bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis of prostate cancer using cell-free DNA methylation profiles from expressed prostatic secretions.
Authors: Shen Wenhao , Dong Hang , Tang Haoran , Zhang Yue , Jia Shidong , Luo Yang 
Published: March 2023

389 Background: Urinary and seminal cell-free DNA (cfDNA) have been recognized as promising biomarkers of prostate cancer. DNA methylation signal in tumor is increasingly used as tumor diagnosis and longitudinal monitoring indicator. However, the clinical utility of cfDNA from expressed prostatic secretions (EPS) remains unknown. Methods: The prospective study includes 50 prostate cancer (PC) patients and equivalent benign prostatic hyperplasia (BPH) patients, where EPS samples were collected after the prostatic massage of each patient. Cell-free DNA from EPS was extracted and treated by PredicineEPIC, a liquid biopsy comprehensive DNA methylation assay. The study developed integrated bioinformatic algorithms to profile the genome-wide epigenomic characteristics and investigate tumor-specific methylation patterns. Results: The initial exploratory cohort included 5 PC and 11 BPH cases. PredicineEPIC whole-genome DNA methylation of EPS identified over 300 differentially methylated regions (DMRs). Prostate cancers were distinguished from the BPH group by an unsupervised clustering method, suggesting that the identified DMRs embody the specific profiles of malignant tumors. Additionally, this study detected genome-wide copy number variation burden (CNB) in parallel. A risk model was built for cancer risk assessment based on methylation and CNB characteristics. Conclusions: This study demonstrated the feasibility of methylation profiling of cfDNA in EPS in prostate cancer. This non-invasive liquid biopsy approach could sensitively navigate prostate cancer from benign prostatic hyperplasia, suggesting future direction of methylation-based liquid biopsy in detecting prostate cancer.
Long-term rates of biochemical recurrence after primary external beam radiation therapy (EBRT) for prostate cancer.
Authors: Escobar Domenique , Wang Lufan , Banton Jasmin , Cowan Janet E. , Washington Samuel L. , Mohamad Osama , Menon Mani , Carroll Peter 
Published: March 2023

393 Background: Radiation therapy is a common form of treatment for men with prostate cancer. Biochemical recurrence (BCR) is most commonly defined using the Phoenix definition of PSA nadir + 2. We sought to characterize long term rates of biochemical recurrence in a large, well-characterized and well-followed cohort of men treated with primary EBRT. Methods: Patients enrolled in CaPSURE, a national registry of men diagnosed with prostate cancer, from 1995 - 2017 with clinically localized prostate cancer (cN0M0/X, PSA<=50) treated with primary EBRT were included. Cancer risk was defined by NCCN criteria. Cox proportional hazards regressions were used to assess associations between patient characteristics and BCR as defined by PSA nadir + 2. Results: 1193 patients were included. Mean age at diagnosis was 70 (SD 6.82), median PSA at diagnosis was 7.6 and mean number of follow up PSA tests was 5. Overall rates of BCR were 17.4% at 5 years and 39.4% at 10 years. Rates of BCR were significantly associated with NCCN risk with high-risk patients having the highest rates of recurrence, followed by intermediate- and low-risk groups (61.5%, 36.4% and 28.5% respectively at 10 years). NCCN high vs low clinical risk was significantly associated with likelihood of BCR (HR 4.8, CI 2.5 – 9.2). Rates of salvage treatment, usually ADT, were 16% at 5 years and 19% at 10 years and these were also significantly associated with NCCN high vs low clinical risk (HR 3.7, CI 2.3 – 6) and concurrent ADT (HR 1.83, CI 1.2 – 2.7). Overall rates of bone metastases were 2.6% at 5 years and 4% at 10 years. Overall prostate cancer specific mortality was 3% at 5 years and 7% at 10 years. Conclusions: In this analysis, rates of BCR were fairly high and consistent with published RTOG studies, but rates of salvage treatment were relatively low in comparison, indicating that not all patients who recur need, are offered or want treatment. The limitations of this analysis include incomplete information on radiation dose and field size. The strengths of this analysis include the size of the cohort and the length of follow-up. Furthermore, as this cohort largely represents treatment in community settings, the results may be broadly applicable.
National population-based survival estimates after definitive radiation therapy for prostate cancer.
Authors: Herr Daniel , Elliott David , Stensland Kristian , Caram Megan Veresh , Burns Jennifer , Hollenbeck Brent , Sparks Jordan , Shin Chris , Zaslavsky Alexander , Tsodikov Alexander , Skolarus Ted 
Published: March 2023

