Search Results (502)

Pancreatic ductal adenocarcinoma is one of the most aggressive tumours, with an estimated 5-year overall survival rate of 5% and median survival of 5–11 months. Approximately one third of patients die of complications due to local disease progression, especially among patients with borderline resectable or locally advanced disease; hence achieving local control is significant for improved survival outcomes. Stereotactic body radiotherapy (SBRT) allows safe and effective delivery of ablative doses of radiation and is associated with improved locoregional tumour control and progression free survival. Our article describes the rationale and the safe and effective delivery of Linac-based SBRT treatment for pancreatic cancer. Full article

Immune checkpoint blockade has changed the management of several digestive system cancers, but its impact is highly context dependent. This review evaluates evidence for esophageal, gastric and gastroesophageal junction, colorectal, hepatocellular, biliary tract and gallbladder, and pancreatic cancers. Randomized phase III trials have established chemoimmunotherapy or dual-checkpoint strategies in advanced esophageal cancer, biomarker- and regimen-dependent first-line therapy in gastric cancer, PD-1-based therapy for MSI-H/dMMR colorectal cancer, atezolizumab–bevacizumab and STRIDE for unresectable hepatocellular carcinoma, and chemoimmunotherapy for advanced biliary tract cancer. Recent results also expand perioperative treatment: neoadjuvant checkpoint blockade produces high pathological response rates in dMMR colon cancer, adjuvant atezolizumab plus mFOLFOX6 improves disease-free survival in stage III dMMR colon cancer, and perioperative serplulimab improves event-free survival in PD-L1-positive resectable gastric cancer. These advances coexist with important negative findings. Pembrolizumab-containing therapy did not meet superiority end points in KEYNOTE-062, the initial adjuvant signal in IMbrave050 was not sustained, and unselected pancreatic ductal adenocarcinoma remains largely resistant to checkpoint blockade. Early vaccine, cellular, TIGIT, radiomics, spatial, and multi-omics studies remain hypothesis-generating and require external or randomized validation. Clinical interpretation should integrate evidence maturity, biomarker validity, immune-related toxicity, patient-reported outcomes, cost, access, and manufacturing demands rather than response rate alone. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies despite advances in surgical techniques and systemic therapy. Although surgical resection offers the only potential for cure, recurrence is common, underscoring the critical role of multimodal treatment. Over the past two decades, numerous clinical trials have cemented adjuvant chemotherapy as a cornerstone of multimodal management in resected PDAC, with progressive evolution from single-agent regimens to modern multiagent regimens. In contrast, the role of chemoradiation remains debated, with the body of evidence demonstrating conflicting results. Ongoing clinical trials are expected to elucidate optimal treatment modalities. Emerging targeted therapies, biomarker-directed treatment approaches, and immunotherapeutic strategies also hold promise for improving outcomes in select patient populations. This narrative review summarizes the landmark trials that have shaped adjuvant therapy, examines the evolution of adjuvant treatment over time, reviews current management guidelines, and highlights promising emerging therapeutic directions likely to influence the management of localized pancreatic cancer. Full article

Gastrointestinal (GI) cancers represent a diverse group of malignancies that remain a major cause of cancer-related morbidity and mortality worldwide. Their management is increasingly complex, reflecting differences in tumor biology, anatomical location, stage, and molecular profile. In recent years, advances in molecular diagnostics, immunotherapy, and targeted treatment have moved clinical decision-making beyond a purely organ- and stage-based approach toward more individualized, biomarker-guided care. This narrative review summarizes established and emerging biological and targeted therapies used in esophageal, gastric and gastroesophageal junction, colorectal, pancreatic, hepatocellular, and biliary tract cancers. It focuses on immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4; HER2-directed monoclonal antibodies and antibody–drug conjugates; antiangiogenic and anti-EGFR therapies; and newer strategies involving CLDN18.2, FGFR2b, and tumor-agnostic alterations such as NTRK fusions. The review also considers the predictive biomarkers used to guide treatment selection and the growing integration of systemic therapy with surgery in neoadjuvant, perioperative, adjuvant, and conversion settings. However, clinical efficacy alone does not determine whether new treatments become part of routine practice. Regulatory approval, reimbursement, access to molecular testing, and the availability of specialized multidisciplinary care are equally important. The rapidly evolving treatment landscape for GI cancers therefore requires clinical decisions that account for tumor biology, anatomical resectability, molecular eligibility, expected benefit, treatment-related toxicity, and local access to therapy. Expanding access to comprehensive biomarker testing and effective molecularly guided treatments will be essential to translate progress in precision oncology into more personalized and equitable care for patients with GI cancers. Full article

