bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factors for choriocarcinoma syndrome development in high-risk patients with germ cell tumors (GCTs).
Authors: Rejlekova Katarina , Kalavska Katarina , Makovnik Marek , Hapakova Nikola , Chovanec Michal , De Angelis Valentina , Obertova Jana , Palacka Patrik , Sycova Zuzana , Mardiak Jozef , Mego Michal 
Published: June 2021

e17010 Background: Germ cell tumors (GCTs) represent a highly curable cancer. However, a small proportion of patients with super-high-risk characteristics can develop choriocarcinoma syndrome (CS) connected with acute respiratory distress syndrome (ARDS). CS is defined as a syndrome with hemorrhage from metastatic sites in patients with advanced GCTs with high-volume of choriocarcinoma elements, especially those with a choriogonadotropin level over 50,000 IU/l. CS typically develop shortly after the chemotherapy start with high mortality rate. Our retrospective study aimed to determine the risk factors of high-risk GCTs susceptible to CS development. Methods: Using a computerized database and a systematic chart review, we identified the records of 532 patients with GCTs treated in NCI through 2000 to 2018, and 90 eligible patients with high-risk GCTs relying on IGCCCG classification, were identified. All patients were treated with platinum-based induction chemotherapy. Clinicopathological variables were collected and analyzed in correlation to CS development. Results: Nine (10 %) of 90 patients developed CS in a median of 1 day (1- 9 days) after the chemotherapy administration. All patients died shortly after the chemotherapy start with median of 4 days (3-35 days) due to consecutive ARDS development. Predictive factors for CS development were metastatic lung involvement ≥50% of lung parenchyma, choriocarcinoma elements in histology specimen, dyspnea, cough, hemoptysis, ECOG PS ≥2, weight loss and hemoglobin ≤100 g/l at the time of presentation. In multivariate analysis, ECOG PS ≥2 and metastatic lung involvement ≥50% were independently associated with CS. All patients with these two characteristics developed CS compared to 0% with one or zero of these predictive factors (P < 0.000001). Conclusions: In our study we identified predictive factors for CS development. These factors might improve the risk stratification of the patients susceptible to CS development connected with ARDS as well as to find optimal treatment approach for them.
Immune checkpoint inhibitor plus anti-EGFR target therapy plus chemotherapy in patients with locally advanced penile squamous cell carcinoma.
Authors: Han Hui , An Xin , Yan Ru , Guo Shengjie , Xue Cong , Liu Tingyu , Tian Li , Ma Huali , Li Yonghong , Qin Zike , Liu Zhuowei , Zhou Fang-Jian , Shi Yanxia 
Published: June 2021

e17016 Background: Locally advanced penile squamous cell carcinomas (PSCCs) have poor prognosis and limited therapeutic options. We aim to evaluate the safety and the efficacy of neoadjuvant therapy with anti-PD-1 immune therapy (toripalimab) plus anti-EGFR target therapy (nimotuzumab) plus chemotherapy (TIP) in locally advanced PSCCs. Methods: We retrospectively reviewed chemotherapy-naive, unresectable locally advanced PSCCs (T4NanyM0 or TanyN3M0) who received combined neoadjuvant therapy and subsequently radical surgery in Sun Yat-sen University Cancer Center between 2018 and 2020. All patients received toripalimab 240mg on day 1 plus nimotuzumab 400mg on day 1 plus standard-of-care TIP (Cisplatin 25mg/m2 on day 1 to day 3; ifosfamide 1.2g/m2 on day 1 to day 3; paclitaxel 175mg/m2 or albumin-bound paclitaxel 260mg/m2 on day 1) every 3-4 weeks. Pathologic complete response(pCR) rate and toxicity were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier estimation. Results: We screened 12 patients in total who had performed toripalimab plus nimotuzumab plus TIP (TNTIP) as neoadjuvant treatment and subsequently radical surgery. Median age was 51 (95% confidence interval [CI]: 44-60.5) years old. 10(83.3%) patients received 3 or 4 courses of TNTIP neoadjuvant treatment. After neoadjuvant treatment and radical surgery, 8(66.7%) patients had a pCR. 2(16.7%) patients died of disease progress or recurrence, which 1(8.3%) patient occurred bone metastases after 2 courses of TNTIP, and 1(8.3%) patient appeared recurrence after 6 months of radical surgery. The median follow-up time was 21.3 months (95%CI 19.9-22.6). Median PFS and OS were not reached. The 1-year PFS rate was 83.3% and 1-year OS rate was 91.7%. 3(25%) patients experienced grade 3 treatment-related adverse events of fatigue, anemia and neutropenia. No grade 4 or 5 adverse events or death associated with treatment. Conclusions: Compared with other therapeutic options, our results suggest that TNTIP in neoadjuvant stage effectively improve the disease control and prognosis in locally advanced PSCCs. Based on this result, we are conducting a phase II study in Sun Yat-sen University Cancer Center to further validate the efficacy and safety of TNTIP neoadjuvant regimen in locally advanced PSCCs. (ClinicalTrials.gov No. NCT04475016).
Serial ctDNA profiling in patients with metastatic prostate cancer undergoing treatment with radium-223.
Authors: Blanding Dena , Drusbosky Leylah , Gourdin Theodore Stewart , Lilly Michael B. 
Published: June 2021

