Search Results (92)

Background: Based on the demonstrated survival benefits of gemcitabine plus cisplatin (GemCis) therapy in the TOPAZ-1 and KEYNOTE-966 trials, GemCis plus immune checkpoint inhibitor (ICI) therapy has become a standard first-line treatment for unresectable biliary tract cancer. However, its safety and efficacy in elderly patients and those requiring biliary drainage remain insufficiently evaluated in real-world practice. We aimed to evaluate the efficacy and safety of GemCis plus ICI therapy, with a focus on elderly patients and those requiring biliary drainage. Methods: We retrospectively analyzed the clinical characteristics of patients with unresectable biliary tract cancer treated with GemCis plus ICI at our institution between April 2022 and September 2025. Progression-free survival (PFS) was analyzed using the Kaplan–Meier method, and prognostic factors were examined using Cox proportional hazards models. PFS and immune-related adverse events (irAEs) were compared between durvalumab and pembrolizumab. Results: Of the 51 patients diagnosed with unresectable biliary tract cancer during the observation period, 26 (51.0%) received GemCis plus ICI therapy. The median age was 73 years (range, 46–83 years), and 15 (57.7%) patients were male. Distant metastases were present in 22 patients (84.6%), and biliary drainage was performed in 15 (57.7%). The primary tumor sites were intrahepatic cholangiocarcinoma (n = 8), perihilar cholangiocarcinoma (n = 6), gallbladder cancer (n = 11), and cancer of unknown primary origin (n = 1). The ICIs used were durvalumab in 18 patients and pembrolizumab in eight patients. The median follow-up period was 214 days (range, 30–1114). The response rate was 28.6%, the disease control rate was 90.5%, and the transition rate to ICI maintenance therapy was 29.2%. IrAEs occurred in six patients (23.1%), with a significantly higher frequency in the pembrolizumab group than in the durvalumab group (50.0% vs. 11.1%). The median PFS was 8.2 months in the durvalumab group and 8.9 months in the pembrolizumab group, with no significant difference (p = 0.88). Multivariate analysis incorporating age, performance status, metastatic burden, and liver function confirmed that age ≥ 75 years remained the only independent predictor of shorter PFS (HR 5.62; 95% CI, 1.35–23.4; p = 0.02), whereas ICI regimen and biliary drainage were not significant prognostic factors. Conclusions: In clinical practice, GemCis plus ICI therapy showed no statistically significant difference in efficacy between ICI regimens in this small cohort, although this comparison was not statistically powered. Given the exploratory nature of these findings, the lower incidence of immune-related adverse events (irAEs) observed in the durvalumab group should be interpreted with caution. Age ≥ 75 years was associated with shorter PFS. Careful patient selection is warranted when considering GemCis plus ICI therapy in elderly patients with biliary tract cancer. Full article

Endobiliary photodynamic therapy (PDT) in cholangiocarcinoma (CCA) is used mainly for local palliation of malignant biliary obstruction, particularly in extrahepatic and perihilar disease. This Review synthesizes the clinical evidence on endobiliary PDT while using drainage, infection control, stent strategy, light delivery, and systemic-therapy context as an interpretive framework rather than as practice recommendations. This narrative review was informed by targeted searching of PubMed/MEDLINE, Embase, and Web of Science from database inception through to 31 December 2025, supplemented by reference-list screening. We prioritized prospective studies, comparative cohorts, systematic reviews, and relevant guidance documents. Across the literature, the clearest support for PDT concerns selected local biliary palliation, including decompression, stent patency or delayed dysfunction, and symptom relief. Survival signals remain inconsistent: early positive studies contrast with the negative PHOTOSTENT-02 randomized trial and are highly confounded by drainage adequacy, infection control, retreatment strategy, and systemic-therapy access. We therefore interpret PDT as a context-dependent local biliary strategy rather than an established survival-prolonging treatment, and we highlight the clinical variables that make published outcome signals more or less interpretable. Full article

