bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbial characteristics of patients with esophageal squamous cell carcinoma after chemotherapy and after immunotherapy.
Authors: Liu Yanjun , Zuo Jing , Fan Zhisong , Liu Liang , Wang Yudong , Feng Li , Han Jing , Wang Long , Zhang Xue 
Published: June 2022

e16049 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Previous studies have shown that chemotherapy and immunotherapy is affected by esophageal microbiome. The effect of esophageal microbiota on the efficacy of chemotherapy and immunotherapy for ESCC remain poorly understood. Methods: DNA was extracted from blood, oral mucosal, saliva, urine, fecal samples from 14 ESCC patients after chemotherapy and 18 ESCC patients after immunotherapy. Total microbial genomic DNA samples were extracted using an OMEGA Soil DNA Kit (D5625-01). The V3–V4 regions of bacterial 16S rRNA genes were amplified by PCR using the forward primer and the reverse primer and were sequenced with Illumina MiSeq platform. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA were used to analyze differences in β diversity. Functions of 16S rRNA sequences were predicted using the PICRUSt2 and KEGG databases. Results: The α diversity in patients with ESCC after immunotherapy were higher than those in patients with ESCC after chemotherapy. There was a statistically significant difference in β diversities between ESCC patients after chemotherapy and ESCC patients after immunotherapy. In terms of the microbial functions in ESCC patients after chemotherapy and immunotherapy, the metabolic pathways accounted for the most. Conclusions: This study is conducive to exploring new mechanisms for tumor cells to evade host immune surveillance, providing new ideas and new strategies for the microecology-based therapy of ESCC.
FLOT neoadjuvant therapy turns the expression patterns of cancer cells similar to those of non-cancer cells in gastric cancer patients.
Authors: Barra Williams Fernandes , Silva Jessica Costa , Mourao Ronald Matheus da Silva , Anaissi Ana Karyssa , Demachki Samia , Ishak Geraldo , Calcagno Danielle Queiroz , Moreira Fabiano Cordeiro , Assumpção Paulo Pimentel 
Published: June 2022

e16056 Background: FLOT perioperative have emerged as a new standard for locally advanced gastric cancer (LAGC). Nevertheless, the molecular consequences of such therapy remain obscure. Aiming to investigate changes in the tumor transcriptional landscape in LAGC patients treated with FLOT, a comprehensive analysis of messenger RNA (mRNAs) and long noncoding RNA (lncRNAs) expression was developed using next-generation sequencing (NGS). Methods: Paired tumor and non-tumor fresh samples, including 17 patients with intestinal-type LAGC submitted to neoadjuvant FLOT treatment (treated group) and 13 who did not receive neoadjuvant therapy (untreated group), were sequenced and compared. Differential expression analyses were performed using the DESeq2 package. Criteria for differentially expressed (DE) lncRNAs and mRNAs were|Log2(Fold-Change)| > 2; and adjusted p-value < 0.05. In silico analyses were adopted to identify DE lncRNAs with transcription factors (TFs) and RNA-binding proteins (RPBs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) was also performed to elucidate these target proteins’ and mRNAs biological’s roles. Results: In tumor samples from the untreated group, 4443 mRNAs and 961 lncRNAs DE were found, in which 293 mRNAs and 148 lncRNAs accurately discriminated (the area under the curve ROC > 0.9) tumor and non-tumor tissues. Only 265 mRNAs and 29 lncRNAs DE were detected in treated patients, indicating that neoadjuvant therapy led to changes in expression patterns, making tumor tissues similar to non-tumor tissues. Subsequent analyzes identified that non-tumor tissues (treated vs. untreated) showed similar expression profiles. Among tumor samples, 34 mRNAs and 54 lncRNAs DE were found, in which 7 mRNAs and 16 lncRNAs can discriminate between treated and untreated tumors, indicating the effect of neoadjuvant treatment is predominant in the tumor. GO evaluation of genes was significant for 83 terms for biological process. The most annotated terms were the regulation of catalytic activity. We also observed that DE lncRNAs interact with TFs and RBPs were enriched in related cancer development and progression pathways, including transcriptional dysregulation and cellular senescence. Conclusions: Despite the need for further validation to better understand the transcriptional landscape related to neoadjuvant treatment, the present study highlights the functional relevance of lncRNAs in tumor biology and, mainly, shed light on the molecular effects of FLOT neoadjuvant treatment, that might help to guide future investigations aiming to establish personalized management of GC.
Real-world genomic testing, treatment, and outcomes in patients with cholangiocarcinoma with FGFR2 fusions/rearrangements.
Authors: Borad Mitesh J. , Conner Therese , He LiHong , Kazerooni Reza , Salimi Tehseen , Epstein Robert S. 
Published: June 2022

