bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic and demographic disparities in rectal cancer treatment.
Authors: Wu Vernon , Kobritz Molly , Kantarovich Diana , Sidiqi Baho , Tchelebi Leila , Whelan Richard L , King Daniel 
Published: June 2023

e15512 Background: Early treatment (tx) improves survival in rectal cancer (ca). We explored whether socioeconomic and demographic attributes are associated with time to tx initiation for rectal ca patients (pts) in New York's largest and most diverse healthcare system. Methods: 283 rectal ca pts were identified from three multidisciplinary tumor boards from 2019-2022. Time to tx was calculated as time from biopsy to first tx (surgery, chemotherapy, or radiation). Social work assistance was defined as an intervention by a social worker for home care, housing, or transportation assistance. Reasons for tx delay were assessed from physician and social work notes. Results: Median time to tx for all pts was 41 days. Time to tx was longer for Black/African American (BAA) (56.5 days; p < 0.001) and Medicare only (46.5 days; p = 0.005) pts. No differences were seen in time to tx for all pts when stratified by first tx modality (surgery, chemotherapy, or radiation). In a univariable linear regression, BAA pts (vs Asian or White; p < 0.001), Medicare only pts (vs Medicaid, Medicare with Supplemental, or Commercial Insurance; p = 0.001), and pts requesting social work assistance (p = 0.001) predicted longer time to tx. Employed pts (vs unemployed or retired; p = 0.034) predicted shorter time to tx. In a multivariable model, BAA (p = 0.013), Medicare (p = 0.022), and social work assistance (p = 0.029) predicted longer time to tx. The most common reasons identified for tx delay in BAA and Medicare pts were hospitalization during diagnosis (9%), evaluation of metastatic disease (9%), and tx hesitancy (7%). The odds ratio of being hospitalized during initial workup was 2.8 times higher for BAA than Asian or White pts (p = 0.007). Conclusions: Analysis of time to tx in rectal ca showed a notable delay for BAA pts, Medicare only pts, and pts requesting social work assistance. These findings may empower further studies to assess which factors are causal and to implement interventions that promote equity in timely tx for rectal ca pts. Reasons for tx delay were also not well documented and should be further elucidated. [Table: see text]
Translationally controlled tumor protein as a prognostic marker in metastatic colon cancer.
Authors: Stoyanov Dragomir Svetozarov , Penkova Mariya , Conev Nikolay , Donev Ivan 
Published: June 2023

e15513 Background: The translationally controlled tumor protein (TCTP) is a highly conserved protein present in virtually all eukaryotic organisms. TCTP is involved in a variety of normal cell functions and disease processes. Preclinical studies reveal that TCTP has anti-apoptotic properties, promotes cell growth and division, and is involved in cancer progression by promoting invasion and metastasis. Our study explores the potential value of TCTP as a prognostic marker in metastatic colon cancer. Methods: A retrospective analysis of 54 patients with primary metastatic colon cancer was performed. Using immunohistochemistry, TCTP levels in the primary tumor were assessed semiquantitatively via the calculation of cytoplasmic and nuclear H-score. Results: Cytoplasmic TCTP levels in the primary tumor had no statistically significant association with progression-free survival in first-line therapy (PFS1) and overall survival (OS) in our patient population. Patients whose primary tumors had a negative nuclear TCTP expression had significantly better clinical outcomes. The PFS1 for the negative nuclear TCTP expression group was 7.4 months (95% CI, 5.3-9.6) vs 4.5 months (95% CI, 3.4-5.6) in the group with positive nuclear expression (p = 0.023). Patients with a negative nuclear expression of TCTP had a significantly higher median OS (17.1 months; 95% CI, 13.5–20.6) compared to those with positive TCTP nuclear expression (median 11.5 months; 95% CI, 8.5-14.5) (p = 0.031). In Cox regression analyses, a positive nuclear TCTP H-score conferred a higher risk for worse PFS1 (HR 1.960; 95% CI, 1.086-3.537; p = 0.025) and OS (HR 1.882; 95% CI, 1.050-3.371; p = 0.034). The 1-year OS rate in the group with negative nuclear TCTP expression was 80.0% compared to 47.4% in patients with positive nuclear TCTP expression (p = 0.03). Conclusions: The present study suggests that semiquantitative H-score measurement of TCTP levels in the nuclei of tumor cells from the primary tumor is a potential prognostic marker for clinical outcomes in patients with metastatic colon cancer.
Microscopic residual disease (MRD) monitoring and time to disease recurrence across gastrointestinal (GI) malignancies: A single-institution, real-world study.
Authors: Winters Harrison David , Sackstein Paul , Weinberg Benjamin Adam , Debnath Dipanjan , Geng Xue , Wang Hongkun , Chintalacheruvu Saavan , Marshall John , He Aiwu Ruth , Noel Marcus Smith , Mukherji Reetu 
Published: June 2023

