cohorts (aHR = 0.87, 95% CI: 0.49-1.54). Conclusions: Our study strongly supports the prognostic value of HPV status. Incidence of OP SPM is similar in HPV pos and neg OPSCC suggesting that similar surveillance strategies should be employed for all OPSCC pts. Limitations of the study include lack of data on smoking and alcohol use, high rate of HPV unk pts, and SEER-imposed restriction to SPM occurring only in the OP region.
Selected molecular markers as indicators of clinical profile, tumor characteristics and treatment outcome in squamous cell carcinoma of the larynx.
Authors: Iype Elizabeth Mathew , S Lakshmi , Balakrishnan Rajan 
Published: May 2019

e17522 Background: Laryngeal Squamous cell carcinoma is widely prevalent in India and is the fourth leading cancer in males. The possibility that specific tumour characteristics (demonstrable by immunohistochemistry) may aid the clinician in choosing optimal treatments for a specific tumour, holds great promise. Objectives of the present study were to study the expression of select molecular markers p53, Bcl-2 (Apoptotic markers), EGFR, Ki67, Cyclin D1 (Proliferation markers) and Cox-2 (Inflammatory marker) in LSCC so as to form a hypothesis that a particular group of markers will be useful in determining the prognosis of LSCC. Methods: We studied 72 cases of laryngeal squamous cell carcinoma in an attempt to determine relationship between their clinicopathological characteristics and treatment outcome with the six molecular markers. Samples from patients who underwent laryngectomy from Jan 2006 to Dec 2010 were taken and analyzed prospectively and followed up till Dec 2015 or till death. . Immunoreactivity in tissue sections was evaluated as negative when no positive cells were observed within the tumor, weak (1+) , moderate (2+) , and strong or intense (3+) . Data were analyzed using SPSS software package. Chi squared test or exact test were used to test the associations. Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals. The disease free survival time of each patient was calculated by taking the difference between the date of surgery and the recurrence date/ death date/ the last follow up date whichever is applicable. Results: Proliferation markers EGFR, Cyclin D1 and Ki 67, individually and collectively were predictive of extracapsular spread and perineural spread of tumour. Node negative patients having intense expression of Cyclin D1 or Ki 67 has bad prognosis.. The significant expression of Cox-2 was highly predictive of Node positivity. In older patients and in T4 stage the presence of P53 / Bcl-2 resulted in worse overall survival. Markers of aggressiveness were identified as p53, Bcl-2 Cox-2. Markers of invasiveness were EGFR, Cyclin D1 and Ki 67. Markers predicting survival were p53, BCl-2, Cyclin D1 and Ki 67. Conclusions: If Proliferation markers are detected preoperatively in biopsy specimens, has important implications in planning aggressive management Cyclin D1 or Ki 67 in Node negative patients indicate need for a neck dissection or irradiation. Cox-2 assessment will be useful in predicting the occult nodal metastasis for prophylactic treatment