e17018 Background: Assessment of the anti-tumor response to radium-223 (Ra-223) treatment is difficult in individuals. PSA levels seldom fall and imaging of existing bone metastases is imprecise. Circulating tumor DNA (ctDNA) is a non-invasive marker of prostate tumor DNA, with static measurements demonstrating high concordance rates with tumor DNA. Serial monitoring of ctDNA levels may provide insights into therapy response, targetable mutations, and progression of disease. We report changes in ctDNA profiles and clinical associations of 10 patients who had serial ctDNA profiles during Ra-223 treatment. Methods: Serial ctDNA analyses of mutations (73 genes) and amplifications (18 genes) were performed via a commercial provider (Guardant 360; Guardant Health). Assays were performed before treatment, after the third Ra-223 dose, and after the final Ra-223 dose. ctDNA data (minor allele frequencies for mutations, copy number for amplifications) were reviewed to identify clonal mutations with at least 50% change in highest allelic frequency or 30% change in copy number during treatment. Clinical data (performance status (PS), PSA, pain score, prescribed oral morphine equivalents (OME), imaging, progression free survival (PFS), and overall survival) were gathered via chart review. Clinical progression was defined by an increase in at least 2 bone lesions on bone scan, progression of soft tissue disease by RECIST, worsening PS, or at least 20% increase in OME. Results: Three of 10 patients had a reduction in the proportion of mutated or amplified tumor DNA as measured by ctDNA profiling, after receiving Ra-223 (response group). Median PFS defined by time to PSA rise of at least 25% in this group was 120 days (95% CI 83 to 237) compared to 29 days (95% CI 21 to 145) in the group without a reduction (no response group). Median clinical PFS defined as above was 266 days (95% CI 109 to 291) in the response group compared to 83 days (95% CI 33 to 182) in the no response group. There was no difference in baseline pain score between the two groups, though median baseline PSA was higher in the no-response group (97.14 compared to 20.05). Reductions in allelic frequency were noted in several mutated genes, including AR, ARID1A, CDK12, and TP53(G245C), during Ra-223 therapy of subjects in the response group. Decreases in copy number were also seen in several amplified genes, including AR, CCNE1, CDK6, FGFR1. In the no-response group, 4/7 patients had an increase in AR amplification; 3/7 patients had an increase in variant allele fraction of TP53 mutations. In the response group of 3 patients who had a reduction in clonal mutations, none had an increase in the AR amplification. Conclusions: A reduction in proportion of clonal mutations or gene amplification measured in ctDNA may be associated with a longer PFS in patients treated with Ra-223. Mutations in the TP53 gene and amplification of AR gene were associated with shorter PFS.
Evaluating the prevalence and nature of sleep disturbances in prostate cancer patients receiving androgen deprivation therapy using a combination of actigraphy and sleep questionnaires.
Authors: Mangar Stephen , Mondal Shalini , Edwards Steve , Ahmed Hashim Uddin , Wassersug Richard J , Falconer Alison , Iles Ray , Dimitriou Dagmara 
Published: June 2021

