bluuebunny/crossref_metadata_2025 huggingface dataset:
The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis
Authors: Li Huifang , Huang Haoyan , Chen Xiaoniao , Chen Shang , Yu Lu , Wang Chen , Liu Yue , Zhang Kaiyue , Wu Lingling , Han Zhong-Chao , Liu Na , Wu Jie , Li Zongjin
Published: January 2021

Background

Chemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear.

Methods

Doxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing.

Results

MSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis.

Conclusions

Hsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.
Screening of Potential Stress Biomarkers in Sweat Associated with Sports Training
Authors: Nunes Maria João , Cordas Cristina M. , Moura José J. G. , Noronha João Paulo , Branco Luís Cobra
Published: January 2021

Background

Intense and continuous physical training in sports is related with psychological and physiological stress, affecting the health and well-being of athletes. The development of non-invasive sampling methodologies is essential to consider sweat as a potential biological fluid for stress biomarker assessment. In the current work, the identification in sweat samples of potential molecules that may be used as stress biomarkers was pursued.

Methods

A sweat pool sample from football players after a 90-min intense training game was studied.

Results

An analysis method using liquid chromatography with detection by tandem mass spectrometry (LC-MSMS) to attain a screening profile of sweat composition is presented. The major focus was on neurotransmitters (e.g. monoamines and metabolites) and other biological molecules related with physical training, such as precursors of biogenic amines (phenylaniline, tyrosine, etc.).

Conclusions

This study allowed the identification of small biomolecules, neurotransmitters and other related molecules in sweat that are potentially associated with stress conditions. The developed methodology intends to contribute to the assessment and study of physical and psychological stress biomarkers related with intense sports using non-invasive methods.
Energy storage system design for large-scale solar PV in Malaysia: techno-economic analysis
Authors: Laajimi Mahmoud , Go Yun Ii
Published: January 2021

Large-scale solar is a non-reversible trend in the energy mix of Malaysia. Due to the mismatch between the peak of solar energy generation and the peak demand, energy storage projects are essential and crucial to optimize the use of this renewable resource. Although the technical and environmental benefits of such transition have been examined, the profitability of energy storage systems combined with large-scale solar PV has not been studied in Malaysia. This project aims to determine the most profitable business model of power systems, in terms of PV installed capacity, and energy storage capacity, and power system components. A comparative study has been done to compare the economic outcomes from different types of projects, with different scales and multiple configurations of large-scale solar PV combined with energy storage. The lowest values of LCOE are guaranteed with energy storage output to LSS output ratio, A = 5%. In this case, 30-MW projects have the cheapest electricity, equal to RM 0.2484/kWh. On the other hand, increasing the energy storage output to LSS output ratio, A to 60% results in the increase of LCOE, exceeding RM 0.47/kWh. On the economical side, with a difference of 0.06 kWh/m2/day for the analysis carried out in Pahang and Perak, the difference in net present worth is more than 7.5% of the net present cost. The difference between the two locations is comparatively higher for 50-MW projects. It is equal to RM 11.67 Million for A = 60%, while it is equal to RM 13.5 Million with A = 5%. Due to the energy prices in Malaysia, the projects that include large-scale solar only are more profitable technically and financially than those including large-scale solar and energy storage. It is found that adding storage to a large-scale solar project is more profitable technically and financially with greater large-scale solar capacities and smaller storage capacities. Nevertheless, with the current energy prices in Malaysia, projects that include only energy storage are not financially profitable. This study determined the parameters that affect the profitability of large-scale solar energy projects and energy storage projects, and the configurations that maximize financial profits. The findings of this study are useful for the future regulations that intend to enhance the deployment of large-scale solar PV and energy storage in Malaysia.
QTL mapping of agronomic and economic traits for four F2 populations of upland cotton
Authors: LI Hongge , PAN Zhaoe , HE Shoupu , JIA Yinhua , GENG Xiaoli , CHEN Baojun , WANG Liru , PANG Baoyin , DU Xiongming
Published: January 2021

Background

Upland cotton (Gossypium hirsutum) accounts for more than 90% of the annual world cotton output because of its high yield potential. However, yield and fiber quality traits often show negative correlations. We constructed four F2 populations of upland cotton, using two normal lines (4133B and SGK9708) with high yield potential but moderate fiber quality and two introgression lines (Suyuan04–3 and J02–247) with superior fiber quality, and used them to investigate the genetic basis underlying complex traits such as yield and fiber quality in upland cotton. We also phenotyped eight agronomic and economic traits and mapped quantitative trait loci (QTLs).

Results

Extensive phenotype variations and transgressive segregation were found across the segregation populations. We constructed four genetic maps of 585.97 centiMorgan (cM), 752.45 cM, 752.45 cM, and 1 163.66 cM, one for each of the four F2 populations. Fifty QTLs were identified across the four populations (7 for plant height, 27 for fiber quality and 16 for yield). The same QTLs were identified in different populations, including qBW4 and qBW2, which were linked to a common simple sequence repeat (SSR) marker, NAU1255. A QTL cluster containing eight QTLs for six different traits was characterized on linkage group 9 of the 4133B × Suyuan04–3 population.

