bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital admissions and subsequent outcomes from immune-related adverse events.
Authors: Ho Hui Jan , Arneil Melissa , Xu Wen , Atkinson Victoria 
Published: June 2021

e21590 Background: Checkpoint inhibitor (CPI) use has been increasing in recent years. Immune related adverse events (irAEs) are a known complication of CPIs, particularly with the concurrent use of PD-1 and CTLA-4 inhibitors (combination therapy). IrAEs are associated with increased hospital resource utilisation including admissions and immunomodulator therapy. This is a retrospective analysis of patients receiving CPI therapy for metastatic melanoma. Methods: Data was collected from a Queensland Health centre using electronic medical records and immunotherapy prescribing software. Patient demographics, CPIs, irAEs, admissions, and outcomes were recorded from 2015-2019. All patients had metastatic disease; they either received single agent or combination CPI as first line metastatic treatment or received single agent CPI as adjuvant therapy. Patients admitted to hospitals without electronic medical records were not included. Results: 51 out of 343 patients were eligible for analysis, indicating 15% of patients receiving CPI required hospital admissions due to irAEs. The mean age was 64.7 years, with 64.7% male patients. The commonest BRAF status was wild type (60.8%, n = 31). 54.9% (n = 28) of patients received combination therapy, 39.2% (n = 20) received PD-1 inhibitors, and 5.9% (n = 3) received CTLA-4 inhibitors. 24% (n = 12) of patients experienced early toxicity, defined as hospital admission after one dose. The commonest early toxicity was pneumonitis; all had received PD-1 inhibitors. In the rest of the cohort, the most frequent irAE was colitis (35.3%, n = 18). Regardless of CPI, average length of admission was 6-7 days. 17.6% (n = 9) patients had greater than one admission. Rescue immunomodulators were required in eight patients (15.7%), seven of whom had received combination therapy. Of patients with irAE from combination therapy, 28.7% (n = 8) were palliated due to progressive disease (PD), and 25% (n = 7) continued on single agent PD-1 inhibitor. In patients with irAE from PD-1 inhibitors, the majority (70%, n = 14) ceased treatment; of these, 8 had stable disease and 6 developed PD and were subsequently palliated. Conclusions: IrAEs are a well-documented complication of CPIs. Important considerations for CPI use include severe irAEs requiring admission and subsequent hospital resource utilisation. This occurs not infrequently, as demonstrated in this analysis. It is important to consider individual patient risks and benefits prior to commencement of treatment.
Clinical significance of next-generation sequencing in Chinese patients with relapsed/refractory Wilm’s tumor.
Authors: Wang Juan , Sun Fei-fei , Hu Wanming , Zhang Lian , WANG Qing , Zhen Zijun , Zhu Jia , Lu Suying , Huang Junting , Que Yi , Sun Xiaofei , Zhang Yizhuo 
Published: June 2021

e22003 Background: Medical advances have been greatly improved in the survival rate for Wilms’ tumor, but the survival is still dismal for relapsed/refractory (R/R) patients. In the present study, we aimed to investigated the genomic profiling and the incidence of germline cancer susceptibility mutations of Chinese patients with R/R WT. Methods: From Jun 18, 2020 to Dec 22, 2020, the tumor specimens with matched blood samples obtained from R/R pediatric WT in Sun Yat-Sen University Cancer Center were performed next-generation sequencing (NGS) using a 539 cancer-related gene panel in a CAP-certified laboratory (Simcere Diagnostic Co, Ltd). Clinical information including age, gender and tumor histology were collected. Somatic and germline variations including single nucleotide variants (SNV), insertion-deletion variants (Indels), copy number variations (CNVs) and fusion, as