bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient characteristics associated with treatment of cervical cancer in the United States.
Authors: Corman Shelby , Nwankwo Chizoba , Kwon Youngmin , Shah Ruchit
Published: May 2019

e17020

Background: Treatment options for cervical cancer include surgery, radiation therapy, chemotherapy, and immunotherapy depending upon the disease stage. There is limited real-world evidence providing us with a clinical profile for a treated cervical cancer patient. The objective of this study was to compare cervical cancer patients who were currently receiving treatment versus those not receiving treatment. Methods: This was a retrospective, cross-sectional analysis of Medical Expenditure Panel Survey (MEPS) data (2006-2015). Cervical cancer cases were identified using ICD-9 CM code 180 or clinical classification software code 26. Patients receiving only chemotherapy, radiation therapy, undergoing surgery, or a combination of these treatments in a given year were regarded as “currently receiving treatment”. The comparator cohort included patients “not currently receiving treatment”. The two cohorts were compared in terms of patient clinical characteristics using bivariate analyses. Results: The analytic cohort consisted of 275,246 cervical cancer cases (mean age: 42 years, Caucasian: 88.0%, having private insurance: 55.3%) of which 115,639 (42.01%) were “currently receiving treatment”. The most common treatment option was undergoing surgery only (88.21%), followed by combination therapy (6.82%), chemotherapy only (3.84%), and radiation therapy only (1.12%). The “currently receiving treatment” cohort had a significantly higher proportion of patients having a history of myocardial infarction (4.21% vs 3.50%), congestive heart failure (2.73% vs 1.42%), chronic obstructive pulmonary disorder (29.5% vs 23.2%), connective tissue disease (20.5% vs 11.6%), renal disease (2.49% vs 0.48%), and diabetes (17.7% vs 11.7%) compared to those “not currently receiving treatment”. The latter cohort had a higher proportion of patients with moderate/severe liver disease (0.46% vs 5.32%). Conclusions: The observed real-world patient characteristics and treatment patterns were indicative of a cohort of largely early stage cervical cancer patients. Patients receiving treatment appeared to have a higher comorbidity burden which may subsequently result in poorer quality of life and activity limitations.
Economic burden associated with cervical cancer: An analysis of patient-reported outcomes in the United States.
Authors: Nwankwo Chizoba , Way Nate Alexander , Li Vicky Weitian
Published: May 2019

e17021

Background: Although much is known about the prevention, screening, and treatment of cervical cancer (CC), less is known about its economic burden. This study compared patient-reported outcomes (PROs) between women diagnosed and treated for CC, women diagnosed and untreated for CC, and women without CC. Methods: Data were aggregated from the 2013-2015 US National Health and Wellness Surveys, a nationally-representative, self-administered, internet-based survey of adults (N = 269,447). Controlling for baseline patient demographics and characteristics, three matched cohorts were compared in multivariable analysis: treated CC, untreated CC, and no CC. Treated CC and untreated CC patients with other forms of comorbid cancer were excluded from analyses. Economic outcomes included healthcare resource use (HCRU) over the past six months and annualized direct costs. Direct costs were calculated using Medical Expenditure Panel Survey data. Results: Adjusted means are reported. Treated CC (N = 192), untreated CC (N = 829), and no CC (N = 1,018) cohorts largely differed by number of healthcare provider (HCP) visits (0.95 vs. 0.89 vs. 0.84, p’s < 0.05), hospitalizations (0.18 vs. 0.09 vs. 0.10, p’s < 0.05), and ER visits (0.29 vs. 0.19 vs. 0.16, p’s < 0.05), though the difference between untreated CC and no CC cohorts was not significant for hospitalizations nor ER visits. Treated CC, untreated CC, and no CC cohorts also largely differed by HCP costs ($14,143 vs. $11,187 vs. $10,573, p’s < 0.01), hospitalization costs ($12,006 vs. $4,202 vs. $4,908, p’s < 0.01), ER costs ($2,104 vs. $995 vs. $872, p’s < 0.01), and total direct costs ($30,768 vs. $16,613 vs. $16,776, p’s < 0.01), though the difference between untreated CC and no CC cohorts was not significant for HCP costs nor total direct costs. Conclusions: These results indicate substantial economic burden in women diagnosed with CC in the US. In terms of HCRU and direct costs, treated CC patients incur the greatest burden, untreated CC patients incur the second greatest burden, and individuals without CC tend to incur the least burden.
Mutational landscape of cervical cancer identified by prospective clinical sequencing in a nationwide cancer network.
Authors: Schink Julian C. , Alvarez Ricardo H. , Elvin Julia Andrea , Moran Amber , Rollins Rebecca , Geisler John P. , McIntosh David , Godbee Natalie , Tan Bradford A. , Markman Maurie
Published: May 2019

