tbuckley/cabot-search huggingface dataset:
Acute cardiac complications in colorectal cancer compared to other gastrointestinal malignancies: A 10-year retrospective study.
Authors: Ayobami Gbenga Olafimihan, Ekrem Turk, Inimfon Jackson, Jeremiah Bello, Gbolahan Olatunji, Emmanuel Kokori, Nicholas Aderinto, Youjin Oh, Praise Fawehinmi, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2024)

e15652 Background: Patients diagnosed with gastrointestinal (GI) cancers have long-term risks of cardiovascular disease and mortality. However, research comparing patients with colorectal cancer (CRC) to other GI cancers to assess their risk of acute cardiac complications is lacking. We evaluated the risk of hospitalization with acute cardiac complications (acute myocardial infarction [MI], arrhythmias and heart failure [HF]) among patients with CRC versus other GI cancers. Methods: A ten-year retrospective study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, patients with diagnoses of GI cancers were identified. Multivariate logistic regression analysis was used to evaluate the odds of admission with an acute cardiac complication among patients with a diagnosis of CRC when compared to other GI cancers (esophageal, gastric, intestinal, hepatobiliary, and pancreatic cancers). Results: Among 4,408,321 GI cancer hospitalizations, 82,592 (0.18%) were for acute cardiac complications. Of these, 43.1% were in CRC patients and 56.9% were in those with other GI malignancies (P &lt; 0.001). Multivariate analyses revealed that patients with CRC had more than two-fold higher odds of acute MI compared to other GI cancer patients (Adjusted Odds Ratio (AOR): 2.47; 95% Confidence interval ( CI): 2.30-2.65), 1.8 times higher risk of arrhythmia (AOR: 1.78; 95% CI: 1.69-1.87) and 2.2 times higher risk of HF (AOR: 2.23; 95% CI:2.11-2.36). Overall, in comparison to other GI cancers, CRC patients were twice as likely to be admitted for acute cardiac complications (AOR: 2.09; 95% CI:2.02-2.16). Conclusions: Colorectal cancer patients have significantly higher odds of hospitalizations with acute cardiac complications relative to other GI malignancies. Older age and pre-existing comorbidities of CRC patients are unlikely to sufficiently explain these findings. CRC patients would benefit from active surveillance for cardiac diseases as well as further research on the long-term survival impact of acute cardiac complications on CRC patients. [Table: see text]
CK2 expression in cancer and associated clinical characteristics.
Authors: Nicholas Wilson, Isabelle Kreber, Cristián Figueroa, Isabel M. Dominguez
Journal: Journal of Clinical Oncology (2024)

e15156 Background: The protein casein kinase 2 (CK2) is a ubiquitously expressed, highly pleiotropic kinase. CK2 may have incredibly varied substrate specificity and catalytic activity, as it functions as both a tetrameric and monomeric enzyme. CK2 participates in many cellular processes such as cellular proliferation, growth, and survival, and has significant potential to assist in oncogenic signaling. We and others have demonstrated CK2 gene and protein overexpression, and sometimes underexpression, in a variety of cancers. Here we investigate how the expression of CK2 subunits in cancer is associated with clinical characteristics in several distinct cancer types. Methods: Data analysis was performed on 32 non-overlapping cancer datasets obtained from The Cancer Genome Atlas (TCGA) and Broad GDAC Firehose Legacy projects, one dataset from Cancer Cell Line Encyclopedia (CCLE), and normal tissue datasets from Gene Expression Omnibus. Statistical analysis was performed using RStudio to explore the relationship between the expression levels of the three CK2 alpha transcripts (CSNK2A1, CSNK2A2, and CSNK2A3) and beta transcripts (CSNK2B) with sample clinical characteristics provided by TCGA/Broad. Relationships between CK2 expression and cancer-type specific characteristics were also explored, such as KRAS mutations in colorectal adenocarcinoma and serum AFP at sample procurement in hepatocellular carcinoma. CCLE data was used to explore correlations between cancer-type dependent CK2 gene expression and half maximal inhibitory concentration (IC50) of over 250 anticancer drugs. Tumor Immune Estimation Resource (TIMER) 2.0 was used to assess the relationship between CK2 subunit expression and tumor immune infiltration. Results: As seen in our previous analysis, CK2 transcripts were upregulated in the majority of cancer types analyzed. We also found that CK2 transcript upregulation correlated with worse survival outcomes in several previously unstudied cancers. CK2 expression differed significantly between cancer subtypes such as in ductal carcinoma and lobular carcinoma in breast cancer. CK2 expression significantly correlated with tumor grade, TNM staging, clinical staging in certain cancer types. CK2 expression significantly correlated with altered response to various anticancer drugs in certain cancers. CK2 expression was associated with both increased and decreased immune infiltration in a variety of cancers. Conclusions: Overall, this study demonstrates that CK2 transcript expression correlates with a variety of cancer-type dependent characteristics and clinical outcomes. As a result, CK2 may be useful as a prognostic biomarker and therapeutic target.
The effect of HER2-targeted inhibitors as second-line or later-line regimens in the treatment of HER2-positive advanced colorectal cancer: A systematic review and meta-analysis.
Authors: Qianyuan Zhang, Haiyu Liu, Suyun Zhang, Jinghan Chen, Qiong Luo, Qian Xu, Xiangqi Chen, Sheng Yang
Journal: Journal of Clinical Oncology (2024)

