Search Results (1,087)

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

Epidermal growth factor receptor (EGFR) inhibitors remain a cornerstone in the treatment of metastatic colorectal cancer with RAS and BRAF wild-type cancer. Yet, primary and acquired resistance limit their benefit for many patients. A growing body of evidence reveals that resistance is not random but rather driven by a complex network of molecular alterations that sustain tumor growth independent of EGFR signaling. These include amplification of ERBB2 (HER2) and MET, activation of the PI3K and AKT pathways, EGFR extracellular domain mutations, and rare kinase fusions. The concept of negative hyperselection has emerged as a powerful strategy to refine patient selection by excluding tumors with these resistance drivers. Multiple clinical trials have consistently shown that patients who are hyperselected based on comprehensive molecular profiling achieve significantly higher response rates and improved survival compared to those selected by RAS and BRAF status alone. Liquid biopsy through circulating tumor DNA has further transformed this landscape, offering a noninvasive tool to capture tumor heterogeneity, monitor clonal evolution in real time, and guide rechallenge strategies after resistance emerges. Together, negative hyperselection, ctDNA-guided monitoring, and emerging therapeutics define a precision-oncology framework for identifying, tracking, and overcoming resistance to anti-EGFR therapy in mCRC, moving the field toward more effective and individualized care. Looking ahead, the development of innovative therapeutics such as bispecific antibodies, antibody drug conjugates, and RNA-based therapies promises to further expand in this challenging clinical scenario. These advances move precision oncology in colorectal cancer from concept to clinical reality, reshaping the standard of care through molecular insights. Full article

Background/Objectives: Patients with non-small cell lung cancer (NSCLC) being evaluated for stereotactic body radiation therapy (SBRT) are frequently staged non-invasively with positron emission tomography/computed tomography (PET/CT). Performing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in addition to PET/CT scanning may increase clinical certainty in lymph node staging, but the magnitude of added benefit of EBUS-TBNA over non-invasive staging methods is unclear. Methods: A single-center prospective cohort study involving patients with suspected or confirmed Stage I or IIa NSCLC referred for EBUS-TBNA prior to SBRT was performed. The primary outcome was concordance between PET/CT and EBUS-TBNA for nodal metastases. Secondary endpoints included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT, and clinical outcomes based on staging results. Results: Among 115 patients, the concordance between PET/CT and EBUS-TBNA was 84.3% (95% CI: 0.76 0.90). EBUS-TBNA led to a stage shift in 15.7% of cases: 4 of 98 PET/CT N0 patients (4.1%) had nodal metastases, while 14 of 17 PET/CT N1 patients (82.4%) were downstaged to N0. PET/CT sensitivity was 42.9% (95% CI: 0.09–0.81), specificity 87% (95% CI: 0.79–0.93), PPV 17.6% (95% CI: 0.04–0.43), and NPV 95.9% (95% CI: 0.90–0.99). PET/CT-positive, EBUS-TBNA-negative patients had worse survival (HR 4.25, 95% CI: 1.24–14.53, p = 0.021) compared with double-negative patients. Conclusions: EBUS-TBNA improves staging accuracy over PET/CT in early-stage NSCLC, impacting SBRT candidacy. However, PET/CT-positive, EBUS-TBNA-negative patients had worse outcomes in comparison to double-negative patients, suggesting a need for additional therapy or surveillance in that population. Full article

Perioperative/neoadjuvant chemo-immunotherapy is a standard treatment for patients with resectable non-small cell lung cancer (NSCLC). However, several key clinical questions remain unresolved, including the monitoring of tumor response during neoadjuvant treatment, detection of residual disease after neoadjuvant treatment or after surgery, stratification of recurrence risk, and earlier detection of disease recurrence. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to address these challenges. Data from several recent clinical trials of perioperative/neoadjuvant chemo-immunotherapy demonstrated that ctDNA clearance before surgery was associated with higher rates of major pathological response. Additionally, landmark ctDNA positivity after surgery identified patients at high risk of disease recurrence, and longitudinal ctDNA monitoring enabled earlier detection of recurrence compared with radiographic surveillance. Several ongoing trials are incorporating ctDNA as a biomarker to guide treatment decisions, including optimizing the duration of neoadjuvant therapy, evaluating the need for surgery, and tailoring adjuvant strategies. These trials, together with further development of ctDNA detection technologies, will clarify the role of ctDNA analysis in refining perioperative treatment strategies and may ultimately enable individualized care in patients with resectable NSCLC. In this review, we discuss the current research data on ctDNA analysis in NSCLC in this era of perioperative chemo-immunotherapy. Full article