Background: Hepatic malignancies are a major global health burden, with rising incidence, high mortality, and frequent diagnosis at advanced or unresectable stages. Although surgical resection, locoregional therapies, and systemic treatments have improved outcomes, many patients remain ineligible for curative strategies because of tumor burden, anatomical constraints, or liver dysfunction. Liver transplantation (LT) has therefore evolved from a treatment limited to selected hepatocellular carcinoma (HCC) cases within strict morphological criteria to a broader oncologic option guided by tumor biology and treatment response. This review provides an updated overview of the expanding role of LT in hepatic malignancies and the transition toward precision transplant oncology. Methods: We conducted a narrative review of current evidence on LT in HCC, cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM), focusing on candidate selection, neoadjuvant strategies, molecular profiling, immunological aspects, and future perspectives. Results: In HCC, expanded criteria and bridging/downstaging strategies, including immunotherapy, have increased transplant eligibility, although concerns remain regarding rejection risk and post-transplant management. In CCA, especially perihilar disease, standardized neoadjuvant protocols followed by LT have achieved encouraging long-term survival in highly selected patients, whereas intrahepatic CCA remains investigational within prospective biomarker-driven studies. In CRLM, once considered an absolute contraindication, recent evidence supports LT in selected patients with liver-confined and biologically favorable disease, emphasizing the importance of tumor kinetics, molecular features, and response to systemic therapy. Conclusions: Integration of molecular oncology, immunology, and advanced therapies is redefining LT indications for hepatic malignancies. Future progress will depend on biomarker-driven selection, precision medicine, and multidisciplinary decision-making to optimize outcomes while addressing ethical challenges in organ allocation. Full article

In the hepatobiliary system, the majority of neoplasms grow within the hepatic parenchyma; however, some arise, grow, and/or spread within the lumen of the intrahepatic large bile ducts and the perihilar/distal bile ducts (collectively referred to as large bile ducts), representing specialized ductal organs associated with unique peribiliary glands and being distinct from the intrahepatic small bile ducts and bile ductules embedded within the hepatic parenchyma. Precursors of cholangiocarcinoma (CCA) arising within the lumen of large bile ducts have recently been proposed. Neoplasms growing and spreading within the lumen of large bile ducts have been categorized into four groups and are discussed here in light of updated pathological findings. (i) Precursor(s) of CCA arising in the large bile ducts (large-duct-type intrahepatic CCA and perihilar/distal CCA): These precursors include high-grade biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal oncocytic papillary neoplasm (IOPN). High-grade BilIN presents as a flat, microscopic lesion with dysplastic cytoarchitectural alterations and grows along the luminal surface of large bile ducts, whereas the latter two present as grossly visible polypoid or tumorous lesions composed of papillary, villous, or tubular proliferation of neoplastic epithelium with delicate fibrovascular cores. These lesions may eventually progress to invasive CCA. Intraductal tubulopapillary neoplasm of the bile duct (ITPN), previously categorized as another precursor of CCA arising in large bile ducts, appears to represent a heterogeneous group of neoplasms with respect to progression and presumed cell of origin. Some ITPNs are frequently associated with nodular invasive carcinoma resembling small-duct-type intrahepatic CCA (SD-iCCA) and share genetic alterations with SD-iCCA; such cases may arise in association with small bile ducts or bile ductules. In contrast, other ITPNs exhibit cystic changes with tubulopapillary features and may arise in association with peribiliary glands or cysts. (ii) Secondary growth and spread of biliary neoplasms: This category comprises several patterns. First, intraepithelial neoplastic spread directly and continuously from the primary neoplastic lesion is observed in almost all cases of high-grade BilIN, IPNB, and IOPN; it spreads laterally along the luminal surface of the proximal and distal bile ducts and extends vertically into the adjacent peribiliary glands. Intraluminal cast-like spread in the bile ducts adjacent to the primary neoplastic lesion also occurs in some precursor lesions, particularly in ITPN. Implantation of a biliary neoplasm from one part of the biliary tract to another results in discontinuous, multifocal biliary neoplasms, particularly in IPNB, and occurs mainly in the distal bile ducts relative to the main tumor. Multicentric tumorigenesis may contribute to the multifocal development of precursors and CCA in the bile ducts. The accumulation of additional genetic alterations, beyond the common mutations detected in primary tumors, may contribute to metachronous recurrence of CCA after curative resection of the primary biliary tumor. Cancerization of the duct (COD) by CCA may also contribute to secondary growth and spread within the bile duct lumen. Specifically, flat-type cancerization of pre-existing non-neoplastic bile ducts, resembling high-grade BilIN, occurs in approximately one-third of hilar CCA cases. Intraductal polypoid, cast-like cancerization within the lumen of adjacent bile ducts, resembling polypoid precursors of CCA, can also occur in approximately one-tenth of SD-iCCA. (iii) Prominent intraductal polypoid growth of invasive CCA: Invasive CCA rarely presents with predominant intraductal polypoid carcinoma that is continuous with periductal infiltrating CCA; this pattern can be referred to as polypoid invasive CCA. (iv) Nonbiliary neoplasms presenting bile duct tumor thrombus (BDTT): BDTT associated with hepatocellular carcinoma and with extrahepatic malignancies extending into the bile duct lumen can mimic the intraluminal growth and spread patterns of the above-mentioned biliary neoplasms. In conclusion, intraluminally growing biliary neoplasms in the large bile ducts comprise a heterogeneous group that can be reasonably classified into four categories. This categorization may facilitate understanding of these intrabiliary growing neoplasms. Full article

