bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implications of next-generation sequencing on pediatric solid tumors.
Authors: Guo Wei , Xie Lu , Xu Jie , Chen Lijuan , Wang Liwei , Wang Aodi , Wang Mingmin , Dong Xiaowei , Mei Lei , Chen Hui , Yuan Shaohua , Wang Kai 
Published: June 2022

e22012 Background: To assess the impact of next-generation sequencing (NGS) on Chinese pediatric cancer, we reported the first study of largest cohort in Chinese children with genomic landscape and highlighted the potential application with respect to molecular diagnosis and predictive biomarkers etc. Methods: A retrospective analysis was conducted on patients aged < 19 years diagnosed with solid tumors sequenced by targeted NGS panel. Somatic variants were analyzed following CAP/CLIA-certificated workflows, including Single Nucleotide Variant (SNV), Copy Number Variation (CNV), large insertion and deletions (Lindel) and gene rearrangements. Results: A total of 356 patients enrolled with three major cancer types including osteosarcoma (OS) (n = 78), rhabdomyosarcoma (RMS) (n = 51), Ewing sarcoma (EWS) (n = 13). Hepatocellular carcinoma (n = 9), medulloblastomas (n = 7) and colorectal adenocarcinoma (n = 5) were also included. 3487 somatic alterations were identified, TP53 (16%), EWSR1 (8.7%), CDKN2A (7.8%), BCOR (7%) and RB1 (5.6%) rank the top five reported. TP53 (21% % vs 7.9%), RB1 (10% vs 5.3%) mutations showed higher frequency in OS and BCOR (14% vs 17.6%) showed lower frequency in RMS compared to published paper (Gröbner et al 2018). We found PIK3CA mutations presented in RMS with 11.7% frequency, twice than reported (5.8%), mostly occurring at the known oncogenic codon E545. The obscure boundary of soft tissue tumor and bone tumor perplexed the pathologic diagnosis, NGS provide an important auxiliary examination. In 140 soft tissue tumor and bone tumor patients, 14.2% patients were further diagnosed with different subtype, 4.2% patients with unknown subtype were diagnosed with a specified subtype by supportive genetic alterations. Moreover, 41.5% (138/356) patients received treatment recommended . Twelve NTRK-fusions were detected and the patients were recommended therapy method upon Larotrectinib, recruitment in matched clinical trial is still on-going. Conclusions: We investigated the different genetic profiling of Chinese pediatric solid cancer and found the clinical value of NGS in pathological diagnosis and biomarker discovery.
Use and correlates of carotid ultrasound in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Bryce Yolanda C , Armstrong Gregory T. , Leisenring Wendy M. , Whitton Jillian , Chow Eric Jessen , Weil Brent R. , Dieffenbach Bryan , Howell Rebecca M. , Oeffinger Kevin C. , Nathan Paul C. , Tonorezos Emily S. 
Published: June 2022