e17022

Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of cervical cancer (CC) patients assayed in a nationwide cancer network. Methods: 118 Pts with advanced CC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 47 years (range, 27-71), 69% were Caucasian. GA were identified in 88% (104/118) of CC, of which 87 (74%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most commonpresent in 73.5% (64/87) of CC. CRGA in other targetable pathways were identified: 24.1% (21/87) in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2), 9.1% (8/87) in HRD (BRCA1/2, ATM, PALB2, BRIP1) and 24.1% (21/87) in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). One patient was MSI-high and one patient was TMB-high. 29.8% (26/87) of CC patients were ordered a genomically-matched treatment, and 24 pts received treatment; 61.5% (16/26) were agents that were FDA approved in a different tumor type, and 34.6% (9/26) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The PFS for non study related patients was 7 weeks and OS was 19 weeks. Conclusions: In a large series of Cervical Cancer patients assayed with CGP, 27.5% (24/87) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.
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.
New biomarkers to predict platinum resistance in ovarian cancer patients.
Authors: Trifanescu Oana , Gales Laurentia Minea , Gruia Maria Iuliana , Gusoiu Bianca Andreea , Torliceanu Florina , Rodica Maricela Anghel
Published: May 2019

e17085

Background: Epithelial ovarian cancer is the second most common gynecologic malignancy and is characterized by the highest mortality of all gynecological cancers. Despite of initial response, platinum resistance develops and contributes to the poor outcome of advanced stage ovarian cancer patients. The aim of the study was to identify biomarkers helpful in predicting treatment response to platinum salts. Methods: Forty eight patients with advanced ovarian (stage II, III and IV) cancer were prospectively enrolled between 2014 and 2017. All patients underwent surgery followed by platinum-based chemotherapy. Serum reactive oxygen species parameters such as malondialdehyde, ceruloplasmine, and serum VEGF were measured before each cycle of chemotherapy. Results: Mean age at diagnostic was 51.3 +/- 8.1 years, (range 42 - 78). Median follow up was 39 months (range 12-56). Twenty tree percent were platinum resistance. Median progression free survival was 22 months and estimated median overall survival was 84 months, 77% of patients being alive at 3 years. VEGF levels were significantly higher in patients with platinum resistance disease (1210 pg/ml) compare to platinum sensitive (mean VEGF levels 945pg/ml, p = 0.0003). We used a ROC curve to estimate the sensitivity and specificity of VEGF as a predictor to platinum response and find out that the aria under the curve (AUC) was 0.874, p = 0.003, 95% CI 0.734-1 and cut-off value (80% sensibility, 80% specificity) was 1085pg/ml. Malondialdehyde levels were statistically significant higher in patients with platinum resistance disease (mean value 11.1 μmol/100 ml vs. 7.4 μmol/100 ml in platinum sensitive, p = 0.02. The ROC curve for malondialdehyde identify an aria under the curve of 0.818, p = 0.0001 and CI 95% (0.744-0.893) and a cut-off value of 7.74 μmol/100 ml to estimate with 81.3% sensitivity and 64% specificity platinum response validating this bio markers as predicting platinum response. For Ceruloplasmine AUC was 0.706, p = 0.0001, 95% CI (0.617,-0.796). Conclusions: Malondialdehyde, ceruloplasmine and VEGF can estimate with precision the resistance to platinum salts in advanced ovarian cancer patients.
Dynamic of molecular subtypes of high‐grade serous ovarian cancer in paired primary and relapsed biopsies.
Authors: Braicu Elena Ioana , Kulbe Hagen , Dreher Felix , Taube Eliane T , Ringel Frauke , Welsch Gabriele , Darb-Esfahani Silvia , Keunecke Carlotta , Kessler Thomas , Wierling Christoph , Jank Paul , Denkert Carsten , Lammert Hedwig , Hummel Michael , Sehouli Jalid
Published: May 2019