e16168 Background: Several fibroblast growth factor receptor (FGFR) inhibitors have been recently approved or are in development for the treatment of cholangiocarcinoma (CCA) with FGFR2 fusions/rearrangements (f/r), such as the ATP-competitive inhibitors pemigatinib and infigratinib (FDA-approved in 2020/2021) and the covalent inhibitor futibatinib, which has shown efficacy in a pivotal phase 2 trial. To inform future evaluations of the impact of these agents in clinical practice, and understand other existing gaps in care, we investigated the characteristics and clinical management of patients with CCA and FGFR2 f/r prior to 2021. Methods: This real-world, retrospective cohort study used de-identified, patient-level electronic health records data from Cancer Treatment Centers of America (CTCA) to identify adults with a diagnosis of advanced intrahepatic CCA (iCCA) who received genomic testing between 2013-2021. Clinical/demographic characteristics, time to genomic testing, treatment patterns, and outcomes of patients with and without FGFR2 f/r were described. Results: 23 patients with FGFR2 f/r and 88 with FGFR wild-type (wt) iCCA were identified. Compared to FGFR wt, FGFR2 f/r had a higher proportion of female (65.2 vs 45.5%) and Black (39.1 vs 18.2%) patients (Table). Mean age at diagnosis was ̃60 y and >60% were diagnosed with stage 4 disease in both cohorts; 91.3% of f/r and 78.4% of wt patients had an ECOG PS 0/1. Median time from diagnosis to genomic testing was ̃5 mo; upon entry to CTCA, median time to testing was <2 mo. 17/23 patients in the f/r cohort had FGFR2 fusions (4 BICC1, 13 other). Three FGFR2 f/r patients received an FGFR inhibitor (pemigatinib) as next treatment after testing in 2020. A trend towards longer median overall survival in the f/r vs wt group (24.5 vs 17.8 mo), and a correlation of survival with ECOG PS were observed. Conclusions: This analysis provides insight into the real-world characteristics, clinical management and outcomes among patients with iCCA and FGFR2 f/r, predominantly prior to the introduction of FGFR inhibitors, providing a baseline for further study as the treatment landscape evolves. Of note, the time lag between diagnosis and genomic testing before entry to CTCA underlines the need for earlier testing to guide optimal therapy in clinical practice. [Table: see text]
Circulating tumor DNA is a potential prognostic risk factor of recurrence in patients with hepatocellular carcinoma treated by liver transplantation.
Authors: Jiang Nan , Zeng Xinchen , Tang Jianxin , Liang Ziming , Qi Xiaofang , Huang Lujia , Pang Fei 
Published: June 2022

e16196 Background: Liver transplantation (LT) is one of the most effective therapeutic strategies for hepatocellular carcinoma (HCC), however, tumour recurrence after LT often leads to poor outcomes. At present, clinical characteristic profile, imaging diagnosis as well as level of serum biomarkers prior to LT could predict the prognosis in HCC patients treated by LT. However, the sensitivity and specificity of these biomarkers are limited, highlighting the crucial need to identify novel biomarkers. Previous clinical studies have shown that postoperative circulating tumor DNA (ctDNA) can be used as a predictive biomarker for the risk of recurrence in stage I-III solid tumor. This study aimed at investigating the relationship between the level of ctDNA and the probability of recurrence in HCC patients treated by LT. Methods: HCC patients receiving LT treatment were enrolled. Peripheral blood samples before LT and available matched tissue samples were collected. Targeted sequencing of 328 cancer-related genes were conducted. The clinicopathologic data of the patients was retrospectively analyzed. The predictive efficiency for recurrence after LT of different clinicopathologic parameters and ctDNA were accessed. Results: A total of 45 patients were enrolled, including 42 males (93%) and 3 females (7%), with a median age of 51 (range 31-76 years). Thirty-five patients (78%) had detectable ctDNA before LT while gene alterations were identified in tumor tissue of all the patients. Larger tumor size (> 5cm), cirrhosis, portal vein tumor thrombus (PVTT) and elevated AFP level (≥400ng/ml) prior to LT were associated with higher percentage of positive ctDNA (94% vs 73%, 84% vs 75%, 88% vs 79%, 88% vs 76%, respectively). Patients with micro-vessel invasion (MVI) had higher ctDNA abundance (maxVAF, P < 0.05). Interestingly, after over 3 years’ follow-up, clinical factors including MVI, PVTT, BCLC stage, maximum tumor diameter and serum AFP failed to predict disease free survival (DFS) and overall survival (OS). In contrast, the recurrence rate was remarkably augmented (48.6% vs 0%) and the median DFS was significantly decreased (390 days vs not reached, p< 0.05) in patients with detectable ctDNA. Conclusions: In conclusion, ctDNA could be a potential biomarker to sensitively predict the recurrence in patients with HCC treated by LT, which may help to improve the post-transplant management of these patients.
A phase 1b/2 trial of SHR-1701 in combination with gemcitabine and nab-paclitaxel in patients with untreated locally advanced or metastatic pancreatic cancer.
Authors: Zhou Jun , Yu Xianjun , Li Zhihua , Zhou Yuhong , Li Jialin , Xue Ran , Xia Ye , Han Hongxia , Wu Yiwen , Shen Lin 
Published: June 2022

