bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor immune environment in colitis-associated colorectal cancers: Comparison with sporadic colorectal cancers.
Authors: Li Wenliang , Xu Ning , Huang Fengchang , Yu Kun , Yang Quan 
Published: June 2023

e15531 Background: Persistent inflammatory diseases such as ulcerative colitis (UC) and Crohn’s disease (CD) contribute to the tumor initiation and progression in colitis-associated cancers (CAC). Intestinal damage caused by persistent inflammation promotes clonal expansion of somatic and epithelial cells and alters the immune microenvironment. A comprehensive investigation in comparing the tumor immune environment in CAC with sporadic colorectal cancers (CRC) will provide more clinical usefulness of immunoprofiling in CRC. Methods: Thirteen patients with CAC (6 with UC and 7 with CD) and 10 patients with sporadic colorectal cancer from our hospital were enrolled in the study. FFPE samples from patients were analyzed for the tumor infiltrating lymphocytes [PD-L1+, CD3+, CD4+, CD8+, CD20+, CD68+, CD163+] by multiplex immunofluorescence technique. The core and peritumor areas annotated by pathologists on images. Then artificial intelligence (AI) algorithms delineated the tumor-enriched segments and stroma, and calculated the density and percentage of each marker in two regions. A nonparametric approach (Kruskal–Wallis) was used to compare the density and percentage of immune cells between CAC and sporadic colorectal cancer groups. Results: In the stroma area, the density (counts per mm2) of PD-L1+CD68+ cells in patients with CAC were significantly higher than those in sporadic cancer patients (p < 0.05). However, the density of PD-L1+CD68+ did not show significant differences related to disease types (CAC or sporadic CRC) in the tumor-enriched segments. Significantly, the density of CD3+CD4+ cells and the percentage of CD68+CD163- cells in patients with CAC showed a trend of higher density than those in sporadic cancer patients in the stroma area (all, 0.05 < p < 0.1). The density and the percentage of CD20+ cells in CAC patients had a higher density tendency than those in sporadic cancer patients both in the tumor-enriched segments and stroma (all, 0.05 < p < 0.1). Other indicators in tumor-enriched segments and stroma, such as CD3+, CD4+, CD8+, CD68+CD163+ and PD-L1+, had no significant difference between CAC and sporadic CRC patients, regardless of the percentage or the density. Conclusions: We identified that the tumor immune environment of CAC was different from that of sporadic CRC. Some tumor infiltrating lymphocytes such as PD-L1+CD68+ cells infiltrated more in CAC than those in sporadic cancer, suggesting that CAC may respond better to immunotherapy than sporadic CRC. However, this hypothesis requires a further validation with a larger sample size.
Determining MSI status by a one-step PCR melting curve analysis of Chinese-specific mononucleotide repeats.
