Search Results (399)

Background/Objectives: Unhealthy lifestyles lead to chronic low-grade inflammation, increasing the risk of colorectal cancer. Few studies in East Asia have examined the association between the dietary inflammation potential and colorectal cancer incidence. Therefore, we aimed to investigate this association further in the Japanese population. Methods: This study included 38,807 men aged 45–74 years who participated in the Japan Public Health Center-based prospective study (JPHC Study). The energy-adjusted dietary inflammatory index (E-DII) was derived from a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Differences in risk due to a combination of E-DII and lifestyle were examined using interaction term. Results: During 14 years of follow-up, 1415 colorectal cancer cases occurred. A tendency to increased colorectal cancer risk was observed with consumption of pro-inflammatory diets among Japanese men (adjusted HR [95% CI] for the highest quintile: 1.20 [0.99–1.46], p trend = 0.08), with a significantly increased risk of colon cancer (HR: 1.28 [1.01–1.63], p trend = 0.03). A possible interaction was observed with alcohol consumption (p = 0.07), which was statistically significant for proximal colon cancer (HR: 1.14 [1.05–1.25] in drinkers; p interaction = 0.01). No significant interactions with other lifestyle factors were found. Conclusions: Consumption of pro-inflammatory diets increases colorectal cancer risk among Japanese men; alcohol consumption further increases this risk for drinkers. These findings suggest that colorectal cancer may be prevented through dietary modification. Full article

Colonoscopy is central to colorectal cancer (CRC) prevention, and its effectiveness is determined by the quality of mucosal inspection and lesion detection. The adenoma detection rate (ADR) remains the most widely validated quality benchmark due to its strong inverse association with interval CRC. However, reliance on ADR alone is increasingly recognized as insufficient, particularly given the growing understanding of the serrated neoplasia pathway, which contributes up to one-third of sporadic CRCs. This has driven the emergence of complementary metrics, such as the sessile polyp detection rate (SPDR) and adenomas per colonoscopy (APC). Although SPDR offers important advantages for capturing serrated pathology, challenges persist, including interobserver variability, inconsistent pathology thresholds, limited endoscopist training, and the absence of standardized benchmarks. Alongside these evolving metrics, technological advancements such as image-enhanced endoscopy, computer-aided detection, high-definition optics, and distal attachment devices have demonstrated measurable improvements in detecting subtle lesions and reducing operator-dependent variability. Large real-world registries, including GIQuIC, now support the development and validation of composite models that integrate ADR, SPDR, and APC to better reflect the full spectrum of neoplasia detection. As the field advances, redefining colonoscopy quality will require reconciling established metrics with newer indicators that more comprehensively address both conventional adenomas and serrated lesions. Full article

Background/objectives: Metabolic abnormalities, independent of excess weight, may contribute to cancer risk even among individuals of normal weight, though their role remains unclear. This study sought to ascertain if metabolically unhealthy normal-weight (MUNW) individuals, generally characterized by a normal body mass index alongside the presence of metabolic abnormalities, have higher cancer risk than metabolically healthy peers, to analyze variations in risk across obesity-related cancer types, and to examine which single specific metabolic components can predict cancer independently in normal-weight individuals. Methods: Two authors systematically searched the PubMed, EMBASE, and Web of Science databases for longitudinal studies, published from inception to July 2025, that included normal-weight adults, classified participants by metabolic health status, and reported incident cancer outcomes in metabolically unhealthy versus healthy normal-weight groups. Hazard ratio (HR) estimates were extracted from each study and were pooled using random-effects inverse-variance model with empirical Bayes variance estimator. Results: Thirty-five studies involving 18,210,858 participants (56.0% females, mean age = 53.8 years) were included. A total of 280,828 new cancer cases were diagnosed during follow-up (mean = 10.6 years). In comparison with metabolically healthy normal-weight individuals, MUNW individuals had a 20% higher risk of cancer (HR = 1.20, 95% confidence interval [CI]: 1.13–1.28). Increased risks were observed for gastric cancer (HR = 1.40, 95% CI: 1.04–1.87), pancreatic cancer (HR = 1.37, 95% CI: 1.21–1.54), and colorectal cancer (HR = 1.34, 95% CI: 1.14–1.57), which were the cancer types showing statistically significant associations in subgroup analyses. Normal-weight participants presenting specific metabolic factors like central adiposity or glucose metabolism abnormalities had a 20% (HR = 1.20, 95% CI: 1.13–1.37) and 23% (HR = 1.23, 95% CI: 1.06–1.41) increased cancer risk, respectively. Conclusions: MUNW individuals are at higher risk of cancer, with specific metabolic abnormalities, particularly central adiposity and impaired glucose regulation, emerging as the factors most strongly associated with increased risk in normal-weight individuals. Routine metabolic screening and detailed phenotyping are crucial to identify these risks. Full article