e16264 Background: The current standard first-line therapy is nab-paclitaxel plus gemcitabine and prognosis of this patient population remains poor. Immune checkpoint inhibitors in combination with chemotherapy have shown substantial clinical activity in several metastatic malignancies, but evidences in pancreatic cancer are limited. This phase 1b/2 trial is designed to evaluate the antitumor activity and safety of SHR-1701 (a bifunctional fusion protein targeting PD-L1 and TGF-β) combined with chemotherapy in patients with untreated locally advanced or metastatic pancreatic cancer. Methods: Eligible patients had histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma and had never received systemic antitumor therapy for advanced or metastatic diseases. Patients received SHR-1701 (30 mg/kg) on day 1 plus gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on day 1 and 8 of each 3-week cycle by intravenous infusion. The primary endpoint of phase 1b part was recommended phase 2 dose (RP2D). In the phase 2 part, the primary endpoint was ORR per investigator according to RECIST v1.1. Results: No dose-limiting toxicities were observed among the first six patients; the RP2D of SHR-1701 was 30 mg/kg. From Dec 03, 2020 to Sep 17, 2021, a total of 56 patients were enrolled and received at least one dose of study drug treatment. As of data cutoff on Nov 19, 2021, with a median follow-up period of 4.2 months (range 0.2-10.6), 28 (50.0%) of the 56 patients were still on treatment. Of the 56 patients, ORR per investigator was 33.9% (95% CI 21.8-47.8; n = 19, with 13 patients confirmed) and DCR was 75.0% (95% CI 61.6-85.6; n = 42, all confirmed). Of the 52 patients who had at least one post-baseline radiographic assessment, the ORR was 36.5% (95% CI 23.6-51.0) and DCR was 80.8% (95% CI 67.5-90.4). 20 (35.7%) PFS events and 9 (16.1%) OS events occurred in the 56 patients as of data cutoff, and both PFS and OS data were immature. Treatment-related AEs of any grade or grade ≥3 were reported in 56 (100%) or 25 (44.6%) patients, respectively. The incidence of SHR-1701-related AEs was 92.9% (52 patients). Grade ≥3 SHR-1701-related AEs occurred in 13 (23.2%) patients, with increased gamma-glutamyltransferase (3 patients, 5.4%) and decreased white blood cell count (3 patients, 5.4%) as the most common ones. Serious SHR-1701-related AEs occurred in 6 (10.7%) patients and SHR-1701-related death occurred in 1 (1.8%, gastrointestinal hemorrhage) patient. Conclusions: Combination of SHR-1701 with gemcitabine and nab-paclitaxel showed preliminary antitumor activity in untreated locally advanced or metastatic pancreatic cancer. This combination therapy was well tolerated without unexpected safety signal. Further clinical investigations are warrant to confirm our results. Clinical trial information: NCT04624217.
Racial disparities in the burden of depression and anxiety in patients with pancreatic cancer.
Authors: Franco Diana , Farooq Umer , Anwer Faiz 
Published: June 2022

