bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive genomic profiling of MET rare tumors in China.
Authors: Li Ning , Wang Shuhang , Li Qin , Chen Rongrong , Fang Yuan , Ma Peiwen , Jiang Ning , Yu Yue , Miao Huilei 
Published: June 2022

e15058 Background: The mesenchymal epithelial transition factor receptor (MET) is a potential therapeutic target in a number of cancers, commonly activated by amplification, mutation and fusion. Methods: Rare tumor was defined as solid tumors with an incidence lower than 2.5/100,000 per year. We retrospectively analyzed the next-generation sequencing and clinicopathological data of 3453 Chinese rare tumors patients in the Geneplus database, including 1021 genes, MSI loci, tumor mutational burden (TMB), and programmed cell death ligand-1 (PD-L1) expression analysis information. Results: MET-positive was identified in 115 patients (3.3%), including 109 cases of amplification (3.2%), 8 cases of exon 14 skipping (0.2%) and 1 cases of fusion. The prevalence of MET-positive varied widely across tumors systems and subtypes. Urinary, neural, skin and respiratory systems were the top 4 systems with 8.3% (1/12), 7.9% (58/732), 4.2% (1/24) and 2.9% (6/207) MET-positive rate, respectively. Considering the tumor subtypes, glioblastoma, sarcomatoid carcinoma, neuroendocrine tumor and glioma were higher, reaching 15.7% (16/102), 13.2% (7/53), 9.8% (4/41), and 7.4% (36/487) respectively (Table). Totally, 73.0% of patients had at least one common targetable gene mutation, including ATM，BRAF，BRCA，CDKN2A，EGFR substitution, ERBB2, FGFR1,2,3, KIT, NF1, PIK3CA, PTEN and RET. The proportions of TMB-H (≥9 mut/Mb) and MSI-H were very low, with only 8.9% and 2.2%, while PD-L1 positive rate reached to 60.9%. Conclusions: The treatment options for rare tumors are still limited. The approval of MET receptor tyrosine kinase has brought hope to patients with Non-Small Cell Lung Cancer. The MET-positive rate in rare tumors is higher than 2.7% in lung adenocarcinoma, so MET receptor tyrosine kinase have great application potential in rare tumors. However, since most patients co-occurred with other targetable driver mutations or PD-L1 positive, how to choose the best treatment strategy should be solved. The deployment of the best treatment strategy is a problem that should be solved in the follow-up study.[Table: see text]
Some plant metabolites from Petasítes sp. and their effect on cancer cells motility in vitro.
Authors: Timofeeva Sofia V. , Kit Oleg I. , Filippova Svetlana Yu , Sitkovskaya Anastasia O. , Mezhevova Irina V. , Gnennaya Nadezhda V. , Shamova Tatiana V. , Novikova Inna A. , Enin Yaroslav S. , Burov Oleg N. , Zlatnik Elena Yu , Menshenina Anna P. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Zhenilo Oksana E. , Poryvaev Yuriy A. , Myagkova Tatiana Yu. , Pozdnyakova Viktoria V. , Adamyan Meri L. 
Published: June 2022

e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.
Risk of second primary malignancies among appendiceal cancer survivors in the United States.
Authors: Wong Krista Michelle , Ramsawak Seshma , Abuamsha Hasan 
Published: June 2022

