Search Results (279)

CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article

Purpose: Predicting colorectal cancer liver metastasis (CRLM) is essential for prognostic assessment. This study aims to develop and validate an interpretable multimodal machine learning framework based on multiparametric MRI for predicting CRLM, and to enhance the clinical interpretability of the model through SHapley Additive exPlanations (SHAP) analysis and deep learning visualization. Methods: This multicenter retrospective study included 463 patients with pathologically confirmed colorectal cancer from two institutions, divided into training (n = 256), internal testing (n = 111), and external validation (n = 96) sets. Radiomics features were extracted from manually segmented regions on axial T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). Deep learning features were obtained from a pretrained ResNet101 network using the same MRI inputs. A least absolute shrinkage and selection operator (LASSO) logistic regression classifier was developed for clinical, radiomics, deep learning, and combined models. Model performance was evaluated by AUC, sensitivity, specificity, and F1-score. SHAP was used to assess feature contributions, and Grad-CAM was applied to visualize deep feature attention. Results: The combined model integrating features across the three modalities achieved the highest performance across all datasets, with AUCs of 0.889 (training), 0.838 (internal test), and 0.822 (external validation), outperforming single-modality models. Decision curve analysis (DCA) revealed enhanced clinical net benefit from the integrated model, while calibration curves confirmed its good predictive consistency. SHAP analysis revealed that radiomic features related to T2WI texture (e.g., LargeDependenceLowGrayLevelEmphasis) and clinical biomarkers (e.g., CA19-9) were among the most predictive for CRLM. Grad-CAM visualizations confirmed that the deep learning model focused on tumor regions consistent with radiological interpretation. Conclusions: This study presents a robust and interpretable multiparametric MRI-based model for noninvasively predicting liver metastasis in colorectal cancer patients. By integrating handcrafted radiomics and deep learning features, and enhancing transparency through SHAP and Grad-CAM, the model provides both high predictive performance and clinically meaningful explanations. These findings highlight its potential value as a decision-support tool for individualized risk assessment and treatment planning in the management of colorectal cancer. Full article

Gastric cancer traditionally affects older adults, and its precursor lesions and risk factors are well-documented in this population. Helicobacter pylori (H. pylori) infection remains highly prevalent in Saudi Arabia and contributes to gastric pathology. However, early-onset gastric cancer (EOGC), diagnosed in individuals aged ≤ 45 years, presents unique challenges and remains poorly understood in young populations. Therefore, we conducted an observational cohort study using a prospective longitudinal design (2021–2024) involving 1823 Saudi nationals aged 18–45 years who underwent zoom high-definition chromoendoscopy to evaluate the prevalence of premalignant gastric lesions (PGLs) and EOGC. We found a high H. pylori prevalence (78.0%) with PGLs in 1.9% of participants and EOGC-adenocarcinoma in 0.7% of patients. All EOGC cases arose from dysplasia, with most PGLs being classified as OLGA/OLGIM stage II/III. Multiple risk factorswere significantly associated with PGLs and EOGC, including H. pylori infection (p = 0.022), increasing age (p < 0.001), a family history of gastric cancer (p < 0.001), poor dietary habits (p < 0.001), obesity (p < 0.001), and smoking (p < 0.001). Additional EOGC risk factors include dage of 36–45 years (p = 0.018), EBV infection (p = 0.016), and diabetes mellitus (p = 0.001). These findings demonstrate the notable presence of PGLs and EOGC in young Saudi adults and emphasize the importance of early detection and risk factor management in this vulnerable population. Full article

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article

Background: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). Methods: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. Results: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2–4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3–28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8–21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. Conclusions: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort. Full article

The 26th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Saskatoon, Saskatchewan, on 17–18 October 2024. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with hepatocellular and biliary tract cancers. Specialists from the fields of medical and radiation oncology, interventional radiology, pathology and laboratory medicine, and general and hepatobiliary surgery participated in presentations and discussions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular and biliary tract cancers. Full article

