bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of gene expression of CDC37 in colorectal cancer (CRC).
Authors: Arai Hiroyuki , Baca Yasmine , Battaglin Francesca , Algaze Sandy , Jayachandran Priya , Soni Shivani , Wu Zhang , Lo Jae Ho , Sohal Davendra P.S. , Goldberg Richard M. , Hall Michael J. , Scott Aaron James , Hwang Jimmy J. , Lou Emil , Weinberg Benjamin Adam , Marshall John , Goel Sanjay , Xiu Joanne , Lenz Heinz-Josef 
Published: January 2023

237 Background: CDC37-HSP90 axis is an essential chaperoning system for stabilization of kinases. CDC37 determines selectivity of client kinases recognized by HSP90. We previously showed patients with CDC37-dependent ( CDC37 high expression) colorectal cancer (CRC) derived more benefit from regorafenib and bevacizumab both of which target HSP90 client kinases or signaling pathway, but not from cetuximab which targets HSP90 non-client kinase. However, molecular characteristics and interaction with relevant signaling pathways in CDC37-dependent CRC are largely unknown. Methods: We retrospectively reviewed CRC patient samples submitted to a commercial CLIA-certified laboratory (Caris Life Sciences, Phoenix AZ). Next-generation sequencing of DNA and RNA (whole-transcriptome sequencing) and immunohistochemistry were performed. Molecular profiles between top quartile transcripts per million for CDC37 expression (Q4, CDC37-high: n = 5056) and bottom quartile (Q1, CDC37-low: n = 5056) were compared for gene mutations, microsatellite instability (MSI) status, PD-L1 expression, co-expression of HSP90 genes ( HSP90AA1 and HSP90AB1), MAPK pathway activity score (MPAS), T-cell inflamed signature, and cell infiltration in the tumor microenvironment (TME) assessed by QuantiSEQ. Gene set enrichment analysis (GSEA) was performed between CDC37-high (Q4) and CDC37-low (Q1) tumors. Results: KRAS mutations trended higher in CDC37-high tumors compared to CDC37-low tumors (49.5% vs 47.1%) while APC (76.9% vs 72.3%), TP53 (75.5% vs 71.8%) and TCF7L2 (5.0% vs 3.5%) mutations were significantly higher in CDC37-high tumors compared to CDC37-low tumors (q < 0.05). No significance in expression quartiles were observed for dMMR/MSI-H or PD-L1 expression. HSP90AA1 and HSP90AB1 expression levels were significantly higher in CDC37-high tumors (2.9-fold and 2.6-fold in median, respectively; both q< 0.05). Both MPAS and T-cell inflamed signatures were significantly higher in CDC37-high tumors ( q< 0.05). Infiltration of NK cells, Tregs, neutrophils, M1 macrophages, and B-cells were greater in CDC37-high tumors (q < 0.05). GSEA showed several signaling pathways, such as KRAS, TGF-beta, hypoxia, WNT-beta catenin, and PI3K-AKT-MTOR, were enriched in CDC37-high tumors. Conclusions: Highly CDC37-expressed (CDC37-dependent) CRC was associated with aberrant TME where abundance of immune cell infiltrate and broad activation of kinase-related signaling pathways were evident. Our results support the kinase-stabilizing function of CDC37 in CRC. Further investigations combined with survival data are warranted to address the prognostic and predictive values of CDC37 expression in targeted therapies of CRC.
Deep learning–assisted colonoscopy images for prediction of mismatch repair deficiency in colorectal cancer.
Authors: Hu Jiancong , Hu Huabin , Cai Yue , Chen Xijie , Liao James , Han Ming , Shi Lishuo , Chen Junguo , Liu Wei , Su Mingli , Wang Chao , Huang Yan , He Xiaosheng , Lan Ping , Deng Yanhong 
Published: January 2023