e22023 Background: Survivors of childhood cancer with history of radiation therapy (RT) to the head/neck/chest are at increased risk for stroke. Children’s Oncology Group Guidelines recommend carotid ultrasound (CU) when clinically indicated or 10 years after RT ≥ 40Gy to the neck. Yet, the use of CU has not been previously described. Methods: 8,693 survivors of childhood cancer (median age at diagnosis 8.0 years, range 0-20; median age at evaluation 37.4, range 18-65) diagnosed between 1970-1999 were asked if they had ever had a CU. Cardiovascular disease (CVD) was defined as any of the following: stroke, congestive heart failure, hypertension, myocardial infarction, coronary heart disease, or arrythmia. Prevalence ratios (PR) were calculated; age and sex-adjusted multivariable Poisson regression models evaluated factors associated with CU. Results: 4.9% (427) of survivors had a history of stroke and 28% (2,442) had a history of any CVD. Of these, 40.0% (171) with a history of stroke and 28.6% (748) with any CVD had CU. Comparatively, 14.6% (1,404) without a stroke and 11.1% (798) without any CVD had a CU (both p<0.0001 vs those with condition). Among survivors without CVD, having seen only a primary care physician was not associated with CU (PR 0.84 95% CI 0.58-1.25, p = 0.36), while seeing a cancer specialist (+/- a primary care physician) (PR 1.83 95% CI 1.23-2.79, p = 0.036) was associated with increased likelihood of CU compared to seeing neither. Survivors who had had other surveillance studies, including a colonoscopy (PR 1.76 95% CI 1.44-2.17, p<0.0001), skin cancer exam (PR 1.62 95% CI 1.30-2.03, p=0.0002), or mammogram (PR 2.06 95%CI 1.42-3.07, p<0.0001) were more likely to have a carotid ultrasound, compared to those without that test. Having a history of anthracyclines or RT to the neck were associated with higher prevalence of CU, with RT to the neck exhibiting a dose-response relationship (Table). Conclusions: CU was more common among survivors with a history of stroke or other CVD event. In those without CVD, CU use was associated with anthracyclines and RT dose exposures and with care provided by a cancer specialist. A high proportion (70%) of survivors who received >40Gy RT to the neck have never had a CU, suggesting that greater awareness of guidelines is needed.[Table: see text]
Development and validation of the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Japanese version.
Authors: Kato Miho , Yoneoka Daisuke , Urayama Kevin , Kiyotani Chikako , Matsumoto Kimikazu , Sato Satomi 
Published: June 2022

e22025 Background: The lives of childhood cancer survivors (CCS) may be impacted by symptoms of neurocognitive dysfunction. Decline in executive function, one component of the construct concept of neurocognitive function, may affect the ability to be independent in later life; thus,ssessment and intervention are important. In the United States, the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) developed by St. Jude Children’s Research Hospital has been widely utilized in clinical practice. It is a self-administered scale for screening daily difficulties regarding organization, emotional regulation, memory, and task efficiency which all fall under the concept of the executive function. To expand the tools for executive function assessment in Japan, we developed the CCSS-NCQ Japanese version and performed a validation study among the adolescent and young adult (AYA)-CCS population. Methods: The Japanese version of the CCSS-NCQ was developed by conducting linguistic validation. Japanese AYA-CCS of all cancer types were recruited and asked to complete this 32-question self-administered questionnaire. Exploratory and confirmatory factor analysis (FA) with the Promax rotation were conducted. Results: In total, 106 participants responded. The mean age of participants was 20.6 ± 5.3 years, and 49.1% were male. The mean age at diagnosis was 8.7 ± 4.8 years; 46.2% of participants were diagnosed with brain tumors, 37.7% with hematological malignancy, and 12.3% with solid tumors. The FA identified the similar four-factor structure of organization, emotional regulation, memory, and task efficiency as the original CCSS-NCQ with factor loading set at 0.4. The Cronbach’s alpha was 0.84 - 0.92. Conclusions: Neurocognitive dysfunction could be a crucial late complication of childhood cancer, and maintaining executive function, in particular, is essential for sustaining the quality of life among CCS. The CCSS-NCQ Japanese version is the first internationally translated CCSS-NCQ. The successful validation in the Japanese population will expand opportunities for future international collaboration to identify race/ethnicity-based disparities, as well as scale enhancement for application to CCS worldwide.
The implementation of fertility guidelines and impact on the rate of pre-therapy fertility risk discussions in pediatric oncology: A retrospective cohort study.
Authors: Crowell Cameron , Digout Carol , Romao Rodrigo L. P. , Flanders Annette , Howitt MaryJean , Erker Craig 
Published: June 2022