Authors: Chen Huang , Jie Jianzheng , Jiang Ruiying , Wang Xiaowei , Wang Ye , Feng Qianqian , Niu Yun , Wang Bei , Luo Jie , Su Wenqing , Li Youcai , Gai Fei , Song Roman , Zhu Changbin , Zhong Dingrong 
Published: June 2023

e15532 Background: Microsatellite instability (MSI) is a hypermutated phenotype primarily caused by the deficiency of DNA mismatch repair activity. Conventional MSI detection platforms are time consuming and need extra normal tissue. Due to the short DNA sequences of microsatellite loci in MSI samples, the method can be simplified to a one-step approach to differentiate MSI status by observing the melting curve. Herein a novel feasible MSI status detection method based on one step-PCR in single tumor tissue was developed, and validated in colorectal cancer samples. Methods: Specific microsatellite sites shorter than 12 bp in length (feasibility of fluorescence probes) were selected from public databases for analysis. In tumor tissues from 98 CRC patients with known MSI status, microsatellite sites with the highest receiver operating characteristic (ROC)-area under the ROC curve (AUC) were eventually selected for the final PCR panel design. The cut-off value of this assay was defined by the number of melting peaks in a specific Tm value range. An independent set of 199 tumor tissues from CRC patients with known MSI by Sanger sequencing was recruited to validate the performance of this novel PCR MSI kit. Results: The ROC-AUCs of the pre-selected eight mononucleotide repeats were 0.82, 0.93, 0.79, 0.78, 0.98, 0.95, 0.92, and 0.79. When 0 or 1 marker had a melting peak within the specified Tm value range, the sample was identified as "MSS/MSI-low (MSI-L)"; when 2 or more markers had melting peaks within the specified Tm value range, the sample was determined to be "MSI-high (MSI-H)". In the clinical sample set, compared with the results given by conventional MSI detection method, the sensitivity of the 8-gene panel for MSI-H was 99.4% (166/167), the specificity of the 8-gene panel was 100%, and the overall concordance reached to 99.5%. Conclusions: The novel PCR-MSI detection method using 8-gene panel developed in this study was feasible and accessible in clinical practice, and a large-scale clinical validation is in progress. [Table: see text]
High rates of detection of metastatic/recurrent colorectal cancer on clinical imaging at the time of molecular residual disease testing following operative management.
Authors: Trotier Danny , Lemmon Kayla , Golner Danielle , Buratti Maddie , DeZeeuw Alyssa , LoConte Noelle K. , Lubner Sam Joseph , Uboha Nataliya Volodymyrivna , Kratz Jeremy D. , Patel Monica Arun , Carchman Evie , Matkowskyj Kristina A. , Zhang Wei , Burkard Mark E. , Deming Dustin A. 
Published: June 2023

e15543 Background: Detection of circulating tumor DNA (ctDNA) following operative management for colorectal cancer (CRC) as part of molecular residual disease (MRD) assays has shown significant prognostic implications. The majority of studies examining the time to detection of cancer recurrence have been done retrospectively without the treating physician knowing the results of the assay. Limited prospective data exists regarding the probability of detecting cancer on imaging at the time of a positive MRD test following operative management of all sites of disease. Here, we analyze the association of positive MRD testing with imaging findings of recurrent or metastatic CRC using a cohort of patients that underwent prospective MRD testing. Methods: Patients with stage I-IV intestinal cancers at University of Wisconsin Carbone Cancer Center who underwent prospective Natera Signatera MRD testing following operative management of their disease were identified and consented to an IRB-approved registry protocol. Those consented patients who had a positive test without being on systemic therapy and had clinical imaging within 45 days were analyzed further. The presence of definitive cancer, indeterminate findings, and no evidence of cancer was recorded per the treating physician using standard of care clinical imaging. The presence of cancer on imaging was then correlated with the quantity of ctDNA (mean tumor molecules (MTM)/ml). Results: 163 patients with stage I-IV CRC and 1 small intestinal cancer underwent MRD testing. 30 positive ctDNA tests with imaging were available across 22 unique patients (median age 54 years (29-84) 7 females). 23 samples were in the resected metastatic setting, 5 stage III and 2 stage I. Cancer was seen on imaging in 19/30 (63%) of positive tests, indeterminate in 3 (10%) and negative for cancer in 9/30 (27%). With ctDNA levels > 10 MTM/ml (n = 7), cancer was detected on imaging in all cases. With ctDNA levels of 1-10 MTM/ml cancer was detected in 42% and at < 1 MTM/ml in 64%. A trend towards greater detection of cancer was observed when MRI or PET/CT was performed. Radiologic disease detection in patients with positive MRD analysis was higher in those with stage IV disease (70%) vs. stage I-III (43%). Conclusions: ctDNA MRD positivity is associated with high rates of detection of recurrent/metastatic CRC, especially in patients with resected stage IV disease and with a quantity of > 10 MTM/ml. Clinical imaging should be considered at the time of detection of ctDNA.