well as tumor mutational burden (TMB)/microsatellite instability (MSI) were analyzed. IHC staining for PD-L1 expression was performed by FDA-approved VENTANA PD-L1(SP263) assay. Results: Eight patients with R/R WT were enrolled in this study, including 5 males and 3 females, with a median age of 6 years old (range, 3-14). All of the pathology was identified as favorable histology WT (FHWT). Of the specimens, 8 were from pulmonary and 1from peritoneum. We identified 152 reportable molecular aberrations, with a median of 19 (0-24). CNVs accounted for the majority of the total somatic aberrations, followed by SNVs, the percentage was 77% and 22%, respectively. Genes with either CNVs or SNVs were detected in FGFR1 (n=4), ERBB2(n=3), MYCN(n=4), MET(n=2), CDK4/6(n=2), TP53(n=2), CTNNB1(n=2), MYC(n=2), NF1(n=2), MDM4(n=2), CHEK2(n=1), FBXW7(n=1), EGFR(n=1). Notable cancer driver mutations were also characterized, such as the amplifications of ERBB2/MET/EGFR/FGFR1, and the point variations of CHEK2/FBXW7/NF1. Besides, a novel ASB12 intergenic region- AMER1 fusion was identified. Both of the patients available for PD-L1 evaluation showed negative PD-L1 expression on tumor cells. The median TMB was 1.47 (range, 0-7.8). All patients were microsatellite stabilization (MSS). A 4-year-old patient suffering peritoneal relapse harbored a germline pathogenic mutation in FANCA (c.1777-1G>C, intron 19), this locus has never been reported in WT before. Conclusions: We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients. Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.
The efficacy and safety of irinotecan plus doxorubicin liposome in relapsed/refractory Wilms’ tumors: A retrospective study.
Authors: Wang Juan , Zhang Lian , Que Yi , Zhen Zijun , Zhu Jia , Sun Feifei , Lu Suying , Huang Junting , Wu Liuhong , Cai Ruiqing , Zhang Yizhuo , Sun Xiaofei 
Published: June 2021

e22007 Background: To evaluate the efficacy of the regimen of combination of irinotecan and doxorubicin hydrochloride liposome in relapsed/refractory pediatric Wilms’ tumor. Life quality and toxicity are seriously considered and assessed. Methods: The project stipulated 5-day course of irinotecan 50 mg/m2 (90-minute infusion) and doxorubicin hydrochloride liposome 40mg/m2 every 3 weeks. Granulocyte colony-stimulating factor was applied when the number of neutrophil count was lower than 1,000/ L. Results: 16 patients received 1to 8 courses (median, 3 courses) of this regimen, including 8 males and 8 females, with a median age of 4.2 years old (range, 0.5-11) . 2 patients were not assessable for response (1were treated in third CR, and 1with refractory WT received only one course as part of complex salvage regimens). Of 14 patients treated for relapsed or refractory Wilms’ tumor and accessed for response, 2 patients had complete responses (CR), 5 patients had partial responses (PR). Of 2 patients had stable diseases (SD), including 1 patient showed objective response on pulmonary lesion. The disease control rate was 64% (2 CR, 5 PR, and 2 SD), and the objective response rate was 50% (2 CR, 5 PR). The median progression-free survival was 3.5 months (range 0.5-12), and the median survival duration was 8 months (range 1-28). Myelosuppressive and gastrointestinal adverse effects were self-limited and clinically controllable with routinely intervention, and this therapeutic regimen was generally continued without delayed therapy. Multiple courses of this regimen had no cumulative toxicity and achieved disease control in relapsed or refractory Wilms’ tumor. Conclusions: The regimen of combination of irinotecan and doxorubicin hydrochloride liposome has positive effect on relapsed/refractory Wilms’ tumor with gentle toxicity without reducing the efficacy, and achieves good quality of life.
Evaluation of the relationship between antenatal and postnatal tobacco smoke exposure and childhood cancers.