395 Background: Understanding contemporary radiation therapy outcomes for prostate cancer (i.e., metastasis, death) is important for shared decision-making and setting expectations for patients and providers. Unfortunately, long-term outcome estimates are often derived from meta-analyses of outdated prospective clinical trials or population-based data lacking reliable clinical details (e.g., incident metastatic disease). For these reasons, we used a recently validated, natural language processing algorithm to identify incident metastatic prostate cancer within the electronic medical records of men treated with radiation therapy for localized prostate cancer in order to conduct an innovative and contemporary population-based survival outcomes study. Methods: We used national administrative, cancer registry, and electronic health record data for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy (ADT) within the Veterans Health Administration from 2005 to 2015. We used National Death Index data through 2019 for overall and prostate cancer-specific survival, and identified the date of incident metastatic prostate cancer using a validated natural language processing algorithm. We estimated metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods. Results: We identified 41,876 patients treated with definitive radiation therapy for prostate cancer from 2005 through 2015, and followed them for over 8 years (follow up, median, 8.7 years, age at diagnosis, median, 65 years). Most patients had intermediate (42%) and high risk (33%) disease, with nearly half treated with ADT as part of initial therapy (44%). Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low, intermediate, and high risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low, intermediate, and high risk disease. Unadjusted overall survival was lower across disease risk categories at 77%, 71%, and 62% for low, intermediate, and high risk disease. Conclusions: These data provide population-based benchmarks for clinically relevant endpoints, including metastasis-free survival, among patients with low, intermediate, and high risk prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high risk disease, in particular, compare favorably with historical outcomes.
Source of funding and enrollment disparity in prostate cancer (PCa) clinical trials.
Authors: Riaz Irbaz Bin , Naqvi Syed Arsalan Ahmed , Islam Mahnoor , Ikram Waleed , Khakwani Kaneez Zahra Rubab , Ijaz Hafsah , Ayaz Ahsan , Singh Parminder , Bryce Alan Haruo 
Published: March 2023

40 Background: Previously we have reported enrollment disparities in PCa clinical trials. Funding source can influence minority representation in clinical trials. Hence, we aimed to evaluate the impact of source of funding on enrollment disparities in PCa clinical trials. Methods: MEDLINE and EMBASE were searched to identify phase II/III PCa trials. All relevant trials reporting age by 65 years were considered eligible for inclusion. Trials recruiting from the United States (US) were considered eligible for analysis by race and ethnicity. The trial proportions of age, or racial/ethnic subgroup category and the global incidence in the corresponding age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database) were used to compute enrollment incidence ratio (EIR) at each trial. EIRs with corresponding 95% confidence intervals (CI) were then meta-analyzed using a random-effects model and stratified by sources of funding (industry, US-government, and others [academic and non-US govt]). A univariate meta-regression was conducted to assess the temporal changes in EIR by each funding category. Results: Of 127 trials recruiting from the US, 89 (70%) reported race, and 35 (27%) reported ethnicity. Among those, 57 (64%), 14 (16%), and 18 (20%) trials reported industry, US-government, and other sources of funding, respectively. Of those reporting ethnicity, 23 (66%), 4 (11%), and 8 (23%) trials reported industry, US-government, and other sources of funding, respectively. Among the 287 eligible trials, 49 trials (17%) reported age by 65 years. Of those, 36 (73%), 6 (12%), and 7 (13%) reported industry, US-government, and other sources of funding, respectively. In terms of racial/ethnic enrollment, Black patients were significantly under-represented in industry funded trials (0.33; 0.27-0.41). No significant disparity was observed in US-government funded trials (0.75: 0.57-1.00). The P-value of interaction was <0.0001. Hispanics were significantly under-represented in industry funded clinical trials (0.56; 0.43-0.74). The number of US-government funded trials reporting Hispanics were small (<10) which precluded any meaningful statistics. No significant disparity was observed in terms of older adults (EIR: 1.00; 95% CI: 0.95; 1.05) overall and by funding sources. Black patients’ representation in industry funded PCa trials has significantly decreased over the last three decades. No significant change was observed in US-government funded PCa trials over the last three decades (P:0.004). Conclusions: Black and Hispanic men with PCa are likely to be under-represented in industry sponsored clinical trials. Black patients’ representation in industry sponsored trials has declined over time, thus widening the cancer-care inequities in these patients.
Longitudinal evaluation of plasma miR371 to detect minimal residual disease and early relapse of germ cell tumors.
Authors: Nappi Lucia , Saxena Neetu , Pautasso Sara , Mazurek Sylwia , Ozgun Guliz , Kollmannsberger Catarina , Trottier Chi Max , Morin Coulombe Antoine , Soleimani Maryam , Chi Kim N. , Eigl Bernhard J. , Black Peter C. , So Alan , Gleave Martin , Kern Sean , Daneshmand Siamak , Adra Nabil , Einhorn Lawrence H. , Nichols Craig R. , Kollmannsberger Christian K. 
Published: March 2023