Background and Objectives: Systemic inflammation, nutritional status, and host immune response play pivotal roles in cancer progression and patient prognosis. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel inflammation-based biomarker integrating these parameters. This study aimed to evaluate the prognostic value of the preoperative CALLY index in patients undergoing pancreaticoduodenectomy for pancreatic head adenocarcinoma. Materials and Methods: This retrospective study included 101 consecutive patients who underwent pancreaticoduodenectomy with curative intent for histopathologically confirmed pancreatic head adenocarcinoma at Çukurova University Faculty of Medicine between 2010 and 2021. Demographic, clinicopathological, perioperative, and survival data were analyzed. The CALLY index was calculated using preoperative serum C-reactive protein, albumin, and lymphocyte levels, and the optimal cutoff value was determined by receiver operating characteristic (ROC) curve analysis. Results: Using an optimal cutoff value of 1.38, patients were categorized into low (n = 58) and high (n = 43) CALLY index groups. Patients with a low CALLY index experienced significantly higher rates of intraoperative and postoperative complications, surgical site infection, reoperation, unplanned hospital readmissions, and 30- and 90-day mortality (all p < 0.05). Moreover, the low CALLY index group demonstrated significantly poorer overall survival than the high CALLY index group (p < 0.001). Receiver operating characteristic (ROC) analysis for overall mortality yielded an area under the curve (AUC) of 0.701 (95% CI, 0.591–0.811). On multivariable Cox regression, a low CALLY index remained an independent predictor of poorer overall survival (adjusted hazard ratio [aHR], 2.45; 95% CI, 1.47–4.08; p < 0.001) after adjustment for age, tumor size, lymph node status, resection margin, and differentiation. On multivariable logistic regression, a low CALLY index was independently associated with surgical site infection (adjusted odds ratio [aOR], 11.5; 95% CI, 3.9–34.2; p < 0.001) and overall postoperative morbidity (aOR, 5.3; 95% CI, 2.0–14.0; p < 0.001). Conclusions: The preoperative C-reactive protein–albumin–lymphocyte (CALLY) index is a simple, inexpensive, and readily available biomarker with significant prognostic value in patients undergoing pancreaticoduodenectomy for pancreatic head adenocarcinoma. A low CALLY index was associated with poorer overall survival and increased postoperative morbidity and mortality. The CALLY index may serve as a practical tool for preoperative risk stratification and prognostic assessment. However, prospective multicenter studies are warranted to validate standardized cutoff values and further establish its clinical applicability. Full article

Background: Pancreatic steatosis (PS) has emerged as a potential risk factor for pancreatic ductal adenocarcinoma (PDAC). While increasing evidence supports its role in pancreatic carcinogenesis, its prognostic significance after PDAC diagnosis remains unclear. We performed a systematic review to evaluate the association between PS and survival outcomes in patients with pancreatic cancer. Methods: A systematic search of PubMed and Scopus was conducted in May 2026 according to PRISMA guidelines. Observational studies assessing pancreatic steatosis by imaging or histology and reporting survival outcomes in PDAC patients were included. Risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool. Results: Five studies met inclusion criteria, comprising three imaging-based and two histology-based papers. Three studies reported findings suggestive of an adverse prognostic role of PS, whereas two found no significant association with survival. The strongest evidence originated from a study using quantitative histological assessment of pancreatic fat, which demonstrated that greater pancreatic fat accumulation was independently associated with poorer overall survival and recurrence-free survival following surgical resection. In contrast, imaging-based studies yielded inconsistent results. Histology-based studies consistently supported a negative prognostic impact, whereas CT-derived attenuation measures showed substantial variability. Risk of bias was moderate to high in most studies, largely due to retrospective designs, small sample sizes, heterogeneous definitions of pancreatic steatosis, and incomplete adjustment for metabolic confounders. Conclusions: Current evidence regarding the prognostic value of pancreatic steatosis in PDAC is limited and conflicting. While histology-based studies suggest an adverse impact on survival, imaging-based data remain inconsistent. Full article