Extrahepatic cholangiocarcinoma (eCCA) is a highly aggressive malignancy arising from the biliary epithelium, with surgical resection representing the only potentially curative treatment. The predominant periductal infiltrating growth pattern, characterized by subepithelial tumor spread and desmoplastic stromal reaction, severely limits the diagnostic sensitivity of conventional endoscopic sampling techniques, which primarily assess the luminal mucosal surface. This review provides a histomorphology-oriented diagnostic framework for indeterminate extrahepatic biliary strictures, integrating advanced endoscopic technologies with emerging optical diagnostic approaches. ERCP combined with cholangioscopy demonstrates superior sensitivity for perihilar strictures, while EUS-guided tissue acquisition shows higher diagnostic yield in distal cholangiocarcinoma, also providing locoregional staging. Advanced EUS technologies—including elastography, contrast harmonic EUS, and Detective Flow Imaging—further improve characterization of indeterminate strictures by evaluating tissue stiffness, microvascular architecture, and periductal infiltration. Ex vivo fluorescence confocal laser microscopy (FCM) enables real-time microscopic evaluation of biopsy specimens, reducing diagnostic turnaround time and minimizing inadequate sampling. A location-adapted diagnostic algorithm integrating cross-sectional imaging, ERCP, cholangioscopy, and EUS is proposed. An integrated, biology-informed endoscopic approach tailored to tumor location and ductal wall involvement may significantly improve early eCCA detection and guide patient selection for curative treatment. Full article

Liver transplantation has emerged as a curative treatment option for selected patients with unresectable hepatic malignancies beyond hepatocellular carcinoma, marking a paradigm shift in transplant oncology. For colorectal cancer liver metastases (CRLM), prospective trials have demonstrated that highly selected patients achieve 5-year OS rates of 60–83%, with the Oslo score identifying optimal candidates for transplantation. Perihilar cholangiocarcinoma (pCCA) has been successfully treated using strict patient selection criteria combined with neoadjuvant therapy, achieving 5-year OS rates of 50–68%, though emerging data suggests chemotherapy-based approaches may be preferable to radiation in selected cases. Intrahepatic cholangiocarcinoma (iCCA), previously considered a contraindication to transplantation, can now achieve excellent long-term outcomes (79.5% 5-year OS) in patients demonstrating sustained response to neoadjuvant chemotherapy and radioembolization, with metabolic tumor volume < 70 cm³ serving as an objective prognostic marker. Across these three emerging indications, successful outcomes depend on strict patient selection based on tumor biology, intensive multimodal neoadjuvant therapy, multidisciplinary evaluation in high-volume centers, and careful observation during treatment to exclude patients with aggressive disease. This evolution in transplant practice offers curative intent therapy to patients that previously only had palliative therapeutic options, fundamentally transforming hepatobiliary and oncologic surgery. Full article