e15514 Background: Appendiceal cancer (AC) survival rates have improved over the last decade. The risk of second primary malignancy (SPM) in AC survivors has become an important concern. Therefore, this study aimed to estimate the risk of SPM in patients with primary AC. Methods: We performed a retrospective cohort study of patients ≥18 years of age diagnosed with AC between 2000-2016 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The study endpoint was the occurrence of SPM diagnosed after two months of the index AC. We calculated the standardized incidence ratio (SIR) with 95% confidence intervals (CI) for SPM in AC survivors by using the SEER software. Results: Of 9578 patients with AC, 598 (6.2%) developed a SPM. The overall risk of SPM for all sites was significantly increased in AC patients (SIR = 1.46, 95% CI 1.34-1.58). The highest risk of developing a SPM was seen in ages < 60 years, females, and Asian/Pacific Islanders, respectively (SIR = 1.84, 95% CI 1.64-2.07; SIR = 1.55, 95% CI 1.38-1.74; SIR = 1.72, 95% CI 1.12-2.52). The SPM sites associated with increased incidences included the small intestine, followed by the appendix, splenic flexure of the colon, and peritoneum/omentum/mesentery. There was an increased risk of developing non-Hodgkin lymphoma, but no elevated risk with developing second leukemias. Surgery and chemotherapy were associated with an increased incidence risk of SPM, respectively (SIR = 1.45, 95% CI 1.33-1.57; SIR = 1.47, 95% CI 1.25-1.71). Conclusions: AC survivors have an increased incidence of developing SPM, most notably in the small intestine, which suggests a pathophysiological process affecting derivatives of similar embryological origin. Long-term surveillance for SPM is recommended for AC survivors, especially those at high risk.[Table: see text]
Impact of hospital teaching status on outcomes of colorectal cancer in hispanic patients: A nationwide analysis.
Authors: Farooq Umer , Franco Diana , Ghous Ghulam , Ma Irene 
Published: June 2022

e15520 Background: Previous studies described lower mortality in teaching hospitals after colorectal surgery. Hispanics represent a growing minority in the USA. Given their scarcity of representation in clinical studies, it is imperative to study the impact of teaching status on hospital outcomes from colorectal cancer (CRC) in the Hispanic population. Methods: We investigated the National Inpatient Sample 2017-2019 using International Classification of Diseases-10 (ICD-10) codes to include adult Hispanics with CRC. Mortality, morbidity, resource utilization, and surgical outcomes were compared stratified by hospital teaching status. Analyses were performed using STATA (v 14.2), considering 2 sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student's t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: Out of 72,599 included patients, 15,895 were treated at non-teaching and 56,704 at teaching hospitals. Patients treated at teaching hospitals had 21% lower odds of inpatient mortality (Adjusted odds ratio (aOR) for mortality 0.79, 95% confidence interval (CI): 0.64 – 0.97, P= 0.03). There were no differences between markers of resource utilization (length of stay, hospital charges, and ICU admission). Patients at teaching hospitals had higher odds of acute renal failure (aOR 1.15, 95% CI: 1.02 – 1.30, P= 0.02). Rates of acute respiratory failure, lower GI bleeding, and sepsis were comparable between the two groups. Colectomy and procedure-related complication rates (including intubation, post-operative DVT/PE) were equal between the two studied groups except for post-operative adhesions, which were higher at teaching hospitals (aOR 1.29, 95% CI: 1.05 – 1.58, P= 0.01). Conclusions: There appears to be no difference in colectomy rates in teaching or non-teaching hospitals, which results in comparable in-hospital mortality in Hispanics. However, ARF and post-operative adhesions were more in teaching hospitals. Continued efforts are required to provide better access to healthcare and address morbidity disparities while caring for minorities.[Table: see text]
Investigation of the DPYD, TYMS, ENOSF1, MTHFR, CDA, CES2, and UGT1A1 genes in patients who developed fatal fluoropyrimidine-associated toxicity in Northern Brazil.
Authors: Fernandes Marianne R. , Costa Danielle Feio da , Barra Williams Fernandes , Rodrigues Juliana Carla Gomes , Gonçalves Millene Arruda Bechara , Fontoura Raiza Martins , Moraes Francisco Cezar Aquino de , Pereira Esdras Edgar Batista , Burbano Rommel Mario Rodriguez , Assumpção Paulo Pimentel , Latorre-Pellice Ana , Amigo Olalla Maroñas , Guerrero Raquel Cruz , Santos Sidney Emanuel Batista dos , Álvarez Ángel María Carracedo , Santos Ney Pereira Carneiro dos 
Published: June 2022