e15542 Background: To systematically evaluate and meta-analyze the efficacy and safety of Human Epidermal Growth Factor Receptor-2 Inhibitor (HER2 Inhibitor) as a second-line or later-line antitumor regimen in the treatment of HER2-positive advanced colorectal cancer and provides a new method to treat metastatic colorectal cancer who failed with first-line treatment. Methods: Literature focusing on the use of HER2-targeted inhibitors in the treatment of HER2-positive mCRC was downloaded from Pubmed, Web of Science, EMBASE and Google Scholar databases from January 1, 2019 to October 31, 2022, and the final included articles were determined by screening and relevant data were extracted, including Objective Response Rate (ORR), disease control rate (DCR), Progression-Free-Survival (PFS), Overall Survival (OS), and Serious Adverse Events (SAEs) (Grade 3/4 adverse events). Binary variables were compared using 95% confidence intervals (CI) and odds ratios (OR); for continuous variables, heterogeneity was checked using Cochran's Q Test (p values and I²) and Weighted mean difference (WMD) and 95% CI. P &lt; 0.05 or I² &gt; 50% denote statistical significance, and results were combined using a random-effects model. The efficacy and safety of adding HER2-targeted inhibitors in treating HER2-positive mCRC were further discussed using the above methods. Results: The systematic review and meta-analysis included 17 studies with a total of 267 patients, with an overall DCR of 57% (95% CI: 43%-70%), an ORR of 29% (95% CI: 21%-37%), a median OS of 13.11 months (95% CI: 10.57-15.64), a median PFS of 4.40 months (95% CI: 3.64-5.15), and SAEs of 20% (95% CI: 0.11-0.29). The efficacy of the second-line and later-line treatment was significantly better than that of the well-known EPIC study, ML18147 study, CONCUR study and FRESCO-2 study. Conclusions: Systematic review and meta-analysis show that HER2-targeted inhibitors as second-line or later-line regimens demonstrate ideal antitumor efficacy and safety in HER2-positive mCRC, which is better than the standard regimen without anti-HER2 therapy. Specifically, the new ADC drug (A antibody-drug Conjugate, ADC) should be able to improve the treatment effect of these patients more effectively. Therefore, HER2-targeted inhibitors can effectively improve the efficacy of second-line and later-line therapy for HER2-positive mCRC. Furthermore, it is still worth exploring its therapeutic effects application as first-line therapy, which is expected to offer new strategies for the clinical diagnosis and treatment of HER2-positive advanced colorectal cancer.
First-in-human study of ABBV-400, a novel c-Met–targeting antibody-drug conjugate, in advanced solid tumors: Results in colorectal cancer.
Authors: Manish Sharma, John H Strickler, David Sommerhalder, Yasutoshi Kuboki, Ruth Perets, Jonathan Cohen, Judith Raimbourg, Takako Eguchi Nakajima, Noboru Yamamoto, Marcia Cruz-Correa, Bert O'Neil, François Ghiringhelli, Kanwal Pratap Singh Raghav, Rui Li, Gladys Morrison Thiele, Martha Raluca Neagu Aristide, Kevin Jay Freise, Carla Biesdorf de Almeida, Athanasios Vasilopoulos, John D. Powderly
Journal: Journal of Clinical Oncology (2024)