Malignant biliary obstruction (MBO) represents a critical clinical challenge characterized by bile duct compromise leading to severe complications, including intractable jaundice, recurrent cholangitis, biliary cirrhosis, and hepatic failure. Classification into distal MBO (DMBO) and hilar MBO (HMBO) guides therapeutic decision-making, with the former predominantly caused by pancreatic head adenocarcinoma and extrahepatic cholangiocarcinoma, while perihilar cholangiocarcinoma represents the principal etiology of the latter. The high morbidity and mortality associated with MBO necessitate prompt, expert intervention. While endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary biliary drainage (TBD) has traditionally served as the cornerstone of management for unresectable tumors, endoscopic ultrasound (EUS)-guided biliary drainage has emerged as a compelling alternative, particularly when conventional ERCP proves technically unsuccessful or anatomically unfeasible. This review comprehensively examines current endoscopic strategies for MBO, emphasizing the complementary roles of ERCP and EUS-based techniques. Optimal outcomes require intervention by experienced endoscopists at high-volume tertiary centers, with individualized treatment selection based on anatomical considerations, tumor characteristics, patient factors, and local expertise. Full article

Background and Objectives: Cholangiocarcinoma (CCA) is an aggressive tumor that originates in the biliary tract and is subdivided anatomically into intrahepatic (iCCA) and extrahepatic (perihilar-pCCA and distal-dCCA). Diagnosis remains challenging, particularly for extrahepatic forms (pCCA and dCCA). We aimed to assess the relation between systemic inflammatory markers—specifically lymphocyte-related ratios—and tumor characteristics in a Romanian cholangiocarcinoma cohort. Materials and Methods: We conducted an exploratory single-center study including adult patients with a confirmed CCA histopathological diagnosis. We excluded patients with an uncertain diagnosis or tumors of the ampulla of Vater or gallbladder. Demographic and clinical data were retrospectively collected from medical records. Results: Tumor localization was the strongest predictor of metastatic disease. The odd of metastasis was 7.3 times higher for iCCA than dCCA and 4.5 times higher for iCCA than pCCA. Although several evaluated inflammatory biomarkers showed statistically significant associations, their clinical relevance was limited. The odds ratios for these biomarkers were characterized by lower bounds near the null value and wide confidence intervals, reflecting considerable patient heterogeneity, model instability, and inconclusive effect sizes. Conclusions: Our findings suggest a potential biological link between systemic inflammation, metastatic spread, and tumor differentiation grade that deserves further investigation using more accurate systemic inflammation biomarkers than those routinely collected. Full article

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation. Full article

Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was to evaluate the clinical impact of EUS for suspicious LN in patients with presumed resectable CCA. Methods: In this single-center cohort study, patients with potentially resectable CCA who underwent preoperative linear EUS between 2019 and 2024 were retrospectively included. The primary aims were the percentage of malignant LN detected and the clinical impact of EUS, which was defined as the percentage of patients who were precluded from surgical exploration due to pathologically confirmed LN metastases found with EUS tissue acquisition (EUS-TA). The secondary aim was the complication rate of EUS-TA. Results: A total of 135 patients were included, of whom 12 (8.9%) had intrahepatic CCA (iCCA), 65 (48.1%) had perihilar CCA (pCCA), 13 had (9.6%) middle bile duct CCA (mCCA), and 45 (33.3%) had distal CCA (dCCA). Across 148 EUS procedures, 139 LNs were identified, and EUS-TA was performed on 63 LNs among 55 patients. LN metastases were detected by EUS-TA for iCCA, pCCA, mCCA, and dCCA, in 25%, 6.2%, 15.4%, and 4.4%, respectively. EUS and EUS-TA influenced surgical work-up for iCCA, pCCA, mCCA, and dCCA in 25%, 1.5%, 15.4%, and 0.0%, respectively. No complications associated with EUS were noted. Conclusions: Preoperative EUS for nodal staging had an important clinical impact in patients with presumed resectable iCCA and mCCA, but less for pCCA and dCCA. Further prospective studies should investigate whether systematic nodal staging with EUS could improve preoperative decision making even further. Full article