Conclusions

These findings will provide insights into the genetic basis of simultaneous improvement of yield and fiber quality in upland cotton breeding.
Can microRNA become next-generation tools in molecular diagnostics and therapeutics? A systematic review
Authors: Saini Vandana , Dawar Rajni , Suneja Shilpa , Gangopadhyay Sukanya , Kaur Charanjeet
Published: January 2021

Background

MicroRNAs (miRNAs) represent a novel class of single-stranded RNA molecules of 18–22 nucleotides that serve as powerful tools in the regulation of gene expression. They are important regulatory molecules in several biological processes.

Main body

Alteration in the expression profiles of miRNAs have been found in several diseases. It is anticipated that miRNA expression profiling can become a novel diagnostic tool in the future.

Hence, this review evaluates the implications of miRNAs in various diseases and the recent advances in miRNA expression level detection and their target identification. A systematic approach to review existing literature available on databases such as Medline, PubMed, and EMBASE was conducted to have a better understanding of mechanisms mediating miRNA-dependent gene regulation and their role as diagnostic markers and therapeutic agents.

Conclusion

A clear understanding of the complex multilevel regulation of miRNA expression is a prerequisite to explicate the origin of a wide variety of diseases. It is understandable that miRNAs offer potential targets both in diagnostics and therapeutics of a multitude of diseases. The inclusion of specific miRNA expression profiles as biomarkers may lead to crucial advancements in facilitating disease diagnosis and classification, monitoring its prognosis, and treatment. However, standardization of methods has a pivotal role in the success of extensive use of miRNA expression profiling in routine clinical settings.
Sigmoid carcinoma with sigmoid-rectal intussusception presenting as rectal prolapse and large bowel obstruction in the ED
Authors: Mazumdar Pallabi , Kumar Pawan , Katiyar Glory , Mulla Muniza , Sardessai Sanjay
Published: January 2021

Background

Intestinal obstruction is a surgical emergency with most cases being small bowel obstruction. Large bowel obstruction is comparatively uncommon and colonic malignancies are a usual cause. Such lesions cause intestinal obstruction by luminal narrowing or rarely serve as lead point of intussusception.

Case presentation

Herein, we describe an unusual case of sigmoid carcinoma causing sigmoid-rectal intussusception, rectal prolapse, and eventually large bowel obstruction.

Conclusion

Pre-operative CT should be done in all adult large bowel obstruction to look for possible site and cause of obstruction and to rule out malignancy as a cause of obstruction. Conversely, every case of rectal prolapse should be diligently evaluated to rule out intussusception, which if present in an adult indicates a high likelihood of underlying malignancy.
COVID-19 pneumonia: a pictorial review of CT findings and differential diagnosis
Authors: Shirani Fattane , Shayganfar Azin , Hajiahmadi Somayeh
Published: January 2021

Background

The gold standard for verifying COVID-19 mostly depends on microbiological tests like real-time polymerase chain reaction (RT-PCR). However, the availability of RT-PCR kits can be known as a problem and false negative results may be encountered. Although CT scan is not a screening tool for the diagnosis of COVID-19 pneumonia, given the widespread acquisition of it in the pandemic state, familiarity with different CT findings and possible differential diagnosis is essential in this regard.

Main text

In this review, we introduced the typical and atypical CT features of COVID-19 pneumonia, and discussed the main differential diagnosis of COVID-19 pneumonia.

Conclusions

The imaging findings in this viral pneumonia showed a broad spectrum, and there are no pathognomonic imaging findings for COVID-19 pneumonia. Although CT scan is not a diagnostic and screening tool, familiarity with different imaging findings and their differential diagnosis can be helpful in a rapid and accurate decision-making.
Infection biology as the basis of integrated control of apple canker (Neonectria ditissima) in Northern Europe
Authors: Weber Roland W. S. , Børve Jorunn
Published: January 2021

Background

European canker, caused by Neonectria ditissima, is a disease of worldwide importance in apple production, yet knowledge about it is limited, highly regional and sometimes contradictory. This is an obstacle to successful disease management. Key aspects for Northern Europe are reviewed, based on research results from Northern Germany and Norway and on international literature data.

Main topics

Trunk cankers developing on young trees within the first 1–3 seasons of explanting can often be traced back to latent infections initiated in the nurseries. The most important nursery infection is a lateral canker on the main trunk of ‘knip’ trees, which are the standard tree type in Northern Europe. In strongly affected batches, up to 25% of trees have to be uprooted after the first growing season due to such trunk cankers. The establishment and maintenance of healthy orchards requires clean nursery material, especially in the case of susceptible cultivars. In Northern Germany, infections within commercial orchards most often proceed through wounds caused by fruit picking or leaf fall in autumn, as shown by the appearance of cankers in the following spring and by the high efficacy of fungicide treatments at leaf fall. Ascospores, commonly thought to be relevant for long-distance spread of infections, are not released until the end of leaf fall even in wet autumn seasons in Northern Germany. Therefore, their role in the disease remains unclear. Strong nitrogen-induced vegetative growth favours apple canker. In field trials conducted under conditions of current commercial practices, autumnal sprays with copper hydroxide or copper oxide were consistently more efficacious than copper oxychloride or captan in preventing new infections.