24 Background: Deficient mismatch repair (or microsatellite instability) is a major predictive biomarker for the efficacy of immune checkpoint inhibitors of colorectal cancer. However, routine testing is time-consuming and incur substantial costs. We developed and validated a deep learning-based classifiers (MMR-Scopy) to detect mismatch repair-deficient status from routine colonoscopy images. Methods: We retrospectively obtained the colonoscopy images from the imaging database at Endoscopic Center of the Sixth Affiliated Hospital of Sun Yat-sen University. Colorectal cancer images from patients that had undergone colonoscopy procedures, surgery and the mismatch repair immunohistochemistry test were eligible for this study. Colonoscopy images from a prospective trial (Neoadjuvant PD-1 blockade by toripalimab with or without celecoxib in mismatch repair-deficient or microsatellite instability-high locally advanced colorectal cancer, PICC) were used to test MMR-Scopy. The primary outcome was dMMR status. The primary performance metrics were accuracy, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). Results: A total of 5226 eligible images from 892 tumors from the consecutive patients were utilized to develop and validate the deep learning model. 2105 CRC images from 306 tumors were randomly selected to form model development dataset with a class-balanced approach. 3121 images of 488 pMMR tumors and 98 dMMR tumors were used to form the independent dataset. The MMR-Scopy model achieved an AUROC of 0.948 (95% CI 0.919- 0.977) on the test dataset. On the independent validation dataset, the AUROC was 0.807 (0.760- 0.854), and the NPV in was 94.2% (95% CI 0.918-0.967). On the PICC dataset, the model identified 29 tumors among the 33 dMMR tumors (87.88%). Conclusions: MMR-Scopy achieved a high NPV in detecting dMMR colorectal cancers. This model might serve as an automatic screening tool, one that might potentially assist doctors in determining a new treatment strategy. [Table: see text]
Twitterchats as a means to educate patients with CRC and caregivers and stimulate collaborations.
Authors: George Manju , Parikh Aparna Raj , Loree Jonathan M. , Sanford Nina Niu , Jethwa Krishan 
Published: January 2023

255 Background: During the COVID-19 pandemic, Twitter has been instrumental in accelerating knowledge dissemination and forging collaborations within the medical community and amongst patient advocates. Tweetchats within Twitter are scheduled conversations on a specific topic. In oncology, Tweetchats have been used by cancer advocates to spread awareness and for patient and caregiver education. A colorectal cancer (CRC) specific tweetchat did not previously exist. This abstract describes the creation, and experiences with a CRC specific tweetchat. Methods: The #CRCTrialsChat tweetchat was created by a patient advocate for colorectal cancer patients, caregivers and clinicians to meet and exchange clinical trial-related information. Two gastrointestinal (GI) medical oncologists and two radiation oncologists were enlisted as moderators. The topic for each session is chosen by the patient advocate, who creates an outline and divides the content, which is designed to last a one hour session. The idea is to create engaging, technical, but easy to understand content. Each moderator then works on the answers to their assigned section, which is edited to fit tweet character limit. Sessions may also have guest moderators with expertise on a specific topic. Through tweeting, moderators answer specific questions that come up during the session and later. Results: To date, we have had four sessions covering the following topics: Clinical trial basics, CRC Updates from ASCO22, ClinicalTrialFinders and BRAF-mutated tumors. The content created has been simple and engaging, the format has functioned smoothly, and the reach of #CRCTrialsChat has been steadily increasing. After the most recent session on BRAF in September 2022, the @CRCTrialsChat has 281 followers, 17K impressions and 14.6K profile visits, a reflection of its excellent content. From a clinician perspective, this is a great format to interact with colleagues, discuss enrolling trials and also become familiar with using Twitter. Conclusions: A CRC clinical trial focused tweetchat is an engaging way to deliver trial-related content to an audience of clinicians, patients and caregivers. The current format appears to be an effective way to create and disseminate information. Future sessions will focus on ctDNA, molecular markers such as KRAS and HER2, and rectal cancer trials. Our hope is that #CRCTrialsChat will stimulate continued patient and clinician engagement, increase awareness of clinical trials, enhance trial participation and initiate patient-centric research and collaborations.
Nivolumab (NIVO) plus chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 3-year follow-up from CheckMate 649.
Authors: Janjigian Yelena Y. , Shitara Kohei , Moehler Markus H. , Garrido Marcelo , Gallardo Carlos , Shen Lin , Yamaguchi Kensei , Wyrwicz Lucjan , Skoczylas Tomasz , Campos Bragagnoli Arinilda Silva , Liu Tianshu , Tehfe Mustapha , Elimova Elena , Bruges Maya Ricardo Elias , Cleary James M. , Karamouzis Michalis , Soleymani Samira , Lei Ming , Amaya-Chanaga Carlos , Ajani Jaffer A. 
Published: January 2023

