bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple and rapid enrichment of circulating tumor cells (CTCs) for RNAseq in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Morrison Gareth , Cunha Alexander , Jojo Nita , Manojlovic Zarko , Xu Yucheng , Robinson Peggy S. , Dorff Tanya B. , Quinn David I. , Goldkorn Amir 
Published: May 2019

e16587 Background: CTCs have the potential to reflect not only genomic alterations but also cancer-relevant transcriptomic phenotypes. However, CTC gene expression has been hampered by signal-to-noise: rare CTC-derived transcripts are drowned out by abundant leukocyte-derived RNA. To date, a few specialized labs have achieved CTC RNAseq by capturing and analyzing single cells, a laborious and expensive approach not suitable for routine analysis of numerous samples. To address this need, we developed and validated a simple, rapid method for enrichment of live CTCs for RNAseq. Methods: Blood was drawn with informed consent under an IRB-approved protocol. Prostate cancer cell line spike-in samples were used to optimize live CTC enrichment by sequential leukocyte depletion (RosetteSep, Stem Cell Technologies) and size-based enrichment (Parsortix, Angle). Cancer-specific gene expression was first measured by multiplexed prostate specific qRT-PCR and subsequently by whole transcriptome amplification (WTA, SMARTer V2, Clontech) and RNAseq. Four patient samples were similarly analyzed by enrichment and RNAseq, along with spike-in positive controls and matched unenriched buffy coat negative controls. Results: Processing “from patient to RNA” took < 3 hrs. and achieved mean CTC recovery of 30% (range 28-33%) and mean leukocyte background of 100 (range 47-179), a 100,000-fold enrichment. Prostate specific genes (AR, PSA, PSMA) were consistently detected by qRT-PCR from enriched samples but not from unenriched samples. When analyzed by RNAseq, patient samples clustered with spike-in positive controls and away from matched buffy coat controls by principle component analysis and by unsupervised hierarchical clustering. Differential gene expression (enriched vs. matched buffy coat) identified prostate cancer-relevant transcripts. Conclusions: We developed a simple and efficient method for live CTC enrichment and expression profiling, applicable to large numbers of patient samples. This approach can be used serially over time to detect known cancer-specific transcripts and to discover new gene expression signatures that reflect tumor biology and inform disease management.
Automated prostate lesion detection and PI-RADS assessment with deep learning.
Authors: Yoon Choongheon , Van Jasper , Bardis Michelle , Bhatter Param , Ushinsky Alexander , Glavis-Bloom Justin , Chantaduly Chanon , Chow Daniel S. , Houshyar Roozbeh , Chang Peter 
Published: May 2019

e16605 Background: Prostate Cancer is the most commonly diagnosed male cancer in the U.S. Multiparametric magnetic resonance imaging (mpMRI) is increasingly used for both prostate cancer evaluation and biopsy guidance. The PI-RADS v2 scoring paradigm was developed to stratify prostate lesions on MRI and to predict lesion grade. Prostate organ and lesion segmentation is an essential step in pre-biopsy surgical planning. Deep learning convolutional neural networks (CNN) for image recognition are becoming a more common method of machine learning. In this study, we develop a comprehensive deep learning pipeline of 3D/2D CNN based on U-Net architecture for automatic localization and segmentation of prostates, detection of prostate lesions and PI-RADS v2 lesion scoring of mpMRIs. Methods: This IRB approved retrospective review included a total of 303 prostate nodules from 217 patients who had a prostate mpMRI between September 2014 and December 2016 and an MR-guided transrectal biopsy. For each T2 weighted image, a board-certified abdominal radiologist manually segmented the prostate and each prostate lesion. The T2 weighted and ADC series were co-registered and each lesion was assigned an overall PI-RADS score, T2 weighted PI-RADS score, and ADC PI-RADS score. After a U-Net neural network segmented the prostate organ, a mask regional convolutional neural network (R-CNN) was applied. The mask R-CNN is composed of three neural networks: feature pyramid network, region proposal network, and head network. The mask R-CNN detected the prostate lesion, segmented it, and estimated its PI-RADS score. Instead, the mask R-CNN was implemented to regress along dimensions of the PI-RADS criteria. The mask R-CNN performance was assessed with AUC, Sørensen–Dice coefficient, and Cohen’s Kappa for PI-RADS scoring agreement. Results: The AUC for prostate nodule detection was 0.79. By varying detection thresholds, sensitivity/PPV were 0.94/.54 and 0.60/0.87 at either ends of the spectrum. For detected nodules, the segmentation Sørensen–Dice coefficient was 0.76 (0.72 – 0.80). Weighted Cohen’s Kappa for PI-RADS scoring agreement was 0.63, 0.71, and 0.51 for composite, T2 weighted, and ADC respectively. Conclusions: These results demonstrate the feasibility of implementing a comprehensive 3D/2D CNN-based deep learning pipeline for evaluation of prostate mpMRI. This method is highly accurate for organ segmentation. The results for lesion detection and categorization are modest; however, the PI-RADS v2 score accuracy is comparable to previously published human interobserver agreement.
Multiparametric magnetic resonance imaging (mpMRI) and PSA density for the prediction of reclassification among patients under active surveillance.
Authors: Viana Públio , Horvat Natally , Pessoa Rodrigo Rodrigues , Horvat Joao , Park Rubens , Guglielmetti Giuliano , Bastos Diogo Assed , Cordeiro Mauricio , Coelho Rafael , Vargas Hebert Alberto , Nahas William Carlos 
Published: May 2019

