bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shifting patterns of care in localized prostate cancer: Impact on patient reported outcome measures (PROMs).
Authors: Connell Brendan James , Patel Rima , Chang Hong , Luongo Tony , Zhuang Liyan , DiPetrillo Thomas A. , Mignano John , Carpinito Gennaro , Mathew Paul 
Published: May 2019

e16603 Background: In localized prostate cancer (LPC), evolving therapeutic techniques and patterns of care including the use of active surveillance (AS) are expected to have had a positive effect on quality of life. A longitudinal assessment of changes in disease presentations and patterns of care in LPC correlated to PROMs is required. Methods: All cases of LPC (T1-T4, N0-N1) at a tertiary care institution were identified between 2005 and 2015. Two cohorts (C1: 2005-10, C2: 2010-15) with a minimum of 2-years follow-up, were identified. Demographics, disease characteristics and management strategies were compared across cohorts. To assess PROMs, a one-time questionnaire including EPIC-26 and Clark’s Quality of Life was administered. Domain summary scores were compared across cohorts. Results: 873 patients met criteria [C1: 422, C2: 535]. Demographics were well balanced (p = 0.10): overall 64.1% white, 12.7% AA, 12.7% Asian. D’Amico risk scores increased over time (p = 0.001): fewer low-risk cases [C1: 49.2%, C2: 43.7%], higher intermediate-risk disease [C1: 34.6%, C2: 40.3%], and stable high-risk proportions [C1: 15.7%, C2: 14.9%]. Patterns of care shifted significantly (p = 0.005) with a marked decrease in radiation therapy [C1: 25.7%, C2: 15.4%], unchanged radical prostatectomy rates [C1: 47.9%, C2: 51.0%], a shift to robotic surgery [C1: 23.8%, C2: 90.3%], and an increase in AS [C1: 21.8%, C2: 30.8%], particularly in low-risk disease [C1: 32.4%, C2: 53.5%]. Questionnaire response rate was 45.1%. Using multivariate regression, C2 demonstrated an improvement in bowel function (p = 0.031) but not in urinary, sexual, or psychometric scores. Conclusions: Notwithstanding an increase in AS utilization for low-risk disease, an improvement in bowel function and lack of improvement in urinary/sexual PROMs in LPC across time-cohorts was noted. This may be accounted for by increased presentations of higher-risk disease managed with robotic surgeries at the expense of radiation therapy. Although time-length bias can influence comparisons, given national trends with a similar shift in presentation and care patterns, these PROM correlations are likely generalizable to the U.S. population.
The relative contributions of the Genomic Prostate Score and comorbidity profile in predicting outcomes in surgically treated men with clinically low and intermediate-risk prostate cancer.
Authors: Cullen Jennifer , Pierre-Victor Dudith , Lawrence H. Jeffrey , Kuo Huai-Ching , Sesterhenn Isabell , Rosner Inger L. 
Published: May 2019

e16607 Background: The 17-gene Oncotype Dx Genomic Prostate Score® (GPS™) assay has been validated as a predictor of aggressive prostate cancer (PCa) in men treated with radical prostatectomy (RP) for clinically low and intermediate risk PCa. This study examined the performance of the GPS assay as a predictor of adverse pathology (AP) and biochemical recurrence (BCR)-free survival (BRFS), after adjusting for the presence of major comorbidities commonly seen in older men. Methods: Additional analyses were performed using data from a prior clinical validation study of the GPS assay. GPS values (scaled 0-100), determined from diagnostic biopsy tissue, were categorized into 3 levels: lowest quartile (Q1), middle quartiles (combined Q2-Q3) versus the highest quartile (Q4). Major comorbidities included heart disease, stroke, COPD, and other cancers. The associations between GPS result and the presence of ≥1 major comorbidity and outcomes were examined. AP was defined as high-grade (Gleason Score ≥ 4+3) and/or pT3 tumor. BCR was defined as 2 successive PSA levels > 0.2 ng/mL. Logistic regression analysis was used to examine AP; Cox proportional hazards analysis was used to model BRFS. Results: Among 389 eligible men, median age at diagnosis and follow-up time was 62 and 5.6 years, respectively. The prevalence of ≥1 major comorbidity differed significantly across GPS category, rising from 10.2% to 19.7% to 25.5% for GPS Quartiles 1, 2-3, and 4, respectively (p = 0.0024). However, presence of ≥1 major comorbidity was not a significant predictor of AP or BCR in multivariable models with GPS, age, race, and NCCN risk stratum. Men whose GPS result was in the highest quartile had 4-fold higher odds of AP (OR: 4.1; 95% CI = 2.1-7.99, p < 0.0001) at RP and a 3.5 times higher risk of BCR (HR = 3.49; 95% CI = 1.59-7.64, p = 0.002) compared to men in the lowest GPS quartile (Table 1). Conclusions: A high GPS result remains the strongest predictor of BCR and AP in this cohort of low and intermediate risk PCa men, after adjusting for the presence of major comorbidities. Further work will explore the relationships between specific comorbidities and metabolic syndrome, with GPS testing and PCa outcomes.
Weighted gene co-expression network analysis combined with machine learning to identify prognostic biomarkers for cervical squamous cell carcinoma.
Authors: Li Yimin , Lan Mei , Peng Xinhao , Zhang Zijian , Lang Jin Yi 
Published: May 2019

