bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of degree of destructive stromal invasion in early stage endocervical adenocarcinoma.
Authors: Lea Jayanthi Sivasothy , Holloway Steven , Zheng Wenxin , Chen Hao , Rivera Glorimar 
Published: May 2019

e17023 Background: Recent evidence has suggested that stratifying endocervical adenocarcinomas based on degree of destructive stromal invasion and desmoplastic response may help further identify risk of lymph node metastasis (1,2). We sought to explore the prognostic influence of the above histopathologic stratification in women undergoing treatment for early stage cervical adenocarcinoma. Methods: Women with stage IA1 – IB2 endocervical adenocarcinoma who underwent radical hysterectomy were included. Demographics and clinico-pathologic data were collected. Three independent gynecologic pathologists performed pathology review for all specimens and tumors were categorized into patterns A, B, and C based on the criteria described by Silva et al (2). Briefly, these criteria include adenocarcinoma without destructive stromal invasion or desmoplastic response (pattern A), minimum destructive invasion (pattern B), and frank invasion (pattern C). Clinico-pathologic data were reviewed and all cases were stratified as either low, intermediate (GOG 92 criteria) or high-risk (positive nodes, parametria, margins). Chi square and Fisher exact test were used for statistical analysis. Results: 46 patients with cervical adenocarcinoma were identified with the following stage distribution: 6 stage IA, 34 stage IB1 and 6 stage IB2. All patients with stage IA disease had pattern A or B tumors. Ten patients with pattern A or B tumors had stage IB1 (N = 9) or IB2 (N = 1). 30 patients had pattern C tumor, all of which were stage IB1-IB2. LVSI was identified in 40% of pattern C versus 6% of pattern B tumors (p < 0.02). All patients who were high-risk for recurrence had pattern C tumors. 16/17 patients who were intermediate-risk had pattern C versus 1/17 with pattern B tumor (p < 0.01). Lymph node metastasis was identified in 11% of pattern C and none in patterns A and B tumors (p < 0.01). All recurrences were diagnosed in patients with pattern C tumors (p < 0.01). Conclusions: Recurrent cervical adenocarcinoma was seen only in patients with pattern C tumors, while no patient with pattern A or B tumors recurred. This histopathologic stratification could be utilized to propose individualized therapy for women with newly diagnosed endocervical adenocarcinoma. References: 1. Diaz De Vivar A al. Int J Gynecol Pathol. 2013;32(6):59;22. Roma AA. Et. al. Gynecol Oncol. 2016; 141: 36.
Overall survival trends for cervical cancer in the modern era: A U.S.A. population based analysis.
Authors: Huang Andrew Jonathan , Huang Karen Elisabeth 
Published: May 2019

e17024 Background: In the past two decades, several advancements have been made in the treatment of cervical cancer such as concurrent chemotherapy, robotic surgery, intensity modulated radiotherapy, 3D brachytherapy planning, and MRI visualization, yet most published survival data is based on historical treatment paradigms. We sought to report domestic treatment outcomes in the modern era to determine if current treatment paradigms resulted in higher overall survival rates. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for patients with cancers of the cervix uteri diagnosed between 2004-2010, had 5-year survival data recorded, and a specific AJCC 6th edition stage assigned. We excluded patients diagnosed after 2010 as the dataset only included survival information until the end of 2015. We used the FIGO 2006 report on cervical cancer as our historical comparator. Chi-square tests were used to determine statistical significance. Results: 32,028 patients in the database met the criteria specified above. The 5-year survivals by stage are compared in the table below. Survival was statistically inferior in SEER patients with stage IIa disease but superior in SEER patients with stage IIIb, IVa, and IVb disease. When comparing SEER patients diagnosed in the earlier (2004-2007) versus the later half of the study period (2008-2010), there were no clinically relevant differences in 5-year survival except in stage IVA patients (19.8% vs 26.6%, p < 0.0001). Conclusions: The 5-year overall survival rates in women with cervical cancer here in the USA in the modern era were similar to those published in the 2006 FIGO report. Inferior outcomes were seen in stage IIa patients but superior outcomes were seen in stage IIIb+ patients. [Table: see text]
Treatment outcome for primary cervix large B-cell lymphoma: A clinical analysis of thirty-seven cases.
Authors: LIU Xiaojian 
Published: May 2019