Authors: Tacyildiz Nurdan , Güzel Adil , Bakar Ateş Filiz , Özyörük Derya , Unal Emel Cabi , Dincaslan Handan 
Published: June 2021

e22011 Background: The incidence of childhood cancers increased by 1 % per year over the last three decades. Life style changes and increased variety of environmental exposures are accused of this trend. One of these environmental factors is cigarette smoking and parental smoking is the main source of tobacco smoke exposure of children. There are strong reasons for considering parental smoking behaviour as a risk factor for childhood cancers. Many tobacco related compounds are detected in fetal tissues, breast milk and tissues of children of smoking parents. However, it is hard to make causal relationship between parental smoking and childhood cancers. One of the reasons is the difficulty to detect tobacco smoke exposure. Questionnaires, commonly used method to detect tobacco smoke exposure, are prone to biases. Cotinine is the main metabolite of nicotine which is the abundant organic compound in tobacco and a good biomarker to detect tobacco smoke exposure. Methods: 104 newly diagnosed, 0-18 years aged pediatric cancer patients from two pediatric oncology centers ( Ankara University Children’s Hospital and Ankara City Hospital) and 99 healthy children aged 0-18 applied to the Ankara University Children’s Hospital participated our study. Parental smoking behaviours (preconceptional, during pregnancy and current smoking) and environmental tobacco smoke exposures (ETS) of children were compared between two groups. ETS exposures of cancer patients and healthy children were evaluated by hair cotinine ELISA analysis and questionnaire. For hair cotinine analysis, 30 mg of hair samples were taken from occipital part of scalp by a stainless scissors. Samples were processed according to manufacturer's instructions. Parents of two groups were surveyed about their smoking behaviours and ETS exposures of their children. Results: We found no differences between two groups by means of maternal preconceptional smoking, smoking during pregnancy and current smoking behaviours. Paternal preconceptional smoking and smoking during pregnancy rates were significantly low in cancer patients (p < 0,05) according to questionnaire. Environmental tobacco smoke exposures were found statistically low in cancer patients according to questionnaire (p < 0,05). However, quantitative exposure assessment by hair cotinine analysis revealed that cancer patients are exposed to tobacco smoke more than healthy children (p < 0,001). Conclusions: Our findings support that smoking could be a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We thought, social desirability bias of father of cancer patients could be a reason of their low smoking rates according to questionnaire. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.
Associations between diet and chronic disease burden in adult survivors of childhood cancer in the St. Jude Lifetime Cohort (SJLIFE) study.
Authors: Foley Elizabeth M. , Hyun Geehong , Zhang Fang Fang , Krull Kevin R. , Bhakta Nickhill , Ehrhardt Matthew J. , Brinkman Tara M. , Lanctot Jennifer Q. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. 
Published: June 2021

e22017 Background: Nutritional intake can impact health. Data describing associations between diet or specific dietary components and chronic health conditions in long-term survivors of childhood cancer are limited. This study evaluated the associations between specific components of diet and chronic disease burden in childhood cancer survivors. Methods: Adult survivors (≥5 years) of childhood cancer participating in SJLIFE (n = 2822), who completed a clinical evaluation and the Block Food Frequency Questionnaire were included. 168 chronic conditions were graded using a modified Common Terminology for Adverse Events. Conditions were summed within grade category, multiplied by weights (1, 2, 3, and 8 for grades 1-4, respectively) and standardized (z-scores) with higher scores indicating more disease burden. Adherence to the 2015 Dietary Guidelines for Americans was scored with the Healthy Eating Index-15 (HEI). Intake of key food groups and nutrients was estimated and divided into quartiles for analysis. Multivariable logistic regression, adjusted for sex, age, and race was used to compare dietary intake and higher disease burden (defined as a z-score > 0). Results: Survivors (median [range] survival time 23 [10-49] years, diagnosis age 7 [0-24] years, 47.6% female, 16.9% non-white, 38.0% leukemia, 19.5% lymphoma, 10.3% CNS tumor, 32.2% other solid tumor) had an average of 10.0 (95% CI 9.7-10.3) conditions by 30 years of age and had a mean score on the HEI of 57.9±12.2 (out of 100 where the population average is 59). Scores on the HEI were not associated with disease burden z-score. Compared to those in the lowest quartile, survivors who consumed in the highest quartile of dark green vegetables (OR 0.77, 95% CI 0.61-0.97), legumes (OR 0.74, 95% CI 0.59-0.92), and whole grains (OR 0.75, 95% CI 0.60-0.95) were less likely to have a disease burden z-score > 0, whereas those who consumed in the highest quartile of white potatoes (OR 1.31, 95% CI 1.05-1.64), refined grains (OR 1.26, 95% CI 1.01-1.58), and added sugars (OR: 1.27, 95% CI 1.01-1.56) were more likely to have a disease burden z-score > 0. Conclusions: Specific components of diet are associated with chronic disease burden in long term survivors of cancer. Dietary interventions may have potential to decrease chronic disease burden in this population.