e16606 Background: To study the role of mpMRI and PSA density in predicting the likelihood of disease reclassification on re-biopsy and on final pathology among men with low-risk prostate cancer (PCa) enrolled in active surveillance (AS) protocol. Methods: In this IRB-approved prospective study, consecutive patients on AS for low-risk PCa (clinical stage cT1–T2a, Gleason score ≤6, serum PSA < 10 ng/mL, no more than 3 positive cores on biopsy, and all biopsy cores with < 50% of tumor involvement) from March 2015 to August 2017 were selected. The exclusion criteria were previous PCa treatment, contraindication to mpMRI or transrectal ultrasound-guided (TRUS) biopsy. All patients underwent mpMRI ≥3 months from initial biopsy and MRI-targeted TRUS-guided re-biopsy within 6-12 months. One experienced radiologist evaluated all mpMRI studies using the PI-RADS v2. The performance of mpMRI and PSA density for the prediction of reclassification on re-biopsy and final pathology was assessed. A single genitourinary pathologist reviewed all the final specimens who was blinded to the initial biopsy results. Results: A total of 154 patients were included in the final analysis. Among patients classified as PI-RADS ≤3, 11/69 (15.9%) were upgraded on re-biopsy whereas 65/85 (76.5%) were upgraded among those with PI-RADS 4 or 5 lesions. With regards to prostatectomy 7/49 (14.2%) patients classified as PI-RADS ≤3 were upgraded, while 42/49 (85.7%) were upgraded among those with PI-RADS 4 or 5. mpMRI sensitivity was 85.5% and specificity 74.4% on re-biopsy and 85.7% and in predicting upgrade on reclassification. Patients with PI-RADS 4 or 5 and PSA density > 0.15 ng/mL/cm3 had 94.6% of chance of having clinically significant PCa, while patients with PI-RADS 1, 2 or 3 and PSA density ≤ 0.08 ng/mL/cm3 had only 4.2% probability. Conclusions: mpMRI and PSA density are significant tools for predicting severity reclassification on re-biopsy and final pathology among patients under active surveillance. Reclassification was low among patients with PI-RADS ≤3 and low PSA density. Overall, patients with PI-RADS 4 or 5 and PSA density > 0.15 were almost invariably found to harbor significant prostate cancer.
Interdisciplinary surgery for advanced gynecologic malignancies: Outcome and complication rate.
Authors: Boeckhoff Jelena , terGlane Luisa , Wagner Uwe A. G. , Hofmann Rainer , Hegele Axel 
Published: May 2019