e17025 Background: Cervical lymphoma is a rare condition and may be difficult to diagnose and treatment. Large B-cell lymphoma is among the most common sub-type of Cervical Lymphoma.No standard treatments for patients with primary cervix large B-cell lymphoma have been introduced currently. Only case reports published in the literature and indicated the R-CHOP regimens in combination with involved field radiation therapy (RT) are effective. Shanghai Cancer Center is one of the top pathological consultant center in China. We retrospectively analyse the 37 patients with primary cervix large B-cell lymphoma and outcome after R-CHOP in combination with RT. Methods: Thirty-seven untreated primary cervix large B-cell lymphoma patients received R-CHOP like regimens. Fourteen of them underwent subsequent RT. Thirteen of them received subsequent salvage chemotherapy. Results: Of 37 patients underwent R-CHOP chemotherapy, only 3 patients received the radical surgery. An overall response rate (ORR) was 78.3% after completion of chemotherapy.The PFS and OS rate at 5 years were 58% and 69%, respectively. For 14 patients who received RT after R-CHOP, an estimated ORR were 89.2%. For all patients, The PFS reached the platform after 2 years follow up and the OS after 3 years according to the survival curve analysis. The international prognostic index (IPI) score were the only predictor of worse outcome. Conclusions: R-CHOP regimens plus involved field radiation therapy led high response rate in primary cervix large B-cell lymphoma. Patients with high IPI had a trend of less satisfied with R-CHOP regimens plus IFRT. Future prospective and multicenter studies are needed. By the way, we are conducting a gene expression profile between DLBCL-unspecified and primary cervix large B-cell lymphoma by NGS in order to get the valuable information to improve the treatment outcome even by using some targeted drugs. The data will be show in the next few months.
The value of tumor paramaters and dosimetry on prognostic nomograms for cervical cancer.
Authors: Lu Shun 
Published: May 2019

e17026 Background: A range of prognostic factors had been reported to be associated with clinical outcome of cervical cancer patients. However, most of these parameters were measured before the start of treatment but without consideration of tumor response to RT. We believed that it might be possible to provide locally advanced cervical cancer patients an opportunity to modify and guide the treatment strategies in the midway of treatment based on the early response evaluation during RT. To establish effective prognostic nomograms using clinical features including tumor volume and size mesured by MRI before treatment and after the completion of external beam radiotherapy (EBRT), and detailed dosimetry of brachytherapy dose for high-risk clinical target volume (HRCTV)D90 and Low-risk Clinical Target Volume(LR-CTV)D90. Methods: The nomogram for local control (LC) was based on a retrospective study of 316 patients who underwent IMRT at our hospital from 2010 to 2015. The predictive accuracy and discriminative ability of our nomogram models were determined by concordance index and calibration curve, and were compared with the nomogram models combining clinical features with FIGO stage. The results were validated using bootstrap resampling and a cohort study of 141 patients. The same data cohort was used to predict the progress-free survival (PFS) of cervical cancer with 3:1 training cohort (N = 310) and validation cohort (N = 155). Results: The following factors were assembled into our prognostic survival nomogram models: Age, tumor volume and size (TV & TS) before treatment, TV and TS after the completion of external beam radiotherapy (EBRT), brachytherapy dose of high-risk clinical target volume (HRCTV)D90 and Low-risk Clinical Target Volume(LR-CTV)D90. The calibration curves showed good agreement between nomogram-predicted and actual survival. Our nomogram models for LC and PFS, provided better results than the nomogram models combining clinical features with FIGO stage. Results were further confirmed in the validation set. Conclusions: Clinical features including tumor size and volume mesured before treatment and after EBRT, as well as detailed dosimetry of brachytherapy dose are able to improve the performance of prognostic nomograms for patients with cervical cancer.
Prognostic value of tumor parameters measured by MRI in cervical cancer patients receiving CCRT.
Authors: Sun Chang , Lu Shun , Wang Ran Lin , Zhang Hanyi , Tan Mingyu , Lang Jin Yi 
Published: May 2019