The real-world BRCA1/2 germline mutations in Chinese solid tumors.
Authors: Chen Jian , Gong Zhaohua , Sun Dengjun , Song Shujie , Zhang Weiwei , Luo Ningning , Zhang Qin , Lu Guanghua , Qi Yingxue , Wu Yaqing 
Published: June 2021

e22500 Background: Breast cancer susceptibility genes BRCA1 and 2 are tumor suppressor genes and they play an important role in DNA damage response and repair during homologous recombination. Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant disease due to BRCA1 and 2 germline mutation. Germline mutations of BRCA1 and 2 genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and a broad range of cancers. PARP inhibitor (PARPi) monotherapy and combinations have shown promising efficacy against a variety of cancer types with BRCA mutations. Nevertheless, the knowledge of incidence of BRCA1 and 2 germline mutations in solid tumor remains poorly understood. Herein, next generation sequencing of 539-gene profiling was performed to explore the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors. Methods: We retrospectively analyzed the BRCA1 and BRCA2 germline mutations from a comprehensive 539-gene profiling of 8535 Chinese patients with pan-cancer. 539-gene profiling contains the somatic mutations in tumor tissue or blood ctDNA and the germline mutations in blood leukocyte. We screened out the pathogenic and likely pathogenic mutations in BRCA germline mutations, and calculated the mutation frequency and the median age in every cancer type. Results: In 8535 patients with pan-cancer, 110 patients were found pathogenic or likely pathogenic germline mutations in BRCA gene and the mutation frequency was 1.29%, of which 40 BRCA1 mutations and 70 BRCA2 mutations were found in patients, respectively. The total median age was 58.15. Eliminated a few types of cancers that had a smaller number (less than 50), the higher frequency of mutations contained ovarian cancer (14.78%, media age 58), prostatic cancer (6%, media age 58.33), breast cancer (5.2% media age 57.33). The details of the top 8 cancer types with mutation frequency and media age were shown in Table. Conclusions: This was the first report of the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors, which expanded the understanding of BRCA1/2 and provided a direction for clinical trial design of PARPi monotherapy and combinations.[Table: see text]
Final report from a registry study of patients with active cancer undergoing ecological staging.