e17046 Background: Sleep disturbances and cancer related fatigue are commonly associated. Prostate cancer patients may suffer from disturbed sleep as a result of their diagnosis and following treatment, especially with androgen deprivation therapy (ADT). Wrist actigraphy is a non-invasive objective method of sleep data collection. This feasibility study compares sleep data obtained by actigraphy with subjective data from sleep questionnaires in order to determine the nature and severity of sleep disturbances in patients with and without ADT use. Methods: A prospective cross-sectional pilot study was conducted on 74 patients with prostate cancer attending a regional oncology clinic. Two validated subjective sleep questionnaires namely the Pittsburgh Sleep Quality Index [PSQI] and the Epworth Sleepiness Scale [ESS] were used. Patients wore actigraphy watches for a minimum of five consecutive days. The parameters of interest included: actual sleep time, sleep efficiency, fragmentation index, daytime napping frequency and duration. The questionnaire and actigraphy data were compared between 20 patients receiving ADT and 41 who were treatment-naive. Results: The compliance rate for completed actigraphy was 85%. Complete data sets with actigraphy and questionnaires were available from 61 patients. Those already receiving ADT were on LHRH analogues for a median duration of 2.35 years. Poor sleep quality as self-identified by patients from the PSQI (cut-off > 5) was 49% in the treatment-naive group which increased to 70% for those on ADT. For daytime sleepiness as assessed by ESS (cut-off > 10) this was 16% and 20% respectively. Actigraphy showed that patients on ADT reported longer sleep duration (7.4 vs 6.5 hours, p = 0.02), higher levels of nocturnal wakings (51.1% vs 36.7%, p = 0.002), with greater daytime napping duration (80.7mins vs 53.0mins, p = 0.04), and frequency (8.6 vs 5.6, p = 0.02) compared to treatment-naive patients. Conclusions: Self-reported poor sleep quality is common in prostate cancer patients, which appears worse for those receiving ADT. In patients receiving ADT, data derived from actigraphy suggests that although they were sleeping for longer at night, the quality of sleep was poor which, in turn, may be responsible for an increase in the frequency and duration of daytime napping. Based on the current findings, we recommend the use of actigraphy to characterise patients’ sleep patterns and to assess if sleep treatment is needed. Actigraphic data may allow for direct comparisons of different hormonal agents on sleep whilst identifying those with specific sleep disorders amenable to therapeutic intervention.
Accelerated epigenetic age among HIV-infected Nigerian women with invasive cervical cancer.
Authors: Musa Jonah , Kim Kyeezu , Zheng Yinan , Travis Lois B. , Gursel Demirkan , Silas Olugbenga A. , Abdulkareem Fatimah Biade , Imade Godwin , Akanmu Alani , Wei Jian-Jun , Kocherginsky Masha , Kim Kwnag-Youn , Wehbe Firas Hazem , Achenbach Chad , Anorlu Rose , Simon Melissa A. , Sagay Atiene , Ogunsola Folasade , Murphy Robert , Hou Lifang 
Published: June 2021

e17504 Background: Invasive cervical cancer (ICC) is one of the HIV-associated cancers with a high burden in Nigeria. ICC occurs at relatively younger age in HIV infected women, with HIV known to promote aging and related diseases, including cancer. DNA methylation changes with increasing age, various health-related exposures, and age-related health outcomes, suggesting a role of DNA methylation in biological aging and disease. We sought to understand the effect of HIV infection on epigenetic age acceleration (EpiAgeAccel) in Nigerian women with ICC. Methods: Epigenetic age (EpiAge) was estimated by Horvath’s calculator using genome-wide methylation data in 116 cervical tissue samples from three groups of women: a) HIV positive with ICC (n=39); b) HIV positive and cancer-free (n=53); and c) HIV negative with ICC (n=24). EpiAgeAccel was computed as the regression residuals of EpiAge against chronological age (ChronAge), representing the independent deviation of EpiAge from ChronAge. We compared EpiAgeAccel across the 3 HIV/ICC groups using multiple linear regressions adjusting for ChronAge, education, parity, employment, cancer stage, body mass index, and study site. Among the ICC women, we compared EpiAgeAccel between 26 tumor tissues and their surrounding normal tissues using paired t-tests, stratified by HIV status. Results: EpiAgeAccel among HIV positive women with ICC was 4.5 years higher than HIV positive and cancer-free women (p=0.019). We did not find substantial differences in EpiAgeAccel between HIV-positive women with ICC and HIV-negative women with ICC. EpiAgeAccel was 7.9 and 2.9 years higher in tumor tissues compared to the surrounding normal tissues among HIV positive women (p=0.021) and negative women (p=0.295), respectively. Conclusions: EpiAge is accelerated in cervical tissue of HIV-infected women with ICC. EpiAgeAccel may be a potential biomarker for ICC screening and early detection for women living with HIV in low- and middle-income countries.
The diagnostic value of core needle biopsy in cervical cancer: A retrospective analysis.
Authors: Lia Massimiliano , Horn Lars-Christian , Sodeikat Paulina , Höckel Michael , Aktas Bahriye , Wolf Benjamin 
Published: June 2021

e17512 Background: The aim of this retrospective study was to evaluate the accuracy, sensitivity, specificity, and predictive values of preoperative core needle biopsy (CNB) assessment of histological characteristics in primary cervical cancer. Methods: We reviewed 318 cases of primary cervical carcinoma with available pathology reports from preoperative CNB assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying lymphovascular space invasion (LVSI) and tumor grade. Results: CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma (SCC), 92.9% and 96.6% for adenocarcinoma (AC), 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of lymphovascular space invasion (LVSI) was 61.9% and was positively influenced by tumor size in preoperative MRI and negatively influenced by strong peritumoral inflammation. High tumor grade was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. Conclusions: CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques. Factors such as peritumoral inflammation, tumor size or tumor subtype may influence the accuracy of histologic Evaluation and should be taken into account when interpreting the results.
Expression of multidrug resistance marker MDR1 in patients with ovarian cancer and its possible predictive significance.
Authors: Ulianova Elena P. , Yakubova Darya Yu. , Sagakyants Aleksandr B. , Zhukova Galina V. , Nepomnyashchaya Evgeniya M. , Menshenina Anna P. , Shulgina Oksana G. , Ardzha Anna Yu. , Zhenilo Oksana E. , Verenikina Ekaterina V. 
Published: June 2021