e15518 Background: Circulating tumor DNA (ctDNA) is a powerful tool that can detect early evidence of cancer relapse, or MRD. While most GI MRD studies to date are in colorectal adenocarcinoma (AC), a limited but growing body of evidence supports its use in other GI cancers. We describe the outcomes of patients (pts) with various GI cancers who underwent real-world MRD testing at our institution. Methods: In this retrospective analysis, we identified GI cancer pts with at least 1 tumor-informed ctDNA test (Natera, Inc) ordered between June 2020-August 2022. Descriptive statistics were used to characterize clinicopathologic factors, clinical contexts of ctDNA testing, rates of ctDNA positivity (ctDNA+), and relapse rates. Median relapse-free survival (mRFS) and overall survival (mOS) were calculated using Kaplan-Meier methods, comparison between groups by log-rank test, and hazard ratios (HR) by Cox proportional hazard models. Results: In total, 228 GI cancer pts underwent ctDNA testing for MRD monitoring. Pts had stage I (20.6%), 2 (32.0%), 3 (38.2%), and 4 (9.2%) disease at diagnosis. Testing started after an initial curative therapy attempt in 82% of pts and after a repeat curative attempt for disease recurrence in 18% of pts. The median follow-up time was 15.0 months (mo). ctDNA testing was successful in 222 pts (97.4%). The cancer subtypes, ctDNA, and clinical outcomes are reported (table). Collectively, 61/222 of pts had at least 1 ctDNA+ test, and 59.0% of these pts had relapse on their next scan performed after a median interval of 40 days (IQR 22-70) from the first positive test. Of the 62/222 pts who relapsed, ctDNA detected relapse before imaging in 43 pts (69.4%) with a median lead time of 57 days (IQR 29-128). The relapse rates were 82.0% vs. 7.5%, mRFS 10.8 mo vs. not reached (NR) (HR 18.6; 95% CI 9.8-35.3), and mOS 43.1 mo vs. NR (HR 5.0; 95% CI 1.8-13.9) in anytime-ctDNA+ pts compared to never-ctDNA+ pts. Similar trends were observed in the colon, rectal, and pancreas AC subgroups. Conclusions: ctDNA was utilized successfully across GI cancers and detected relapse before imaging in most pts. Anytime-ctDNA+ status predicted worse outcomes. About 40% of pts had a ctDNA+ test with no evidence of disease on an immediate subsequent scan, highlighting a prevalent “new stage” of high-risk pts that may benefit from novel treatments. [Table: see text]
Efficacy of PD-1 inhibitors for colorectal cancer and polyps in patients with Lynch syndrome.
Authors: Yu Jiehai , Xiao Binyi , Tang Jinghua , Li Dandan , Wang Fang , Ding Ya , Han Kai , Kong Ling-Heng , Ling Yi-hong , Mei Wei-Jian , Hong Zhigang , Liao Leen , Yang Wanjun , Pan Zhi-Zhong , Zhang Xiao-Shi , Jiang Wu , Ding Pei-Rong 
Published: June 2023

