Search Results (48)

Background: Bone metastasis (BM) prevalence is underreported in biliary tract cancers (BTC). This study aimed to assess BM prevalence in a real-world BTC population, alongside examining its relationship to prognosis and genomic alterations. Methods: Patients with histology-proven BTC as reviewed at a university cancer centre between January 2019 and August 2022 were assessed. Data extracted from records included BTC subtype, molecular profiling and systemic anti-cancer therapy (SACT) use. Stratification by BTC subtype and metastasis sites occurred. Median overall survival (mOS) was defined as time from relapse or metastases to death. Survival analysis was conducted using the Cox Proportional Hazard model. Results: Of 197 patients, 74 (37.6%) had intrahepatic and 67 (34%) had extrahepatic cholangiocarcinoma. Thirty-four patients had BM (17.3%), with 14 identified at initial diagnosis. OS was not influenced by bone (HR 1.15; p = 0.48) or liver metastases (HR 1.09; p = 0.6). Stratifying for age and gender, no significant difference in OS was observed. Actionable alterations were equally likely in patients with (52.4%) and without BM (58.5%). Age of BTC onset (<65 or ≥65) did not significantly influence prevalence of actionable alterations. Patients receiving matched, targeted SACT had a mOS of 29.9 months, compared to 13.3 months in those with actionable alterations but no SACT matching (HR 0.35; p < 0.005). Conclusions: In advanced BTC, BM do not affect OS. Across all cohorts, actionable alterations improved OS when treated with matched SACT. Full article

Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3–4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases. Full article

Background/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004–2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan–Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson–Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6–2.7) and HR 2.94 (95% CI 2.3–3.8)) and ECC (HR 2.1 (95% CI 1.8–2.5) and HR 3 (95% CI 2.4–3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor. Full article

Objectives: This study focused on the presence or absence of vascular invasion and extrahepatic metastasis in hepatocellular carcinoma (HCC) and examined their impact on systemic treatment outcomes. Methods: We retrospectively analyzed 362 patients with unresectable HCC who received first-line systemic therapy. The prognostic evaluation was based on the presence of vascular invasion and extrahepatic metastasis at the time of treatment initiation. Results: Patients with vascular invasion or extrahepatic metastasis (advanced group) had significantly worse outcomes than those without these features (intermediate group), with median survival times of 434 and 658 days, respectively. Further subdivision of the advanced group into three categories—patients with only extrahepatic metastasis (m group, n = 77), patients with only vascular invasion (v group, n = 78), and patients with both vascular invasion and extrahepatic metastasis (vm group, n = 52)—revealed that the m group had significantly better outcomes than those in the other two groups, with median survival times of 649, 323, and 187 days, respectively. A comparison of the clinical backgrounds among the three groups demonstrated that the m group had significantly better liver function at the time of treatment initiation than that in the other two groups. Multivariable analysis, including performance status, Child–Pugh score, and the use of immune checkpoint inhibitors as first-line therapy, identified the m group as an independent and significant prognostic factor (hazard ratio, 0.50). Conclusions: Unresectable HCC with extrahepatic metastasis and no vascular invasion represents a novel staging category for systemic treatment. Full article

Atezolizumab and bevacizumab show promise for treating hepatocellular carcinoma (HCC), but identifying responsive patients remains challenging, due to tumor heterogeneity. This study explores immune dynamics following this combination therapy. Between 2020 and 2023, 29 patients with advanced HCC who received atezolizumab plus bevacizumab at Severance Hospital, Seoul, were enrolled in this study. Peripheral blood mononuclear cells were analyzed using flow cytometry and statistical methods to assess immune alterations and identify biomarkers. Baseline characteristics showed a diverse HCC cohort with a mean age of 64 years and 82.8% male predominance. Absence of extrahepatic metastasis was associated with better overall survival. Immune responses revealed distinct CD4⁺ T-cell phenotypes between the ‘partial response (PR) + stable disease (SD)’ and ‘progressive disease (PD)’ groups, with an overall increase in CD8⁺ T-cell phenotypes. Patients with higher frequencies of CD8⁺PD-1⁺Ki-67⁺ T cells experienced significantly improved overall survival, while those with lower frequencies of CD4⁺Foxp3⁺PD-1⁺LAG3⁺ T cells also had notable survival benefits. These findings enhance the overall understanding of immune responses to this combination therapy, facilitating improved patient stratification and personalized therapeutic approaches for HCC. Full article

BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC. Full article

Introduction: Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis, with an overall 5-year survival rate of 5–10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patient survival and response to treatment. We set out to review the results of 275 patients who underwent liver resection for CRCLM at the McGill University Health Center (MUHC) and analyze their clinical outcome, mutational burden, and pattern of cancer progression in light of their HGPs, and to consider their potential effect on surgical decision making. Methods: We performed a retrospective multivariate analysis on clinical data from patients with CRCLM (n = 275) who underwent liver resection at the McGill University Health Center (MUHC). All tumors were scored using international consensus guidelines by pathologists trained in HGP scoring. Results: A total of 109 patients (42.2%) were classified as desmoplastic and angiogenic, whereas 149 patients (57.7%) were non-desmoplastic and vessel co-opting. The 5-year survival rates for angiogenic patients compared with vessel co-opting patients were 47.1% and 13%, respectively (p < 0.0001). Multivariate analysis showed patients with vessel co-opting CRCLM had a higher incidence of extrahepatic metastatic disease (p = 0.0215) compared with angiogenic CRCLM. Additionally, KRAS mutation status was a marker of increased likelihood of disease recurrence (p = 0.0434), as was increased number of liver tumors (p = 0.0071) and multiple sites of extrahepatic metastatic disease (p < 0.0001). Conclusions: Multivariate analysis identified key clinical prognostic and molecular features correlating with the two HGPs. Determining liver tumor HGPs is essential for patient prognostication and treatment optimization. Full article

Background/Objectives: Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods: Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan–Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results: Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions: PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy. Full article

Background: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. Methods: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). Results: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029–2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017–3.841, p = 0.041). Conclusions: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases. Full article

Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we tested the hypothesis that the site of tumor growth influences extra-hepatic metastasis formation. To this end, we implanted murine colon cancer organoids into the primary tumor site (i.e., the caecum) and into the primary metastasis site (i.e., the liver) in immunocompetent mice. The organoid-initiated liver tumors were significantly more efficient in seeding distant metastases compared to tumors of the same origin growing in the caecum (intra-hepatic: 51 vs. 40%, p = 0.001; peritoneal cavity: 51% vs. 33%, p = 0.001; lungs: 30% vs. 7%, p = 0.017). The enhanced metastatic capacity of the liver tumors was associated with the formation of ‘hotspots’ of vitronectin-positive blood vessels surrounded by macrophages. RNA sequencing analysis of clinical samples showed a high expression of vitronectin in liver metastases, along with signatures reflecting hypoxia, angiogenesis, coagulation, and macrophages. We conclude that ‘onward spread’ from liver metastases is facilitated by liver-specific microenvironmental signals that cause the formation of macrophage-associated vascular hotspots. The therapeutic targeting of these signals may help to contain the disease within the liver and prevent onward spread. Full article

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0–78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258–2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028–1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105–2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112–2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients. Full article

Pancreatic neuroendocrine neoplasms (Pan-NENs) may exhibit a heterogeneous clinical course, ranging from indolent to progressive/metastatic behavior. In the latter scenario, streptozocin (STZ) is considered the cornerstone of systemic treatment; however, response to STZ-based chemotherapy may vary among individuals. In this narrative review, we aimed to identify the predictive factors of response to STZ in advanced Pan-NENs. We performed an extensive search in international online databases for published studies and ongoing clinical trials evaluating STZ in Pan-NENs. We found 11 pertinent studies evaluating 17 patient-, tumor-, or treatment-related factors. Age, CgA blood levels, tumor grade, Ki-67% index, anatomical location of the primary tumor, tumor stage, site of metastasis origin, liver tumor burden, extrahepatic spread, functional status, O6-methylguanine-methyltransferase (MGMT) status, line of therapy, and response to previous treatments were all statistically associated with radiological response and/or survival. The identified predictors may help clinicians make appropriate treatment decisions, in this way improving clinical outcomes in patients with advanced Pan-NENs. Full article

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009–2013, n = 86; period 2: 2014–2018, n = 132; period 3: 2019–2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1–3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin–bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival. Full article

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. Methods: A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan–Meier analysis with the log-rank test was used to compare different risk groups. Results: The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02–4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02–11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18–0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). Conclusion: The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice. Full article

Distant metastasis of cholangiocarcinoma is most commonly diagnosed in the liver; however, it can also be found in the lungs, distant lymph nodes, bones, and brain. Distant lymph node metastasis outside the abdominal region without concurrent abdominal metastasis is exceedingly rare in extrahepatic cholangiocarcinoma. Herein, we present interesting ¹⁸F-FDG PET/CT images of a 49-year-old male patient with common bile duct cancer. In this case, the patient, who was scheduled for surgery, unexpectedly showed axillary lymph node metastasis on a preoperative ¹⁸F-FDG PET scan, which was subsequently confirmed via histological examination. Although such cases are exceptionally rare, this accurate diagnosis prompted a modification of the treatment plan, leading to a positive therapeutic response. Full article