Mutational and DNA fragment analysis may help in the triage of FIT+ patients enrolled in colorectal cancer screening programs.
Authors: Scimia Mauro , Pepe Francesco , Russo Gianluca , Malapelle Umberto , Tanaka Hiromi , Scimia Simone , Troncone Giancarlo , Bianco Maria Antonia 
Published: June 2023

e15546 * F. Pepe made an equal contribution Background: Mutational and DNA fragment analysis have already been investigated for a possible role in the detection of colorectal cancer. This pilot study, conducted at ASL NA 3 SUD (Naples, Italy) with the University of Naples Federico II, attempts to understand their possible role in the detection of Advanced Adenomas+ (AA+) and their potential ability to triage subjects with a positive FIT test for referral to colonoscopy. Methods: 160 FIT+ subjects of both genders, aged 50-74, participating in a colorectal cancer screening program were enrolled in a clinical trial focusing on a novel biomarker for colorectal cancer diagnostics. Of these, 14 subjects had disease (12 AAs and 2 colorectal cancers, from now on “CRC”). After ethical committee’s approval and release of informed consents, a 20 ml whole-blood sample was collected from each subject. Samples were centrifuged following standard procedures and stored at -80°C. DNA extraction was later performed using a Minielute kit (Qiagen). Mutational and DNA fragment analysis were performed using a qPCR-based technology: the ColoScape™ 2.5 kit (DiaCarta Inc, Pleasanton, CA). A logistic regression was run to determine the probability of disease in subjects showing positivity for predictors. Estimates of sensitivity, specificity, PPV, NPV (with 95% C.I.), PLR, NLR and Youden’s Index were also obtained. Results: The logistic regression showed statistical significance, with a p-value < 0.0001, that is, the logistic regression model with provides a better fit than the model without the independent variable. ColoScape identified 12 subjects with disease out of 14, for a sensitivity of 86% (67%,100%); both CRCs were picked up by ColoScape together with 10 AAs. 2 AAs were missed. Out of 146 healthy subjects, 107 were successfully identified as negatives, for a specificity of 73% (66%, 80%). PPV was 24% (12%, 35%). NPV was 98% (96%, 100%). PLR, NLR and Youden’s Index were 3.21, 0.19 and 0.59 respectively. Conclusions: This pilot study was intended to provide performance indicators to design a larger population study that is currently underway. These preliminary findings suggest that liquid biopsy-based mutational and DNA fragment analysis can play a role in selecting subjects with a higher risk of returning a positive colonoscopy, thus potentially improving the quality of colorectal cancer screening programs and patients’ experience.
Does severity of periodontal disease influence the risk of developing gastrointestinal malignancies?
Authors: Iqbal Umar , Mendes Duarte Poliana , Duncan William D. , Galochkina Zhanna , Zhang Zhongyue , Kostewicz Stephen H , Borobia Manuel E , Lee Ji-Hyun , Rogers Sherise C. 