Conclusions

Restricted fertilisation and other measures to curb excessive vegetative growth during the first few years of an orchard, repeated canker pruning and well-timed treatments with effective fungicides in autumn are essential for IPM of apple canker. Nonetheless, canker remains capable of severely impairing the commercial success of susceptible cultivars in regions with wet climates even if all available measures are taken. This opens up long-term perspectives for the breeding of more resistant cultivars.
Population-based analysis of National Comprehensive Cancer Network (NCCN) guideline adherence for patients with anal squamous cell carcinoma in California.
Authors: Kumar Priyanka , Del Rosario Michael , Chang Jenny , Ziogas Argyrios , Jafari Mehraneh D. , Bristow Robert E. , Tanjasiri Sora Park , Zell Jason A.
Published: January 2021

1

Background: Oncology-specific evidence-based treatment guidelines aim to improve cancer care. Our study analyzed adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for anal squamous cell carcinoma in California and the associated impacts on survival. Methods: Patients aged 18 to 79 years diagnosed with anal squamous cell carcinoma (SCC) between January 1, 2004 and December 31, 2017 with follow-up through November 30, 2018 were identified in the California Cancer Registry. Patient demographics, socioeconomic status (SES) and tumor stage were identified. We determined whether patients received NCCN guideline-adherent care (AdC) by pre-defined criteria. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for receiving AdC. Overall survival (OS) and disease specific-survival (DSS) were calculated using Cox regression models. Results: Of 4,740 patients with a diagnosis of anal SCC in California, 926 (19.5%) did not receive AdC (non-AdC). Non-AdC had worse DSS (HR 1.96, 95% CI = 1.56, 2.46, p < 0.0001) and worse OS (HR 1.87, 95% CI = 1.66, 2.12, p < 0.0001). Females were more likely to receive AdC (OR 1.38, 95% CI = 1.18, 1.62, p < 0.0001). Medicaid patients were less likely to receive AdC (OR 0.75, 95% CI = 0.57, 1.00, p = 0.0476). Patients with the lowest SES were less likely to receive AdC (OR 0.65, 95% CI = 0.50, 0.83, p = 0.0007). Characteristics associated with DSS and OS included female gender, black race, Medicare/Medicaid, and SES (particularly, lower-middle SES). Conclusions: NCCN guideline-adherent care was associated with improved disease-specific and overall survival in anal SCC patients in California.
Genomic profiling of gastrointestinal cancers by comprehensive tumor-normal sequencing.
Authors: Alyaqoub Fadel S. , Noel Pawan , Szelinger Szabolcs , Natarajan Thanemozhi G. , Dombrowski Susan M. , Ozols Audrey A. , Goodman Laurie Jane , LoBello Janine , Royce Thomas , Basu Gargi D.
Published: January 2021

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Background: Gastrointestinal cancers (GIC) account for 26% of global cancer incidence and 35% of cancer-related deaths. We investigated the molecular landscape and therapeutic targets across 18 types of GIC using whole exome (WES) and whole transcriptome sequencing (WTS). Methods: GEM ExTra assay was performed on 603 paired samples (ages 18-90 years, median = 61 years). Targeted sequence coverage was 180X for germline DNA and 400X for tumor DNA. Reportable somatic alterations included single base substitutions, indels, Copy Number Alterations, gene fusions, alternate transcripts, as well as tumor mutational burden (TMB) and microsatellite instability (MSI) status. Germline subtraction identified somatic-specific alterations. Results: Analysis of 603 GIC patient samples, including esophageal, gastric cancer (GC), biliary tract (BT), pancreatic cancer (PC), colorectal cancer (CRC), and other cancers, identified 434 actionable targets. The median number of alterations was 3 per GIC patient. The 5 most common actionable alterations were in APC, KRAS, CDKN2A, ARID1A and PIK3CA. Activation of Wnt signaling was found in 264/603 (44%), with the majority being in CRC cases. Alterations in cell cycle genes including CDKN2A, CDK4/6 and others were noted in 129/603 (21%) cases, with the majority in PC, suggesting benefit from CDK4/6 inhibitors. Activation of PI3K/PTEN/Akt/mTOR pathway was noted in 105/603 (17%), with the majority harbored in CRC, suggesting benefit from targeting this pathway. ERBB2 amplification and mutations were noted in 22/603 (4%) across different GIC tumor types. Alterations in homologous recombination genes predicting platinum and PARP inhibitor response was noted in 181/603 (30%) samples distributed across GIC subtypes. KRAS (G12C) mutation was found in 7% of all KRAS mutations across GIC subtypes, thus allowing patients to enroll in clinical trials with G12C-specific inhibitors. The majority of cases with MSI- and TMB-high status were identified in GC and CRC tumors and may be predictive of response to immunotherapy. WTS identified actionable fusions, including FGFR1/2/3 and novel NRG1 fusions in BT cancers. Conclusions: Our study revealed actionable targets used in patient selection for precision therapies, in addition to other mutational profiles of clinical significance. Overall, comprehensive genomic profiling enabled detection of established and novel actionable alterations, including fusions, which may have gone undetected using hotspot panels.
Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients.
Authors: Henriksen Tenna V , Tarazona Noelia , Reinert Thomas , Carbonell-Asins Juan Antonio , Renner Derrick , Sharma Shruti , Roda Desamparados , Huerta Marisol , Roselló Susana , Iversen Lene H. , Gotschalck Kåre Andersson , Madsen Anders Husted , Andersen Per Vadgaard , Thorlacius-Ussing Ole , Løve Uffe S. , Sethi Himanshu , Aleshin Alexey , Cervantes Andres , Andersen Claus Lindbjerg
Published: January 2021