407 Background: Active surveillance is routinely recommended to manage patients (pts) with clinical stage I (CSI) germ cell testicular tumors (GCT), the most common presentation of newly diagnosed GCT. Circulating plasma miR371a-3p (miR371) has shown high sensitivity and specificity in pts with metastatic non teratoma GCT or in pts with clinically detectable testicular GCT prior to orchiectomy. However, limited data are available about this biomarker accuracy to detect minimal residual disease post-orchiectomy in pts on active surveillance for early stage disease. Methods: CSI GCT pts with available plasma samples after radical orchiectomy enrolled in the British Columbia provincial biobank research program were selected for this study. RT-PCR was used for qualitative miR371 analysis. Sensitivity, specificity, negative and positive predictive values (NPV, PPV) and AUC in predicting tumor recurrence were evaluated for miR371 and compared to the same operating characteristics of current gold standard diagnostic tests. Relapse free survival (RFS) was correlated to post-orchiectomy miR371 (positive or negative) status. Fisher’s exact test was used to evaluate the sensitivity and specificity, unpaired t-test for comparison of miR371 expression. RFS was calculated using the Kaplan-Meier method, and differences between groups were estimated using the log rank test, 2-sided and with 5% significance threshold. Results: With a median follow-up of 41 months, 101 pts with CSI GTCwere included, of whom 35 (34.6%) experienced a disease relapse during the follow-up. miR371 was positive in 22/35 (62.8%) of the relapsed pts. miR371 positivity preceded clinical evident disease by a median of 3 months (range: 1-12 months).The specificity and PPV were 100% (95% CI: 94.5 - 100 for both), sensitivity 62.8% (95% CI: 44.9 - 78.5), NPV 83.5% (95% CI: 76.7 - 88.6) and AUC 0.81 (95% CI: 0.71 - 0.91). No false positive results were observed. The RFS of the pts with positive post-orchiectomy miR371 was significantly shorter (median: 3.5 months vs. not reached; p<0.0001) compared to the pts with a negative post-orchiectomy miR371 (HR: 16.9; 95% CI: 2.1 - 135.7; p<0.0001). miR371 sensitivity correlated with tumor burden, time between tumor relapse and miRNA testing and histology (nonseminoma > seminoma). Conclusions: miR371 has high specificity and PPV in detecting GCT at an early stage and could be used to guide treatment selection after orchiectomy. Further studies, including the SWOG S1823 clinical trial, are ongoing or have been planned in this setting for validation of clinical utility.
European Association of Urology (EAU) Testicular Cancer Guidelines Panel: A new prognostic factor risk group classification for patients with clinical stage 1 seminoma in active surveillance.
Authors: Boormans Joost , Sylvester Richard J , Anson-Cartwright Lynn , Glicksman Rachel , Hamilton Robert James , Daugaard Gedske , Lauritsen Jakob , Wagner Thomas , Avuzzi Barbara , Nicolai Nicola , Aparicio Jorge , Garcia del Muro Xavier , Laguna Pilar 
Published: March 2023