Published: June 2023

e15549 Background: In recent years, multiple observational studies have suggested increased risk of developing gastrointestinal (GI) malignancies in patients with prior periodontal disease (PD). Our aim was to determine whether a difference in incidence of GI malignancies exists amongst patients with pre-existing mild-moderate vs. severe PD. Methods: This was a single institution retrospective IRB approved study. We identified a cohort of patients between 2011-21 with PD and concurrent registration in independent dental and medical electronic health record systems at the University of Florida. Patients were stratified into 2 groups based on severity of PD (mild-moderate or severe). Descriptive statistics were used to compare the 2 groups based on demographics and medical history. Cumulative incidence curves were used to compare GI malignancy incidence between the 2 groups. Multivariable logistic regression was used to identify predictors of developing GI malignancies. Results: A total of 2168 patients with PD were identified with a median follow up of 4.7 (IQR 2.6-6.8) yr. Of these, 54% had severe PD and 46% had mild-moderate PD. Severe PD was more common within males (58% vs 50% in females), Black race (62% vs 52% in Caucasians), diabetics (59% vs 52% in non-diabetics), cigarette smokers (60% vs 51% in non-smokers) and excessive alcohol intake (70% vs 61% in moderate alcohol intake). There was no significant difference in cumulative incidence rates of GI malignancies (colon, pancreatic, gastric, hepatic, and esophageal) between the PD groups stratified by severity (12% in severe vs 11% in mild-moderate, p = 0.6 at 5 yr follow up). In univariable logistic regression, severe vs mild-moderate PD OR was 1.12 [95% CI: 0.87,1.46], thus more severe form of PD is not associated with developing a GI malignancy. In multivariable logistic regression, severe vs mild/moderate PD adjusted OR was 1.04 [95% CI: 0.79,1.36], thus also not statistically significant, with other risk factors of developing GI malignancies identified in Table 1. Conclusions: There was no association between the severity of periodontal disease and subsequent development of GI malignancy. [Table: see text]
Trends and disparities in incidence and mortality of early-onset colorectal cancer (EOCRC) in the United States (1999-2019).
Authors: Grewal Udhayvir Singh , Sohal Davendra 
Published: June 2023

e15551 Background: There has been a startling rise in the reported incidence of colorectal cancer (CRC) among adolescents and young adults (AYA; ages 15-39 years) in the US.These patients are often diagnosed with advanced stage and have a relatively poor prognosis.Population-based data on disparities and trends in incidence and mortality in this understudied population are lacking. Methods: We used the Centers for Disease Control WONDER cancer statistics database to extract data on annual age-adjusted incidence (AAIR) and mortality (AAMR) rates per 100,000 population for colon and rectal cancer in AYA. We compared AYA statistics with the overall as well as the non-AYA population (40-85 years). Sex and race comparisons were analyzed. Variations in AAIR and AAMR over time, assessed with Joinpoint regression modelling (Joinpoint regression program 4.9.1.0), were expressed as estimated average annual percentage change (AAPC). Comparisons were reported using average annual percentage change difference (AAPCD). Results: 83,371 cases of EOCRC were reported between 1999-2019. We recorded an increase in AAIR of EOCRC (AAPC 2.9, p < 0.001). We noted a concomitant decline in AAIR of CRC overall (AAPC -2.4, P < 0.001) and among the non-AYA population (AAPC -2.4, p < 0.001). Subgroup comparisons showed statistically significant differences in AAIR of EOCRC for females vs males (AAPCD 0.6, p = 0.04), Whites vs Blacks (AAPCD 1.8, p < 0.001), and White females vs White males (AAPCD 0.6, p = 0.02) [table]. AAMR increased for EOCRC over the study period (AAPC 0.8, p = 0.001), as opposed to a decline in AAMR of CRC overall (AAPC -2.5, p < 0.001) and among the non-AYA population (AAPC -2.5, p < 0.001). The increase in AAMR of EOCRC was similar among males and females (AAPCD 0.3, p = 0.351), but higher among Whites vs Blacks (AAPCD 1.1, p = 0.007). Conclusions: This analysis from a large population-level database shows an increasing trend in incidence and mortality of EOCRC in the US, despite a concomitant decline in the incidence and mortality of CRC overall. The incidence appears to be rising more rapidly among females, particularly White females. Both incidence and mortality of EOCRC appear to be rising more rapidly among Whites compared with Blacks. Our analysis underscores the critical need to develop strategies to identify high-risk AYA populations who may benefit from more aggressive CRC screening and prevention interventions. [Table: see text]
Disparities in presentation, treatment, and overall survival for South Asian American patients with colorectal cancer.