e17091

Background: Previously four molecular subtypes of high grade serous ovarian cancer (HGSOC) with distinct biological features and clinical outcome have been described: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative). Using Nanostring technique and a minimal signature of 39 classifier genes could reproduce the subtypes identified by microarray gene expression profiling (Leong HS et al. Australian Ovarian Cancer Study. J Pathol. 2015). Methods: We characterized paraffin embedded tissue samples from 279 HGSOC patients for molecular subtypes, utilizing the 39 classifier signature and 9 control genes by Nanostring nCounter Analysis System. From 16 patients paired primary and relapsed samples were available. Only chemonaive primary HGSOC patients were included in the study. FFPEs and clinical data were provided by TOC ( www.toc-network.de ). For each sample, probability scores for the four molecular subtypes (C1, C2, C4, and C5) were calculated. The highest calculated score determined the most likely subtype of the tumor. Results: Of all analyzed primary tumor samples, 88 (31.5%) were classified as C1, 83 (29.8%), 53 (19.0%) and 55 (19.7%) as subtypes C2, C4 and C5, respectively. Our results confirmed data by the AOCS study, which described the distribution of HGSOC with 40.2% (C1), 22.5% (C2), 20.1% (C4) and 17.2% (C5), respectively. Within the paired samples, for 12 of the 16 patients dynamic changes in the molecular subtypes between primary and relapse occurred, while in the remaining 4 patients the phenotype was stable. Conclusions: Molecular subtypes of HGSOC using Nanostring technology with a small panel of classifier genes can be confirmed. Furthermore, the data showed that a change of the established molecular subtype might occur during the evolution of the disease, and therefore translate in a different clinical outcome.
Oncologic outcomes and morbidity following heated intraperitoneal chemotherapy at cytoreductive surgery for primary epithelial ovarian cancer: A systematic review and meta-analysis.
Authors: Bouchard-Fortier Genevieve , Cusimano Maria Christine , Fazelzad Rouhi , Lu Lin , May Taymaa , Bouchard-Fortier Antoine , Ferguson Sarah
Published: May 2019

e17093

Background: Heated intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery in the treatment of primary epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy was associated with a significant 12 months improved overall survival (OS) in a well-designed randomized controlled trial. Nonetheless, there remains uncertainty about the benefit and safety of HIPEC in ovarian cancer. The aim of this review was to assess efficacy and safety of HIPEC in primary EOC. Methods: We conducted a systematic search in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to February 22nd 2018 for observational and randomized studies of patients with primary EOC undergoing HIPEC at cytoreductive surgery with no language restrictions . We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Quality Scale for double-arm studies. We determined the pooled proportion of 30-day grade 3-4 morbidity, reoperation, and postoperative death. Results: Thirty-five articles including 1937 patients with primary EOC met inclusion criteria. Timing of HIPEC and type of chemotherapy regimens were not consistent between studies. There was significant variation in the reported OS of patients treated with HIPEC at cytoreductive surgery for primary EOC (3-year OS:48-77%; 5-year OS:17-72%). Thirteen articles were including in a meta-analysis to determine to the safety of HIPEC. The pooled proportions for 30-day Grade 3-4 morbidity, 30-day reoperation, and 30-day postoperative death were 33.0% (95% CI 23.0-45.0), 9.0% (95% CI 5.0-17.0) and 3.0% (95% CI 1.0-5.0) respectively. Conclusions: The use of HIPEC in primary EOC is associated with significant morbidity. There is significant heterogeneity in current literature. Higher quality, large prospective randomized control trials are needed to further support the benefit of HIPEC at cytoreductive surgery in the first-line treatment of primary EOC.
Exploring racial disparities of actionable mutations in gynecologic cancers.
Authors: Jhaveri Vasanti , Fanfan Dino , Cotta Jared Addison , George Sophia , Slomovitz Brian M. , Huang Marilyn
Published: May 2019