e15532 Background: Fluoropyrimidine-based treatments are still considered challenging due to the wide variability in efficacy and toxicity rates presented by patients. This variability can be explained, partially, by individual genetic differences that contribute significantly to the response of the drug, with 30% of patients experiencing severe toxicity related to dihydropyrimidine dehydrogenase (DPD) deficiency and 5-Fluorouracil (5-FU) metabolism. Methods: This study analyzed the exome of the main genes involved in the fluoropyrimidine metabolism pathway ( DPYD, TYMS / ENOSF1, MTHFR, CDA, CES2, and UGT1A1) in seven patient who developed fatal 5-FU toxicity diagnosed with gastric or colorectal adenocarcinoma and underwent fluoropyrimidine-based cancer treatment. The genotyping service was carried out at CEGEN-PRB3-ISCIII; it is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. Results: A total of 74 genetic polymorphisms were identified, 25 of which stand out due to their potential role in the safety of 5-FU administration. Eight variants are exclusive of the studied population (two found in the DPYD gene, two in the MHFR, one in the CES2, and three in the UGT1A1 gene) and 17 have already been associated with fluoropyrimidine efficacy and/or toxicity events: 10 of them are located in the DPYD gene (rs1801159, rs2297595, rs72728438, rs17376848, rs1801160, rs1801265, rs22447512, rs5568, rs56038477, rs56276561, and rs56293913), two in the intergenic region of the TYMS/ ENOSF1 genes (rs11280056 and rs699517), two in the MTHFR gene (rs1801131 and rs1801133) and three in the CDA gene (rs1048977, rs2072671, and rs3215400). Conclusions: The current study has allowed us to obtain a global profile of genetic variants in the pharmacokinetic and pharmacodynamic pathways of fluoropyrimidines in patients with high genetic miscegenation in the northern region of Brazil who have evolved to death due to the fatal toxicity resulting from 5-FU-based therapies. Keywords: Pharmacogenomics; Exome; 5-Fluorouracil; Drug toxicity; Brazil.
Impact of metastasectomy for extrahepatic disease in stage IV colon cancer: A retrospective cohort NCDB analysis.
Authors: Fabregas Jesus C. , Sahin Ilyas , Rogers Sherise C. , Ramnaraign Brian Hemendra , Nassour Ibrahim , Hughes Steven J. , George Thomas J. 
Published: June 2022

e15548 Background: Stage IV colon cancer has a dismal prognosis with a 5-yr survival rate of only 14%. The role of liver metastasectomy is well established. However, it is not clear if there is a survival benefit for metastasectomy in cases of extrahepatic disease. Methods: We conducted a retrospective cohort study, US hospital-based. The NCDB version 2017 was accessed. Exposure variable: metastasectomy for extrahepatic distant disease, analyzed as binary. Outcome: overall survival. Kaplan Meier curves and log rank test were used for survival analysis. The primary endpoint was to estimate the association between metastasectomy and survival. Covariates demographic factors, age, sex, race, insurance status, site of metastatic disease – lung, liver, bone, brain. A Cox proportional hazards model was used to evaluate the impact of metastasectomy of extrahepatic disease in patients with stage IV colon cancer. 95% confidence intervals and p values of less than 0.05 were used for statistical significance. Missing data as handled with complete and available case analysis. Statistical analysis was done using Stata 16. Results: A total of 68,334 adult patients with stage IV colon cancer diagnosed in from 2010 -2016 were included in the final analysis. Median age was 64 years (SD 14.1). Prevalence of metastases in this stage IV population was as follows: Liver 72.12%, Lung 20.12%, Bone 5.06%, Brain: 1.6%. A total of 10,595 patients (15.5%) had metastasectomy. Median overall survival were as follows: Lung, 21.59 months with surgery vs 8.41 months no surgery. Bone, 7.03 mo vs 4.53 mo respectively; Brain 9.3 mo vs 3.15 mo; Liver 33.28 mo vs 10.97 mo. In univariate analysis, patients with lung metastases had an improved survival if they had metastasectomy (vs no surgery, HR 0.58, p < 0.0001, 95% CI 0.52 – 0.60). The same benefit was observed in patients with bone (HR 0.80, p 0.001, 95% CI 0.69 – 0.91) and brain metastases (HR 0.56, p < 0.001, 95%CI 0.49 – 0.65). In multivariable analysis the survival advantage was still significant. In a sensitivity analysis, excluding patients with liver metastases, the improvement in survival persisted. Conclusions: Metastasectomy for extrahepatic disease improved overall survival in patients with colon cancer in this retrospective analysis. Further research is needed before routinely incorporating it in clinical practice.[Table: see text]
Irinotecan combined with Panitumumab or cetuximab as third-line treatment for metastatic colorectal cancer.
Authors: Braghiroli Maria Ignez , Vicentini Maria Fernanda Batistuzzo , Fonseca Leonardo Gomes da , Souza Karla Teixeira , Bonadio Renata Colombo , Braghiroli Oddone Freitas Melro , Mathias Maria Cecília Machado , Talans Aley , Zambrano Mendoza Maria Elizabeth , Martins Juliana Goes , Sabagga Jorge , Moniz Camila Venchiarutti Motta Venchiarutti , Hoff Paulo Marcelo 
Published: June 2022