Previous haplotype Genome Wide Association Studies (GWASs) have suggested several rare loci with a shared increased risk of colorectal, gastric, and prostate cancer. This study aimed to find out more about markers specifically addressing the shared risk of colorectal and gastric cancer, as well as the shared risk of colorectal and prostate cancer. One analysis used 426 colorectal cancer cases with gastric cancer, with no prostate cancer cases in their families, and another analysis used 324 colorectal cancer cases with prostate cancer but no gastric cancer among relatives. The computational program PLINK v1.07 was used for the analysis and for the calculation of corresponding ORs, standard errors, and 95% confidence intervals (CI). The study found support for the loci from previous studies and many new loci with a shared risk of colorectal cancer and gastric cancer. There were no significant loci from the second analysis for a shared risk of colorectal and prostate cancer. Altogether, more than 100 new loci with a shared risk of colorectal cancer and gastric cancer were suggested. A shared risk of colorectal and prostate cancer at some loci could not be ruled out. Haplotype GWAS has again demonstrated its ability to find rare risk loci mostly associated with coding genes. Full article

Background: Liver cirrhosis increases perioperative risk in colorectal cancer surgery, yet data on long-term outcomes remain limited. In this study, we evaluated postoperative morbidity, mortality, and survival in cirrhotic patients. Methods: In this single-center retrospective cohort, 53 cirrhotic patients undergoing elective colectomy or proctectomy (2011–2022) were propensity score-matched 1:1 with non-cirrhotic controls. Perioperative variables, complications, and survival were analyzed. Subgroup analyses were performed for right hemicolectomy and non-right hemicolectomy procedures. Kaplan–Meier and logistic regression analyses were implemented to assess outcomes and risk factors. Results: Cirrhotic patients had higher preoperative MELD-Na scores and lower albumin and hemoglobin levels. They experienced greater blood loss, longer operative times, more ICU admissions, and higher rates of major complications (18.9% vs. 3.8%, p = 0.01). Mortality was higher at in-hospital (7.5% vs. 0%), 3-month (9.4% vs. 0%), and 60-month (66% vs. 28.3%) intervals, and these patients’ overall survival was shorter (70.7 vs. 116.8 months, p < 0.001). The subgroup analysis showed that the adverse impact of cirrhosis persisted for both right hemicolectomy and non-right hemicolectomy procedures, with significantly worse long-term survival in cirrhotic patients. Postoperative complications after right hemicolectomy did not differ significantly between groups. Among cirrhotic patients, Child–Turcotte–Pugh class B predicted worse survival than class A (40.1 vs. 84.8 months, p = 0.006). Preoperative hypoalbuminemia (<3.5 g/dL) independently predicted long-term mortality (HR = 3.93). Conclusions: Elective colorectal surgery in patients with cirrhosis is associated with increased perioperative complications and significantly reduced long-term survival. However, postoperative outcomes after right hemicolectomy in cirrhotic patients were comparable to those of non-cirrhotic patients, despite their persistently poorer long-term survival. Optimization of nutritional status and careful preoperative assessment of hepatic reserve are essential to improving outcomes in this high-risk population. Full article