Authors: Cunningham James R. , Dodd Cheryl , Rittenbach Jon , Clemens Mitch 
Published: June 2021

e22501 Background: The host-cancer relationship can be viewed as a set of tumor supportive and inhibitory interactions, that is as an ecosystem. An advantage of such a perspective might include a more dynamic understanding of the selection pressures affecting tumor evolution. If so then a means of detecting and measuring those forces would be of help in understanding that drive and point to potential therapeutic clinical interventions. Towards this goal a registry study of patients with invasive cancer was conducted to examine readily available clinical measures to inform an ecological staging system. Methods: Eligibility for registry participation included age of 18 years or older, active cancer requiring treatment, life expectancy estimated to be at least six months and willingness to provide informed consent for this IRB-approved study. Ecological staging was then conducted at entry assessing 22 separate clinical parameters from history, physical exam and laboratory known to effect tumor biology, grouped into eight profiles and scored using a trichotomization of data, increasing score corresponding to an increase in positive tumor selection. To aggregate data from the profiles, a geometric figure, an octamer, or ecogram, was constructed, vertices representing the net score of each of the eight profiles. We hypothesize that the area bounded by the polygon, ecogram area (EA) would reflect an index of adverse, tumor-supporting ecological influence. Overall survival was determined from time of diagnosis of cancer until time of registry closure. Results: 15 subjects, eight female, seven male, ages 53-84 (median 64) participated in the registry. Complete ecological staging was obtained from all participating subjects, an indication of feasibility for collection of such data in the clinic. Resulting EA ranged 12-fold (0-12.1) across subjects suggesting sensitivity of EA to differences in selection pressures among the participants; ecogram morphology from individual subjects demonstrated unique shapes, an indication of specificity for character of individual tumor ecological landscape. Mean overall survival for participants from time of cancer diagnosis was 265 weeks. For 12 subjects with advanced stage disease, overall survival was inversely related to ecogram area (r = -.45). Conclusions: Ecological staging of cancer from clinical parameters proved feasible in this registry study of patients with active cancer. Ecological information from those parameters when aggregated using a geometric figure, an ecogram, demonstrated both sensitivity and specificity for differences among participants. For those subjects with advanced stage disease, ecogram area was inversely related to overall cancer survival. Ecological staging may be a useful tool in gauging selection pressures affecting cancer evolutionary tendency and of potential benefit to oncologists in forecasting such development.
Hereditary breast cancer associated with the CHEK2 gene: Study through NGS in a Spanish cohort.
Authors: Alonso Marin Natalia , Ocáriz Maitane , Gascon Ruiz Marta , Sesma Goñi Andrea , Zurera Berjaga Maria , Zapata-Garcia Maria , Ruiz Moreno Ines , Moratiel Pellitero Alba , Marti Pi Maria , Goas Gomez Ana , Cruellas Mara , Alvarez Maria , Andrés Raquel , Isla Dolores , Lastra Rodrigo 
Published: June 2021

e22502 Background: Inherited mutations in the CHEK2 gene have been associated with an increased lifetimerisk of develop breast cancer (BC). The main objective of the study is to identify in our population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, as well as to evaluate the phenotypic characteristics of the tumour and family history. Methods: A genetic study was performed in 396 patients diagnosed of BC at the University Hospital Lozano Blesa of Zaragoza (Spain). We selected 9 patients with genetic variants in the CHEK2 gene and performed a descriptive analysis of the clinical variables, a bibliographic review of the genetic variants and a co-segregation study. Results: We identified 2 pathogenic variants ( CHEK2 c.349 A>G and c.507delT) and 6 variants of uncertain significance (VUS). The genotypic characteristics of the VUS are summarized in the table. In all cases there was a family history of BC in first and /or second degree relatives. The variant cosegregated with the disease in one of the families. Conclusions: The pathogenic missense variant c.349A>G was found in two families. This is a rare missense variant. Studies have shown that this variant had a significant impact on the protein based on in silico prediction and has been associated with BC. In our study, this variant was found in a patient with renal carcinoma and was identified in a proband with a strong family history of pancreatic and ovarian cancer (OC). However, there aren’t exist data about the risk of developing other cancer, different of BC, with this specific mutation. The other pathogenic variant detected was CHEK2 c.507delT in a family with history of BC and OC. This variant is a frameshift mutation, predicted to cause loss of normal protein function. CHEK2 507delT was reported in one of 12 BC families in one series and is possible its relation with OC. With regard to the VUS the cosegregation analysis in selected families may help understand if a variant could have played a role in developing cancer. In conclusion, CHEK2 mutations have been associated with increased risk for BC. However, the frequency of carriers may vary depending on the population, and different mutations may be associated with different cancer risks. More studies are needed to establish a complete range of risks associated with CHEK2 mutations. [Table: see text]