e15551 Background: Literature suggests that the addition of cetuximab can overcome the resistance to irinotecan treatment for metastatic colorectal cancer (mCRC). It is unknown if the combination of panitumumab with irinotecan could also revert treatment resistance and offer a better response rate after progression on irinotecan monotherapy. In this study, we aim to compare the impact of panitumumab plus irinotecan (P+I) or cetuximab plus irinotecan (C+I) on overall survival as a third line mCRC treatment. Methods: This is a single institution, retrospective cohort analysis, evaluating the overall survival of mCRC patients exposed to an anti-EGFR antibody plus irinotecan, upon progression on irinotecan monotherapy. Overall survival function was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: We identified 460 patients with mCRC that fulfilled inclusion criteria, treated between July 2008 and April 2018. One hundred eighty-three (183) patients received (I+C), and 277 received (I+P). Upon diagnosis, the median age was 55.9 years (range, 19 - 83 years), with a male to female ratio of 1.3:1. All patients received the combination of irinotecan and anti-EGFR targeting antibodies for at least one cycle (D1 and D15). Partial response occurred in 22.6% of patients [23.5% for (I+C) and 22.0% for (I+P)], and 25,2% had stable disease [27.8% for (I+C) and 23.6% for (I+P)]. Interestingly, response rate in patients with right-sided tumors was 3.3% in the (I+C) regimen and 14.3% in the (I+P) regimen. The disease control rate was 50.3% in the (I+C) combination and 45.7% in the (I+P) combination (p = 0.358). The median overall survival (mOS) for all patients was 9.63 months, 8.97 to the group C+I and 10.74 to P+I (p = 0.73). Regarding primary tumor location, the mOS was 6.34 mo for right-sided tumors and 10.74 mo for left-sided tumors (p = 0.022). The 3-year survival rate was 5.6% for the (C+I) treated patients and 3.2% for (P+I). Conclusions: (P+I) and (C+I) combinations showed similar response rate and mOS as a third-line treatment for mCRC, suggesting that both anti-EGFR agents can be used in this setting. A perceived tendency for a superior response with the (I+P) regimen in right-sided tumors might warrant further investigation in prospective studies.
Comprehensive landscape of tumor angiogenesis via integrating RNA sequencing and three-dimensional microphysiological system.
Authors: Ko Jihoon , Hyung Sujin , An Minae , Park Se Hoon , Kim Seung Tae , Kang WonKi , Jeon Noo Li , Lee Jeeyun 
Published: June 2022