e22027 Background: Pediatric cancer patients undergoing treatment are often at risk for infertility or subfertility. Healthcare providers do not consistently deliver fertility information prior to therapy. Our objective was to assess if development and implementation of a fertility guideline improves the frequency of pre-treatment fertility discussions with pediatric cancer families. Methods: This retrospective cohort study analyzed all consecutively eligible patients over two time periods. The pre-guideline time period was 18 months prior to implementation and the post-guideline time period was 12 months after implementation. Guideline implementation included an education session with oncology staff. Eligible patients were < 19 years old at cancer diagnosis and received chemotherapy and/or radiation therapy. Patients treated with palliative intent were excluded. Pre-guideline rate of pre-treatment fertility discussions was estimated at 40%. An estimated 40 participants in the post-guideline cohort can detect a 30% increase in fertility discussions with β 0.8 and α 0.05. Exploratory analysis assessed factors associated with the frequency of fertility risk discussions. Results: Ninety-five patients were included. Fifty-seven percent were < 10, 26% were 10-15, and 17% were ≥ 16 years old. Pre- and post-guideline cohorts are compared in table. In the pre-guideline cohort, 41% of patients had a discussion about risks of fertility impairment documented, while post-guideline cohort had 49% documented ( p = 0.531). Exploratory assessment of combined cohorts found males (OR 0.2.7, 95% CI 0.1.2-6.3-0.87) and patients ≥ 10 years old (OR 5.0, CI 2.1-12.1) were more likely to receive fertility discussions prior to therapy. Radiation and cancer type did not influence whether fertility discussions occurred. Conclusions: Implementation of a fertility guideline did not increase discussions of fertility risk, and less than half of patients had a documented fertility risk discussion. Male patients and age ≥ 10 years old were more likely to have documented discussions about risks to future fertility. Effective strategies are needed to improve the rate of discussions regarding fertility risk to ensure families receive this information prior to therapy. [Table: see text]
How to regulate vaping products to advance cancer prevention: Evidence from online stores.
Authors: Shang Ce 
Published: June 2022

e22502 Background: The use of electronic cigarettes has significantly increased in the past decade, and online stores are one of the most common outlets for e-cigarette users to purchase vaping products. The goal of this study is to examine the appeal of different e-liquid flavors to vapers, using a revealed preference method to estimate consumer demand. Methods: We collected data on e-liquid sales prices, volume (in ml), and a variety of product flavors, from online vaping stores using web data extraction. We standardized prices for e-liquid products and used the hedonic pricing model to assess the associations between standardized e-liquid prices and flavors, controlling for nicotine concentration (in mg) and product VG/PG ratio. In total, we collected data of 10,870 e-liquid products from four popular online vaping stores that sell nationwide across the U.S. Results: Higher e-liquid prices (standardized to $/ml) are associated with higher nicotine concentrations. E-liquid products with fruit tobacco flavors are associated with higher sales prices. E-liquid prices are higher when VG/PG ratio deviates from 70/30 except for 90/10: the prices of e-liquid products with a 90/10 VG/PG ratio are lower than the prices of products with a 70/30 ratio. All of the findings above are statistically significant at a 5% level. Conclusions: Higher nicotine concentration and fruit flavors are associated with higher e-liquid prices in national online vaping stores, suggesting that they are preferred attributes and are in greater demand among vapers in the market of heterogeneous e-liquid products.
A binational cancer registry analysis of Hispanic patients in Mexico and the United States.
Authors: Lopez Pineda Arturo , Garrido-Sanchez Josue Abinadi , Gonzalez-Arroyo Gilberto , Alvarez-Aguilar Cleto 
Published: June 2022