e17098

Background: Next Generation Sequencing (NGS) guides targeted therapy and clinical trial enrollment for patients with gynecologic malignancies. South Florida is a key region to explore biomarkers and molecular alterations common in Hispanic (H) patients due to the high proportion of H individuals. While NGS testing is increasingly used in clinical practice to aid in treatment planning, ethnic minorities are at risk for health disparity including clinical trial enrollment. The objective of this study was to determine if frequently reported mutations are also common in a predominantly H population with gynecologic cancers. Methods: Clinicopathologic data was obtained from women treated at our institution from Jan. 2014 to Jan 2019 for gynecologic malignancies. Women with ovarian (OC), endometrial (EC), and cervical cancer (CC) with NGS results from Caris Life Sciences were included for analysis. Women self-report ethnicity based on initial hospital intake form. Mutations based on point mutations, indels, fusions and copy number variations were identified. Descriptive statistics are reported. IRB approval was obtained. Results: A total of 233 patients with 117 ovarian (OC), 24 cervical (CC) and 92 endometrial cancers (EC) were included. Among the 233 women, 96 (41%) were H, 137 (59%) identified as NH. There were 38 H and 48 NH patients with EC; 50 H and 62 NH OC patients; and 8 H and 13 NH CC patients. Among EC patients, TP53 appeared in 42% vs. 47%, PTEN 26% vs. 30% , PIK3CA 32% vs. 17%, CTNNB1 32% vs. 17% , and KRAS 16% vs. 21% of H and NH cases respectively. In the OC cohort, TP53 appeared in 74% vs. 75% , BRCA1/2 10% vs. 19%, KRAS 16% vs. 16% and PIK3CA 8% vs. 6% of H and NH cases respectively. In CC patients, TP53 appeared in 25% vs. 23%, KMT2C 12.5% vs. 7.6% and PIK3CA 0 vs. 38% of H and NH cases respectively. There were no statistical differences in the mutation rates between the two groups. Conclusions: There is limited data reported on the variation of mutations based on ethnicity in women with gynecologic cancers. Our study suggests there may be different driver mutations based on ethnicity. Future studies in larger cohorts are needed to further assess genomic differences, potential responses to treatment and further increase H population enrollment into clinical trials.
Predictive factors of cytoreductive surgery in epithelial ovarian cancer in a Mexican women cohort.
Authors: Vasquez Flavia Morales , Gonzalez Ricardo Raziel Peña , López Basave Horacio Noé
Published: May 2019

e17099

Background: Cytoreductive surgery is the most important prognostic factor in ovarian cancer. To identify in a timely manner the patients who are not candidates for optimal debulking, does not delay and optimize the treatment. Objetive: Identify the presurgical factors that characterize patients in whom optimal cytoreduction is not possible. Methods: Observational study in a retrospective cohort (n = 255) that compared pre-surgical factors between patients with optimal debulking (n = 65) and suboptimal (n = 190). Non-parametric tests were used, a Cox proportional hazards model was constructed and survival curves were drawn by method of Kaplan y Meier. Results: 255 patients were included. 75% achieved optimal debulking. 9 out of 10 evaluated tomography criteria showed association (p < 0.001) with suboptimal cytoreduction. The best cut-off value of Ca-125 to predict suboptimal surgery was 774 IU / mL. Only clinical ascites showed association with the result of the surgery (p < 0.001). There was no difference in complications between both groups (p = 0.267). The rate of optimal debulking has improved over time (p = 0.049). The turn of the surgeries has no impact on the overall survival of the patients (p = 0.792). Conclusions: Objective parameters (tomography and laboratory) should be used to select patients who are not candidates for surgery. The Clinical evaluation without objective parameters is not enough
Half-dose olaparib reduction: Safe and efficient dose in multi-treated Mexican ovarian cancer patients.
Authors: Gallardo-Rincon Dolores , Alamilla Gabriela , Montes-Servín Edgar , Michel-Tello David , Montes-Servín Elizabeth , Toledo-Leyva Alfredo , Bahena-Gonzalez Antonio , Gonzalez-Ibarra Ernesto , Morales-Vasquez Flavia , Cano Blanco Claudia , Espinosa-Romero Raquel
Published: May 2019