Primary hepatic gastrointestinal stromal tumours (PHGISTs) are rare and frequently misdiagnosed due to their atypical presentation and uncertain origin. The purpose of this article is to present the case of a 79-year-old female patient with a gigantic PHGIST characterized by a predominantly cystic nature—an extremely rare presentation, as most cases of PHGIST are solid. Despite extensive imaging and exploratory laparotomy, the primary origin remained uncertain, leading to questioning about whether it was a true primary hepatic GIST or an atypical metastatic lesion. The initial therapeutic approach involved a surgical procedure aimed to confirm the diagnosis and achieve reductive tumourectomy. Following the surgery, the patient was administered imatinib with a favourable clinical response for four and a half years—an atypical pattern of resistance, as most patients typically develop therapeutic resistance within two to three years. A second surgical intervention was performed to address a cystic lesion localized in the left hepatic lobe, followed by an atypical segment III hepatectomy to achieve macroscopic resection. Subsequently, the patient received sunitinib for two and a half years, which resulted in temporary disease stabilization. However, the sunitinib treatment was associated with hypertension and leukopenia. The patient’s overall survival was 8 years, suggesting that individualized therapeutic strategies and close monitoring might be the key in such cases. Furthermore, this case confirms the role of surgical intervention even in advanced disease stages, with multiple major resections contributing significantly to prolonged survival. The interplay between surgical and oncologic therapies remains essential to guiding clinical decisions. Given the unusual cystic presentation, this case highlights the necessity to expand the pathological and molecular profiling of PHGISTs. Furthermore, the atypical timeline of resistance development and treatment-related toxicity emphasizes the importance of further research into the genetic and pharmacological determinants of PHGISTs. These findings advocate for the refinement of diagnostic, therapeutic, and surveillance protocols tailored to rare GIST subtypes. Full article

Exposure to high-linear energy transfer (LET) heavy ions, such as ²⁸Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of ²⁸Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc^1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc^1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or ²⁸Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, ²⁸Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the ²⁸Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in ²⁸Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to ²⁸Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after ²⁸Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions. Full article

The 2018 Farm Bill legalized hemp-derived cannabidiol (CBD) products containing less than 0.3% tetrahydrocannabinol (THC) in the United States. This legislative shift catalyzed both public and scientific interest in CBD’s potential health benefits. However, the rapid expansion of the CBD market has considerably outpaced rigorous scientific research, leaving many health claims largely unsubstantiated. While preclinical studies suggest that CBD may exert antitumorigenic effects in colorectal cancer (CRC) by modulating cell proliferation, apoptosis, and inflammation, clinical evidence supporting these effects remains limited. This review critically examines the current evidence on the role of CBD in colorectal tumorigenesis, with particular attention to its molecular mechanisms and interactions with the serotonergic system—a signaling pathway implicated in the development of CRC and possessing potential dual anti- and pro-tumorigenic properties. By influencing the serotonergic system, CBD may confer both protective and potentially deleterious effects during CRC development. This review underscores the need for further research to elucidate the complex mechanisms of CBD in colorectal tumorigenesis and to evaluate its therapeutic potential in clinical settings. Understanding these interactions could pave the way for novel prevention and treatment strategies, optimizing the anticancer efficacy of CBD while mitigating unintended risks. Full article

Background: The impact of adjuvant chemotherapy (AC) on outcomes in real-world patients with locally advanced rectal cancer (LARC) remains uncertain. Methods: Consecutive patients with LARC (stage II/III) undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were identified in the Canadian Health Outcomes Research Database. The impact of AC on clinical outcomes, including disease-free survival (DFS) and overall survival (OS), was evaluated using the Kaplan–Meier method and Cox proportional hazards modeling. Results: A total of 1448 patients had sufficient data available to be included for analysis with 1085 (74.9%) receiving AC. Of AC patients, 40.5% received oxaliplatin-based treatments. With a median follow-up of 66.43 months, the 5-year DFS rate was 67.7% (95% CI: 64.5–70.1%) vs. 58.7% (95% CI: 52.8–64.2%) in the AC group and non-AC group, respectively (p < 0.001). The 5-year OS rate of the whole cohort was 74.3% (95% CI: 71.5–76.85%) while the 5-year OS rate of the AC group was 77.8% (95% CI: 74.7–80.6%) compared with 63.8% (95% CI: 57.9–69.2%) for the non-AC group (p < 0.001). On multivariate analysis, patients who received AC had improved DFS (HR 0.6, 95% CI: 0.49–0.73, p < 0.001) and OS (HR 0.46, 95% CI: 0.36–0.58, p < 0.001). Conclusions: This large multi-institutional database analysis supports the use of AC in real-world LARC patients treated with nCRT followed by surgical resection. Full article

Colorectal cancer (CRC) is the third most common malignancy worldwide and the second leading cause of cancer-related mortality in the United States. The incidence of early-onset colorectal cancer (EOCRC) has been increasing over the past several decades. While the etiologies for this rising incidence remain unclear, genetic factors likely play an important role. DNA polymerase epsilon (POLE) mutations occur at a higher rate than average-onset colorectal cancer (AOCRC). DNA polymerase epsilon (Pol ε) is a high-fidelity, processive polymerase that is a promising target for immune checkpoint inhibitors due to its association with various human malignancies, including colorectal cancer. EOCRC remains a major area of focus, and POLE mutations leading to the high-TMB subtype constitute a potential therapeutic target. Full article