e17002 Background: Advanced gynecologic malignancies are known to have a poor prognosis. Due to local invasion in adjacent organs, finding the most suitable therapeutic option is often difficult. This study aims to assess the outcome of interdisciplinary surgery for locally advanced gynecologic malignancies focusing on women treated by pelvic exenteration (PE). Methods: All women that were treated with PE at the University Hospital Marburg between 04/2011 and 06/2016, were enrolled in this retrospective study. A data sheet was prepared assessing e.g. demographic informations, tumor type and previous therapies. Furthermore, complication rate (Clavien Dindo, follow-up and outcome were evaluated. Results: From the 57 women identified, the indications for PE were malignancies of the cervix (47.2%), vagina (15.1%), vulva (13.2%), endometrium (11.3%), ovaries (5.7%) and undifferentiated (uterus) (1.9%). 51.9% were treated for recurrent cancer. 26% received no treatment prior to PE, 16%, 38%, 20% received 1, 2 or 3 previous treatments respectively (chemotherapy, radiation, surgery). 54.7% of the patients underwent anterior, 37.8% total and 7.5% posterior PE. Urinary diversion was predominantly ileum conduit (76%). Major complications (Clavien Dindo > 2) were observed for 40.4%, 19.2% had no complications. No correlation with clinical parameters (e.g. BMI, age, time of surgery), previous therapy or urinary diversion could be shown. Renal function improved significantly postoperatively (p < 0.05). Mean hospital stay was 25 d. Median overall survival (OS) was 15.2 months. It was not influenced by the entity of the tumor. Two years survival rate (SR) was 38.2%; 3 years SR 27.3%. After 47 months median follow-up time, 23.7% of the treated women were still alive. Conclusions: PE remains to be a meaningful treatment option for women with invasive gynecologic malignancies also after multiple previous therapies, showing acceptable complication rates and satisfactory OS in regard to the extensive nature of the malignancies and the procedure.
Post-treatment clinical status of patients with cervical cancer.
Authors: Kruze Polina A. , Verenikina Ekaterina V. , Nikitina Vera P. , Cherkasova Anna A. , Selezneva Olga G. , Poryvaev Yuriy A. , Chernikova Natalia V. , Chalabova Tatiana G. , Nikitin Ivan S. , Menshenina Anna P. , Zhenilo Oksana E. , Adamyan Meri L. 
Published: May 2019

e17007 Background: Extended hysterectomy with fixation of preserved ovaries to the round ligaments of the uterus and subsequent transposition of the gonads from the irradiation area have already become a routine procedure in the treatment of cervical cancer in young women in order to avoid castration syndrome. The aim of the study was to analyze clinical characteristics of patients with cervical cancer 10 years after treatment. Methods: Clinical and hormonal status of 216 patients with stage Ib cervical cancer after complex treatment was studied. The majority of women (160 patients, 74%) remained fertile at the time of the study, and 56 patients (26%) were peri- and postmenopausal (from 46-55 years). The presence or absence of climacteric symptoms was assessed by a questionnaire; functional ovarian insufficiency (FNU) was determined as mild, moderate, and severe. Plasma levels of steroid and gonadotropic hormones were evaluated by radioimmunoassay. Results: Analysis of menopausal complaints according to questionnaires showed that the symptoms increased with the age of patients. Only 8 patients of the reproductive age reported hot flashes (Table 1). In this group of patients, levels of sex and gonadotropic hormones were common for this age. Patients aged 45-50 years reported also dry skin and mucous membranes, dyspareunia and dysuric disorders, which indicated perimenopause. And in postmenopause, urogenital disorders were very persistent. This group included patients treated 6 and 10 years ago. Conclusions: Thus, the function of preserved ovaries "faded away" independently according to the age, providing a smooth transition to menopause and optimal medical and social rehabilitation of patients.[Table: see text]
Inpatient burden of cervical and uterine cancer in the United States.
Authors: Corman Shelby , Nwankwo Chizoba , Kebede Nehemiah , Shah Ruchit 
Published: May 2019