3515 Background: c-Met (MET protein) is frequently overexpressed in several advanced solid tumors including colorectal cancer (CRC). There are no approved therapies specific for c-Met–overexpressing tumors in CRC. The antibody-drug conjugate ABBV-400 comprises c-Met–targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. A phase 1 study of ABBV-400 was initiated for adults with advanced solid tumors and progression on standard therapies (NCT05029882); results from dose escalation (ESC) at doses 1.6–6.0 mg/kg once every 3 weeks (Q3W) were previously presented and showed preliminary efficacy (Sharma et al. ASCO 2023. Abstract 3015). We present data from dose ESC and expansion (EXP) cohorts in CRC. Methods: During EXP, patients (pts) with CRC were randomized to receive ABBV-400 at 1.6, 2.4, or 3.0 mg/kg Q3W. Primary objectives were to evaluate the safety, tolerability, pharmacokinetics, preliminary efficacy, and the recommended phase 2 dose of ABBV-400. Results: As of Oct 2023, 122 pts (ESC: 29; EXP: 93) were included. Median age: 56 years; 65 (53%) males. Median prior treatments was 4. Follow-up was longer in ESC vs EXP (14.8 vs 3.8 months). Seventy-eight (64%) pts had a grade (G)≥3 treatment-emergent adverse event (TEAE); 41% had a serious TEAE. Most frequent hematologic TEAEs were anemia (52%; G≥3: 30%), neutropenia (37%; G≥3: 25%), leukopenia (25%; G≥3: 12%), and thrombocytopenia (23%; G≥3: 12%); nonhematologic TEAEs were nausea (57%, G≥3: 3%), fatigue (43%; G≥3: 2%), and vomiting (39%, G≥3: 4%). G≥3 diarrhea was &lt; 1%. Unadjudicated interstitial lung disease/pneumonitis rate was 7% (G≥3: 2%). Treatment-related AEs leading to discontinuation occurred in 11 (9%) pts. Preliminary efficacy outcomes are shown in the Table. The majority of tissues expressed c-Met. In pts with higher c-Met expression, an increased ORR of &gt; 30% was observed at efficacious doses (≥2.4 mg/kg). Activity was also seen at lower c-Met expression levels (10–15% ORR). Conclusions: ABBV-400 at 2.4 and 3.0 mg/kg Q3W has a tolerable and manageable safety profile, with promising antitumor activity. Long-term tolerability appears improved at 2.4 relative to 3.0 mg/kg, with higher relative dose intensity and generally lower TEAEs. The study is also evaluating ABBV-400 with bevacizumab in pts with CRC. Clinical trial information: NCT05029882 . [Table: see text]
Antibiotic exposure and colon carcinogenesis: In-depth profiling of a 492-patient cohort, with a focus on antibiotic classifications and subtypes.
Authors: Dilichukwu Chudy-Onwugaje, Ahmed Elsayed Salem, Bani Roland
Journal: Journal of Clinical Oncology (2024)

e15643 Background: To investigate whether the use of specific antibiotics is associated with an increased risk of colon cancer incidence. Methods: We conducted a retrospective cohort study comprising 492 patients diagnosed with colon cancer between 2012 and 2022, with no prior malignancies and a minimum 5-year follow-up period. We collected demographic data, medical histories, and records of antibiotic exposure, categorizing antibiotics systematically based on the Anatomical Therapeutic Chemical (ATC) classification system. Patient antibiotic histories, including drug names, dosages, durations, and therapeutic indications, were included. Antibiotics were classified as broad-spectrum, narrow-spectrum, or extended-course. We performed univariate and multivariate logistic regression models and used propensity score matching to control for potential confounding variables, such as age, gender, co-morbidities, and concurrent medications. Subgroup analyses were conducted to identify specific antibiotic classes associated with an increased risk of colon cancer. Results: The mean age of the cohort was 65.7 years (SD ± 8.3), with an equal gender distribution. Adenocarcinoma was the predominant histological subtype (429 cases, 87%), with rare subtypes accounting for the remaining cases. Common co-morbidities included hypertension (226 cases, 46%), diabetes mellitus (108 cases, 22%), and hyperlipidemia (88 cases, 18%). The most frequently prescribed antibiotics were fluoroquinolones (158 cases, 32%), followed by cephalosporins (108 cases, 22%), and macrolides (88 cases, 18%). Extended-course antibiotics were administered in 138 cases (28%). Preliminary analysis revealed a statistically significant correlation between the use of extended-course antibiotics and the risk of colon cancer (Odds Ratio = 1.89, 95% Confidence Interval: 1.32-2.71, p &lt; 0.05). No substantial association was observed with broad-spectrum or narrow-spectrum antibiotics. Subgroup analysis identified specific agents within the extended-course antibiotics, such as fluoroquinolones and clindamycin, with an elevated risk profile. Conclusions: This study suggests a potential association between the use of extended-course antibiotics and the development of colon cancer. Further validation through larger-scale, prospective studies is strongly recommended to confirm these findings. Further in-depth mechanistic inquiries, particularly in cellular signaling pathways and microbial interactions within the gut microbiome, are warranted to elucidate the underlying biological mechanisms driving this association.
Real-world multi-target stool DNA adherence in an underserved and vulnerable prison patient population.
Authors: Jeffrey Kasselman, Mallik Greene, Timo Pew, William Johnson, Burak Burak Ozbay, Durado Brooks, Paul J. Limburg
Journal: Journal of Clinical Oncology (2024)