e15521 Background: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. Methods: LS patients with CRC who had evaluable tumors and received ≥2 cycles of PD-1 inhibitors were included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies including anti cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analyzed. Results: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3 to 71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses (CRs) and 42.7% (n = 32) partial responses (PRs). Three cases of LS CRCs displaying pMMR/MSS or discordant MMR/MSI status were not responsive even with a high tumor mutation burden (TMB). Mucinous/signet-ring cell differentiation was associated with a lower ORR ( P= 0.013). The 3-year OS and PFS was 91.2% and 81.0%, respectively. Colorectal polyp/adenoma was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment and their maximum diameters were all larger than 7mm. Conclusions: PD-1 inhibitors are highly effective for dMMR/MSI-H LS CRCs, but not for pMMR/MSS LS CRCs or those displaying discordant MMR/MSI status or mucinous/signet-ring cell CRC. Some of the large LS adenomas may also be sensitive to anti-PD-1 treatment.
Colorectal cancer screening and treatment before and during the COVID-19 pandemic at a Southeast Texas community hospital.
Authors: Abdelhakeem Ahmed , Siddiqi Muhammad , Thaimuriyil Nigil , Peters Chelsey , Blevins Samantha , Naqvi Tahir A. 
Published: June 2023

e15522 Background: The COVID-19 pandemic imposed significant restraints on healthcare systems, raising concerns regarding care delays and excess cancer-related deaths. We aimed to investigate the impact of COVID-19 on colorectal cancer (CRC) screening and the time to treatment initiation (TTI) for cases with a confirmed diagnosis of CRC. Methods: We conducted a retrospective study in which we included all patients who underwent screening colonoscopy between April 2019 and March 2021 at our hospital. Patients with a diagnosis of CRC have been confirmed with the data from our cancer center to check if they could continue cancer staging workup and start their treatment. Patients were stratified into pre-COVID-19 (April 2019-March 2020) and COVID-19 (April 2020-March 2021) groups. Descriptive statistics and multivariate regression analysis were applied using SAS software, version 9.4. Results: A total of 1439 patients underwent screening colonoscopies during the study period. 746 during pre-COVID-19 group, and 693 during COVID-19 group (p = 0.1624). In the pre-COVID-19 group, 47 patients were found to have CRC, and 25 patients (53%) continued cancer staging workup and started treatment in our cancer center. Among 36 patients with confirmed CRC diagnosis in the COVID-19 group, only five patients (14%) continued cancer staging workup and started treatment (p = 0.0003). All patients with confirmed CRC in the COVID -19 group had localized disease compared to 25 patients (96%) in the pre-COVID-19 group. TTI in the COVID-19 group (mean of 21 days ± 13.3) was shorter compared to the pre-COVID-19 group (mean of 33 days ± 46.7) (p = 0.025). Comparative analysis between the study groups didn’t show any statistically significant difference based on age, sex, race, or insurance status. Conclusions: In our hospital, the COVID-19 pandemic didn’t appear to affect the accessibility to CRC screening or delay in TTI. However, a limited number of patients with confirmed CRC during the COVID-19 pandemic were able to continue cancer staging workup and receive treatment.
Preliminary study of microRNA expression profiling in non-metastatic colorectal cancer.
Authors: Kluz Natalia , Petniak Alicja , Ciechański Aleksander , Kocki Janusz , Gil Kulik Paulina 
Published: June 2023