Authors: Ahmed Kaleem Sohail , Marcinak Clayton Thomas , Krebsbach John K. , Schiefelbein Andrea M , Varley Patrick , LoConte Noelle K. , Zafar Syed Nabeel 
Published: June 2023

e15554 Background: The South Asian population in America is growing. Colorectal Cancer (CRC) is one of the most common cancers amongst South Asian Americans (SAA), however few studies have looked at differential presentation, treatment, and outcomes. The objective of this study was to compare differences in presentations, and investigate disparities in treatment and overall survival (OS) amongst SAAs compared with non-Hispanic whites (NHW). Methods: We performed a retrospective analysis of patients with colon or rectal adenocarcinoma in the National Cancer Database (NCDB) years 2004-2020. We compared differences in patient demographics, socioeconomics, stage at presentation, and treatments received between SAA and NHW populations using chi square, and t tests as applicable. OS was evaluated using Kaplan-Meier analysis and the log-rank test. Multivariable Cox regression stratified by stage was used to compare OS between the two groups. Results: We analyzed data from 773,223 NHW and 3,448 SAA patients with colon cancer (CC) and 285,769 NHW and 1,826 SAA patients with RC. At presentation SAAs were younger (61.2 years vs 69.2 years, p<0.001 for CC, and 57.9 vs 63.9, p<0.001 for RC), less likely to have government insurance (44.1% vs 64.1%, p<0.001 for CC, and 35.4% vs 50.6%, p<0.001 for RC), more likely to be living in metropolitan areas (97.9% vs 83.2%, p<0.001 for CC, and 97.4% vs 81.0%, p<0.001 for RC), and more likely to have advanced stages of disease (47.4% vs 42.7%, p<0.001 for CC, and 40.9% vs 38.9%, p<0.001 for RC). SAAs had significantly longer delay in receipt of surgical intervention or radiation therapy (p <0.001) and were less likely to receive surgery for stage 4 for CC (54.6% vs 60.5%, p<0.001). On multivariate cox regression, adjusted for age, sex, insurance status, urban/rural location, and comorbid conditions, SAAs with either colon or rectal cancer were more likely to survive across all cancer stages (p<0.001). Conclusions: In this national study, when compared to NHW patients, SAA patients with CRC, present at younger ages and with more aggressive disease. Despite SAAs being less likely to receive timely cancer care, they have better overall survival. [Table: see text]
Real-world safety and effectiveness of MVASI in metastatic colorectal cancer patients in Canada.
Authors: Cheung Winson Y. , Samimi Setareh , Ma Kim , Knight Gregory John , Kassam Shaqil Nadirali , Colwell Bruce , Beaudoin Annie , Vincent Mark David , Trinkaus Mateya , Filion Alain , Karachiwala Hatim , Asmis Timothy , Sideris Lucas , Nunez Leyla , Wani Rajvi , Cirone Morris Carlye , Ngan Elaine , Du Yinhao , Inam Naila 
Published: June 2023

e15555 Background: MVASI is a biosimilar to the reference product, bevacizumab, and is the first biosimilar approved by Health Canada for the first-line (1L) treatment of metastatic colorectal cancer (mCRC). This study addresses the limited real-world evidence by describing the safety and effectiveness of MVASI as 1L therapy in mCRC. Methods: Retrospective data were collected in two waves of sites across Canada, at least 1 year (wave 1) or 2 years (wave 2) after commercial availability of MVASI at each site. Adult patients treated with ≥ 1 MVASI cycles as their 1L therapy for mCRC were included. Baseline demographic and clinical characteristics were collected 6 months prior to MVASI initiation (index date). Medical history, adjuvant treatment, and CRC diagnosis were collected within 5 years of pre-index date. Outcomes were gathered between index and chart review dates. Results: Among the 75 patients in wave 1, 36 (48.0%) were male and the median age was 62 years. Of the 164 patients in wave 2, 98 (59.8%) were male and the median age was 67 years. Most patients in wave 1 (42/69; 60.9%) and wave 2 (87/141; 61.7%) had a RAS mutation. The median time from mCRC diagnosis to MVASI initiation among wave 1 and 2 patients was 3.1 (IQR [2.1, 4.2]) and 2.3 months (IQR [1.6, 3.7]), respectively. At least one safety event of interest (EOI) was recorded for 26/75 (34.7%) wave 1 and 70/164 (42.7%) wave 2 patients (Table 1). The median progression free survival (PFS) for wave 1 and 2 patients were 9.47 and 21.38 months, respectively. Median overall survival (OS) for wave 1 patients was not estimable and was 26.45 months for wave 2 patients. Conclusions: In this real-world study, mCRC patients treated with 1L MVASI were generally representative of the Canadian mCRC population treated with 1L bevacizumab. Compared with clinical trials of MVASI and reference bevacizumab, the EOI profile and the OS data are similar, but lower rates of individual EOIs are observed in this real-world setting. The shorter PFS observed in wave 1 may be due to higher rates of comorbidities at baseline and longer time from mCRC diagnosis to index. [Table: see text]
Efficacy and safety of radiation therapy combined with anti-angiogenic agentsand immunotherapy for MSS/pMMR metastatic colorectal cancer: A real-world study.