410 Background: Between 4%- 30% of patients with clinical stage 1 (CS I) seminoma testis (ST) in active surveillance (AS) relapse depending on pathological risk factors tumor size (TS) and rete testis invasion (RTI). The level of evidence supporting these pathological risk factors in clinical decision-making is low due to heterogeneous study design and reporting and the difficulty to analyze patient subgroups according to combination of these factors. The objectives of the present study were to identify the most important pathological prognostic factors predicting relapse in CS I seminoma patients with normal post-orchidectomy serum tumor marker (STM) levels in AS and to construct risk-groups for guiding treatment decision-making and follow-up. Methods: Individual patient data from 1016 CS I-ST patients diagnosed between February 1994 and January 2019 in AS were collected from 9 institutions. Central pathology review was not routinely performed in all institutions; therefore, pagetoid and stromal RTI were not differentiated explicitly in most cases. Assessing patient age, pre-orchidectomy STM b-human chorionic gonadotropin and lactate dehydrogenase, pathological TS, RTI, lympho-vascular invasion (LVI), multi-focality, and GCNIS, multivariable Cox proportional hazards regression models were fit to identify the most important prognostic factors for the time to first relapse by imaging and/or markers (primary endpoint). Probabilities of relapse were estimated using Kaplan-Meier curves. Results: After median follow-up of 7.7 years, 149 (14.7%) patients relapsed, 104 identified by imaging alone, 44 by imaging with elevated STMs and 1 by elevated STMs alone. Excluding 18 patients with unknown LVI from the multivariable analyses, TS (≤ 2 cm, between 2 and 5 cm, > 5 cm), presence of RTI and presence of LVI were used to form three risk groups: very low, low and high-risk (Table). Five-years probability of relapse varied from 8% in the very low risk-group to 44% in the high risk-group. The new model outperformed the current model with TS < 4cm vs ≥ 4 and RTI (Harrell's C index 0.65 vs 0.61) and identifies a subgroup of patients with a higher risk of relapse. Conclusions: The new risk-group stratification for CS I -ST patients in AS outperforms the histopathological model based on TS and RTI. It will serve to better inform patients on the risk of relapse during follow-up after orchidectomy but requires an independent validation. [Table: see text]
Peripheral blood immune cell profiling in survivors of testicular germ cell tumors.
Authors: Chovanec Michal , Mlcakova Andrea , Sestakova Zuzana , Kalavska Katarina , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Sycova Zuzana , De Angelis Valentina , Orszaghova Zuzana , Lesko Peter , Sekaninova Kristina , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Mego Michal 
Published: March 2023

417 Background: Testicular germ cell tumors (GCT) achieve exceptional cure rate with cisplatin-based chemotherapy. Survivors of GCTs represent a unique population to study post-cancer treatment physiology and late toxicities. The impact of cancer treatment on the immune-cell profile in long-term GCT survivors is unknown. In this study, we performed an immune-phenotyping in survivors of GCTs. Methods: Whole peripheral blood was obtained from GCT survivors (N = 202) at National Cancer Institute of Slovakia within the protocol of the ongoing survivorship study on a day of their annual follow-up visit. The median follow-up was 11 years (2-25). GCT survivors were distributed into treatment groups: RT – radiotherapy to the retroperitoneum (N = 18), CT - chemotherapy (N = 143), CTRT - chemotherapy + radiotherapy (N=9); and a control group: AS - active surveillance/orchiectomy only (N=32). Immuno-phenotyping of peripheral blood leukocyte populations was performed with flow-cytometry. Immune cell subpopulations were statistically assessed for associations with received treatment. Results: Survivors treated with RT vs AS had higher no of classical dendritic cells (DCs) (mean ± SEM = 82.0 ± 1.9 vs 76.5 ±1.5, p = 0.03) and non-significantly lower no of plasmacytoid DCs and CD16+ DCs (0.11 ± 0.01 vs 0.15 ± 0.01, p = 0.06 and 54.4 ± 4.1 vs 64.8 ± 3.2, p = 0.07, respectively). Survivors treated with CT vs AS had higher no of CD19+ B cells (11.9 ± 0.3 vs 10.4 ± 0.7, p = 0.04)and lower no of CD8+ T cells (26.0 ± 1.3 vs 23.7 ± 0.6, p = 0.04). Similarly, survivors treated with CTRT vs AS had higher no of CD19+ B cells (13.6 ± 1.4 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (20.7 ± 2.4 vs 26.0 ± 1.3, p = 0.04). Survivors treated with ≥ 400mg/m2 of cisplatin-based chemotherapy vs AS had no of CD19+ B cells (12.2 ± 0.5 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (23.4 ± 0.9 vs 26.3 ±1.3, p = 0.04). The immunoregulatory index CD4/CD8 was higher in CTRT vs AS (2.5 ± 0.3 vs 1.8 ± 0.1, p = 0.04). Conclusions: Certain subpopulations of leukocytes differ according to received treatment in survivors of GCTs. Our results may suggest that chemotherapy and/or radiotherapy may produce long-term immunomodulatory effects. Interplay between B and T cells may be a contributing mechanism of late toxicities. Further research is needed to uncover the causal relationship to the long-term health of GCT survivors.
Prognostic value of circulating cell-free DNA in association with choriocarcinoma syndrome development in patients with germ cell tumors.
Authors: Rejlekova Katarina , Celec Peter , Vlkova Barbora , Kalavska Katarina , Hapakova Nikola , Makovnik Marek , Chovanec Michal , De Angelis Valentina , Obertova Jana , Palacka Patrik , Sycova-Mila Zuzana , Mardiak Jozef , Mego Michal 
Published: March 2023