11

Background: Timely detection of recurrence, as well as identification of patients at high risk of recurrence after surgery and after completion of adjuvant therapy, are major challenges in the treatment of colorectal cancer (CRC). Postsurgical circulating tumor DNA (ctDNA) analysis is a promising tool for the identification of patients with minimal residual disease (MRD) and a high risk of recurrence. The objective of this prospective, multicenter study was to determine whether serial postsurgical ctDNA analysis could identify the patients at high risk of recurrence, provide an assessment of adjuvant therapy efficacy and detect relapse earlier than standard-of-care radiological imaging. Methods: The cohort comprises 265 stage I-III CRC patients, the to-date largest cohort assessed for ctDNA. All patients had the tumor resected and a subset of 62.6% (166 /265) was additionally treated with ACT. Plasma samples (n = 1503) were collected at various time points for a median follow-up of 28.4 months (range: 1.2-51.0 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic single nucleotide variants (SNVs) were identified. Personalized multiplex PCR assays were designed to track tumor-specific SNVs (Signatera, bespoke mPCR NGS assay) in each patient’s plasma sample. Results: Postoperative ctDNA status prior to ACT was assessed in 218 patients, of which 9.17% (20/218) were identified to be MRD-positive and 75% (15/20) eventually relapsed. The remaining 25% (5/20) of MRD-positive patients that did not relapse, received ACT. In contrast, only 13.6% (27/198) of MRD-negative cases relapsed (HR: 11: 95% CI: 5.7-20; p < 0.001). Longitudinal ctDNA-positive status, post-definitive therapy (n = 202) was associated with a HR of 36 (95% CI: 16-81; p < 0.001). For a subset of 155 patients postoperative CEA and ctDNA measurements were compared, wherein, ctDNA-positive status was found to be significantly associated with RFS (HR, 7.1; 95% CI, 3.4-15; P < 0.001) compared to CEA (HR, 1.2; 95% CI, 0.46-3.1; P = 0.73). Serial ctDNA analysis detected MRD up to a median of 8 months (0.56 - 21.6 months) ahead of radiologic relapse. Conclusion: Postoperative ctDNA positive status was associated with markedly reduced RFS compared to CEA. The study also shows that effective therapy can be curative in a portion of MRD-positive patients. In a longitudinal setting, ctDNA analysis predicted the risk of recurrence and is a more reliable biomarker for treatment response monitoring.
Relationship of HER2 alteration and MSI status in colorectal adenocarcinoma.
Authors: Qiu Miao-zhen , He Cai-Yun , Xu Rui-hua
Published: January 2021

121

Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with MSI-H is an open question. Methods: From February 2017 to February 2020, CRC patients who received tumor specimens next-generation sequencing and detail record of clinic-pathologic information were enrolled. HER2 alteration and its relationship with MSI-H were analyzed. Results: There were totally 55 patients (7.5%) with HER2 alteration including 29 (4.0%) HER2 somatic mutations, 24 (3.3%) HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. For HER2 mutated cases, 48.3% were MSI-H, while none of HER2 amplification cases were MSI-H. MSI-H was found in 5.2% in our cohort and 36.8% MSI-H patients were HER2 mutated. MSI-H had less frequency of lung metastasis. The mPFS for first line chemotherapy was significantly higher in MSS cases than in MSI-H cases, 11.5 months vs 3.5 months, P = 0.032. MSI-H patients with HER2 mutation had significantly worse mPFS for PD-1 antibody than those without HER2 alteration, P = 0.036. Conclusions: High MSI-H rate is found in HER2 mutated cases but no MSI-H in HER2 amplification cases. MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without.
Impact of adjuvant chemotherapy and patient age on patterns of metastatic recurrence in stage III colorectal cancer.
Authors: Gard Grace , To Yat Hang , Gately Lucy , Croxford Matthew , Jones Ian , Faragher Ian , Steel Malcolm , Hong Wei , Wong Rachel , Lee Margaret , Tie Jeanne , Kosmider Suzanne , Wong Vanessa , Ananda Sumitra , Jalali Azim , Gibbs Peter
Published: January 2021