e17101

Background: Ovarian cancer (OC) is the most common gynecological cancer worldwide, and in Mexico stands as the 2nd gynecological cancer-related death cause with 4,759 new cases yearly. PARP inhibitors in BRCA1/2 mutated patients offer disease control after response to chemotherapy with few side effects and minimal impact on quality of life. The primary objective of this study was to evaluate the clinical benefit of Olaparib half-dose reduction in multi-treated Mexican OC patients. Methods: Nineteen OC BRCA1/2 positive patients were enrolled (Nov 2016-Dec 2018), at the Instituto Nacional de Cancerología, Mexico. Eligible patients had received > 2 previous platinum-based lines. Olaparib dose was 800 mg/day, as maintenance therapy after complete or partial response. Half-dose administration was allowed in grade 3 toxicity events. Median PFS curves were estimated by the Kaplan–Meier method. Results: The most common mutation in OC patients was BRCA1 (78.9%), four patients had founder mutation (Del9-12). Eleven patients (57.9%) received Olaparib in ≥4 lines. Nine patients required dose adjustment following hematological (42.1%) and gastrointestinal toxicity (5.2%). There was not statistical differences between complete-dose and half-dose administration groups. However patients with founder BRCA1 mutation did not require dose adjustment ( P= 0.033) and multi-treated (≥4 lines) patients were more susceptible to develop hematological toxicity ( P= 0.030). The median PFS was 12.02 months, patients HGSP histology had a better PFS compared with endometroid histology (14.8 Vs 5.19; P= 0.020). BRCA1 founder mutated patients had a better PFS compared with other BRCA mutations (NR Vs 11.30; P= 0.050). The median PFS in first, second and third or more recurrence was NR Vs 14.8 Vs 8.3; P= 0.050. We did not find statistical difference in the PFS in half-dose reduction compared with complete-dose groups (9.6 Vs NR; P= 0.221). Conclusions: We provide evidence that using Olaparib in first and second recurrence had better outcome compared with third or more recurrence. However the recommended dose exhibits a high toxicity profile; therefore half-dose reduction in multi-treated patients needs to be suggested in Olaparib OC guidelines as a safety and effective strategy.
Effect of postoperative adjuvant treatment in the therapeutic management of stage I, morcellated uterine leiomyosarcoma: A Korean multicenter study.
Authors: Kim Se Ik , Choi Chel Hun , Kim Kidong , Hong Deok Ho , Park Jeong-Yeol , Kwon Byung Su , Lee Keun Ho , Hong Dae Gy , Shin So-Jin , Park Sang-Il , Kim Yun Hwan , Lee Seung-Ho , Lee Sanghoon , Hong Jin Hwa , Lee Jung-Yun , Kim Yong Beom , No Jae Hong , Suh Dong-Hoon
Published: May 2019

e17106

Background: To evaluate the effectiveness of postoperative adjuvant treatment for morcellated, uterus-limited leiomyosarcoma in a multicenter setting. Methods: We included primary FIGO stage I uterine leiomyosarcoma patients treated between 2003 and 2016. All received one of the following morcellation methods: (1) intracorporeal morcellation using motorized device; (2) intracorporeal morcellation using surgical knife or electrocautery; and (3) vaginal morcellation. Patients’ survival outcomes were compared according to the implementation of postoperative adjuvant treatment. Results: In total, 55 patients were enrolled from 13 institutions, and 24 and 31 patients were assigned to surgery alone group and adjuvant treatment group, respectively. Characteristics including age, mass size, morcellation methods, and extent of surgery were similar between the two groups. On pathologic examination, there were no differences in degree of nuclear pleomorphism, necrosis, and lymphovascular space invasion. In adjuvant treatment group, 67.7%, 19.4%, and 12.9% received chemotherapy, concurrent chemoradiation therapy, and radiation, respectively. While the two groups showed similar overall survival ( P= 0.959) after a median follow up of 50.5 months, adjuvant treatment group showed a trend towards worse progression-free survival (PFS; 3-year survival rate, 78.2% vs. 46.1%; P= 0.060). However, in multivariate analyses, adjuvant treatment did not influence PFS (adjusted HR, 3.478; 95% CI, 0.659–18.367; P= 0.142). Confined to 17 cases where motorized morcellation device was used, surgery only and adjuvant treatment groups also showed similar PFS (3-year survival rate, 57.1% vs. 44.4%; P= 0.874). Conclusions: In FIGO stage I, morcellated uterine leiomyosarcoma, post-operative adjuvant treatment did not improve patients’ survival outcomes. Further prospective cohort studies are warranted.