e17009 Background: Limited data on the inpatient burden of cervical and uterine cancer exist. Therefore, this study assessed inpatient mortality, length of stay (LOS), and costs among hospitalized cervical and uterine cancer patients. Methods: This was a retrospective analysis of the 2006–2015 Healthcare Cost and Utilization Project – Nationwide Inpatient Sample (HCUP-NIS). Cervical and uterine cancer cases were identified using ICD-9 codes of 180.9 and 182.0 respectively. Patient demographics, hospital characteristics, and hospital outcomes (hospitalization rates, inpatient mortality, LOS, and costs) were examined. Multivariate logistic regression models were used to determine predictors of inpatient mortality. Generalized linear models were used to determine predictors of LOS and costs. Results: The analytic cohort included 67,429 cervical cancer and 74,394 uterine cancer cases resulting in 55.92 (±1.51) and 61.69 (±1.78) annual hospitalizations (per 100,000 women), respectively. The highest proportion of hospitalizations related to cervical and uterine cancer were among patients aged 45-65 years (38.9%, 45.7%), Caucasians (70.3%, 78.1%), having public insurance (59.6%, 67.4%), and admitted at large (63.3%, 63.1%), urban teaching (54.8%, 56.5%) hospitals. The mean LOS, proportion of patients who died during hospitalization, and hospital charges per stay were 4.22 (±0.02) days, 1.02%, and $9,646 (±$63.06) for cervical cancer and 4.39 (±0.02) days, 1.43%, and $10,790 (±65.47) for uterine cancer related hospitalizations. Age > 65 years (vs 18-45 years) (OR: 3.656; 95% CI: 2.99 – 4.47), and higher Elixhauser mortality score (OR: 1.097; 95% CI: 1.09 – 1.10) were associated with higher inpatient mortality among cervical cancer patients. Predictors of inpatient mortality for uterine cancer were similar. Patient age, insurance, race, hospital size, urban (vs rural) location, region of the country, and Elixhauser mortality score emerged as significant predictors of LOS and cost per hospital discharge across both cancers. Conclusions: Cervical and uterine cancer are associated with considerable inpatient burden. There was considerable variation in inpatient mortality, LOS, and costs based on patient, hospital, and discharge level characteristics.
Comparison of HPV detection in HIV-infected and HIV-uninfected Kenyan women with or without cervical dysplasia.
Authors: Omenge Elkanah , Tong Yan , Tonui Philip , Ong’echa John M. , Muthoka Kapten , Kiptoo Stephen , Maina Titus , Itsura Peter , Moormann Ann , Wong YeungChing , Ermel Aaron , Liu Tao , Hogan Joseph , Loehrer Patrick J. , Brown Darron , Cu-Uvin Susan 
Published: May 2019

e17015 Background: Cervical cancer, a malignancy caused by human papillomavirus (HPV) infection, is the most common malignancy in women living in sub-Saharan African countries including Kenya. HIV co-infection accelerates the natural course of cervical cancer. To determine the specific HPV type distribution in HIV-infected women compared to HIV-uninfected women, with and without evidence of cervical dysplasia. Methods: Demographic information, behavioral data, and a cervical swab were collected from women 18 and 45 years of age, HIV-infected or HIV-uninfected, who presented for cervical cancer screening at Moi Referral and Teaching Hospital in Eldoret, Kenya. Women were triaged based on the presence or absence of cervical dysplasia. HPV testing was performed using the Roche Linear Array Assay. Results were compared between women with or without HIV co-infection and between those with or without cervical dysplasia, using Chi-square tests or Fisher’s exact tests. Results: 223 women had normal VIAs. All had HPV testing, 221 had valid results: 115 HIV-infected women (mean age 37 years) and 106 HIV-uninfected (mean age 33 years). 175 women had abnormal VIAs. 143 women had HPV testing performed, 140 had valid results: 70 HIV-infected women (mean age 38.5 years) and 70 HIV-uninfected (mean age 31.3 years). Greater than 90% of all HIV-infected women in both projects were receiving anti-retroviral therapy at enrollment. HPV of any type was detected in 48% of all women with normal VIA vs. 61% of women with abnormal VIA (P = 0.018). High risk (HR)-HPV was detected in 38% of all women with normal VIA vs. 51% of all women with abnormal VIA (P = 0.012). HIV-uninfected women with normal VIA had significantly lower detection of all HPV (P = 0.026), high risk-HPV (P = 0.018), IARC high risk-HPV (P = 0.047), A9 types (P = 0.050), and individual types HPV 16 (P = 0.0274), HPV 18 (P = 0.007), and HPV 51 (P = 0.009) than HIV-uninfected women with abnormal VIA. Among HIV-infected women, there was no difference in detection of any group of HPV types or individual types with respect to VIA results. Conclusions: HIV-uninfected women without cervical dysplasia had lower detection of oncogenic HPV than HIV-uninfected women with dysplasia. In contrast, HPV detection did not differ among HIV-infected women between those with or without cervical dysplasia. In addition, VIA appears to lack specificity for HPV-associated cervical dysplasia, as 39% of women with abnormal VIA examinations did not have any HPV detected, and 49% of women with abnormal VIA examinations did not have any HR-HPV detected.
Visceral adiposity as a predictor of survival in patients with epithelial ovarian cancer receiving platinum and taxane-based chemotherapy.
Authors: Staley Stuart-Allison Moffat , Tucker Katherine , Oldan Jorge , Moore Dominic T. , Newton Meredith , Ertel Michelle , West Lindsay , Bae-Jump Victoria 
Published: May 2019