e15528 Background: MicroRNAs (miRNAs) are non-coding single-stranded RNAs (18–25 nucleotides in length) that regulate gene expression at the posttranscriptional level by promoting the degradation of mRNAs or by blocking mRNA translation. However, the clinical significance in colon cancer is not yet determined. This study aims to identify differentially expressed miRNAs in colorectal cancer by comparing colon cancerous tissues with normal tissues, exploring the potential roles. Methods: The miRNA expression microarray was employed on tumors from patients diagnosed with adenocarcinoma of the colon. The pilot study included samples from 6 patients (3 women and 3 men), aged 55 to 72 years (mean 62.5±8.4 years). The tumour was located in the rectum, TNM status was as follows: cT (all patients at stage T3), cN (3 patients – N1, 3 patients – Nx), cM (all patients at stage M0). Average tumor size 4.6±2.5 cm. Normal colon tissue was used as a control. The studies were performed with the consent of the patient and according to the protocol accepted by the Bioethics Committee at the Medical University of Lublin No. KE-0254/12/2018. The material was collected during tumor removal surgery, then transported and stored in RNAlater. In the next step, microRNAs were isolated using the RNeasy Micro Kit (Qiagen). The quality and quantity of isolated RNA was assessed with NanoDrop 2000c followed by Bioanalyzer 2100 (Agilent), for the next step samples with RIN above 7. The microRNA expression profile was then evaluated using the GeneChip™ miRNA 4.0 Array (Applied Biosystems). Results: On the basis of a pilot microarray study, the profile of differentially expressed miRNAs was successfully screened. 1.39% of 36 222 tested genes showed a significant at least twofold increase in expression, while 1.75% showed a significant at least twofold decrease in expression. Three novel, not yet described in literature, miRNAs i.e. miR-3154 (p-value 0.015), miR-3921 (p-value 0.036), and miR-5006 (p-value 0.007) appeared to be involved in colorectal carcinogenesis. Conclusions: The present study suggests that mentioned miRNAs after confirmation on a greater group of patients may be used as diagnostic markers for the detection of early stage colon cancer in the general population. This paper was created as part of the project “The Best of the Best! 4. 0.” implemented under the Operational Programme: Knowledge Education Development 2014-2020 and co-financed by the European Social Fund.
Use of circulating tumor DNA analysis to predict recurrence and need for adjuvant chemotherapy in stage I-IV colorectal cancer.
Authors: Li Li-Ren , Fan Wenhua , Xia Zhiyuan , Chen Rongrong , Lin Dagui , Li Fang , Zheng Yang , Luo Jiongyong , Xiong Yuanyuan , Yu Pengli , Gao Wei , Gong Yuhua , Zhang Sen , Zhang Feiran 
Published: June 2023

e15537 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Methods: We enrolled 309 patients with stages Ⅰ to Ⅳ CRC who underwent definitive surgery. Tumor tissues from those patients were sequenced by a custom-designed next-generation sequencing (NGS) panel to identify somatic mutations, and plasma was analyzed using ctDNA-based molecular residual disease (MRD) assay which integrated tumor genotype–informed and tumor genotype–naïve ctDNA analysis. Results: ctDNA was detected after surgery in 5.4%, 13.8%, 15% and 30% of patients with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease, respectively, and in 17.5% of all longitudinal samples. Detection of MRD after surgery and in serial plasma samples during follow-up were associated with shorter disease-free survival (DFS) (hazard ratio [HR], 13.17; P < 0.0001 and HR, 14.44; P < 0.0001, respectively) independent of tumor site, stage, and MSI status. Within the population, only 13 patients (6.6%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 93.4%. Correspondingly, the positive predictive value of longitudinal detectable MRD was 79.6%, with a median lead time of 10.1 months. Further subgroup analyses revealed that adjuvant therapy did not confer a superior survival for patients with undetectable or detectable MRD. Moreover, lung-only and peritoneal metastases were less detectable by MRD. Conclusions: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and MSI status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.
Assessment of genomic profiling in patients with colorectal cancer treated in community oncology practices.
Authors: Cosgrove David , Paul Emily , Harrell Robyn , Espirito Janet L. , Robert Nicholas J. , Oliver Robert J. 
Published: June 2023