e22513 Background: A marked disparity in cancer burden exists between regions of the world. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow estimates for different geographic areas. We investigate the data differences, clinical characteristics, tumor information, and patient outcomes of Hispanic patients in North America. Methods: We used data from Mexico’s National Cancer Registry and the United States Surveillance, Epidemiology, and End Results Program (SEER) program with four years of follow-up on each registry. of Mexican registry, we excluded outliers and records with more than 80% missing variable; of the United States registry, only patients identified as hispanic or latino were included. On the Mexican registry we re-coded all variables and the United States registry data on secondary neoplasm was excluded to match boths registry. Baseline characteristics and a geographical information system was constructed to map cancer registries and their relative frequencies. A survival analysis was done to understand the correlation between covariates. Lastly, we build machine learning models to predict 3-year overall survival. Results: The Hispanic cancer database (HCB) consists of 291,178 patients (19,904 from Mexico, and 271,274 from the United States). The top three most frequent cancer types were breast, prostate and hematological. The age of diagnosis was 55±17 years. Mexico has a slight skewness towards the earlier age of diagnosis of females. The registries with the highest burden of cancer were New Mexico (USA) and Baja California Sur (Mexico). Average survival months seem very stable across registries in the United States, but not in Mexico. Our linear regression model achieved a coefficient of determination (R-squared) of 0.49, while the logistic regression achieved an AUC of 0.82, with an F1-score of 0.88. Conclusions: Cancer registries are important tools for prevention and development of control programs. Hispanics are a traditionally neglected population in oncological clinical trials, with low enrollment of patients outside of the United States. Mexico enacted its National Cancer Registry Law in 2017, which alongside the Hispanic data on the SEER program in the United States offers enormous opportunities for continued collaboration and understanding of cancer. Both Mexico and the United States can strengthen their cancer prevention strategies and generate trans-border collaboration, research, and patient-support networks.
Spatiotemporal distribution of liver cancer mortality rate in Peru between 2003-2017.
Authors: Flores Claudio J. , Lopez Pereyra Mariano Francisco , Chirinos Luis , Carrion Pamela , Enriquez Daniel 
Published: June 2022

e22521 Background: Liver cancer represents the sixth most frequent neoplasm and the third leading cause of cancer death worldwide, although it possesses an heterogenous incidence and mortality. In Peru, its mortality rate distribution is unknown. We aimed to explore the spatio-temporal distribution of liver cancer mortality rate according to Peruvian geographical regions. Methods: We obtained data from liver cancer deaths between 2003-2017 from the Peruvian Ministry of Health Registry. Population data was obtained from The National Institute of Statistics and Informatics (INEI, Peru). Age-standardized mortality rate (ASMR) was calculated based on the 2011 world standard populations. Spatial autocorrelation was determined according to Moran’s Index and the Local G Cluster Map to explore the cluster patterns between regions. Results: During the study period, 18,427 deaths for liver cancer were reported on the national death system. The liver cancer mortality rate in Peru increased from an ASMR of 4.1 (95% CI: 3.4, 4.8) in 2003 to 4.4 (95% CI: 3.8, 5.0) in 2017, with an average mortality rate of 4.9 (95% CI: 4.6, 5.2) by 100 000 persons-year. According to the political regions of Peru, the mortality rate distribution showed a spatial variation (ASMR of 0.6 to 12.2 per 100 000 persons-year); the mortality rate was high in coast regions and low among highlands regions. The ASMR spatial distribution showed a significant spatial autocorrelation (Moran’s I: p < 0.05). During the study period, the ASMR showed a significant increasing and decreasing mortality in several geographic regions and remained constant in other regions. Conclusions: In Peru, the liver cancer mortality rate shows a spatial and temporal variation according to geographical regions. The increase in the mortality rate in some regions requires further identification of local risk factors to implement programs aimed at reducing incidence and mortality.
Unusual prevalence of cancer genetic mutations in a cohort of predominantly non-Caucasian cancer patients.
Authors: Kyaw Nay Yee Wint , Natarajan Vijaya , Durana Theresa , Bhasin Pooja Gogia , Best Jacob , Toom Sudhamshi , Xu Yiqing 
Published: June 2022