e17027 Background: This study aimed to evaluate the response of solid tumors after the completion of external beam radiotherapy (EBRT) and investigate the prognostic value of tumor parameters such as tumor volume and size (TV & TS) and tumor volume reduction rate (TVRR) early during the treatment in local advanced cervical cancer patients. Methods: We retrospectively reviewed 310 Chinese patients with locally advanced cervical cancer. They were all received concurrent chemoradiotherapy (CCRT) during the treatment based on intensity modulated radiotherapy (IMRT). Clinical data at the time of diagnosis, including FIGO stage, TV and TS were measured by pelvic magnetic resonance imaging (MRI) before and after EBRT were available. Information about distant metastasis, relapse and date of death was also collected, with a follow-up until Aug 2018. Youden index was used to identify the optimal cut-off point of continuous tumor parameters and divide patients into subgroups. Prognostic factors (age, FIGO stage, RT dose, pre-RT TS and TV, mid-RT TS and TV, TVRR) were using the log-rank test and Cox regression models to analyze the association between predictors and time-to-event outcomes. Results: The median follow-up time was 50 months. In univariate analysis, the FIGO stage, TVRR, TV and TS were associated with overall survival rate. Interestingly, the group of higher TVRR showed a better OS, PFS and LRFS than the group of lower TVRR ( P <0.05). Moreover, the groups of lower TV and TS showed better OS, PFS and LRFS than the higher groups, respectively. In the OS-related multivariate analysis, the mid-RT TV remained statistically significant after adjustment for age and FIGO stage ( P < 0.05). In the PFS-related multivariate analysis, the tumor volume reduction rate (TVRR) remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P <0.05). In addition, in the LRFS-related multivariate analysis, TVRR also remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P <0.05). Conclusions: Our results confirmed that tumor parameters including TS, TV and TVRR, measured before the completion of CCRT, are valuable prognostic factors in patients with locally advanced cervical cancer.
Sarcopenia as a predictor of survival in patients with epithelial ovarian cancer (EOC) receiving platinum and taxane-based chemotherapy.
Authors: Staley Stuart-Allison Moffat , Tucker Katherine , Newton Meredith , Ertel Michelle , Zhang Yingao , Doherty Irene , Gehrig Paola A. 
Published: May 2019

e17030 Background: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. This relationship has recently been demonstrated in women with metastatic breast cancer, but there is a paucity of data regarding this correlation in women with EOC. Thus, our goal was to evaluate if sarcopenia, as assessed by computed tomography (CT) morphometric measurements, was associated with worse survival outcomes in EOC patients undergoing primary platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and descriptive statistics was utilized to describe characteristics between the two groups. Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. Seventy-six percent of patients were diagnosed with Stage III or IV disease, with high-grade serous as the most common histology (74%). Median age at diagnosis was 61 years. Approximately one third were obese. Body mass index was greater in the SMI > 41 group compared to the SMI ≤ 41 group (31.3 vs 26.3, p < 0.001). There was no difference in the prevalence of chronic conditions, including diabetes, coronary artery disease, hypertension, chronic kidney disease, or tobacco use, between the two groups. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). Conclusions: Based on this patient cohort, sarcopenia was not associated with worse survival outcomes in EOC patients receiving first-line platinum and taxane-based chemotherapy. Further prospective studies are needed to explore other diagnostics that may allow us to provide improved accuracy and individualization in the care of women with advanced ovarian cancer.
Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.
Authors: Wimberger Pauline , Passek Simon , Link Theresa , Vassileva Yana , Kramer Michael , Kuhlmann Jan Dominik 
Published: May 2019

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.
GPR30 signaling to regulate epithelial-mesenchymal transition and predict survival in ovarian cancer.
Authors: Fujiwara Satoe , Terada Shinichi , Kogata Yuhei , Maruoka Hiroshi , Tanaka Yoshimichi , Tanaka Tomohito , Tsunetoh Satoshi , Sasaki Hiroshi , Ohmichi Masahide 
Published: May 2019

