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Background Risk evaluation of lymph node metastasis for early-stage (T1 and T2) colorectal cancers is critical for determining therapeutic strategies. Traditional methods of lymph node metastasis prediction have limited accuracy. This systematic review aimed to review the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers. Methods A comprehensive search was performed of papers that evaluated the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers. Studies were appraised using the Joanna Briggs Institute tools. The primary outcome was summarizing artificial intelligence models and their accuracy. Secondary outcomes included influential variables and strategies to address challenges. Results Of 3190 screened manuscripts, 11 were included, involving 8648 patients from 1996 to 2023. Due to diverse artificial intelligence models and varied metrics, no data synthesis was performed. Models included random forest algorithms, support vector machine, deep learning, artificial neural network, convolutional neural network and least absolute shrinkage and selection operator regression. Artificial intelligence models' area under the curve values ranged from 0.74 to 0.9993 (slide level) and 0.9476 to 0.9956 (single-node level), outperforming traditional clinical guidelines. Conclusion Artificial intelligence models show promise in predicting lymph node metastasis in early-stage colorectal cancers, potentially refining clinical decisions and improving outcomes. PROSPERO registration number CRD42023409094. [ABSTRACT FROM AUTHOR]

Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance. [ABSTRACT FROM AUTHOR]

The individualized treatment rule (ITR), which recommends an optimal treatment based on individual characteristics, has drawn considerable interest from many areas such as precision medicine, personalized education, and personalized marketing. Existing ITR estimation methods mainly adopt 1 of 2 or more treatments. However, a combination of multiple treatments could be more powerful in various areas. In this paper, we propose a novel double encoder model (DEM) to estimate the ITR for combination treatments. The proposed double encoder model is a nonparametric model which not only flexibly incorporates complex treatment effects and interaction effects among treatments but also improves estimation efficiency via the parameter-sharing feature. In addition, we tailor the estimated ITR to budget constraints through a multi-choice knapsack formulation, which enhances our proposed method under restricted-resource scenarios. In theory, we provide the value reduction bound with or without budget constraints, and an improved convergence rate with respect to the number of treatments under the DEM. Our simulation studies show that the proposed method outperforms the existing ITR estimation in various settings. We also demonstrate the superior performance of the proposed method in patient-derived xenograft data that recommends optimal combination treatments to shrink the tumour size of the colorectal cancer. [ABSTRACT FROM AUTHOR]

Background For cancer screening programmes to be effective in early detection it is important that those invited can access screening services and understand the benefits of participation. A better understanding of the factors that matter to potential participants of cancer screening programmes can assist in developing strategies to increase current uptake. Methods We conducted an overview of systematic reviews to answer the question: What factors influence the uptake of cancer screening services (breast, bowel and cervical) in high-income countries? A thematic approach supported by tabular summaries and qualitative heat maps was used to categorize factors, described as 'barriers' or 'facilitators'. Results A total of 41 systematic reviews met the criteria for inclusion. The barrier with the greatest number of 'hot spots' across all three screening programmes was a fear of the unknown regarding a possible diagnosis of cancer or abnormal screening results, followed closely by a general lack of knowledge surrounding cancer screening programmes. The greatest collective facilitator to uptake was recommendation by a healthcare provider to attend screening. Conclusion Across all factors 'trust' and 'building trusted relationships' can be seen as integral to the success of cancer screening programmes and must be reflective of collaborative efforts to mitigate barriers and enhance facilitators to uptake. There is future scope to consider interventions that (i) increase demand for screening services, (ii) reduce barriers to uptake of services and/or (iii) are relevant to the healthcare system and those providing services. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics. [ABSTRACT FROM AUTHOR]

We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC). We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%). Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed. Here, we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors. To efficiently identify repurposed drugs for CRC, we developed a robust organoid-based drug screening system. By combining the repurposed drug library and computation-based drug prediction, 335 drugs were tested and 34 drugs with anti-CRC effects were identified. More importantly, we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns: differentiation induction, growth inhibition, metabolism inhibition, immune response promotion, and cell cycle inhibition. The anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft (PDOX) system in vivo. We found that fedratinib, trametinib, and bortezomib exhibited effective anticancer effects. Furthermore, the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were evaluated. Our study offers an innovative approach for drug discovery, and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC. [ABSTRACT FROM AUTHOR]

Introduction Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. Methods This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. Results 239 patients were included; 75% (n  = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n  = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n  = 106/239) of respondents sold property, 29% (n  =  70/239) asked for charity from public, family, or friends, and 16% (n  = 37/239) took loans with interest to fund cancer treatment. Conclusion Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care. [ABSTRACT FROM AUTHOR]

Background Right-sided colon cancer (RCC) differs in mutation profile and risk of recurrence compared to distal colon cancer. Circulating tumour DNA (ctDNA) present after surgery can identify patients with residual disease after curative surgery and predict risk of early recurrence. Methods This is a prospective observational biomarker trial with exploration of ctDNA in 50 non-metastatic RCC patients for which oncological right-sided colectomy was performed. Blood samples were collected preoperatively, within 1 month post surgery, 3 months (not mandatory), 6 months and every 6 months thereafter. Plasma cell free DNA and/or tumour was investigated for cancer-related mutations by the next-generation sequencing (NGS) panel AVENIO surveillance specifically designed for ctDNA analysis. Detected mutations were quantified using digital droplet PCR (ddPCR) for follow-up. Recurrence-free survival was explored. Results 50 patients were recruited. Somatic cancer-related mutations were detected in 47/50 patients. ddPCR validated results from NGS for 27/34 (plasma) and 72/72 samples (tumour). Preoperative ctDNA was detected in 31/47 of the stage I/III patients and the majority of ctDNA positive patients showed reduction of ctDNA after surgery (27/31). ctDNA-positive patients at first postoperative sample had high recurrence risk compared to patients without measurable ctDNA (adjusted hazard ratio: 172.91; 95% c.i.: 8.70 to 3437.24; P : 0.001). Conclusion ctDNA was detectable in most patients with non-metastatic RCC before surgery. Positive postoperative ctDNA was strongly associated with early recurrence. Detectable postoperative ctDNA is a prognostic factor with high (100%) positive predictive value for recurrence in this cohort of non-metastatic RCC. Clinical Trial Registration ClinicalTrials.gov ID: NCT03776591 [ABSTRACT FROM AUTHOR]

This article presents a study that aimed to replicate previous research on the relationship between a genetic polymorphism in the COX-2 gene promoter and peritoneal infection after colorectal cancer surgery. However, the study found that the previous findings could not be replicated, and there was a non-significant reverse association between the genetic polymorphism and peritoneal infection. The study suggests that factors such as sample size, analytic differences, outcome definition, and allele frequencies may have contributed to the differences in results. The study concludes that more research is needed to gain a better understanding of the relationship between the genetic polymorphism and peritoneal infection. [Extracted from the article]