e16283 Background: The prevalence of depression ranges from 33% to 45% in pancreatic cancer, the highest among gastrointestinal malignancies. Psychiatric illnesses impact the quality of life and compliance with treatment and regular physician visits. Therefore, we sought to examine ethnic differences in the prevalence of depression and anxiety in pancreatic cancer. Methods: We investigated the National Inpatient Sample 2019 employing International Classification of Diseases-10 (ICD-10) codes to include adult patients with pancreatic cancer. Multivariate linear or logistic regression was used (for continuous and categorical variables, respectively). The confounders adjusted for in the regression models were: history of MI and stroke, coronary artery disease, sleep disorders, chronic pain disorders, smoking, alcohol, obesity, PTSD, sexual abuse, arthritis, and physical disability, in addition to patient and hospital-level variables. We used Stata, version 14.2, to perform analyses considering 2 sided P < 0.05 as statistically significant. Results: A total of 116,055 patients with pancreatic cancer were included. 13,825 (11.91%) had depression and 16,845 (14.51%) had anxiety. The prevalence of depression in various ethnic categories was: 13.63% in Whites, 7.59% in Blacks, 8.47% in Hispanics, and 5.63% in Asians ( P< 0.001). Anxiety prevalence was: 16.25% in Whites, 9.92% in Blacks, 11.65% in Hispanics, and 7.29% in Asians ( P< 0.001). On multivariate analysis, compared to Whites, all ethnic groups had lower odds of depression (Blacks; adjusted odds ratio (aOR): 0.45, 95% confidence interval (CI): 0.38–0.52, P< 0.001, Hispanics; aOR: 0.60, 95% CI: 0.49–0.73, P< 0.001, Asians; aOR: 0.43, 95% CI: 0.31–0.59, P< 0.001). Similar results were seen for anxiety when ethnic groups were compared to Whites (Blacks; aOR: 0.49, 95% CI: 0.43–0.56, P< 0.001, Hispanics; aOR: 0.67, 95% CI: 0.55–0.82, P< 0.001, Asians; aOR: 0.44, 95% CI: 0.33–0.59, P< 0.001). Conclusions: Whites had the highest burden of depression and anxiety in pancreatic cancer. However, Hispanics represented the ethnic minority with a greater prevalence of psychiatric disorders. Further research needs to establish the factors responsible for these ethnic differences.[Table: see text]
Complementary role for circulating tumor DNA and tumor tissue to detect clinical relevant alterations in patients with castrate-sensitive prostate cancer.
Authors: Yang Bin , Dong Baijun , Chen Wei , Zhao Tingting , Yang Guanjie , Xie Jun , Wang Ruiliang , Wang Hong , Huang Longfei , Liu Tongtong , Zhang Menghuan , Huang Hang , Peng Bo , Xue Wei , Yao Xudong 
Published: June 2022

e17050 Background: Targeted sequencing of circulating tumor cell DNA (ctDNA) has been well studied in patients with metastatic castration-resistant prostate cancer (mCRPC), while its application in patients with castrate-sensitive prostate cancer (CSPC) is relatively limited. This study aimed to analyze the concordance of somatic alterations in ctDNA and matched tumor tissue samples oand investgate the clinical significance of genomic alterations in CSPC patients. Methods: 184 CSPC patients from three Chinese Hospitals were included (24 with localized PCa (LP), 46 with lymph node metastases (LNM), 42 with distant metastases of low tumor burden (LTB), and 72 with distant metastases of high tumor burden (HTB)). All patients had ctDNA samples and matched tumor tissues collected at time of primary biopsy (n = 78) or radical surgery (n = 106) for high-throughput targeted sequencing of multiple-gene. 36 prostate cancer clinical relevant genes were selected for analysis. Kaplan–Meier survival curves and Cox regression analyses were used to determine the associations of genomic alterations and the time to CRPC. Results: Overall, 70.6% of CSPC patients had somatic alterations in tumor tissues, which was much higher than that in ctDNA (31.5%). The concordance for alterations detected in ctDNA and matched tumor tissue was 29.2%. In subgroup analysis, the concordance for LP, LNM, LTB and HTB group were 0%, 5.3%, 3.3%, and 49.1%, respectively. Most of alterations identified were unique in tumor tissues or ctDNA. Number of alterations in tumor tissue alone was 23, 54, 58 and 56 in LP, LN, LTB and HTB group, respectively. Number of alterations alone in ctDNA was 16, 27, 9 and 37 in LP, LN, LTB and HTB group, respectively. Combined analysis of the genomic alterations identified in ctDNA and tumor tissue demonstrated that the most frequent altered gene was FOXA1 (35%), TP53 (16%), SPOP (12%), CDK12 (12%) and NCOR2 (9%). For patients with distant metastases harboring any pathogenic somatic or germline alterations of CDK12/TP53/BRCA1/BRCA2/PTEN/RB1, the median time to CRPC was significantly shorter than wide-type patients (median, 17.3 mo vs Not reached；p＜0.005). In the multivariate COX analysis, alterations of CDK12/TP53/BRCA1/BRCA2/PTEN/RB1 was still found to be significant (P = 0.00737). Conclusions: The concordance of gene alterations in ctDNA and mathced tumor tissue in CSPC patients increased with disease progression. ctDNA or tumor tissue alone was insufficient to capture all clinically relevant alterations, and therefore combined use of them may provide more comprehensive information about prognosis and clinical treatment guidance for CSPC patients. Alteration of CDK12/TP53/BRCA1/BRCA2/PTEN/RB1 was an independent prognostic factor for the time to CRPC.
Prevention of radiation-induced rectal injuries with perirectal blocks in radiation therapy.
Authors: Rodionova Olga G. , Sakun Pavel G. , Sheiko Elena A. , Karnaukhova Elena A. , Pustovalova Alla V. , Chalabova Tatiana G. , Savchenko Dmitriy A. , Kabanov Sergey N. , Adamyan Meri L. , Kruze Polina A. , Poryvaev Yuriy A. , Chernikova Natalia V. , Voshedskiy Vitaliy I. , Tolmacheva Ekaterina A. , Vasilieva Ekaterina O. , Solntseva Anna A. , Zhenilo Oksana E. , Cherkasova Anna A. , Krokhmal Yulia N. 
Published: June 2022