Background/Objectives: Incidence of malnutrition varies greatly among gastrointestinal (GI) cancer patients and has a major impact on prognosis. We performed a meta-analysis to identify risk factors for malnutrition risk, malnutrition diagnosis, and cachexia in patients with GI cancer. Methods: A systematic search was performed on 31 October 2025 on the PubMed (Medline), Embase, and Cochrane Library databases. Eligible studies reported on risk factors for malnutrition risk, malnutrition diagnosis, malnutrition-related complication risk and cachexia in adult patients with GI cancer. Articles on neuroendocrine tumours, primary cancer outside the GI tract, and the paediatric population were excluded. The random-effects model yielded the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the investigated risk factors. Results: A total of 37,624 records were identified. Data from 262,525 patients from 578 articles were included in the analysis. Older age (≥65) was associated with higher odds for malnutrition risk across all GI cancers. In gastric cancer, males had a lower odds for malnutrition risk (OR 0.84; 95% CI 0.75–0.95); however, the sex difference across other cancer types was heterogeneous, and mostly not significant. Tumour location influenced the odds for malnutrition-related complication risk in pancreatic ductal adenocarcinoma (head vs. body/tail—OR 1.48; 95% CI 0.98–2.23) and colorectal cancer (colon vs. rectal—OR 1.39; 95% CI 1.07–1.81; right-sided vs. left-sided—OR 1.54; 95% CI 1.34–1.77). Increased C-reactive protein alone indicated higher odds for malnutrition risk at baseline. Conclusions: Inflammatory biomarkers and tumour characteristics may indicate malnutrition risk in GI cancer at baseline. There is a great need for standardised and harmonised approaches in nutritional status assessment in GI cancer. Full article

Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD −0.37; 95% CI −0.63 to −0.10; p = 0.006; I² = 0%) and butyrate (pooled SMD −0.59; 95% CI −1.10 to −0.07; p = 0.026; I² = 64.4%), whereas propionate did not differ significantly (pooled SMD −0.02; 95% CI −0.85 to 0.82; p = 0.971; I² = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC. Full article

Background and Objectives: Anastomotic leakage (AL) is a major complication following sphincter-preserving surgeries for left-sided colorectal cancer. In this study, we aimed to evaluate the association between circular stapler diameter and the risk of AL. As a secondary objective, we investigated whether preoperative serum protein levels were associated with leakage development. Materials and Methods: We conducted a retrospective case–control study including 99 patients who underwent elective colorectal surgery with stapled anastomosis for left-sided colorectal cancer between January 2020 and May 2024. A total of 99 patients were included (60.6% male), with a mean age of 66.1 ± 10.7 years. The patients were categorized into small (≤29 mm) and large (≥30 mm) stapler groups. Demographic, clinical, and laboratory variables were collected. Anastomotic leakage was defined as an International Study Group of Rectal Cancer (ISREC) Grade B or C leak requiring intervention. Univariate analyses and multivariate logistic regression analyses were performed, and results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A STROBE-compliant flow diagram was prepared. Results: Anastomotic leakage occurred in 10 patients (10.1%), and leakage rates were not significantly different between stapler-size groups (≤29 mm: 10.9% vs. ≥30 mm: 7.5%, p = 0.365). In multivariate analysis, stapler size was not independently associated with leakage (OR 1.68, 95% CI 0.40–6.97, p = 0.480). Lower preoperative serum protein levels were identified as the only independent predictor of leakage (OR 0.28, 95% CI 0.10–0.74, p = 0.011). Postoperative hospital stay was significantly longer for patients with leakage (median 17 vs. 7 days, p < 0.001). Conclusions: We found no significant associations between circular stapler diameter and anastomotic leakage in left-sided colorectal cancer surgery. Conversely, low serum protein levels were independently associated with increased leakage risk, highlighting the importance of preoperative nutritional assessment. Given the retrospective design, small number of leakage cases, and unmeasured confounders, these findings should be interpreted with caution. Further multicenter, prospective studies should be conducted to clarify the influence of stapler size and patient-related factors on anastomotic outcomes. Full article