Background/Objectives: We report on the association of clinical, demographic, and peri- and intraoperative factors with patient outcomes in large- and, separately, medium-vessel acute ischemic stroke (AIS) occlusions treated with mechanical thrombectomy or medical thrombolysis. Increasingly, neuroimaging, particularly novel markers of collateral status, has become useful in predicting response to endovascular treatment (EVT) among AIS patients. However, the relationship between these neuroimaging markers, documented predictors of stroke outcomes, and post-EVT functional status in anterior circulation large-vessel occlusions (LVOs) as compared to medium-vessel occlusions (MeVOs) remains unclear. We evaluated whether shared predictors of 90-day post-EVT functional outcomes in LVO compared to MeVO AIS patients within our institution exist. Methods: We retrospectively evaluated AIS patients treated at our institution between 9 January 2017 and 10 January 2023. The following were the inclusion criteria were applied: (i) CTA confirmed anterior circulation large or medium vessel occlusion; (ii) diagnostic CT perfusion was performed; (iii) mechanical thrombectomy was performed. A low modified Rankin score (mRS) indicating good functional outcomes (i.e., functional independence) was defined as less than or equal to 2, in accordance with prior studies. Univariate and multivariate logistic regression analyses were conducted to determine associations between demographic, clinical, and radiologic factors and mRS ≤ 2. Results: A total of 249 LVO (mean age 65.3 ± 16.2, 53.8% female) and 91 MeVO (mean age 68.9 ± 13.3, 46.2% female) patients met the inclusion criteria. Upon multivariate regression adjusted for race, age, hypertension, diabetes mellitus, radiologic features, IV alteplase, admission NIHSS, and reperfusion status, young age (p = 0.004), low admission NIHSS (p = 0.0001), and good reperfusion status (p = 0.007) were associated with good functional outcomes in LVO stroke. By contrast, no factors were significantly associated with good functional outcomes in MeVO stroke. Conclusions: Known factors, including young age, low admission stroke severity, and successful reperfusion predict EVT outcomes in LVO stroke but not necessarily in MeVO stroke. Further studies regarding predictors of MeVO outcomes in nonsurgical cases, including collateral status, may guide optimal medical management for this population. Full article

Background/Objectives: The diagnosis of osteomyelitis is typically based on clinical suspI icion supported by imaging and lab findings. Various nuclear medicine imaging, including bone SPECT/CT, is emerging as an effective tool to guide the diagnosis of osteomyelitis. This study investigates whether the preoperative ^99mTc DPD bone SPECT/CT uptake \ratio correlates with intraoperative tissue culture positivity in patients with suspected lower extremity osteomyelitis. Methods: We retrospectively reviewed 46 patients who underwent surgery for suspected osteomyelitis of the lower extremity between February 2020 and May 2025. Bone SPECT/CT was performed using ^99mTc DPD, and uptake values were measured using Syngo.via software. Lesion-to-Background Ratio (LBR) was calculated by comparing uptake in the lesion with the contralateral bone. Intraoperative culture was conducted at the region with high uptake in SPECT/CT. Results: Among the 46 patients who underwent surgery, 28 had positive tissue cultures, and 18 were negative. The mean LBR was significantly higher in culture-positive cases (14.5 ± 4.5) than in culture-negative cases (6.8 ± 8.0, p = 0.0002) Inflammatory markers (WBC, ANC, ESR, CRP) and the antibiotic-free interval before surgery did not significantly differ between groups or correlate with LBR. ROC analysis identified an LBR threshold of 9.44, yielding a sensitivity of 71.4% and specificity of 88.9% for predicting positive cultures (AUC = 0.81). Conclusions: ^99mTc DPD bone SPECT/CT uptake ratio may serve as a useful tool for the preoperative assessment of suspected lower extremity osteomyelitis, providing a more reliable prediction of intraoperative microbial culture results compared to serum inflammatory markers or the duration of antibiotic-free intervals. High tracer uptake may also be observed in various other conditions and thus should be interpreted in a multidisciplinary context in conjunction with other modalities. Full article