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Background: The patterns of metastatic relapse for Stage III colorectal cancer (CRC) are known to be influenced by the primary site and mutation status. Whether the use of adjuvant therapy also influences recurrence patterns, due to a variable chemotherapy impact by metastatic site, has yet to be explored. Patient age 70 years has consistently been associated with a lack of benefit from the addition of oxaliplatin to a fluoropyrimidine (FP) chemotherapy. Methods: Data from a multi-site CRC database that prospectively captures, patient, tumour, treatment and outcome data was examined. Patients with de novo metastatic or multiple primary tumours were excluded. Patterns of recurrence were analysed by receipt of surgery and adjuvant chemotherapy (S + AC) or surgery alone (S alone) and by age 70 years and <70 years old. Results: Of 701 patients with stage III colon cancer 397 were male, median age was 68 years (range 33-83) and 574 (81%) were ECOG 0-1. S + AC was administered in 555 (79%), including 228 treated with a FP alone and 324 treated with an oxaliplatin doublet. Metastatic relapse was delayed in S + AC patients, occurring at a median of 17.81 vs 9.43 months (p< 001). Liver metastases were the most common site of relapse overall (40%) and numerically less common in the S + AC group (38% vs 46%, p = 0.06). Brain metastases were less common in S + AC patients (1% vs 3.5%, p = 0.04). When analysed by primary tumour side the only significant finding was that for patients with a right-side primary (n= 208, 76% had S + AC), S+ AC was associated with a lower rate of lung metastases (28% vs 41% p = 0.046). 318 of the 701 (45%) of this relapsed cohort were 70 years old, 220 (69%) of these patients had S + AC. In both the older and younger cohort metastatic relapse was delayed with S + AC (18.7 vs 11.3 months, p < 0.001, 17.08 vs. 6.01 months, p < 0.001) and liver metastases were the most common site of relapse (41% vs 38%, p=0.56). Similar rates of lung metastases (40% vs 34%, p=0.1), peritoneal disease (20% vs 22%, p=0.57) and brain metastases (2.2% vs 0.8%, p=0.13) were seen in the 70 years old and <70 years old patients, with no evident interaction between chemotherapy use and age with respect to recurrence sites. Conclusions: S + AC for stage III colon cancer in this community series delayed time to recurrence and resulted in numerically lower recurrence rates at all disease sites. Brain metastases although uncommon were less frequent in S + AC patients. Patients with a right sided primary had a lower incidence of lung metastases following S + AC patient cohort. There was no significant impact of age on recurrence patterns.
Global BRAF testing practices in metastatic colorectal cancer.
Authors: Kopetz Scott , Grothey Axel , Ciardiello Fortunato , Desai Jayesh , Kim Tae Won , Maughan Tim , Van Cutsem Eric , Wasan Harpreet Singh , Yaeger Rona , Yoshino Takayuki , Gollerkeri Ashwin , Edwards Michelle , Rodriguez Lizaso Montessa , Tabernero Josep
Published: January 2021

128

Background:The BRAF V600E mutation is a marker of poor prognosis in patients with metastatic colorectal cancer (mCRC). Targeted therapy, such as encorafenib plus cetuximab, is approved in the US/Europe for the treatment (tx) of BRAF V600E-mutated mCRC and demonstrated improved survival vs historical standard of care (SOC). Determining BRAF mutation status in mCRC is recommended by NCCN and ESMO guidelines although adherence to guidelines may not be uniform. This report’s objective is to communicate global survey results of mCRC BRAF testing practices. Identifying regions where BRAF testing is not SOC may help identify where education efforts are needed improve effective tx decision making. Methods: Oncology tx centers were identified from a registry and public information. Centers were selected for research experience, historic data quality, and estimated mCRC patients. A BRAF testing practices survey using an online platform of verified centers was conducted March-August 2020; 395 centers/38 countries have responded thus far. Results: Respondents indicated BRAF-mutation testing is performed as SOC for patients with mCRC in most regions; Eastern Europe and South America are exceptions: only 47% (45/95) and 45% (9/20) of centers, respectively routinely performed mutation testing. Most test tumor tissue, few test both tumor tissue or blood, and none conduct blood mutation testing only. Most regions perform BRAF testing at initial diagnosis or confirmation of advanced disease. Individual country statistics will be presented. Conclusions: BRAF testing has global variability, impacting tx decisions. Increased awareness and routine testing may lead to informed decisions regarding targeted therapies, such as encorafenib plus cetuximab where approved, in patients with BRAF V600E-mutant mCRC.