Biliary tract carcinoma (BTC) is a group of highly heterogeneous malignancies arising from the biliary epithelium. Anatomically, BTC is categorized into gallbladder cancer (GBC) and cholangiocarcinoma (CCA), with the latter further subdivided into intrahepatic (iCCA), perihilar (pCCA), and distal cholangiocarcinoma (dCCA). Epidemiological studies reveal a dismal five-year survival rate of less than 20% for BTC patients, with limited responses to current chemotherapy regimens, underscoring the urgent need to unravel its complex molecular pathogenesis. Recent research has increasingly focused on the regulatory networks of post-translational modifications, particularly the ubiquitin-proteasome system (UPS), in tumorigenesis. As the largest subfamily of deubiquitinating enzymes (DUBs), ubiquitin-specific proteases (USPs) regulate the stability of key oncoproteins such as phosphatase and tensin homolog (PTEN) and c-Myc, playing pivotal roles in tumor cell proliferation, apoptosis evasion, invasion, and metastasis. This review systematically summarizes the differential expression profiles of USP family members (e.g., USP1, USP3, USP7, USP8, USP9X, USP21, and USP22) in BTC and their clinical significance, with a focus on elucidating how specific USPs regulate tumor progression through key substrates, including poly(ADP-ribose) polymerase 1 (PARP1), dynamin-1-like protein (DNM1L), and O-GlcNAc transferase (OGT). Furthermore, based on recent advances, we discuss the therapeutic potential of small-molecule USP inhibitors in BTC targeted therapy, providing a theoretical foundation for developing novel precision treatment strategies. Full article

Background/Objectives: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a frequent but insufficiently studied complication in cholangiocarcinoma (CCA). This study aimed to evaluate incidence and risk factors of PEP in CCA. Methods: We retrospectively reviewed 148 CCA patients who underwent ERCP between 2019 and 2022. Demographic, clinical, and procedural data were compared between patients with and without PEP, and logistic regression was used to identify independent predictors. Results: PEP occurred in 26.4% of patients, mostly aged ≥ 66 years, male, and with perihilar CCA. In PEP cases, metallic stents were frequently used, procedures often exceeded 60 min, and 28.2% developed post-ERCP cholangitis. Hospital stay was ≥4 days in nearly 90% of cases. PEP severity was mild (10.3%), moderate (61.5%), and severe (28.2%). Multivariate analysis showed older age, metallic stent placement, and post-ERCP cholangitis as independent risk factors, while bilirubin ≥ 15 mg/dL was protective. Conclusions: PEP occurred in over one-fourth of CCA patients, predominantly of moderate severity. Independent risk factors included older age, metallic stent placement, and post-ERCP cholangitis, whereas bilirubin ≥ 15 mg/dL was protective. Awareness of these factors may aid risk stratification and prevention in this high-risk group. Full article