e16058 Background: The prognosis of gastric cancer (GC) patients with peritoneal metastasis with malignant ascites is very poor. We developed an in vitro tumor angiogenesis platform “TumorAngioChip” to reproduce tumor angiogenesis in 45 gastric cancer patients and mapping their angiogenesis characteristics. This platform, which can predict the features of tumor angiogenesis and drug responsiveness in patient’s samples, opens up potential for a variety of combination therapies, including ramucirumab. Methods: We built a PDC library for the study based on samples of 45 GC patients receiving treatment at Samsung Medical Center. For all patient samples, whole exome and transcriptome sequencing was performed for subtype clustering. TumorAngioChip was fabricated by design prototyping through 3D printing and mass production through injection molding. Patient-derived tumor angiogenesis reconstructed on TumorAngioChip was analyzed using an algorithm for morphological image processing of 3D images obtained through confocal microscopy. Results: Of 45 GC patients, we investigated TumorAngioChip analysis and transcriptome sequencing to classify them as KDR-High (N = 24) and KDR-Low (N = 21) ( P = 4.481e-08, Wilcoxon signed-rank test). In the TumorAngioChip–patient mapping analysis, we clearly demonstrated that GC patients with high KDR level regardless to their GC TCGA subtype had high index of tumor-induced angiogenesis and cancer invasiveness measured by TumorAngioChip ( KDR-High vs. KDR-low group; mean sprouting length: 1.455 × 103 vs. 0.946 × 103, respectively, P < 0.0001; vessel density: 3.470 vs. 2.637, respectively, P < 0.0001; sprouts number: 219 vs. 111, respectively, P < 0.0001; vessel total length: 4.931 × 104 vs. 3.919 × 104, respectively, P = 0.0011). Conclusions: This study is the first attempt to elucidate cancer angiogenesis in large-scale GC patients via a microfluidic-based in vitro system. By integrating transcriptome sequencing and TumorAngioChip-based 3D morphological image processing, we demonstrated tumor angiogenesis mapping for GC patients and further revealed the benefits of ramucirumab in individual patients. The application of TumorAngioChip shows its potential as a novel preclinical drug screening platform to identify effective angiogenesis inhibitors reflecting TME for the first time.
Alofanib in subsequent therapy for advanced gastric cancer: Final results from the phase Ib clinical trial.
Authors: Tsimafeyeu Ilya , Vladimirova Liubov Yu , Mochalova Anastasia , Besova Natalia , Statsenko Galina , Rykov Ivan , Utyashev Igor A. , Raskin Grigory , Kazey Vasily , Artamonova Elena , Moiseyenko Vladimir , Tjulandin Sergei 
Published: June 2022

e16077 Background: Alofanib (RPT835) is a first-in-class allosteric inhibitor that induces conformational changes in the extracellular domain of FGFR2. Here, we present the final results of the phase Ib clinical study (RPT835GC1B) of alofanib. Methods: Patients with metastatic gastric adenocarcinoma resistant to standard therapy with measurable disease were eligible. The dose finding part used a 3+3 design, starting with a dose level of 50 mg/m2, intravenously, 5 days on, 2 days off. Five dose levels were foreseen. Primary endpoint was maximum tolerated dose (MTD). Secondary endpoints included toxicity, PK, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results: 21 patients were enrolled. 4 (19.1%), 14 (66.7%), 9 (43%), 3 (14.3%), and 12 (57%) patients had ECOG PS 2, ≥2 metastatic sites, liver metastases, bone metastases, and 3-6 lines previous therapy, respectively. The MTD has not been reached and dose of 350 mg/m2 has been declared as recommended phase II dose. With median follow-up of 13.0 months 15 (71.4%) patients had any grade treatment related adverse events (TRAE). Grade 3-4 TRAE occurred in 6 (28.6%) patients. Two (9.5%) patients discontinued treatment due to grade 3 diarrhea and grade 4 reactions immediately after injections. There were no treatment-related deaths in the study. One partial response (5.26%) with a duration of 18.53 months was identified. Disease control rate (DCR) was 68.4% and median duration of stable disease was 4.91 months. Median PFS was 3.63 (95% CI 1.58–5.68) months. Median OS was 7.0 (3.82–10.18) months. 6-month OS rate was 57.1%. OS was almost 2 times better in patients with DCR (median 10.05 vs. 5.9 months) and without bone metastases (8.6 vs. 3.1). Only one patient (4.8%) had FGFR2 amplification (time to death was 7 months). PK parameters linearly changed depending on the dose level, but no correlation with efficacy was found. Table summarizes rate of TRAE and DCR in dose cohorts. Conclusions: Alofanib was feasible and showed early signals of efficacy in heavily-pretreated patients with metastatic gastric cancer. A phase 2 randomized trial is planned. Clinical trial information: NCT04071184. [Table: see text]