[Table: see text]
Targetable mutations in gastrointestinal malignancies: A comparison of RAS mutant and RAS wild type tumors.
Authors: Randall Jamie , Wang Hongkun , Elkin Sheryl Krevsky , Payne Gail , Mullaly Sarah , Marchlik Erica , Barnett Dan , Rayes Danny , Wadlow Raymond , Tishman Lindsey , Cannon Timothy Lewis
Published: January 2021

129

Background: KRAS and NRAS (RAS) mutations are considered driver mutations in gastrointestinal malignancies such as colorectal and pancreatic cancer. Our institution obtains broad molecular testing (commercial panels with full exon coverage of at least 300 genes) for all stage IV gastrointestinal malignancies that are reviewed at an internal molecular tumor board (MTB). The MTB subjectively felt there was less benefit from comprehensive molecular testing in RAS mutant tumors and wished to quantify this using standardized analysis according to validated guidelines. Methods: We performed a retrospective cohort study of 209 consecutive genomic sequencing results of advanced gastrointestinal malignancies at our institution dating from March 2016 until December 2019. We compared the number of “targetable” mutations in the RAS mutant and wild type (WT) malignancies, as analyzed by an interpretation service according to the Association of Molecular Pathology (AMP) guidelines. A lower AMP score corresponds to a higher level of evidence as a predictive biomarker. We also compared molecular tumor board specific recommendations for each group (excluding recommendations regarding RAS such as EGFR mAbs). Results: There were 134 RAS mutant and 75 RAS WT cases. Alterations with AMP scores of 1A,1B, and 1C were more commonly seen in the RAS WT population 18/75 and 9/134 respectively (24.0% versus 6.7% p-value=0.0004). 39 of 75 cases in RAS WT and 27/134 in RAS mutant (52.0 versus 20.1%, p-value <0.0001) cohort had at least one alteration that was deemed actionable by our institution’s current MTB criteria. Conclusions: Actionable mutations were significantly less common in the RAS mutant versus RAS WT population, and further studies assessing the value of comprehensive genomic testing in RAS mutant gastrointestinal malignancies may be warranted. [Table: see text]
Trends in hospitalizations among patients with colorectal cancer: Results from the National Inpatient Sample (2007 through 2017).
Authors: Grewal Udhayvir Singh , Patel Harsh , Gaddam Shiva Jashwanth , Sheth Aakash R , Patel Kirtenkumar , Mills Glenn Morris
Published: January 2021

135

Background: Colorectal cancer is the second leading cause of cancer-related deaths in the United States with a rising incidence, especially in young adults. Care for patients with colorectal cancer is associated with significant health care costs and expenditures. We analyzed trends in admissions and outcomes related to hospitalizations in patients with colorectal cancer. Methods: We retrospectively interrogated the National Inpatient Sample for admissions in patients with colorectal cancer from 2007 – 2017. Records were stratified based upon the anatomical site and were analyzed for various inpatient outcomes. SAS version 9.4 (SAS Institute Inc.) was used for statistical analysis. Results: A total of 1,962,705 admissions were identified. About 50.2% patients were males, 64.4% were white and median age was 67.7 (53.8-81.6). Majority (47.8%) of the admissions that were coded for anatomical location of malignancy were for ascending colon cancer. 60.7% of the admissions were non-elective and Medicare was the primary payer for 58.6% of admissions. Most patients admitted for colon cancer belonged to the lower income quartile (28.3%) and were concentrated in large (58.9%), urban teaching hospitals (53.4%) in Southern US (38.8%). Hypertension (53.6%) and diabetes mellitus (18.6%) were the most common co-morbidities (p < 0.0001). Average in-hospital mortality was 4.9% and was lower in patients with ascending colon cancer (2.9, p < 0.001). Median length of stay was 5 days, but was higher in patients with transverse colon cancer (9 days, p < 0.0001). Median cost of hospitalization was found to be $12,295 and was significantly higher for patients with descending colon malignancy ($16,369, p < 0.0001). The number of annual hospitalizations stayed steady overall; the number of annual hospitalizations increased by 98.6% for rectosigmoid cancer. Conclusions: Despite highest number of hospitalizations, patients with ascending colon cancer had lowest in-hospital mortality. Cost of hospitalization and median length of stay were highest for patients with descending colon and transverse colon respectively. Number of annual hospitalizations has significantly increased for rectosigmoid cancer. Our findings may help inform physicians and healthcare administrators to devise appropriate strategies to efficiently channelize healthcare resources in order to decrease the overall economic burden associated with hospitalizations in patients with colorectal cancer.
A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.
Authors: Patel Deven , DiPeri Timothy , Cox Brian , Hendifar Andrew Eugene , Osipov Arsen , Cho May Thet , Fakih Marwan , Gong Jun , Gangi Alexandra
Published: January 2021

139

Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p< 0.001) and predominantly female (65% vs. 35%, p< 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p< 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p < 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.
Real-world outcomes of esophagectomy versus chemoradiotherapy for clinical stage I esophageal squamous cell carcinoma.
Authors: Yukami Hiroki , Sawada Kentaro , Fujiwara Hisashi , Mishima Saori , Kotani Daisuke , Kadota Tomohiro , Inaba Atsushi , Nishihara Keiichiro , Sato Daiki , Nakajo Keiichiro , Yoda Yusuke , Nakamura Masaki , Hojo Hidehiro , Yano Tomonori , Fujita Takeo , Kojima Takashi
Published: January 2021