e15538 Background: Comprehensive genomic profiling is becoming the standard of care for oncology, though actionable biomarkers remain the focus. The value of expansion from single gene tests to large, next-generation sequencing (NGS) based tests can be seen in the application of precision medicine. Additionally, circulating tumor DNA (ctDNA) is becoming a key area of testing during and post treatment. In this study, we explored genetic testing rates in colorectal cancer (CRC) patients (pts). Methods: Pts were identified from the iKnowMedSM EMR data over 4 years (2018-2022) from 113 community oncology practices. Pts were required to have either primary colon or rectal cancer, be at least 20 yrs old at diagnosis, and have at least 2 office visits. All stages of disease were included. Genomic data was assessed from two sources: abstracted data from charts and genomics reports from clinical labs. Genomic tests included detection of mutations for relevant biomarkers, including but not limited to BRAF, KRAS, NRAS, NTRK, microsatellite instability (MSI), and tumor mutational burden (TMB), and entry of germline biomarkers relevant to Lynch syndrome. The use of ctDNA was also evaluated. Results: A cohort of 41,980 pts with CRC was identified. Median age was 66 yrs, 62% white. Of these, 18,782 pts (45%) had biomarker testing performed. Genomic testing rates were observed to have increased by 61% across all stages of disease over the four-year time span. The highest rate of biomarker testing was performed in pts with stage IV disease at diagnosis, representing 21% (n = 9021). Testing results were most often available for BRAF (n = 17576), with nearly 16% of the cohort showing a mutation, 35% of those with the V600E mutation (n = 967). MSI was observed in 14%. Increasing use of ctDNA observed, and 350 pts had multiple genetic reports (3+). Of the pts with genetic information, 245 were enrolled in clinical trials. Conclusions: In this study, we observed the increase of genetic profiling of CRC pts over time. Additional research into the use of targeted therapies and outcomes will be performed. The exploratory regions of the NGS-based assays tested may also provide new potential targets as the database of combined clinical and genetic information grows.
Circulating tumor DNA (ctDNA) dynamics in response to checkpoint inhibitor immunotherapy in colorectal cancer.
Authors: Patell Kanchi , Kurian Matthew , Booker Benjamin , Chung Michelle , Bennett Alexis , Bajor David L , Mohamed AMR , Mahipal Amit , Chakrabarti Sakti , Selfridge J. Eva 
Published: June 2023

e15540 Background: Circulating tumor DNA (ctDNA) is emerging as a sensitive and specific non-invasive marker of active disease in patients (pts) with colorectal cancer (CRC) and may be used for monitoring response to immunotherapy (IO) in all solid tumors. However, the dynamics of ctDNA changes in response to IO and their correlation to radiographic response has not been well-established. Methods: We searched for all pts in our institution who received IO for a solid tumor diagnosis and who also received quantitative ctDNA testing using Signatera. We retrospectively evaluated radiographic treatment response using RECIST v1.1 and correlated radiographic response to time-matched changes in quantitative ctDNA. Objective response rate (ORR) was defined as the percentage of pts achieving radiographic partial response (PR) plus complete response (CR). Results: We identified 6 pts with advanced CRC who underwent serial ctDNA testing while receiving IO; all patients had loss of mismatch repair protein expressions. Median age was 70 years (range 35-90), and 50% of patients were female. All pts were actively receiving IO at the time of data cutoff. Two pts were receiving ipilimumab plus nivolumab, the other 4 pts were receiving pembrolizumab; 1 pt had only received 1 cycle of IO at time of cutoff, thus did not have on-treatment imaging and was excluded from further analysis. For the response evaluable patients, ORR was 100%, with all pts (5/5) achieving PR after median of 3 cycles (range 1-3 cycles) of treatment. Quantitative ctDNA decreased by 83-100% in all pts analyzed. 1 pt had radiographic (pseudo-)progression at time of first radiographic assessment, however at this timepoint, ctDNA had decreased by 60%; this pt continued on immunotherapy based on clinical benefit including ctDNA data. Subsequent radiographic assessment of this pt confirmed partial response and ctDNA response decreased by total of 95% after a total of 3 cycles of IO. Conclusions: In this small patient population, we show that quantitative ctDNA directly corresponds to radiographic response to IO, and may guide treatment decisions by differentiating pseudoprogression from true progression. Further longitudinal studies will show if ctDNA changes correlate to duration of response, early identification of treatment resistance, and ultimately survival.