424 Background: Germ cell tumors (GCTs) represent a highly curable malignancy; however, a small portion of patients can develop choriocarcinoma syndrome (CS) connected with acute respiratory distress syndrome (ARDS) with high mortality rate shortly after the chemotherapy start. The aim of this study was to assess the prognostic value of circulating cell-free – extracellular DNA (ecDNA) in patients with GCTs and its association with CS development and outcome. Methods: This study included 23 patients with poor-prognosis GCTs treated from November 2002 to May 2018 at the National Cancer Institute in Slovakia. Pre-treatment total ecDNA, nuclear (ncDNA) and mitochondrial DNA (mtDNA) were quantified in plasma using fluorometry and real-time PCR and analyzed in association with CS development and survival. Results: Four (17%) patients developed CS and all of them died due to ARDS shortly after the chemotherapy start. Total ecDNA, but not ncDNA or mtDNA were associated with CS development. Four out of 11 (37%) patients with high plasma ecDNA developed CS compared to 0 out of 12 (0%) patients with low plasma ecDNA (p = 0.037). In univariate analysis, higher concentration of ecDNA also positively correlated with ECOG PS ≥2, metastatic lung involvement ≥50%, weight loss ≥10%, hemoglobin ≤100 g/l, and neutrophil to lymphocyte ratio ≥ 3.3 at the time of presentation. Patients with low ecDNA had significantly better PFS (HR = 0.35, 95% CI 0.11-1.17, p = 0.043) and OS (HR = 0.26, 95% CI 0.06-1.20, p = 0.032) compared to patients with high pretreatment concentration of ecDNA. Conclusions: In this study we have proved that quantitative analysis of plasma ecDNA has prognostic value for CS development in patients treated due to GCTs. Further research focused on the biology of ecDNA may help us to understand its role as a biomarker, but also a potentially treatable pathogenic factor for choriocarcinoma syndrome development.
Association of plasma vitamin D with outcomes in patients with germ cell tumour.
Authors: Lesko Peter , Vlkova Barbora , Kalavska Katarina , De Angelis Valentina , Obertova Jana , Orszaghova Zuzana , Palacka Patrik , Rejlekova Katarina , Sycova-Mila Zuzana , Mardiak Jozef , Chovanec Michal , Celec Peter , Miskovska Vera , Mego Michal 
Published: March 2023

429 Background: Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with testicular germ-cell tumours (GCTs). Methods: This study included 120 newly diagnosed and/or relapsed GCTs patients treated from April 2013 to July 2020. Blood samples were drawn at the time before 1st chemotherapy cycle as well as before the 2nd cycle. Plasma vitamin D was measured using ELISA and matched with disease characteristics and correlated with the patient outcome. For survival analysis the cohort was dichotomized to “low” and “high” based on median vitamin D. Results: Mean ± standard error of mean plasma vitamin D in GCTs patients was 15.87±0.68 mg/ml. Patients with brain metastases had significantly lower D vitamin compared to patients without brain metastases (10.9 ± 3.05 vs 15.99 ± 0.7, p=0.034). Vitamin D was not associated with other patient characteristics. Low vitamin D was associated with an unfavorable response compared to favorable responses (11.26 ± 1.84 vs 16.47± 0.74, p=0.016), with disease recurrence (16.19 vs 13.71, p=0.011) and with inferior progression-free survival but not with overall survival (HR= 3.02, 95%CI (1.36-6.71), p=0.014 for PFS and HR= 2.06, 95%CI (0.84 – 5.06), p=0.135 for OS, respectively). Conclusions: Our study suggests a prognostic value of pretreatment vitamin D concentrations in GCTs patients. Low plasma vitamin D was associated with unfavorable response to therapy and disease recurrence. However, it remains to elucidated whether the biology of the disease confirms a causative role of low vitamin D and if its supplementation affects the outcome.