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Background: Recently, JCOG0502 trial have shown a comparable efficacy with chemoradiotherapy (CRT) and esophagectomy as standard treatment in patients with clinical stage (cStage) I esophageal squamous cell carcinoma (ESCC), showing the standard treatment option of CRT. However, there is few reports for comparison of clinical outcomes with these treatments in real-world. The aim of this study was to clarify the real-world outcomes in cStage I ESCC who performed with CRT or esophagectomy. Methods: This retrospective study included patients with clinical stage I ESCC who received thoracoscopic or open esophagectomy with three-field lymph node dissection or CRT mainly consisted of 5-fluorouracil and platinum with concurrent radiotherapy (50.4 Gy/28Fr or 60 Gy/30Fr) between 2009 and 2017 at National Cancer Center Hospital East. Survival outcomes were calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: Among a total of 156 patients, 128 were male and median age was 68 years old. 120 and 36 patients underwent esophagectomy and CRT, respectively. ECOG performance status 0/1/2 were 138/12/6 patients. Tumor location was Ut/Mt/Lt in 16/87/53 patients. Clinical tumor depth (MM-SM1/SM2-SM3) were 33/123 patients. Patients’ characteristics were similar among treatment groups, except clinical tumor depth (SM2-3; 84.2% in esophagectomy group vs. 61.1% in CRT group, p = 0.005). All patients underwent radical surgery in esophagectomy group, while three patients (8.3%) in CRT group were received additional esophagectomy or endoscopic resection due to residual disease. With a median follow-up of 72 months, 5-year overall survival (OS) and progression-free survival rate were 81.5%/77.0% in esophagectomy group and 82.6/74.4% in CRT group (p = 0.89 and p = 0.48). In safety profile, grade 3 or higher stenosis was observed in 21.7% of esophagectomy group. There was no treatment-related death in both groups. In subgroup analysis for OS, elderly patients (75 years and older) tended to have better 5-year OS rate in CRT group (76.9% in esophagectomy group vs. 81.8% in CRT group), while younger patients ( < 75 years) showed comparable 5-year OS rate in both groups (82.4% in esophagectomy group vs. 82.9% in CRT group). Conclusions: Real-world data reproduced the results of clinical trial, supporting CRT as one of the standard treatment options in patients with cStage I ESCC.
Retrospective study of nivolumab monotherapy for advanced esophageal squamous cell carcinoma.
Authors: Mikuni Hayato , Yamamoto Shun , Oshima Kotoe , Hirano Hidekazu , Okita Natsuko , Shoji Hirokazu , Honma Yoshitaka , Iwasa Satoru , Takashima Atsuo , Boku Narikazu , Kato Ken
Published: January 2021

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Background: Based on the results of the ATTRACTION-1 and ATTRACTION-3 trials, nivolumab monotherapy has used for the treatment of metastatic or recurrence esophageal cancer patients who were refractory or intolerant to fluoropyrimidine and platinum since February 2020 in Japan. However, the ATTRACTION-1 trial mainly included patients who received nivolumab monotherapy as third or later-line treatments, which was different from the ATTRACTION-3 trial which mainly included patients as second-line treatment. Therefore, it is still unclear whether the treatment lines affect the efficacy of nivolumab in clinical practice. Methods: Medical records were retrospectively reviewed for patients diagnosed with metastatic or recurrence esophageal squamous cell carcinoma (ESCC) who received nivolumab monotherapy as second- or third or later-line treatments in our hospital. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) based on the RECIST ver1.1, and the incidences of adverse events (AEs) based on the CTCAE ver5.0. Results: Sixty-two patients were identified as the subject of this study. Thirty patients received nivolumab as second-line treatment (48.4%) and 32 patients as third or later-line treatments (51.6%). The median age (range) were 67 (33-80)/61 (52-84), PS 0 were 40.0/21.9%, prior taxane treatment rate were 6.7/93.8%, respectively. The ORR/DCR were 22.7/45.5% in second-line treatment, and 24.1/44.8% in third or later-line treatments (p=1.00). The median PFS (95% CI) was 2.3 (1.4-6.2)/2.3 (1.2-3.6) months in the second-/third or later-line treatments (HR=0.86, p=0.58). AEs of grade 3 or higher were observed in 6.7/6.3% of the second-/third or later-line treatments. Conclusions: There was no clear difference between second -line and third or later-line treatments in the short-term efficacy of nivolumab monotherapy in advanced ESCC patients.
Racial disparity in KRAS mutation frequency and outcomes in colorectal cancer (CRC): A U.S. population based study.
Authors: Bien Jeffrey , Aljehani Mayada , Lee Jerry S.H. , Lin Albert Y.
Published: January 2021