Authors: Lin Zhenyu , Zhai Menglan , Zhang Tao 
Published: June 2023

e15559 Background: The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) can reshape tumor microenvironment, and their effectiveness has been demonstrated in pattients with microsatellite stable (MSS) or mismatch repair profificient (pMMR) metastatic colorectal cancer (mCRC). Radiotherapy (RT) can induce tumor immunogenic cell death, increase infiltration of tumor-infiltrating T lymphocytes and enhance neoantigen expression. Whether the application of RT can further improve the prognosis of pts with MSS/pMMR mCRC receiving anti-vascular drugs and immunotherapy remains to be explored. Methods: We retrospectively identified data on mCRC pts who received anti-angiogenic targeted agents and ICIs after failure of standard therapy at our institution from January 2015 to September 2022. Pts either received RT (RT+TT+IT group) or did not (TT+IT group) during the course of the disease. Baseline characteristics of the groups were compared with the Chi-squared, Fisher's exact, or the independent sample t-test as appropriate. Progression-free survival (PFS) and overall survival (OS) were examined by the Kaplan-Meier method with a log-rank test. Univariate and multivariate Cox regression analysis was conducted to identify prognostic factors for PFS and OS. Results: Of the 89 pts who received anti-angiogenic targeted therapy in combination with ICIs, 43 (48.3%) received RT and 46 (51.7%) did not. All pts were MSS/pMMR. The objective response rate (ORR) of the RT+TT+IT and TT+IT groups was 18.6% (8/43) and 10.9% (5/46) and the disease control rate (DCR) was 83.7% (36/43) and 67.4% (31/46) (both p > 0.05), respectively. The median PFS time was slightly higher in the RT+TT+IT group than in the TT+IT group (5.0 vs. 4.3 months, p = 0.065). In addition, the PFS of RT sequential/simultaneous TT+IT was superior to TT+IT sequential radiotherapy (RT→IT+TT vs. RT-IT+TT vs. IT+TT→RT: median 7.5 vs. 6.1 v.s 3.8 months, p = 0.004). The median OS of RT+TT+IT group was significantly better than that of TT+IT group (15.2 vs. 7.2 months, p = 0.026). Application of RT appeared to be most benefificial in pts aged 56 or younger, advanced stage of initial diagnosis, metastatic lesions involving ≥2 organs, primary lesion not resected, RAS mutations. Cox multivariate regression analysis showed that the number of anti-angiogenic agents plus ICIs cycles > 4 was an independent prognostic factor for OS. No treatment-related deaths were reported, and radiation pneumonia occurred in one patient in the combined radiotherapy group in a manageable manner. Conclusions: The addition of RT during the course of disease can significantly improve the survival benefit of MSS/pMMR mCRC pts treated with anti-angiogenic drugs combined with ICIs posterior line therapy.