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted. Full article

Background/Objectives: Several studies have suggested a contrasting link between a diabetes risk reduction diet (DRRD) pattern and cancer risk; however, their findings have been inconsistent. This study aims to systematically review observational studies and, where possible, quantify the overall effect through a meta-analysis. Methods: Searches were conducted in PubMed, Scopus, and Web of Science through May 2025. Odds ratios (ORs), along with their confidence intervals, were extracted for meta-analysis. The random-effects model was used to combine the ORs. Results: Nineteen studies met the inclusion criteria for the systematic review and meta-analysis. Of these, six reports examined the relationship between the DRRD and breast cancer risk, three assessed liver cancer incidence, two analyzed pancreatic cancer risk, and two focused on endometrial cancer. Additionally, seven studies explored the association with other cancers, including ovarian, colorectal, renal, head and neck, bladder, and lung cancers. The meta-analysis revealed that high adherence to the DRRD is associated with a decreased cancer risk (OR = 0.77, 95% confidence interval [95% CI]: 0.71–0.84, p < 0.001). Conclusions: After stratifying by geographic region, gender, study design, and cancer site, the inverse relationship remained significant across all subgroups. DRRD can be viewed as a beneficial approach associated with a lower cancer risk. Full article

Background/Objectives: This study aimed to assess the efficacy of adjuvant chemotherapy for T1-2 stage III colorectal cancer, a disease with a low recurrence rate. Methods: The efficacies of fluorouracil-based adjuvant chemotherapy (5FU group) and oxaliplatin-based adjuvant chemotherapy (L-OHP group) were assessed and compared with that of surgery alone (surgery group) using data from seven clinical trials conducted by the Japanese Foundation for Multidisciplinary Treatment of Cancer. Propensity score matching was used to compare the three groups. Direct-adjusted survival curves were delineated with consideration of treatment periods. Results: A total of 604 patients with T1-2 stage III colorectal cancer were identified. After adjusting for the patient factors, the hazard ratio of relapse-free survival (RFS) was 0.79 (95% confidence interval (CI): 0.13–4.65, p = 0.79) and 0.64 (95% CI: 0.06–6.40, p = 0.70) in the 5FU and L-OHP groups, respectively. Adjusted 5-year RFS rate was 82.8% (95% CI: 67.2–100%), 86.2% (95% CI: 74.2–100%), and 88.6% (95% CI: 74.0–100%) in the surgery, 5-FU, and L-OHP groups, respectively. Overall and disease-specific survival showed similar trends without significant differences. Conclusions: No significant improvement in prognosis was observed after adjuvant chemotherapy. The potential improvement in the 5-year RFS after adjuvant chemotherapy for resected T1-2 stage III colorectal cancer should be balanced with patient factors and adverse events. Full article

Background: Mast cells are integral components of the tumor microenvironment and have been implicated in the regulation of tumor progression in various malignancies. The association between inflammation and colorectal cancer (CRC) development has become increasingly recognized. Depending on the tumor microenvironment, mast cells may exert either pro-tumorigenic or antitumorigenic functions. Objective: This study aimed to evaluate the relationship between stromal mast cell density and prognostic factors in patients with CRC. Methods: In this retrospective cohort study, 81 patients who underwent curative surgical resection for CRC were analyzed. Immunohistochemical staining for mast cell tryptase (MCT) was performed on paraffin-embedded tumor specimens. Mast cells were quantified in regions of hot spots within the tumor stroma. Patients were categorized as high mast cell density (MCC-H, ≥22 cells/HPF) or low mast cell density (MCC-L, <22 cells/HPF). Associations with clinicopathological parameters were assessed using chi-square or Fisher’s exact tests. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier estimates and log-rank tests. Independent prognostic factors were identified using multivariate Cox proportional hazards regression, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Results: ROC analysis identified an MCC cut-off of 22 cells/HPF (AUC = 0.61; sensitivity = 0.67, specificity = 0.52) for mortality prediction. Multivariate analysis revealed lymph node involvement (HR: 1.41, 95% CI: 1.03–1.94, p = 0.033) and macroscopic tumor perforation (HR: 0.15, 95% CI: 0.04–0.55, p = 0.004) as independent predictors of PFS. High MCC (≥22) independently predicted improved OS (HR: 0.07, 95% CI: 0.006–0.87, p = 0.039). A significant association was observed between OS, MCC, and lymph node stage. Conclusions: Stromal mast cell count is an independent prognostic factor for overall survival in patients with CRC. Our findings suggest that MCC may serve as a reliable prognostic biomarker following surgical resection and could aid in postoperative risk stratification. Full article