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Background: Racial disparity in CRC survival outcome is well documented. Although the reasons for disparity are unclear, a combination of differences in access to care, quality of care, differential treatment response, and underlying cancer biology are implicated. Further, recent studies have observed differences in KRAS mutation frequency between race/ethnic groups. KRAS mutation in metastatic CRC portends a worse response to EGFR-directed therapy, and predicts a poorer prognosis. In this study, we examined whether racial/ethnic differences in KRAS mutation frequency might impact CRC outcomes on a population-based level. Methods: We examined data from 202,237 CRC patients in the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The differences in tumor mutation status by stage and race/ethnicity were examined by χ2 testing. Cause-specific survival (CSS) and overall survival by mutation status were plotted by Kaplan-Meir curves. A multivariable Cox-proportional hazards model was used to construct hazard ratios and 95% confidence intervals (CI) using patient demographics, tumor characteristics, and KRAS mutation status. Results: Overall, about 9% of patients (n = 18,248) in the SEER registry had KRAS status available. In this cohort, tumors from Non-Hispanic Black (NHB) (48%) or Hispanic patients (44%) carried a greater KRAS mutation (mKRAS) rate when compared against Non-Hispanic White (NHW) (39%) or Asian or Pacific Islander (API) patients (37%) (p < 0.01). The assessment of the impact of mKRAS within each race/ethnic group, comparing patients with mKRAS versus wild-type KRAS (wKRAS) on CSS risk show a 7% risk increase for NHW, (HR = 1.07; 95%CI:1.02-1.12), a 15% risk increase for NHB, (HR = 1.15; 95%CI:1.04-1.26) and no significant increase among API, (HR = 1.02; 95%CI:0.92-1.4). Among patients with wKRAS, with NHW for reference, the risk of CSS is 11% higher among NHB (HR = 1.11; 95%CI:1.00-1.23), 14% higher for Hispanic, (HR = 1.14; 95%CI:1.02-1.26) and no significant difference observed among API, (HR = 1.03; 95%CI:0.91-1.16). Evaluation of the interaction between race/ethnicity and KRAS status on the CSS risk shows an increase of: 11% for mKRAS NHW, (HR = 1.11; 95%CI:1.00-1.23), 13% risk for NHB (HR = 1.13; 95%CI:1.01-1.25), 11% for Hispanic wKRAS, (HR = 1.11; 95%CI:1.04-1.18), 31% for Hispanic mKRAS (HR = 1.31; 95%CI:1.18-1.145), 16% for wKRAS API (HR = 1.16; 95%CI:1.03-1.29). In contrast, no significant difference in risk is seen for NHB nor API patients, HR = 1.02 (95%CI:0.90-1.14) and 1.04 (95%CI:0.91-1.20) respectively. Conclusions: mKRAS, compared to wKRAS, connotes worse CSS among NHW and NHB patients. Among wKRAS, NHB and Hispanic patients still experience higher mortality risk. This data suggests the negative prognosis heretofore associated with mKRAS may be linked to race/ethnicity and worthy of further study.
Treatment patterns, healthcare resource use, economic, and survival outcomes associated with nonresectable advanced esophageal cancers in Taiwan.
Authors: Tsai Yiling , Chang Chee Jen , Navaratnam Prakash , Friedman Howard Steven , Xiao Hong , Gricar Joseph
Published: January 2021

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Background: In Taiwan, limited real-world data indicate that initial EC diagnosis tends to occur at an advanced stage with limited therapeutic options and poor prognosis. Methods: This was a retrospective ‘real world’ observational study using the Taiwan National Health Insurance Research Database (NHIRD). Patients having at least one hospital record with a primary ICD-9 or ICD-10 code of EC were selected from Jan 1st, 2013 through Dec 31st, 2018. The first date of EC diagnosis was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified by staging, clinical presentation (i.e. resectable vs. non-resectable advanced) and tumor histotype (squamous cell carcinoma, adenocarcinoma, unknown). Key characteristics such as demographics, clinical parameters, medication utilization, health care resource utilization, costs incurred, and survival were tracked for the overall population, resectable and non-resectable, advanced cohorts. Results: Patients identified with non-resectable advanced EC (N = 4,340) had a mean (SD) age of 59.7 (12.3) years and the vast majority were male (n = 4,044, 93.2%). Approximately half (50.4%) had Stage 3 disease and an additional 36.2% with stage 4, with the remainder Stage 1, 2 or Unknown. The majority (91.8%) were diagnosed with squamous cell carcinoma. 71.3% of patients received first line (1L) chemotherapy, most commonly with fluorouracil + cisplatin (69.9% of 1L) or platinum monotherapy (13.8% of 1L). 36.3% of patients survived one year with mean (SD) annualized post-index EC-related costs of New Taiwan (NT) $791,827.4 (NT$ 582,663.8). Conclusions: In Taiwan, the most common 1L chemotherapeutic treatment modality for Taiwanese patients with EC were fluorouracil + cisplatin. The EC-related costs for these patients appear to be a substantial financial burden in Taiwan.