291 Background: NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and an acceptable safety profile in previously untreated patients (pts) with advanced GC/GEJC/EAC, leading to approvals in multiple countries including the US. NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy after 2 years of follow-up. We present efficacy and safety analyses from NIVO + chemo vs chemo from the 3-year follow-up of CheckMate 649. Methods: Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression. Pts with known HER2-positive status were excluded. Randomized pts received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5. Results: 581 pts were concurrently randomized to NIVO + chemo or chemo. With 36-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts. The objective response rate (ORR) per BICR in pts with PD-L1 CPS ≥ 5 who had measurable lesions at baseline was 60% (95% CI 55–65) with NIVO + chemo vs 45% (95% CI 40–50) with chemo; in all randomized pts, ORR per BICR was 58% (95% CI 54–62) with NIVO + chemo vs 46% (95% CI 42–50) with chemo. Responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 (median [m] duration of response [mDOR] 9.6 mo [95% CI 8.2–12.4] vs 7.0 mo [95% CI 5.6–7.9], respectively) and in all randomized pts (mDOR 8.5 mo [95% CI 7.7–9.9] vs 6.9 mo [95% CI 5.8–7.2], respectively). OS benefit with NIVO + chemo was observed across most prespecified subgroups. No new safety signals were identified. A summary of treatment-related adverse events (TRAEs) is shown here. Conclusions: After 3 years of follow-up, NIVO + chemo continued to demonstrate clinically meaningful long-term survival benefit with an acceptable safety profile, further supporting its use as a standard 1L treatment in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116 . [Table: see text]
Risk of gastric cancer development according to the combination of anti–Helicobacter pylori antibody titer and degree of atrophic gastritis.
Authors: Lim Joo Hyun , Cho Soo Jeong 
Published: January 2023

297 Background: Helicobacter pylori is known as the main risk factor for gastric cancer. It is also well known that gastric atrophy which is the result of long-term H. pylori infection induces spontaneous regression of H. pylori infection and such atrophic status with negative H. pylori infection is related with high risk of gastric cancer, as in so called “ABC method”. However the implication of anti- H. pylori antibody titer is not well investigated. This study was designed to identify the risk for gastric cancer according to the combination of level of anti- H. pylori antibody titer and gastric atrophy. Methods: Those who had health checkups including upper endoscopy and serum anti- H. pylori antibody test between 2003 and 2018 were enrolled. Among them, those who had positive results for anti- H. pylori antibody were included in this study and those who had followed up for less than 1 year were excluded. Kimura-Takemoto classification C3 or more was defined as gastric atrophy. Individuals were classified into 4 groups: low B (low titer without atrophy), high B (high titer without atrophy), high C (high titer with atrophy), and low C (low titer with atrophy). Their risks for gastric cancer were compared under adjustment with other risk factors. Results: During median 5.7 years of follow-up, among 28,311 subjects, 231 developed new gastric cancer. Among them, 159 were intestinal type, 68 were diffuse type, and 4 were type-unknown. For intestinal type gastric cancer, high C group and low C group showed significantly high risk compared with low B group (high C: aHR 10.516; 95% CI, 6.485-17.054) (low C: aHR 11.191; 95% CI, 7.096-17.649). However, for diffuse type gastric cancer, high B group showed higher risk compared with low B group (aHR, 1.713; 95% CI, 1.021-2.875). When those two factors were taken separately, grade of atrophy was related with the risk for intestinal type gastric cancer (aHR, 2.047; 95% CI, 1.862-2.251), while the level of anti- H. pylori antibody titer was related with the risk for diffuse type gastric cancer (aHR, 1.158; 95% CI, 1.041-1.288). Conclusions: Among those with current H. pylori infection, high anti- H. pylori antibody titer is related with diffuse type gastric cancer. The risk was prominent especially among those without atrophy. Therefore, those with high level of anti- H. pylori antibody titer need to be considered as high risk group even without atrophy and should be considered as good candidates for H. pylori eradication and intensive screening.
Disparities and outcomes in young adults admitted for gastric cancer in the US.
Authors: Litvin Rafaella , Deenadayalan Vaishali , Ibrahim Muhammad Bilal , Ishaya Michelle 
Published: January 2023