Since decades, surgery of pancreatic adenocarcinoma is confronted with two major challenges. First, the prognosis of pancreatic adenocarcinoma is the worst of all gastrointestinal malignancies, characterized by late diagnosis and aggressive tumor biology. Second, postoperative mortality and morbidity have been exceptionally high, giving pancreatic resection a reputation of being one of the most dangerous procedures. This narrative review concentrates on the progress in decreasing postoperative mortality by centralization and standardization, the exertion of extended resections for local tumor clearance and multimodal strategies to improve oncologic survival. Research regarding surgical techniques, especially robotic assistance, indicated further progress in minimizing the perioperative trauma. Multimodal treatment concepts have been implemented with adjuvant therapy in resectable and neoadjuvant regimen in borderline and locally advanced cancer. However, significant problems have to be solved. Postoperative morbidity remains high, hindering the administration of adjuvant therapy, and toxicity is an essential factor in neoadjuvant strategies. Despite neoadjuvant therapies, resection rates of locally advanced carcinoma are modest and tumor progression hinders resection of borderline and resectable carcinomas. Obviously, deficits in understanding tumor biology are a central obstacle in improving resection rates and overall survival. Hence, improvement in selection of patients for surgical resection apart from using preoperative anatomical findings is mandatory. The progression of current standards, future developments and the status of surgery in multimodal concepts to treat pancreatic adenocarcinoma are delineated using historical and recent reports, registry data, meta-analysis and randomized controlled trials. Full article

Pancreatic cancer ranks among the most lethal malignancies, characterized by a five-year survival rate of approximately 10%. This dismal prognosis is largely attributable to diagnoses occurring at advanced stages and the inherent limitations of conventional imaging modalities in detecting early lesions, identifying metastases, and assessing tumor heterogeneity. Consequently, there is a critical need for non-invasive imaging techniques capable of visualizing pancreatic cancer lesions to enable accurate diagnosis, risk assessment, and the development of personalized treatment strategies. Molecular imaging, which combines highly specific targeted probes with advanced imaging technologies, offers the potential to elucidate disease-associated pathways. This review provides a comprehensive overview of recent advancements in molecular imaging platforms for pancreatic cancer, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), optical molecular imaging, photoacoustic imaging, and molecular MRI. We begin by elucidating the biological rationale for targeting key molecules, including fibroblast activation protein (FAP), integrins, and programmed death ligand 1 (PD-L1). Moreover, we critically evaluate the development and clinical translation of these probes, highlighting their ability to enhance lesion detectability, characterize intratumoral heterogeneity, and guide both targeted therapy and surgical resection. Compared with existing reviews, this work uniquely integrates a comprehensive cross-modality analysis of the latest molecular imaging strategies for pancreatic cancer. Furthermore, we examine prevailing challenges and emerging frontiers in this domain, specifically focusing on multimodal hybrid imaging, artificial intelligence-driven analytics, and integrated theranostic platforms as pivotal strategies to advance precision oncology. Full article

Immune checkpoint inhibitor (ICI)-based combinations have become central systemic treatment options for advanced hepatocellular carcinoma (HCC) and are now being integrated into selected intermediate-stage settings. As tumor responses have improved, some patients who were not initially candidates for curative-intent treatment may later become candidates for resection, ablation, or liver transplantation. However, radiographic response alone does not define curative-intent candidacy, and no shared framework currently guides how post-immunotherapy response should be translated into a treatment decision. Terminology also differs regionally: Asian literature frames a resection-anchored paradigm, whereas Western practice uses transplant-anchored downstaging. This narrative review proposes a multidisciplinary framework for immunotherapy-based conversion to curative-intent treatment in HCC. We first clarify the lexicon of conversion, downstaging, bridging, neoadjuvant therapy, post-ICI transplantation, and drug-free or treatment-free status. We then summarize conversion-relevant evidence across key clinical decision settings, including transarterial chemoembolization (TACE)-unsuitable intermediate-stage disease, portal vein tumor thrombus or macrovascular invasion, borderline-resectable or locally advanced disease, and transplant downstaging or bridging. The central framework defines curative-intent transition through the intersection of three domains: technical suitability, oncologic suitability, and physiologic or liver-reserve suitability. Biomarkers, imaging response, tumor-marker kinetics, liver function, and treatment-related toxicity are discussed as inputs into candidacy rather than as response measures alone. Finally, we propose a multidisciplinary workflow and highlight lessons from pancreatic cancer, biliary tract cancer, and colorectal liver metastases. As an expert-opinion-based framework, this approach should structure multidisciplinary discussion rather than serve as validated selection criteria; harmonized terminology, prospective conversion registries, and conversion-specific endpoints are needed for prospective validation. Full article