Background: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic malignancy or inflammatory conditions, leading to delayed or inappropriate treatment. Case Series: A 30-year-old man presented with hyperemesis, proptosis, and gait instability. He was found to have colonic stenosis, stomach thickening, pachymeningitis, and polyserositis. Gastroenteric histology and serology confirmed IgG4-RD. Steroids were ineffective, but rituximab produced sustained clinical and radiologic improvement. A 35-year-old woman developed jaundice and cholestasis with a perihilar mass highly suggestive of cholangiocarcinoma. Histopathology revealed IgG4-RD, and rituximab therapy led to marked clinical and serological improvement. A 64-year-old woman with a submandibular mass underwent sialoadenectomy, with histology confirming IgG4-RD; she remained asymptomatic without systemic treatment. Literature Review: A literature review highlighted the diagnostic challenges of atypical IgG4-RD. Gastrointestinal involvement is rare and often misclassified as inflammatory bowel disease. Isolated biliary disease frequently mimics cholangiocarcinoma, while salivary gland involvement may be misdiagnosed as neoplasia. Serum IgG4 levels >135 mg/dL and IgG4/IgG ratio >0.21 may support clinical suspicion, but histopathology remains indispensable for definitive diagnosis and for excluding malignancy. Steroid responsiveness is a hallmark, though relapses after tapering are common, often necessitating B-cell-directed therapy. Conclusions: IgG4-RD should be considered in patients with unexplained, relapsing, or steroid-responsive conditions. Early recognition, multidisciplinary collaboration, and integration of histopathology with clinical features are essential to avoid misdiagnosis and optimize management. Full article

Background: Perihilar cholangiocarcinoma (pCCA), especially the periductal-infiltrating subtype, is notoriously difficult to diagnose due to subtle imaging findings and the absence of a mass. Case Presentation: We describe a 56-year-old man with morbid obesity and deep vein thrombosis (DVT), admitted for severe cholestatic jaundice. Initial ultrasound and two ERCPs were inconclusive, with only mild hilar duct dilation on CT. MRI was not possible due to the severe weight of the patient. Only at the 3rd ERCP with digital cholangioscopy were irregular mucosa and tumor infiltration observed, and a biopsy confirmed moderately to poorly differentiated adenocarcinoma. The patient deteriorated rapidly after discharge, returning in septic shock. Despite laparoscopy excluding cholecystitis and cirrhosis, he died from multiorgan failure. Autopsy revealed diffuse hilar tumor infiltration, nodal metastases, and fatal pulmonary tumor embolism (Bismuth IV). Conclusions: This case highlights the necessity of early escalation to cholangioscopy in unresolved cholestasis, the importance of recognizing paraneoplastic thrombosis, and the value of autopsy in clarifying cause of death. Full article

This review explores how multimodal foundation models (MFMs) are transforming biliary tract cancer (BTC) research. BTCs are aggressive malignancies with poor prognosis, presenting unique challenges due to difficult diagnostic methods, molecular complexity, and rarity. Importantly, intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and distal bile duct cholangiocarcinoma (dCCA) represent fundamentally distinct clinical entities, with iCCA presenting as mass-forming lesions amenable to biopsy and targeted therapies, while pCCA manifests as infiltrative bile duct lesions with challenging diagnosis and primarily palliative management approaches. MFMs offer potential to advance research by integrating radiological images, histopathology, multi-omics profiles, and clinical data into unified computational frameworks, with applications tailored to these distinct BTC subtypes. Key applications include enhanced biomarker discovery that identifies previously unrecognizable cross-modal patterns, potential for improving currently limited diagnostic accuracy—though validation in BTC-specific cohorts remains essential—accelerated drug repurposing, and advanced patient stratification for personalized treatment. Despite promising results, challenges such as data scarcity, high computational demands, and clinical workflow integration remain to be addressed. Future research should focus on standardized data protocols, architectural innovations, and prospective validation studies. The integration of artificial intelligence (AI)-based methodologies offers new solutions for these historically challenging malignancies. However, current evidence for BTC-specific applications remains largely theoretical, with most studies limited to proof-of-concept designs or related cancer types. Comprehensive clinical validation studies and prospective trials demonstrating patient benefit are essential prerequisites for clinical implementation. The timeline for evidence-based clinical adoption likely extends 7–10 years, contingent on successful completion of validation studies addressing current evidence gaps. Full article