e17031 Background: Obesity has been linked to worse outcomes in epithelial ovarian cancer (EOC), due to underlying metabolic dysfunction. Visceral fat (i.e. central obesity) compared to subcutaneous fat is more metabolically active and has been linked to higher rates of obesity-related comorbidities such as hypertension and diabetes, but less is known of the impact of increased visceral adiposity on EOC outcomes. Thus, our goal was to evaluate if visceral adiposity, as determined by computed tomography (CT) morphometric measurements, was associated with worse outcomes in EOC patients undergoing platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 12/2004 and 5/2016 who received neoadjuvant or adjuvant treatment with platinum and taxane-based chemotherapy were included. Data on age, stage, grade, histology, BMI, comorbidities, treatment approaches and outcomes were collected. CT images closest to the time of diagnosis were retrospectively evaluated for mid-waist visceral fat volume (VFV), mid-waist subcutaneous fat volume (SFV) and the ratio of mid-waist VFV/SFV. Visceral adiposity is commonly defined as a VFV/SFV ≥ 0.4. Cox regression models were used to analyze time-to-event outcomes. Results: Two hundred fifty-eight EOC patients were evaluated. Seventy-five percent of patients were diagnosed with Stage III or IV disease, with high grade serous as the most common histology (72%). Median age at diagnosis was 62.4 years. Approximately 65% were obese; the median BMI was 26.8 (IQR 23.1 – 32.6). The median VFV/SFV ratio was 0.46 (IQR 0.32 – 0.70). Patients were categorized into those with a VFV/SFV ratio greater than 0.4 or a ratio less than 0.4. When comparing these two groups, there was no difference in progression free survival (PFS) for women with a VFV/SFV ratio greater or less than 0.4 (p = 0.22). However, a VFV/SFV ratio of greater than 0.4 was associated with worse overall survival (OS) (p = 0.01). Conclusions: We found that visceral adiposity, defined as a VFV/SFV ratio greater than 0.4, appeared to be associated with decreased OS, but not PFS. These findings suggest that body fat distribution may be an important prognostic factor for EOC and should be further explored as we expect the obesity epidemic to continue and influence EOC oncologic outcomes.
Sarcopenia as a predictor of chemotherapy toxicity in patients with ovarian cancer receiving platinum and taxane-based chemotherapy.
Authors: Tucker Katherine , Staley Stuart-Allison Moffat , Newton Meredith , Ertel Michelle , Zhang Yingao , Doherty Irene , Gehrig Paola A. 
Published: May 2019

e17035 Background: Sarcopenia (age-related loss of skeletal muscle mass) is associated with worse oncologic outcomes and adverse events in patients with solid tumors. Limited research in epithelial ovarian cancer (EOC) has shown that sarcopenia is associated with worse patient outcomes. The purpose of this study was to investigate the association of sarcopenia with chemotherapy toxicity in patients with EOC. Methods: EOC patients diagnosed between 6/2000 and 2/2017 who received platinum and taxane-based chemotherapy were included. Age, race, stage, grade, BMI, comorbidities, treatment, and outcomes were collected. Chemotherapy toxicities and associated grades, as well as treatment modifications were recorded. Computed tomography (CT) images within 3 months of diagnosis were evaluated for Skeletal Muscle Area (SMA) at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision(R) radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. This preliminary analysis generated descriptive statistics and compared the distributions of toxicity assessments by sarcopenia, with t-tests, rank-sum, chi-square and fisher’s exact tests. Results: 144 patients were evaluated. The majority presented with Stage III /IV, HGSOC (75%, 73%). Median age was 63 yrs and median BMI was 27.2 (IQR = 23.7-32.8). 61% of patients were sarcopenic. The median SMI was 40 (IQR = 34.2-46.2). There was no significant difference between sarcopenic (S) and nonsarcopenic (NS) patients with respect to dose adjustment (p = 0.37), regimen change (p = 0.998), need for blood transfusion (p = 0.60), toxicity-related hospitalization (p = 0.84) or delay in treatment (p = 0.37). Grade 3-4 toxicity was found in 56.8% of S and 58.9% of NS patients (p = 0.992). Similarly, the distributions of grade 1-2 toxicities in S and NS patients were comparable. Conclusions: In this cohort of patients, there was no significant association between sarcopenia and chemotherapy related toxicities. However, given high prevalence of sarcopenia in ovarian cancer patients, our relatively small sample size, and challenges with retrospective collection of chemotherapy toxicity, further prospective exploration is warranted.