e22524 Background: Genetic testing has been applied increasingly widely in oncology, as detection of hereditary cancer syndromes can guide prophylactic surgery, intensive surveillance and family member testing. We hypothesized that the profile of mutation prevalence may be different from the general knowledge in patients with immigrant background. Methods: Cancer patients who have been treated in Maimonides hospital and have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Patients were randomly approached for consenting for the study. The results from the first 122 patients enrolled in this study were analyzed. Results: Among 122 patients, there were 86 breast, 22 GYN, 8 GI, 5 GU and 1 lung cancer. The ethnicities were African American (n = 38), Asian (n = 36), Caucasian (n = 32), Hispanic (n = 10) and mixed races (n = 6). Six patients had 2 primary cancers and 2 patients had 3 primary cancers. 25 patients (20.49 %) had germline mutations. A complete list of cancer type, mutation type, age of onset and cancer characteristics is shown in the table below. All of the 13 mutation positive breast cancer patients met the NCCN criteria for genetic testing, including 7 for age < 50 and 6 with family history of breast cancer. Among the 2 patients with NF1 mutation, one had no skin change while the other had neurofibromatosis; both had family history, with pancreatic or breast cancer respectively. The patient with APC mutation had family history of numerous cancers including gastric, but no colon cancer. 48% patients had the onset of disease at older than 50 years old. Conclusions: In this multi-ethnicity cohort, 20.49% mutations were detected in patients who met the genetic testing criteria. A higher prevalence of BRCA 2 were found in both breast and ovarian cancer patients, and rare mutations of NF1, APC, FH and ATM were also detected. A large percentage had onset at an older age. More studies should be done in communities enriched with immigrants to gather further knowledge of unusual prevalence of genetic mutations, and an extensive panel for gene testing should be offered.[Table: see text]
Identified potential pathogenic variants of BARD1 in 1449 Chinese high-risk breast cancer patients.
Authors: Wang Rong , Ye Weiwu , Chen Zhanhong , Shao Xiying , Cao Wenming , Wang Xiaojia , Zheng Yabing 
Published: June 2022

e22525 Background: BARD1 (BRCA1-associated ring domain 1), nuclear partner of BRCA1, has been recognized as a breast cancer predisposition gene. Recently, two large-scale population-based case–control studies confirmed that germline loss-of-function mutations in BARD1 were associated with a risk of breast cancer. Since the germline mutation frequency of BARD1 is much less than that of BRCA1/2, the distinct mutation spectrum of BARD1 is still obscure, especially in Chinese breast cancer patients. To verify the utility of BARD1 genetic testing in Chinese population, we assessed the mutational frequency and spectrum of BARD1 in a sequential series of Chinese high-risk breast cancer patients. Methods: A cohort of high-risk breast cancer patients (n = 1449) were collected in Zhejiang Cancer Hospital from 2008 through 2020, including 608 familial breast cancer (BC) cases, 173 bilateral BC cases, 222 triple negative BC cases, 436 early-onset BC cases (≤40 years) and 10 male BC cases. The complete coding sequence and intron–exon boundaries of BARD1 were screened by a 98-gene panel sequencing assay. The SIFT, Polyphen2 and MutationTaster prediction programs were used for analyzing the effect of the variants of unknown significance (VUS) on the BARD1 protein function. Results: A total of three BARD1 pathogenic mutations (c.1348_1349delinsCAT, c.70_71insGT and c.373G > T) were identified, which had been all reported, and accounting for 0.2% (3/1449) in Chinese high-risk breast cancer patients. The frequencies were 0.33% (2/608) and 0.12% (1/841) in familial and non-familial breast cancer patients, respectively. In total, 19 VUSs including 17 missenses, one inframe deletion and one inframe insertion of BARD1 were identified in this study. Based on in silico analysis, nine BARD1 missense variants (c.76A > G, c.1912G > A, c.1693C > T, c.2191C > T, c.127C > A, c.1601C > T, c.443G > A, c.233G > A and c.1972C > T) were classified as potentially damaging. However, the two newly variants c.420_422del and c.68_69insTCCGGGAACGAGCCTCGTTCC still remain VUS, and the other eight variants were classified as benign. Conclusions: Our data presented the germline mutations of BARD1 in a large-scale Chinese high-risk breast cancer population, which accounted for 0.2% in our cohort. Moreover nine potential pathogenic variants were found based on in silico analysis. Clinically, these data may be helpful in genetic counseling of breast cancer patients with BARD1 germline mutation. While the further research on the VUS are needed.