Background/Objectives: The lymphocyte-to-monocyte ratio (LMR) is an inflammation-based prognostic score (IBPS) that can be easily calculated using routine blood tests. Handgrip strength (HGS), a key diagnostic component of sarcopenia, also predicts survival. Nonetheless, the prognostic role of combined LMR and HGS in patients with pancreatic head cancer undergoing pancreaticoduodenectomy remains unclear. This exploratory study aimed to analyze whether the combination of preoperative LMR and HGS is associated with overall survival. Methods: We retrospectively analyzed 105 patients with pancreatic head cancer who underwent pancreaticoduodenectomy at Chiba University Hospital from January 2016 to December 2020. We examined the prognostic values of IBPSs and HGS and compared combinations of preoperatively measurable factors. Results: Multivariate analysis assessing preoperatively measurable factors demonstrated that low preoperative HGS, low preoperative LMR, and high preoperative carbohydrate antigen 19-9 level were associated with poor overall survival (hazard ratio [HR]: 2.41, 95% confidence interval [CI]: 1.29–4.51, p = 0.006; HR: 2.05, 95% CI: 1.12–3.76, p = 0.020; and HR: 2.68, 95% CI: 1.25–5.76, p = 0.011, respectively). The combination of low HGS and low LMR was associated with poor overall survival, although only 12 patients were included in this subgroup. Multivariate analysis evaluating clinicopathological factors demonstrated that this combination was associated with poor overall survival (HR: 2.85, 95% CI: 1.06–7.69, p = 0.038). Conclusions: In this single-center exploratory study, the combination of preoperative LMR and HGS was associated with poor overall survival in patients with surgically resected pancreatic head cancer. Further prospective multicenter validation is required before this combined marker can be used for clinical decision-making. Full article

Background: Coronary artery disease (CAD) is an important comorbidity that may increase perioperative cardiovascular risk in major noncardiac surgery. However, data evaluating its impact on outcomes following pancreatic cancer surgery remain limited. This study evaluated inpatient outcomes among patients undergoing pancreatic cancer resection with versus without CAD in the United States. Methods: We performed a retrospective analysis using the National Inpatient Sample (2016–2022). Adult hospitalizations with ICD-10 diagnosis codes for pancreatic cancer and procedure codes for pancreatic resection were identified and stratified by the presence of CAD. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospitalization cost, and complications such as shock, respiratory failure, acute kidney injury, and transfusion. Results: A total of 49,395 hospitalizations were identified, including 6910 (14.0%) with CAD. Patients with CAD were older and had a greater comorbidity burden. In-hospital mortality was similar between groups (2.32% vs. 2.34%). Most complications were comparable, although shock was more frequent in CAD patients (6.66% vs. 5.44%). Length of stay was similar, while hospitalization costs were modestly higher in the CAD cohort. Conclusions: Pre-existing CAD was not associated with increased in-hospital mortality or longer hospitalization following pancreatic cancer surgery despite a greater comorbidity burden. Full article