Background: Right anterior mini-thoracotomy has gained increasing popularity as a preferred approach for mitral valve surgery due to its numerous advantages. This study aims to evaluate the safety and efficacy of this technique in elderly patients. Methods: Between January 2010 and November 2024, a total of 4092 adult patients underwent mitral valve repair or replacement at our institution. Of these, 1687 patients were treated using a minimally invasive approach. This analysis focuses on elderly patients aged 75 years and older (n = 402), further subdivided into two groups: 75–79 years (n = 253) and 80 years and older (n = 149). Results: The study population comprised 49.8% male patients. A small percentage (1.7%) had a history of endocarditis, and 6.5% had undergone prior cardiac surgery. The median logistic EuroSCORE was 7.68 (IQR 5.83–11.00), and the median EuroSCORE II was 2.75 (1.71, 4.40). Alternative cannulation strategies, guided by AngioCT scans, can expand the applicability of this technique to patients unsuitable for femoral cannulation. Median durations for cardiopulmonary bypass (CPB) and aortic cross-clamping were 99.5 and 80.0 min, respectively. Median ventilation time was 7 h, and the median ICU stay was 2 days. Atrial fibrillation was the most common postoperative complication (20.9%). A significant proportion of patients (47.8%) required blood transfusions, and 3.0% needed re-exploration for bleeding. The in-hospital mortality rate was 3.7%, with 7 (1.7%) patients requiring postoperative dialysis and 5 (1.2%) experiencing sepsis and multiple organ failure. Patients aged 80 years and older exhibited worse renal function and higher EuroSCOREs compared to the younger group (p < 0.001). However, they had shorter CPB (p = 0.004) and cross-clamp times (p = 0.001) and underwent a higher proportion of valve replacements (p = 0.003). Rates of major complications and in-hospital mortality were comparable between the two age groups. Logistic regression analysis identified the logistic EuroSCORE as the only significant preoperative risk factor (p = 0.001). Conclusions: Right anterior minithoracotomy is a safe and reproducible surgical approach, even in elderly patients, promoting faster recovery with a lower risk of complications. Among patients aged >80 years, despite higher comorbidities and elevated EuroSCORE II, in-hospital outcomes are comparable to those aged 75–79 years. Full article

Background: Circulating tumor DNA (ctDNA), shed into bodily fluids by cancer cells through apoptosis, necrosis, or active secretion, is currently used in the field of genomic investigation in clinical settings, primarily for advanced stages of non-small-cell lung cancer (NSCLC). However, its potential role in guiding the multi-omic approach to early-stage NSCLC is emerging as a promising area of investigation. Efforts are being made to integrate the genomics not only in surgery, but also in the definition of long-term prognosis after surgical or radiotherapy and for the prediction of recurrence. Methods: An extensive literature search was conducted on PubMed, covering publications from 2000 to 2024. Using the advanced search tool, titles and abstracts were filtered based on the following keywords: ctDNA, early stage, NSCLC. From this search, 20 studies that fulfilled all inclusion criteria were selected for analysis in this review. Results: This review highlights the growing body of evidence supporting the potential clinical use of ctDNA as a genomic biomarker in managing early-stage NSCLC. Baseline ctDNA levels offer valuable information about tumor molecular biology and histological characteristics. Beyond its prognostic value before treatment, liquid biopsy has proven useful for tracking minimal residual disease and forecasting recurrence following curative interventions such as surgery or radiotherapy. Future adjuvant treatment decisions may increasingly rely on predictive models that incorporate liquid biopsy findings alongside other clinical factors. Conclusions: The potential use of this analyte introduces new opportunities for the integration of genomic data in treatment, as well as relapse monitoring with more accurate and innovative than traditional methods, particularly in patients with early-stage NSCLC Full article

Lung cancer (LC), with non-small-cell lung cancer (NSCLC) as its predominant subtype, remains the leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm in advanced NSCLC, durable responses are confined to a limited subset of patients. A major clinical challenge persists: the inability to accurately predict which patients will derive meaningful benefit, which will exhibit primary resistance, and which are at risk for severe immune-related toxicities. The imperative to individualize ICI therapy necessitates robust, dynamic, and accessible biomarkers. Liquid biopsy has emerged as a transformative, minimally invasive tool that enables real-time molecular and immunologic profiling. Through analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and peripheral blood immune components, liquid biopsy offers a window into both tumor intrinsic and host-related determinants of ICI response. These biomarkers not only hold promise for identifying predictive signatures—such as tumor mutational burden, neoantigen landscape, or immune activation states—but also for uncovering mechanisms of acquired resistance and guiding treatment adaptation. Beyond immunotherapy, liquid biopsy plays an increasingly central role in the landscape of targeted therapies, allowing early detection of actionable driver mutations and resistance mechanisms (e.g., EGFR T790M, MET amplification, and ALK fusion variants). Importantly, serial sampling via liquid biopsy facilitates longitudinal disease monitoring and timely therapeutic intervention without the need for repeated tissue biopsies. By guiding therapy selection, monitoring response, and detecting resistance early, liquid biopsy has the potential to significantly improve outcomes in NSCLC. Full article