e17041 Background: G protein-coupled receptor 30 (GPR30) is a 7-transmembrane　estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that the high expression of GPR30 is associated with a poor prognosis in breast cancer or endometrial cancer. Although the role of GPR30 in ovarian cancer was unclear, we revealed that GPR30 is associated with poor prognosis in ovarian cancer. On the other hand, Epithelial-to-Mesenchymal Transition (EMT) is involved in cancer metastasis. The purpose of this study is to reveal how GPR30 was associated with poor prognosis and whether associated with EMT in ovarian cancer. Methods: We examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis. We also examined the effect of GPR30 on EMT were evaluated in Caov-3, which were cultured both in two-dimensional (2D) culture and three-dimensional (3D) culture model. GPR30 agonist, G1, was used to confirm the regulatory effects of GPR30 on the change of phenotypic modulation and EMT markers expression. Results: The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p < 0.05) and inhibited by a Src family kinase inhibitor. In 3D culture, the stimulation of GPR30 leads the floating and sphere formation in Caov-3. G1-induced EMT was observed with related regulation of EMT markers expression at both mRNA and protein level. G1 induced the decrease of E-cadherin level and the increase of Snail and Vimentin in RT-PCR and Western blotting. Knockdown of GPR30, using siRNA, blocked G1-induced EMT. Conclusions: GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells and changes ovarian cancer cells to the EMT state.GPR30 might be an important molecule related to metastasis process in ovarian cancer.
The developmental origins of high grade serous ovarian cancer.
Authors: Lo Riso Pietro , Villa Carlo Emanuele , Gasparoni Gilles , Luongo Raffaele , Manfredi Anna , Vingiani Andrea , Jungmann Annemarie , Garbi Annalisa , Lupia Michela , Pruneri Giancarlo , Viale Giuseppe , Colombo Nicoletta , Cavallaro Ugo , Cacchiarelli Davide , Walter Jörn Erik , Testa Giuseppe 
Published: May 2019

e17063 Background: The still persistent uncertainty in the identification of the cell of origin of high grade serous ovarian cancer (HGSOC), with two candidate originating tissues identified in the distal tract of the fallopian tube (FI) and the surface epithelium of the ovary (OSE), has hampered the identification of clinically relevant molecular features for this disease to be targeted for therapy. This resulted in only a negligible improvement in patient’s care since the introduction of carboplatin-based treatments. Methods: To solve this issue, here we show an innovative method based on the identification of a cell of origin-specific DNA methylation print (OriPrint) that allows the reliable stratification of human primary HGSOC in FI and OSE-originated tumors. Results: We show that this approach is robust to alternative clustering methods and can discriminate tumors derived from each of the two origins across different datasets. Also, we translated these findings on a well-characterized retrospective cohort, showing that the cell of origin significantly impacts patient’s prognosis. Finally, through RNAseq, we unveil origin-specific transcriptional networks compatible with the differential impact on patient’s survival, mainly involved in inflammatory response and cell survival, movement and signaling. Conclusions: Our approach proves for the first time in human primary samples that both origins can give rise to HGSOC, paving the way to a finer molecular characterization of this disease and to the development of more effective therapeutic regimens for improved care for patients.
Prognosis of ovarian cancer in the United States during 1973 to 2015.
Authors: Zhang Jianfeng , Lu Yingying , Zhang Yuzi , Zhang Zhenghua , Cai Shangli 
Published: May 2019

e17072 Background: Ovarian cancer is the first leading cause of cancer death among gynecologic malignancies. Despite significant efforts to improve treatment strategies, the prognosis of patients with ovarian cancer remains poor. Different diagnostic period and the occurrence of distant metastases may have different impacts on prognosis. In this study, we sought to describe the impact of distant metastases and different diagnostic period on prognosis of ovarian cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with ovarian cancer from year 1973 to year 2015. Kaplan-Meier method was used to estimate the overall survival (OS) and Log-Rank test was used to compare the difference between groups. Results: Total 152729 patients with ovarian cancer were included. Median age was 62 years. The overall rates of distant lymph node metastases, bone, brain, liver and lung were 2.9%, 1.0%, 0.2%, 6.6% and 5.6%. Median overall survival (OS) was 30 months, 6 months, 9 months, 20 months and 20 months for pure distant lymph node metastases, brain metastases, bone metastases, lung metastases and liver metastases, respectively. Patients who were diagnosed from year 2010 to year 2015 had significantly improved OS compared with patients who were diagnosed from year 1973 to year 2009 (54 months vs. 47 months, P < 0.0001). Patients with pure distant lymph node metastases who were diagnosed from year 2010 to year 2015 also had significantly improved OS compared with patients who were diagnosed from year 1973 to year 2009 (30 months vs. 24 months, P = 0.0002). In addition, we also observed a trend of longer OS in patients with bone metastases diagnosed from year 2014 to year 2015 compared with patients who were diagnosed year 2010 to year 2013 (10 months vs. 7 months, P = 0.05). Conclusions: The results of this analysis indicated an improved prognosis in patients with ovarian cancer from 2010 to 2014, especially for patients with distant lymph node metastases. In addition, novel treatment strategies are needed for patients with distant visceral metastases.