Background: The management of resected stage III colorectal cancer (CRC) has long been reliant on fluoropyrimidine-based adjuvant chemotherapy. However, the 10–15% of patients with mismatch repair-deficient (dMMR) tumors derive limited benefit from this approach. While immunotherapy has revolutionized the treatment of metastatic dMMR CRC, its role in the early-stage setting is rapidly evolving, creating a paradigm shift. Methods: A systematic literature review was conducted to identify pivotal clinical trials evaluating therapeutic strategies for non-metastatic dMMR CRC. Databases including PubMed/MEDLINE and conference proceedings from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched up to June 2025. The review focused on phase II and III trials reporting on disease-free survival (DFS), pathological complete response (pCR), and safety. Study selection followed PRISMA guidelines. Results: The systematic review identified 14 key studies that were included for narrative synthesis. The evidence base encompassed three areas: (1) Foundational adjuvant chemotherapy trials (e.g., MOSAIC, IDEA); (2) Pivotal metastatic trials (e.g., KEYNOTE-177) validating immunotherapy efficacy in dMMR CRC; and (3) Modern trials in non-metastatic disease. The phase III ATOMIC trial demonstrated that adding atezolizumab to mFOLFOX significantly improved 3-year DFS versus chemotherapy alone (86.4% vs. 76.6%; Hazard Ratio [HR] 0.50, 95% Confidence Interval [CI] 0.34–0.72; p < 0.001). Concurrently, phase II neoadjuvant immunotherapy trials (e.g., NICHE-2) reported remarkable pCR rates of 68% and a 3-year DFS of 100%, with a more favorable safety profile compared to chemoimmunotherapy. Conclusions: The landscape for non-metastatic dMMR CRC is shifting from a chemotherapy-based model to an immunotherapy paradigm. The ATOMIC trial establishes adjuvant chemoimmunotherapy as a new standard, while robust neoadjuvant data suggest a potential future where short-course, chemotherapy-free immunotherapy could become a preferred strategy. Ongoing trials directly comparing these approaches are awaited. Full article