298 Background: Although global incidence of gastric cancer has been decreasing over the past decades, an upward trend has been reported in younger patients and certain ethnic groups over the past few years. The reason for this epidemiological trend is not fully understood, but differences in presentation and prognosis suggest that gastric cancer in the young might represent a different clinical entity. Here, we seek to identify differences in demographic characteristics and outcomes between young adults and older patients admitted for gastric cancer. Methods: Using the National Inpatient Sample (NIS) database, we identified all adult patients admitted primarily for gastric cancer from 2016 to 2019. We analyzed demographic characteristics of young adults (defined as those aged between 20 and 49-years-old) and older patients (aged 50 and above) as well as differences in in-hospital mortality, total hospital charges, and length of stay. Multivariate logistic regression analysis was conducted to adjust for confounders. Results: During the period studied, 77,720 patients were admitted with gastric cancer, of which 9,650 (12.4%) were young adults and 68,115 (87.6%) were old individuals. Young adults were more likely to be female (42.4 vs. 35.6%, p < 0.01). Hispanics comprised 30.9% of admissions for gastric cancer of young adults (vs. 15% in older adults p-value <0.01). Young adults were also over 3 times more likely to be uninsured than older individuals (9.6 vs. 2.6%, p-value <0.01) and more likely to be cared for in urban (98.2 vs. 96.2%, p < 0.01) and teaching (85.4 vs. 80.8%, p < 0.01) hospitals. Young adults had longer lengths of stay and lower hospital charges (see table). No difference was found in mortality, despite a lower comorbidity burden in young adults based on the Charlson Comorbidity Index, possibly due to young adults being candidates for more aggressive therapy and having more aggressive disease. Conclusions: The higher incidence of gastric cancer in Hispanic and uninsured young adults poses a complex public health issue, especially in the context of recent research suggesting more aggressive disease in this population. The reported findings likely reflect both a shift in the U.S. population over the years as well as a rising incidence among Hispanic young adults. It is important to increase awareness of these epidemiological disparities. Further research is needed to determine whether establishing screening programs for gastric cancer in certain populations might be beneficial in the U.S. [Table: see text]
Comparison of survival between de novo stage IV and recurrent stage IV gastric cancer.
Authors: Ji Jun Ho , Lee Danbi , Lee Yong-Pyo , Huh Seok Jae , Go Se-Il , Kim Jung Hoon , Oh Sung Yong , Kang Jung Hun , Kim Kwang Min 
Published: January 2023

304 Background: The characteristics and prognosis of de novo metastatic gastric cancer and recurrent metastatic gastric cancer have not yet been elucidated. Here, we compare prognosis and characteristics of patients with de novo versus recurrent gastric cancer. Methods: This retrospective study included 301 advanced pathologically confirmed gastric cancer patients who received palliative chemotherapy between 2012 and 2022. The de novo cohort was included of patients who presented with distant metastasis at diagnosis and recurrent metastatic cohort was composed of patients with metastasis after curative gastrectomy. We analyzed prognostic association by Cox regression and compared survival time of both cohorts using the Kaplan-meire method. Results: A total of 167 de novo and 112 recurrent patients were included. There were no differences noted among the patients with de novo disease and recurrent metastatic disease with respect to age, sex, ECOG, primary cancer location and pathologic features. Patients in the recurrent group versus de novo group were longer duration of chemotherapy (1.16 ± 1.18 years versus 0.85 ± 0.84, P = 0.01) and lower mean body mass index. (20.22 ± 2.78 versus 21.93 ± 3.38, p < 0.001) The median overall survival in the de novo group was 11.6 versus s 14.4 months in the recurrent group. ( P = 0.02) In a multivariate analysis, the age of 70 years or older at the time of stage 4 diagnosis was independently associated with shorter survival. Conclusions: De novo and recurrent metastatic gastric cancer characterize distinguished subpopulations. And advanced gastric cancer with distant recurrence has significantly better survival versus those with de novo cohort. This differences between de novo and recurrent gastric cancer could facilitate discussions about patient selection of clinical trial and help with advanced personalized treatment. [Table: see text]
Real-world outcomes of patients with advanced gastric cancer treated with FOLFIRI.
Authors: Fawaz Ali , Tilley Derek , Karachiwala Hatim 
Published: January 2023