e15632 Background: In 2024, colorectal cancer (CRC) is estimated to be the fourth most diagnosed cancer, as well as the second leading cause of cancer death in the United States. While adherence to regular CRC screening has been suboptimal in the general population, this holds to be especially true in populations that are medically underserved. Non-invasive tests, such as the guideline recommended multi-target stool DNA (mt-sDNA) test, offer a more accessible option to increase screening participation in difficult to reach populations. Herein, we evaluated adherence to CRC screening in a cohort of prisoners who received the mt-sDNA test at a Nebraska Department of Corrections facility in Nebraska. Methods: This was a retrospective cohort study in a small prison population. Participants included both males and females between the ages of 45 and 75 years who underwent CRC screening evaluation at the prison’s medical center between June 1 st – December 31 st , 2023 and were offered multiple CRC screening options, including the mt-sDNA test. No inducements were provided for completion of the mt-sDNA test. Baseline demographics were collected for cohort description. The primary variable of interest was mt-sDNA test return rate (adherence), defined as completion of the mt-sDNA test within 60 days of kit receipt. We also evaluated mt-sDNA test results in secondary analyses. Results: Once inclusion criteria were applied, the resulting analysis cohort included 129 patients who were first time mt-sDNA screeners. The cohort was largely male (96.9%) and between the ages of 50-64 years (78.3%). Overall mt-sDNA test adherence was 95.3%, with the average time to test completion being 20 days. No significant difference was seen in test completion among males and females (95.2% vs 100%, respectively). Completion rates increased with patient age, at 90.9% (45-49 years), 95% (50-64 years), and 100% (65-75 years). The shortest time to completion in the population was observed amongst patients who were females (18.8 days), and those between the ages of 45-49 years (17.1 days). Negative and positive mt-sDNA test results were observed in 82.9% and 17.1% of the cohort, respectively. Conclusions: CRC screening with the mt-sDNA test in this single-center study of incarcerated participants yielded exceptionally high adherence rates within 60 days of kit receipt. Assessment of follow up colonoscopy rates for test-positive participants is ongoing. While based on a relatively small sample size in this initial study, the mt-sDNA test exhibited favorable completion rates in a difficult to reach population, supporting further efforts to characterize patient, provider, and system-level benefits that may be obtained through broader adoption of this highly accessible screening approach in this challenging healthcare setting.
Chemotherapy plus EGFR antibody as conversion treatment in RAS wild type, right-sided metastatic colon cancer: A systematic review and meta-analysis.
Authors: Jian Wang, Xiangling Wang, Pingtian Xia, Yanlei Wang, Dong Sun, Sen Guo, Yong Dai, Jing Hao
Journal: Journal of Clinical Oncology (2024)