Background: Muscle-invasive bladder cancer (MIBC) is associated with high recurrence and mortality rates. While cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy remains the standard of care, many patients are ineligible for cisplatin. Recent advances in immunotherapy and biomarker research are reshaping perioperative strategies, aiming to personalize treatment and improve outcomes. Methods: We conducted a comprehensive narrative review of the recent literature and clinical trials on the perioperative treatment of MIBC. We focused on published phase II and III trials assessing neoadjuvant and adjuvant strategies, including immunotherapy, antibody-drug conjugates (ADCs), combination regimens, and circulating tumor DNA (ctDNA)-based approaches. Results: Numerous trials (e.g., PURE-01, ABACUS, NABUCCO, AURA, NIAGARA) have demonstrated the feasibility and efficacy of immune checkpoint inhibitors (ICIs) in both cisplatin-eligible and -ineligible populations. Combination strategies, including ICIs plus chemotherapy or ADCs, have shown promising pathological complete response rates and event-free survival. In the adjuvant setting, nivolumab improved disease-free survival and received regulatory approval. Biomarkers such as PD-L1 and ctDNA are emerging tools for predicting treatment response and recurrence risk, although prospective validation is ongoing. Conclusions: The treatment paradigm for MIBC is shifting toward multimodal and biomarker-driven approaches. Integration of ICIs into perioperative management, especially in combination with chemotherapy or ADCs, may enhance outcomes. ctDNA shows potential as a predictive and prognostic biomarker, guiding therapeutic decisions and surveillance. Future research should focus on refining patient selection, optimizing treatment sequencing, and validating ctDNA-guided strategies to personalize care while minimizing overtreatment. Full article

Medullary thyroid carcinoma (MTC) is a rare (~2–5% of all thyroid cancers) neuroendocrine thyroid malignancy originating from parafollicular C-cells of the thyroid gland with variable biological behavior and potential for early metastasis. Diagnosis, staging, and surveillance are heavily reliant on circulating biomarkers. We aimed to provide a comprehensive overview of circulating biomarkers in the management of MTC and propose an integrated, evidence-based algorithm to guide clinical decision-making using both established and emerging biomarkers. This is a narrative review on the evolving landscape of biomarker-driven management in MTC with emphasis on analytical advancements, clinical applications, and the prognostic implications of individual and combined biomarkers. Calcitonin remains the cornerstone biomarker for MTC, and new generation immunoassays have addressed several pre-analytical and analytical challenges such as pre-analytical degradation, inter-assay variability, and biological confounders. Procalcitonin (ProCT) has emerged as a stable and less interference-prone alternative or adjunct to calcitonin, which is particularly useful in cases with indeterminate calcitonin levels. Carcinoembryonic antigen (CEA) remains a useful complementary biomarker often correlating with aggressive behavior, advanced disease, and distant metastases. Kinetic evaluation (doubling times) of calcitonin and CEA offers independent prognostic information values and those < 6 months are associated with poor survival, whereas those > 2 years suggest favorable outcomes. Newer biomarkers such as pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen 19-9 (CA19-9) show potential in monitoring advanced disease and response to therapy. Their role is still under investigation but appears promising, particularly when used in conjunction with calcitonin and CEA. Our work advances a comprehensive and clinically pragmatic framework for the management of MTC by integrating established and emerging biomarkers with evidence-based algorithms, offering greater diagnostic precision, more reliable prognostic stratification, and improved personalization of follow-up and treatment strategies. Full article

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

Intraosseous hemangiomas (IH) are rare intrabony lesions that represent less than 1% of intraosseous tumors. IH are mostly seen in the axial skeleton and skull. Most commonly, the frontal bone, zygomatic, sphenoid, maxilla, ethmoid, and lacrimal bone can manifest IH. Currently, IH is classified as a developmental condition of endothelial origin. According to WHO, the five histological types of IH are cavernous, capillary, epithelioid, histiocytoid, and sclerosing. IH of the zygoma is an extremely rare condition with female predominance. A systematic review recently estimated that there were 78 cases published in the literature until 2023. The lesion is usually asymptomatic and presents with a gradually deteriorating deformity of the malar area, and the patient might be able to recall a history of trauma. Numbness due to involvement of the infraorbital nerve might also be present; however, atypical skin and bone sensations might also occur. Other symptoms include painful swelling, bone asymmetry, skin irritation, sinus pressure, paresthesia, diplopia, enophthalmos, or atypical neuralgia. A bony lesion with a trabecular pattern in a radiating formation (sunburst pattern) or a multilocal lytic lesion pattern created by the multiple cavernous spaces (honeycomb pattern) is commonly observed during radiologic evaluation. We present a rare case of IH of the zygoma in a 65-year-old generally healthy woman. A cyst-like bone tumor was revealed from the CT scan, which made preoperative biopsy of the lesion problematic. A careful radiological diagnostic differentiation of the lesion should always be conducted in such cases to outline a safe surgical plan and possible alternatives if needed. The patient underwent total tumor resection in the operating room, and the defect was reconstructed with the use of a titanium mesh and a synthetic hydroxyapatite bone graft based on a 3D surgical guide printed model. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article