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria provide a standardized approach for assessing the nutritional status of patients and demonstrate strong predictive value for the prognosis of patients with gastric cancer. However, these criteria do not incorporate indicators of adipose tissue metabolic activity, which may reflect pro-tumor microenvironmental factors. This study investigated the combined predictive value of malnutrition, defined by the GLIM criteria, and preoperative adipose tissue ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake for recurrence-free survival (RFS) in patients with gastric cancer following radical surgery. Methods: A total of 105 patients were retrospectively enrolled and classified into malnourished and non-malnourished groups based on the GLIM criteria. Preoperative ¹⁸F-FDG positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) was used to measure the mean standardized uptake value (SUVmean) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). The predictive values of these indicators for RFS in patients with gastric cancer were assessed. Results: Multivariate survival analysis was used to identify GLIM-defined malnutrition (p = 0.020) and increased preoperative VAT SUVmean (p = 0.042) as independent risk factors for RFS. The combined analysis revealed that patients with both malnutrition and a high preoperative VAT SUVmean had the poorest RFS (HR = 18.41, p < 0.001). The predictive model integrating GLIM criteria and VAT SUVmean outperformed the GLIM criteria alone. Conclusions: This study demonstrated that combining malnutrition defined by the GLIM criteria with preoperative visceral adipose tissue ¹⁸F-FDG uptake optimizes recurrence risk stratification and exhibits superior prognostic predictive efficacy compared to using the GLIM criteria alone. This approach provides new insights into individualized prognostic assessment and intervention strategies. Full article

The knowledge concerning mild-to-moderate renal toxicity of adjuvant chemotherapy (CTH) in colon cancer patients is scarce. We retrospectively evaluated changes in the estimated glomerular filtration rate (eGFR) after three months of adjuvant treatment and the overall renal risk of the 6-month regimen in 145 patients who completed three months of therapy at three oncological centers. A decrease in eGFR of at least 1.5 mL/min/1.73 m² after three months and 3.0 mL/min/1.73 m² after six months was considered relevant in terms of kidney-related cardiovascular risk. Out of 114 patients who completed a 6-month regimen, kidney function deterioration occurred in 62 (54.4%) after 3 months and in 54 (47.4%) after 6 months. Age ≥ 70 years (RR = 2.66; 95% CI: 1.15–6.16) and diabetes (RR = 2.52; 95% CI: 0.98–6.45) were risk factors for kidney outcomes during the first three months of CTH. However, renal function decline during the first three months did not increase the risk of further deterioration on CTH continuation. In conclusion, older age and diabetes are factors increasing the risk of renal function deterioration during adjuvant CTH in colon cancer patients without preexisting chronic kidney disease. However, the decline during the first three months does not allow for predicting further changes under continued adjuvant therapy. Full article

Given the promising outcomes of stereotactic body radiation therapy (SBRT) in treating colorectal cancer liver metastases (CRLMs), we proposed an innovative strategy combining surgery with planned liver SBRT for CRLMs. This retrospective study included patients who underwent curative-intent surgery combined with planned liver SBRT from July 2019 to October 2023. Planned liver SBRT was delivered to residual unresectable and unablatable lesions with maximum diameters of ≤5 cm. Outcomes included local failure (LF), intrahepatic recurrence-free survival (IHRFS), extrahepatic recurrence-free survival (EHRFS), progression-free survival (PFS), overall survival (OS), and radiation-related adverse events. A total of 69 patients were included. The 1-, and 2-year cumulative incidence rates of LF after SBRT were 7.7%, and 9.6%, respectively. The median PFS was 6.2 months, and the median OS was 45.8 months. Multivariate analysis identified RAS/BRAF mutations, extrahepatic metastases excluding lung involvement, and higher CEA as independent predictors of poorer OS. Intrahepatic recurrence was the predominant pattern of first disease progression after combination treatment. Acute grade 1–2 radiation-related adverse events occurred in 56.5% of patients, while grade 3 toxicities were reported in 4.3%. This approach offers favorable long-term outcomes, suggesting its potential to broaden the indications for curative-intent local treatments in CRLMs. Full article

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by perivascular epithelioid cell proliferation. They can occur in various organs, but colonic PEComas are exceptionally rare, showing diagnostic challenges due to their nonspecific clinical presentation and similar features to those of other colorectal tumors. We present a case of a 61-year-old female with defecation accompanied by blood clots, initially diagnosed with a suspected tumor in the sigmoid colon. Despite initial biopsy yielding non-informative material, repeat colonoscopy and imaging studies revealed a malignant tumor with multinucleated giant (osteoclast-like) cells and probable p53 mutation, most likely of mesenchymal origin. Robotic surgical resection was performed, and ultimately pathological examination refined the diagnosis as a malignant PEComa of the colon. This case demonstrates the importance of considering PEComa in the differential diagnosis of colonic tumors. Further research is needed to ascertain the clinical behavior and optimal treatment for colonic PEComas. Full article