e15568 Background: The optimal conversion strategy for right-sided RAS wild type (WT) metastatic colorectal cancer (mCRC) remains a contentious issue, especially regarding the role of EGFR antibodies. EGFR antibody treatment might be an attractive option in patients with contraindications to bevacizumab or in hyperselected patients with microsatellite stable subtypes and without RAS/BRAF/HER2 alterations, potentially allowing a shorter time to conversion surgery. Methods: We performed a systematic search of PubMed/MEDLINE and EMBASE for randomized trials reporting the overall response rate (ORR) and resection rate following chemotherapy (CT) plus anti-EGFR agents (cetuximab or panitumumab) for right-sided mCRC. Studies were selected regardless of whether the resection rate was a study endpoint or not. We used a random-effects model with generic inverse variance to compute pooled ORR and resection rates and to compare CT regimens combined with anti-EGFR or anti-VEGF agents. Results: Ten randomized trials with a total of 4465 mCRC patients were included; seven trials reported the resection rate as a secondary endpoint. 828/4465 (18.5%) patients were right-sided, of whom 419/828 (50.6%) patients received CT doublet or triplet plus anti-EGFR, 263/828 (31.8%) treated with CT plus bevacizumab, and 146/828 (17.6%) patients with CT alone. The ORR was significantly higher in the anti-EGFR group compared to CT alone (50.89% vs 31.03%, OR: 2.23 [95% CI: 1.50-3.32], p &lt; 0.01). No significant difference in ORR was observed between the CT plus anti-EGFR and CT plus bevacizumab groups (50.89% vs 53.32%, OR: 0.89 [95% CI: 0.65-1.21], p = 0.44). Resection rates were 8.08% for CT plus anti-EGFR, 4.79% for CT plus bevacizumab, and 12.24% for CT alone, with no significant differences among the three arms (χ 2 = 2.15, p = 0.34). Subgroup analysis of RAS/BRAF WT patients with right-sided tumors from the PARADIGM and PEAK trials showed no difference in progression-free survival (PFS) between the CT plus anti-EGFR or bevacizumab groups (11.01m vs 11.60m, HR = 1.04 [95% CI: 0.58-1.50]), but there was a trend toward improved overall survival (OS) with anti-EGFR treatment (30.66m vs 28.67m, HR = 0.81 [95% CI: 0.45-1.17]). Conclusions: The data indicate that augmenting chemotherapy with anti-EGFR could be a viable conversion therapy for patients with RAS/BRAF WT right-sided mCRC, underscoring its potential utility in this subset of patients.
Laparoscopic-assisted vs open surgery for low rectal cancer: 5-year outcomes of the LASRE randomized clinical trial.
Authors: Pan Chi, Weizhong Jiang, Xiangqian Su, Jianmin Xu, Huizhong Qiu, Liang Kang, Haijun Deng, Weiping Chen, Qingtong Zhang, Chunkang Yang, Yincong Guo, Ming Zhong, Kai Ye, Jun You, Dongbo Xu, Xinxiang Li, Ke-Feng Ding, Kaixiong Tao
Journal: Journal of Clinical Oncology (2024)

e15630 Background: The long-term efficacy of laparoscopic versus open surgery for low rectal cancer has not yet been established. The primary outcome of 3-year disease free survival (DFS) have been published (Chi et al., ASCO GI 2024). Here, we presented the data of 5-year outcomes, including DFS and overall survival (OS) and locoregional recurrence. Methods: This is a multicenter, noninferiority trial. A total of 1070 patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery from November 2013 to June 2018. All analyses were performed on an modified intention-to-treat (mITT) basis. Results: The final analysis included 1039 patients (median age: 57 years, 620 men; 685 and 354 in laparoscopic and open groups, respectively). Clinical TNM stage was II/III in 659 patients, and I in the remaining 380 patients. The 5-year DFS rate was 76.4% in the laparoscopic group versus 75.6% in the open group (log-rank P = 0.766). The 5-year OS rate was 84.6% in the laparoscopic group versus 86.6% in the open group (log-rank P = 0.405). The 5-year locoregional recurrence rate was 5.5% and 3.1%, respectively (log-rank P = 0.079). Conclusions: The findings of the LASRE trial demonstrate that the noninferiority of laparoscopic surgery compared to open surgery for low rectal cancer, as evidenced by the 3-year outcomes, is sustained over a 5-year period when conducted by skilled surgeons. These results affirm laparoscopic surgery as a secure and minimally invasive option for the treatment of low rectal cancer. Clinical trial information: NCT01899547 .
Prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.
Authors: Mohsin Saleet Jafri, Soukaina Amniouel
Journal: Journal of Clinical Oncology (2024)

e15548 Background: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Here, we aim to use machine learning and genetic profiles to identify precise multi-gene panels that can predict the response to 5-Fluorouracil-based chemotherapy in colorectal cancer patients. Methods: The genetic profiling data, including drug response profiles, were retrieved from the Gene Expression Omnibus (GEO) database. These datasets were used to train and validate machine learning models. Feature selection methods, such as least absolute shrinkage and selection operator (LASSO) and variable selection from random forests (varSelRF) and various algorithms, such as Random Forest and Support Vector Machines, were applied to develop predictive models. Functional enrichment and network analyses were performed using Ingenuity Pathway Analysis (IPA). Results: This study identified relevant gene signatures at two stages of colorectal cancer: primary and metastasis using two different chemotherapy regimens, FOLFOX and FOLFIRI. The predictive models achieved an average prediction accuracy of 93% in identifying drug response outcomes across multiple chemotherapy regimens. The application of the machine learning model suggested that 28.6% of patients who failed the treatment therapy they received would benefit from the alternative treatment. Conclusions: The developed machine learning models demonstrate potential for guiding clinicians in selecting the most effective treatment options based on individual genetic profiles. With additional clinical validation, this approach could lead to improvements in treatment outcomes for patients with CRC and other cancers.