307 Background: Doublet chemotherapy regimens such as 5-fluorouracil and irinotecan (FOLFIRI) appear to be viable first-line treatment options in advanced gastric cancer (AGC). A phase III French intergroup study demonstrated a longer time to treatment failure, improved toxicity profile, and no difference in median OS when using FOLFIRI, compared to epirubicin, cisplatin, and capecitabine (ECX). Purpose: To investigate the real-world efficacy of FOLFIRI in AGC. Methods: Patients diagnosed with AGC in Alberta, Canada from 2012-2020 were identified by the Alberta Cancer Registry. Data points that could not be obtained automatically were obtained by retrospective chart review. Survival was compared by Log-Rank analysis or Cox Regression. Factors associated with FOLFIRI use were determined using logistical regression. Results: A total of 285 patients were analyzed. Eighty-four (29%) patients received FOLFIRI as first-line therapy, 69 received ECX (24%), 82 received CX (29%), 31 received EOX (11%), and 19 received FOLFOX (7%). Thirty-six (12.6%) received a subsequent line of therapy, most commonly FOLFIRI (52.8%). Age, sex, topography (cardia v. non-cardia), or morphology (adenocarcinoma v. signet ring cell v. NOS) did not influence the use of FOLFIRI in the first-line setting. Median overall survival with FOLFIRI was 5.8m vs. 7.4m (p = 0.12) when compared to the patients receiving all other regimens. Conclusions: FOLFIRI had comparable efficacy to other first-line regimens in patients with AGC.
A single center survival analysis of patients with colorectal cancer who underwent next generation sequencing.
Authors: Krzywon Lucyna , Lazaris Anthoula , Gomez Andrea , Kalil Jennifer , Zlotnik Oran , Metrakos Peter 
Published: January 2023

31 Background: Colorectal cancer (CRC) remains a lethal diagnosis with an overall 5-year survival rate of 5-10% for patients with unresectable metastatic disease. The advent of next generation sequencing allows tailored systemic therapy to specific mutations with the goal of improving patient survival. McGill University Health Center instituted next generation sequencing in 2019. Our study aims to evaluate survival outcomes in patients who underwent NGS testing. Methods: A retrospective collection of data on all patients with CRC who were presented at both lower gastroenterology and hepatobiliary tumor boards from January 2019 through July 2022 ( n= 498). Survival and was compared between patients who were found to have genetic alterations identified using the Illumina Miseo platform. Statistical Analysis was performed with GraphPad Prism. Results: A total of 321 (64%) patients had NGS performed on either their primary tumor or a metastasis. A total of 229 (71%) CRC patients had genetic alterations identified on NGS. The most commonly mutated genes were KRAS (41%), APC (17%), PIK3CA (16%) and BRAF (8%). There was no significant difference in median overall survival between patients who had an identified genetic alteration and patients who did not (p = 0.8). Patients with metastatic disease and synchronous presentation had higher rates of genetic alterations (69% and 70%, respectively). Conclusions: This study provides real world data for a single institution initiating Next generation sequencing in colorectal cancer patients. Next Generation testing is an advantageous tool which can help stratify patients into tailored treatment regiments which will lead to improved patient outcomes.