Objective: Existing studies on short-chain fatty acids (SCFAs) and colorectal cancer (CRC) yield contradictory conclusions and are limited to single ethnic groups or sample types. This study aimed to (1) quantify associations between total SCFAs/subtypes (acetate, propionate, butyrate) and CRC/advanced colorectal adenoma (A-CRA) risks; (2) identify modifiers (ethnicity, sample type, intervention); and (3) clarify SCFA–gut microbiota interaction mechanisms via integrative Bayesian meta-analysis and multi-ancestry data integration. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (inception to September 2025) using keywords: “Short-chain fatty acids”, “SCFAs”, “Colorectal cancer”, “CRC”, “Gut microbiota”, “Dietary fiber”, and “High-amylose maize starch butyrate”. Eligible studies included 14 peer-reviewed original studies (7 observational, cohort/case–control/cross-sectional; 7 RCTs) covering Europeans, Asians, and African Americans. Inclusion criteria: Quantitative SCFA data (total/≥3 subtypes), clear ethnic grouping, reported CRC/A-CRA risks or intervention outcomes. Exclusion criteria: Reviews, animal/in vitro studies, incomplete data, low-quality studies (Newcastle–Ottawa Scale [NOS] <6 for observational; high Cochrane risk for RCTs), or limited populations (single gender/rare genetics). A Bayesian hierarchical random-effects model quantified effect sizes (Odds Ratio [OR]/Mean Difference [MD], 95% credible intervals [CrI]), with heterogeneity analyzed via multi-ancestry stratification, intervention efficacy, and microbiota interaction analyses (Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] 2020; International Prospective Register of Systematic Reviews [PROSPERO]: CRD420251157250). Results: Total SCFAs were negatively associated with CRC (OR = 0.78, 95% CrI: 0.65–0.92) and A-CRA (OR = 0.72, 95% CrI: 0.59–0.87), with butyrate showing the strongest protective effect (CRC: OR = 0.63, 95% CrI: 0.51–0.77). Ethnic heterogeneity was significant: Europeans had the strongest protection (OR = 0.71), Asians had weaker protection (OR = 0.86), and African Americans had the lowest fecal SCFA levels and the highest CRC risk. Fecal SCFAs showed a stronger CRC association than serum/plasma SCFAs (OR = 0.73 vs. 0.85). High-Amylose Maize Starch Butyrate (HAMSB) outperformed traditional fiber in increasing fecal butyrate (MD = 4.2 mmol/L vs. 2.8 mmol/L), and high butyrate-producing bacteria (Clostridium, Roseburia) enhanced SCFA protection (OR = 0.52 in high-abundance groups). Conclusions: SCFAs (especially butyrate) protect against CRC and precancerous lesions, with effects modulated by ethnicity, sample type, and gut microbiota. High-Amylose Maize Starch Butyrate is a priority intervention for high-risk populations (e.g., familial adenomatous polyposis, FAP), and differentiated strategies are needed: 25–30 g/d dietary fiber for Europeans, 20–25 g/d for Asians, and probiotics (Clostridium) for African Americans. Future Perspectives: Expand data on underrepresented groups (African Americans, Latinos), unify SCFA detection methods, and conduct long-term RCTs to validate intervention efficacy and “genetics-microbiota-metabolism” crosstalk—critical for CRC precision prevention. Full article

Background/Objectives: Conventional imaging assesses therapy response in stage IV solid-tumor patients in 8- to 12-week intervals, delaying detection of non-responders. We evaluated a quantitative PCR (qPCR) assay that interrogates size-distributed cell-free DNA (cfDNA) fragments to provide earlier insights into treatment efficacy. Methods: In this prospective study, 128 patients with metastatic lung, breast, or colorectal cancer provided plasma 12–21 days after the first dose of a new systemic regimen. The qPCR targets multi-copy retrotransposon element fragments of greater than 80 bp, greater than 105 bp, and greater than 265 bp, as well as an internal control. A model integrates these quantities into a Progression Score (PS) ranging from 0 to 100; higher values indicate probable disease progression. Results: The PS model yielded an area under (AUC) the receiver-operating-characteristic (ROC) curve of 0.93 for predicting radiographic progression at first imaging. Scores were strongly bimodal: 92% of patients with PS > 90 progressed, whereas 95% with PS < 10 did not. Intermediate scores (10–90) comprised a mixed cohort. Assay performance was unaffected by tumor genomic profile. Conclusions: This cfDNA-based Progression Score (PS) assay enables tumor- and therapy-agnostic, non-invasive monitoring of treatment response as early as two weeks after initiation. By flagging ineffective regimens well before standard imaging, the test can accelerate clinical decision-making, reduce exposure to futile therapy, and potentially improve outcomes in stage IV cancer. Early treatment plan changes may also avoid the high costs of ineffective treatments, prevent downstream toxicity-related hospitalizations, and free up limited imaging and infusion-suite capacity—yielding savings for patients, payers, and healthcare systems. Full article