Background: Over 60,000 patients are diagnosed annually with pancreatic cancer in the United States, most with pancreatic ductal adenocarcinoma (PDAC). Despite multimodality treatment, prognosis remains poor, underscoring the need to better define factors associated with improved survival in resectable disease. The aim of this study was to propose “completeness of therapy” in resectable PDAC based on chemotherapy type, relative dose intensity (RDI), duration, and timing of initiation, and to evaluate their association with overall survival (OS). Methods: A systematic review of PubMed identified 34 studies. Hazard ratios (HRs) were extracted and synthesized in forest plots. Outcomes focused on OS in relation to chemotherapy completion (cumulative cycles), time to adjuvant chemotherapy initiation (TTA), RDI, and regimen type. The goal was to conceptualize an evidence-based completeness-of-therapy framework for resected PDAC. Results: Completion of chemotherapy was associated with a 42% reduction in the hazard of death compared with incomplete therapy (HR = 0.58, 95% CI 0.47–0.71, p < 0.01). No significant OS difference was observed for longer TTA within a ≤12-week window after surgery (HR = 1.22, 95% CI 0.95–1.56, p = 0.10). Higher RDI demonstrated a large but non-significant trend toward improved OS (HR = 0.51, p = 0.24). Non-significant trends favoring gemcitabine-based regimens (HR = 0.87, p = 0.26) and FOLFIRINOX (HR = 0.79, p = 0.26) were observed, with FOLFIRINOX suggesting a 21% relative reduction in mortality. Conclusions: Chemotherapy completion is strongly associated with improved OS in resectable PDAC. Initiation of adjuvant therapy within 12 weeks appears sufficient, allowing recovery from surgery. Higher RDI and specific chemotherapy regimens demonstrated numerically favorable hazard ratios; however, these associations were not statistically significant and should be interpreted cautiously. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy. The identification and management of precursor lesions, particularly the increasingly common intraductal papillary mucinous neoplasms (IPMNs), pose a significant challenge, creating a profound clinical dilemma between intercepting pancreatic ductal adenocarcinoma and avoiding surgical overtreatment. This literature review aims to synthesize the latest evidence to facilitate a transition from purely morphology-based surveillance toward a biologically informed risk stratification paradigm. This approach could provide a personalized risk-stratification algorithm that optimizes therapeutic management and enables timely intervention for pancreatic cancer. By using PubMed, Embase, Scopus, and Web of Science, we analyzed and summarized key findings from recent literature (2020–2025), including cohort studies, mechanistic analyses, evidence-based guidelines, and systematic reviews on cyst fluid biomarkers (CEA panels, DNA/RNA sequencing), and emerging AI applications. Prospective and multicenter studies consistently report that NOD is independently associated with high-risk stigmata, cyst progression, and malignant transformation. Mechanistic research suggests a bidirectional interplay between the evolving neoplasia and pancreatic endocrine dysfunction. Updated guidelines underscore the need for more precise diagnostic algorithms. Recent work demonstrates that advanced cyst fluid markers—CEA panels, DNA/RNA sequencing, and multi-omic signatures—significantly improve diagnostic accuracy. Furthermore, explainable AI models show encouraging performance in predicting malignancy and assisting patient triage. Risk stratification in PCLs is shifting from morphology-based assessment toward integrated, multimodal approaches combining clinical, endocrine, imaging, molecular, and computational data. Recent evidence positions new-onset diabetes as a clinically accessible and biologically plausible marker of high-risk IPMNs. Similarly, molecular assays and AI-enhanced analytics provide an additional layer of diagnostic precision. The development of personalized risk prediction algorithms could improve early detection of malignancy while reducing unnecessary surgical resections. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Germline loss-of-function mutations in BRCA1 and BRCA2 markedly increase susceptibility to breast, ovarian, and other cancers. Mechanistically, BRCA2 facilitates RAD51 recruitment to sites of DNA damage, whereas BRCA1 regulates homologous recombination repair (HRR) through double-strand break resection and broader DNA damage response signaling. These insights underpin targeted therapies such as poly (ADP-ribose) polymerase inhibitors (PARPis), which induce synthetic lethality in homologous recombination-deficient tumors. Clinically, PARPis have demonstrated significant benefit in BRCA1/2-mutated breast, ovarian, pancreatic, and prostate cancers. However, resistance remains a major obstacle, with secondary intragenic BRCA1/2 mutations restoring partial protein function representing a prominent mechanism. Despite therapeutic advances, critical gaps persist in understanding how specific BRCA1/2 domains and residual protein activities contribute to tumorigenesis and treatment response. In this review, we summarize the structural and functional domains of BRCA1/2, their pathogenic mutation profiles, and therapeutic strategies targeting BRCA1/2-deficient cancers. Despite therapeutic advances, critical gaps persist in understanding how specific BRCA1/2 domains and residual protein activities contribute to tumorigenesis and treatment response. This review emphasizes the need for functional studies of BRCA1/2 variants to refine risk prediction and develop mutation-tailored therapies. Full article