e17530 Background: Despite the progress made in diagnosis and treatment, ovarian cancer (OC) is still the third most common genital cancer. Poor results of therapy for various forms of OC stimulate the search for fundamentally new approaches to the treatment. One of the main reasons for resistance to chemotherapeutic agents includes multidrug resistance (MDR) of tumor cells. The most characterized of its various mechanisms is the elevated activity of the ABC family protein - ABCB1 (Pgp or MDR1). The purpose of the study was evaluation of the expression of this ABC transporter as a predictive factor in platinum-containing chemotherapy in OC patients. Methods: 100 patients aged 29-79 years with advanced stage IIIC - IV OC with/without ascites were recruited between 2016 and 2020. Depending on the treatment results, patients were divided into 2 groups: group 1 (n = 59) - patients with platinum sensitivity; group 2 (n = 41) - patients with platinum resistance during the treatment or within 6 months after its completion. IHC analysis was performed using rabbit polyclonal anti-MDR1 antibodies (Affinity Biosciences) diluted 1:600 and the Reveal Polyvalent HRP-DAB Detection System. The percentage and the intensity of staining were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. MDR1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: Patients with MDR1+ prevailed in group 2 (98%), and patients with MDR1- in group 1 (32%). The average expression of MDR1 in tumor cells in group 2 (64.0±7.0) was statistically significantly higher by 1.7 times (p = 0.003) than in group 1 (37.2±6.8) by the Mann-Whitney U-test. When distributed according to Pearson's χ2 criterion, positive MDR1 as a risk factor in the platinum-resistant group increased the risks of refractory to platinum therapy by 19 times (95% CI 2.4-148.8). Conclusions: The study demonstrated predictive significance of the MDR1 biomarker in platinum treatment in patients with ovarian cancer.
Factors of VEGF, IGF, and TGF-β1 families in omentum tissues to mark premetastatic niches in ovarian cancer.
Authors: Menshenina Anna P. , Frantsiyants Elena M. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Cheryarina Natalia D. , Yakubova Darya Yu. , Adamyan Meri L. , Chernikova Natalia V. , Chalabova Tatiana G. 
Published: June 2021

e17535 Background: Analysis of the nature of cancer cell release and interaction with the microenvironment determines the fundamental basis of ovarian cancer pathogenesis, which is necessary for the development of new methods for peritoneal dissemination treatment and prevention. The purpose of the study was to analyze levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, TGF-β, IGF-1, IGF-2 and IGFBP3 in omental tissues (O) with and without metastasis (Mts) in ovarian cancer patients. Methods: Samples of O tissues were obtained from 51 ovarian cancer patients aged 60±1.9 years (G2-G3 serous cystadenocarcinoma – AC, Т2-3NxM0-1). 17 non-cancer patients of similar age were controls (C). Levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, IGF-1, IGF-2, IGFBP3 and TGF-β1 were measured in Mts and O tissues by standard ELISA test systems. Results: VEGF-A levels in O of AC patients were 2.6 times higher than in C. In Mts, VEGF-A and VEGFR1 exceeded the levels in C (by 6.3 and 3.1 times) and O (by 2.5 and 2.8 times, respectively). VEGF-C in O was lower than in C by 5.5 times, while VEGFR3 was 2.2 times higher. In Mts, VEGF-C and VEGFR3 exceeded the levels in C (by 7.8 and 3.6 times) and O (by 43.3 and 1.6 times, respectively, p<0.05). Levels of IGF-2 and IGFBP3 in O were similar to the levels in C, while IGF-1 was twice higher. In Mts, IGF-1, IGF-2 and IGFBP3 exceeded the levels in C (by 4.9, 2.8 and 3.4 times) and O (by 2.5, 2.2 and 3.6 times, respectively). Levels of TGF-β1 were higher in O by 2.9 times and in Mts – by 2.3 times. Conclusions: The interaction between VEGF-A, IGF-1, and TGF-β can serve as a regulator of the metabolic state of the “soil” for tumor dissemination, marking the premetastatic niche and providing mesenchymal-epithelial transition of circulating tumor cells.
Chemotherapy response score: Validation of a three-tier system to quantify histopathologic response to neoadjuvant chemotherapy in ovarian carcinoma.
Authors: Kubalanza Kari , Kim Teresa , Zhang Mingyan , Cohen Joshua Garrett , Memarzadeh Sanaz , Zakhour Mae , Salani Ritu , Rao Jianyu , Konecny Gottfried E. 
Published: June 2021

e17539 Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p < 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.