e17000 Background: Cervical cancer represents the fourth most frequently diagnosed malignancy affecting women all over the world. However, effective prognostic biomarkers are still limited for accurate identifying high-risk patients. Here, we provide a co-expression network and machine learning-based signature to predict the survival of cervical cancer. Methods: Utilizing expression profiles of The Cancer Genome Atlas datasets, we identified differentially expressed genes (DEGs) and the most significantly module by differential expression analysis and Weighted Gene Co-expression Network Analysis, respectively. The candidate genes was obtained by combining the both results. Then the prognostic classifier was constructed by LASSO COX regression analysis and validated in testing set. Finally, survival receiver operating characteristic and Cox proportional hazards analysis was used to assess the performance of prognostic prediction. Results: We identified 190 differentially expressed genes (DEGs) between cervical squamous cell cancer(CSCC) and normal samples in purple module. Next we built a 8-mRNA-based signature, and determined a optimal cutoff value with sensitivity of 0.889 and specificity of 0.785. Patients were classified into high-risk and low-risk group with significantly different overall survival(training set: p < 0.0001; testing set: p = 0.039). Furthermore, the prognostic classifier was an independent and powerful prognostic biomarker for OS (HR = 7.05, 95% CI: 2.52-19.71, p < 0.001). Conclusions: The prognostic classifier is a promising predictor of CSCC patients, the novel co-expression network and machine learning-based strategy described in the study may have a broad application in precision medicine.
Survival of patients with cervical cancer and diabetes: An exploratory study.
Authors: Romero Maria Luisa , Gonzalez Vela Jose Luis , Hernandez Barajas David , Velazquez-Pacheco Ascary , Hernández Abrham Josafath , Villarreal Ondarza Irma Anaid , Escobedo Rodriguez Roberto Alejandro , Vidal-Gutiérrez Oscar 
Published: May 2019

e17008 Background: Mexico is the sixth country with the highest number of diabetics, this being the second cause of death. Between 8-18% of cancer patients have Diabetes (DM) as comorbidity. Studies have reported DM has worst prognosis in Overall Survival (OS) and Progression Free Survival (PFS) in patients with Cervical Cancer (CC). Aim: to compare OS in patients (pt) with a diagnosis of CC and DM, and to evaluate this outcome in relation to the clinical stage and the glycemic level at diagnosis of CC. Methods: data was obtained from pt treated for invasive CC between 2006 and 2016. Pt aged ≥20 years, with squamous, adenocarcinoma or adenosquamous histology. 59 pt with CC and DM in group 1 (G1), and 118 pt with CC without DM in group 2 (G2), paired 1:2 according to clinical stage, age and comorbidities. Results: Prevalence of DM in pt with CC was 16%. Follow-up of 142.2 months (median of 40.4 months), lower OS for G1 was seen (74.6% vs 77.1%), without statistical significance (p.803). PFS was similar for both groups (67.8% G1 vs 66.9% G2, p .608). In patients with locally advanced and metastatic disease, a lower OS and PFS were found in G1, without statistical significance. 42.4% diabetic pt had glycemic level < 130 mg / dL). OS was lower in pt with higher glycemic level (70.6% vs 80%), not being statistically significant (p .32). PFS was similar in both groups (G1: 68% vs G2: 67.6%, p.852). Analysis for influence of metformin treatment, evidenced a higher OS among pt receiving metformin (84.8% vs 61.5%), without statistical significance (p 0.65). PFS was higher in the metformin group (78.8 vs 53.8%), with a trend towards statistical significance (p .052). Conclusions: Pt diagnosed with CC and DM do not have different OS compared to those without DM. There was a tendency towards the improvement of PFS in pt with CC and DM, who received metformin.
Revised FIGO staging shows dramatic survival differences in cervical cancer patients with positive lymph nodes in Louisiana.
Authors: Nair Navya , Zhang Lu , Kuan-Celarier Anna , Wu Xiao-cheng , Jernigan Amelia 
Published: May 2019