e17507 Background: The purpose of this study was to evaluate perirectal blocks in prevention of radiation-induced rectal injuries in patients with cervical cancer. Methods: The study included 18 patients diagnosed with stage III cervical cancer (T3bNxM0) receiving chemoradiotherapy. All patients showed pronounced inflammatory and dystrophic changes in tissue planes and organs of the small pelvis due to comorbidities (diabetes mellitus, hypertension, pelvic varicose veins, proctitis, inflammatory and adhesive processes in the small pelvis reducing chemoradiotherapy effectiveness due to impaired microcirculation and increasing the risk of post-radiation complications). All patients received brachytherapy with additional perirectal administration of drugs relieving pain and inflammation and improving neurotrophic processes and microcirculation in tissues (novocaine 0.25% -20.0; milgamma 2.0; ceftriaxone 1 g; dexamethasone 8 mg). The combined administration causes drug potentiation, positively affects the nervous and neuromuscular systems, restores microcirculation and venous outflow, decreases swelling, improves tissue trophism, reduces blood vessel permeability, and improves reflexes from interoceptors. Radiation therapy was completed on schedule with the introduction of radical doses in all patients, which is challenging in patients with comorbidities leading to impaired trophism and tissue hypoxia. Results: Complete tumor regression confirmed by MRI and ultrasound was observed by the end of the treatment in 90% of patients, apparently due to the radiosensitizing effect on cervical cancer and the radioprotective effect on surrounding tissues. Conclusions: Parametrial blocks during brachytherapy improve the status of tissues of the small pelvis which, in turn, prevents radiation damage, contributes to the timely radiotherapy completion, and improves the treatment effectiveness and the quality of life of patients. This technique is especially relevant in view of the increasing number of diseases that disrupt microcirculation, and hence the oxygenation of tissues, causing tumor radio- and chemoresistance.
Multi-omics characterization of productive HPV integration in cervical cancer.
Authors: Sun Chaoyang , Fan Junpeng , Fu Yu , Peng Wenju , Li Xiong , Shen Yuanming , Zou Dongling , Xia Bairong , Song Kun , Chen Gang , Ma Ding 
Published: June 2022

e17508 Background: Cervical cancer (CC), which is caused by high-risk human papillomavirus (HPV), remains a significant public health problem worldwide. HPV integration into the host genome is a critical aetiological event in cervical carcinogenesis and progression and it can be silent or actively transcribed that leads to production of viral-host fusion transcripts. We aim to study the characterization of silent and productive HPV integration in cervical cancer. Methods: Cervical cancer (CC), which is caused by high-risk human papillomavirus (HPV), remains a significant public health problem worldwide. HPV integration into the host genome is a critical aetiological event in cervical carcinogenesis and progression and it can be silent or actively transcribed that leads to production of viral-host fusion transcripts. We aim to study the characterization of silent and productive HPV integration in cervical cancer. Results: Virus capture sequencing revealed 762 virus-host DNA fusion breakpoints and only 142 (18.6%) were actively transcribed into fusion transcripts. The productive HPV integrations were nonrandom, with an increase in breakpoints in the HPV E1 region、 human introns and common fragile sites. They were associated with significant changes in host focal genome structure and gene transcription, but not in protein production in 40 kb region, and produced higher levels of E6 and E7 proteins detected by Western Blot. Clinical, transcriptional, proteomic, phosphoproteomic and single-cell data demonstrated that EMT, proliferation and extracellular matrix associated pathway were enriched in productive HPV integrated tumors and contributed to advanced clinical stage. Conclusions: We demonstrated that productive HPV integration is associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion in situ to advanced disease. This study improves our understanding of the effects of HPV fusion transcripts on the biology and pathophysiology of HPV-driven cervical cancer that has the potential to direct new prevention and therapeutic strategies