e17010 Background: With revisions to FIGO cervical cancer staging system in 2018, patients with positive pelvic or para-aortic lymph nodes (LN) are now classified as stage IIIC. Rationale for this change is based on data published in 1990. Methods for work up and treatment of cervical cancer have advanced since then. We aim to determine if updated FIGO staging reflects contemporary survival differences in women with cervical cancer in Louisiana. Methods: Women with FIGO stage I-III cervical cancer diagnosed between 2010 and 2016 were identified from the Louisiana Tumor Registry. Those with < 30 days follow up were excluded. Patients were classified into 3 groups: true stage I & II (LN negative), revised stage IIIC (old stage I or II but positive LN), previous stage III (old FIGO stage IIIA or IIIB). Cox proportional hazards were used to estimate differences in overall and (OS) cause-specific survival (CSS). Covariates of age, race, insurance, census-tract poverty level, and marital status were controlled. Results: 740 patients were included with a median follow up of 40.6 months. Patients in revised stage IIIC group were younger than the others (45.9 yrs vs 47.9 yrs in true stage I&II vs 55yrs in previous stage III, p < 0.0001). True stage I&II patients were more likely to be privately insured (48.9% vs 32.1% revised stage IIIC vs 27.7% previous stage III, p < 0.0001). The groups did not differ by race, poverty level, or marital status. Revised stage IIIC and previous stage III patients had significantly worse survival outcomes compared to true stage I & II in both OS [revised stage IIIC HR 1.93 (1.20-3.11); previous stage III 5.92 (4.27, 8.22)] and CSS [revised stage IIIC HR 2.54 (1.45-4.44); previous stage III HR 7.95 (5.29, 11.94)]. Kaplan-Meier survival curves demonstrate significant differences in both OS and CSS (p < 0.0001) with best outcomes in true stage I&II and worst in previous stage III patients. Conclusions: LN status is an important prognostic indicator for contemporary cervical cancer patients in Louisiana. This analysis provides recent data to support the revised FIGO staging system in upstaging patients with positive LN to stage IIIC as they have significantly worse survival than the true stage I & II patients. Importantly, revised stage IIIC patients who would have previously been stage I & II have strikingly better survival outcomes than women with stage IIIA and IIIB disease. If staging is to be intuitive, the stage III subcategories may need to be redefined.
Value of adjuvant chemotherapy using paclitaxel plus carboplatin after radical surgery with or without radiotherapy in stage IB-iia cervical adenocarcinoma with risk factors.
Authors: Wu You , Nan Li , An Jusheng , Huang Manni , Ma Shaokang , Wu Lingying 
Published: May 2019

e17016 Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel/carboplatin as an adjuvant systemic chemotherapy for stage IB-IIA cervical adenocarcinoma patients after radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy(RT). Methods: The cases of all patients (n = 152) with FIGO IB-IIA cervical adenocarcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy with or without RT at Chinese academy of medical sciences cancer institute and hospital between January 2008 and January 2017 were reviewed. Of these, 35 patients displayed high-risk prognostic factors (high-risk group), 65 displayed intermediate-risk prognostic factors meeting sedlis criteria(intermediate-risk group),and 54 cases presented poorly differentiated status or LVSI, without other risk factors. In the high-risk group,18 patients received adjuvant radiotherapy and concurrent cisplatin chemoradiotherapy(RT-CCRT ) and 17 received adjuvant radiotherapy plus systemic chemotherapy using Paclitaxel Plus Carboplatin (RT-CT ). In the intermediate-risk group, 47 patients were treated with RT-CCRT and 16 were treated with RT-CT ,among the patients with poorly differentiated status or LVSI ,20 were treated with adjuvant chemotherapy using Paclitaxel Plus Carboplatin (CT ) and 34 received no further treatment (NFT). Results: In the high-risk group, adjuvant RT-CT was significantly superior to RT-CCRT with regard to median PFS and 2-year PFS rate(93.07months vs 52,44months, 94.1% vs 72.2%), but the recurrence rate and survival rate showed no significantly difference(11.8% vs 33.3%,100% vs 83.3%) . In the intermediate-risk group, Patients receiving RT-CT showed a better 2-year PFS rate and recurrence rate compared to those with RT-CCRT (100% vs 90.7%, 6.3% vs 12.6%), but the differences were not statistically significant. Among the patients with poorly differentiated status or LVSI, addition of adjuvant systemic chemotherapy resulted in significantly improved 2-year PFS rate compared with the NFT group (95% vs. 75.2%,p = 0.032). Conclusions: Adjuvant systemic chemotherapy using Paclitaxel Plus Carboplatin improved the prognosis of FIGO stage IB-IIA cervical adenocarcinoma patients in the high-risk group and patients who presented 2 or more intermediate-risk factors. Early cervical adenocarcinoma patients with low differentiation or LVSI can also benefit from postoperative adjuvant TC chemotherapy.
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.