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Cancer Medicine Jun 2024This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in...
AIM
This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC).
METHODS
From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test.
RESULTS
The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors.
CONCLUSIONS
The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Male; Female; Middle Aged; Infusions, Intra-Arterial; Retrospective Studies; Longitudinal Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Hepatic Artery; Biomarkers, Tumor; Treatment Outcome; Prognosis
PubMed: 38819606
DOI: 10.1002/cam4.7319 -
Indian Journal of Surgical Oncology May 2024Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma... (Review)
Review
Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma (HCC) is contributed by various etiological factors like virus infection, excessive alcohol consumption, exposure to toxins, or metabolic disorders. Majority of patients are diagnosed with late-stage HCC, which restricts its management to only palliative care. HCC, if diagnosed early, increases the survival and quality of life. Currently available biomarker (alpha-fetoproteins) have several limitations, that impede the early diagnosis and staging of cancer. This warrants the continous search in pursuit of a novel biomarker. Several research works in diverse areas have contributed to the identification of various novel biomarkers that have shown multifaceted application in early disease diagnosis, which further aid in targeted and effective therapy that can prevent cancer progression. This improves the overall health status of the patient along with significant reduction in caretaker's burden. With the aid of novel technologies, several biomarkers have been investigated and validated in mutliple preliminary research works. Therefore in this review, we have outlined various novel biomarkers that showed promising outcomes in their trials and we have highlighted the developing areas that act as game changers in cancer diagnosis and management.
PubMed: 38817995
DOI: 10.1007/s13193-023-01858-x -
Frontiers in Oncology 2024The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B...
OBJECTIVE
The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis.
METHODS
A total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set ( = 1017) and a validation set ( = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated.
RESULTS
There was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8-86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%-25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine-Gray test < 0.001).
CONCLUSION
The competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.
PubMed: 38817899
DOI: 10.3389/fonc.2024.1398968 -
Cureus Apr 2024Testicular cancer is among the most common solid tumors in young men. Gastrointestinal tract (GIT) metastasis of testicular cancer has been rarely reported. In addition,...
Testicular cancer is among the most common solid tumors in young men. Gastrointestinal tract (GIT) metastasis of testicular cancer has been rarely reported. In addition, metastasis occurs most commonly through retroperitoneal lymph nodes. Manifestations like abdominal pain and obstruction can be present if metastasis to GIT was considered. We report here a case of a 34-year-old male who was admitted to our GIT unit complaining of episodic epigastric pain. Computed Tomogram (CT) scan demonstrated a soft tissue like lesion involving the lumen of duodenum. Moreover, the patient had a right radical orchiectomy 18 months prior to the presentation due to a stage IA non-seminomatous germ cell tumor with no lymphovascular invasion and free surgical margins. Esophagogastroduodenoscopy (EGD) revealed a malignant appearing duodenal lesion and biopsy showed that it was compatible with germ cell tumor. Metastatic embryonal carcinoma to duodenum was diagnosed and confirmed by immunohistochemical stains. Then, the patient's situation was discussed and decided to be on a plan of four cycles of chemotherapy regimens. Testicular malignancy metastasis to GIT is uncommon, but it's important to know that there is a contact between GIT and testicular lymphatic drainage through para-aortic lymph nodes. So, even if it's rare to occur, it's still possible, and we should always be concerned about it. Mostly, diagnosis of testicular tumors begins with evaluating tumor markers such as alpha-fetoprotein (AFP), beta-subunit of human chorionic gonadotropin (B-hCG), and lactate dehydrogenase (LDH). But in contrast, all of these markers were within the normal range of their values in our case. Suspicion for metastasis and GIT involvement must be raised when dealing with a young male who had a history of testicular tumor such as embryonal carcinoma which was reported here in our case. That is very essential for avoiding potential complications and saving time in order to start management.
PubMed: 38817519
DOI: 10.7759/cureus.59332 -
Cureus Apr 2024Alpha-fetoprotein (AFP) is considered one of the best-known predictive serum markers, playing a crucial role in cancer investigation and subsequent treatment. In most...
Alpha-fetoprotein (AFP) is considered one of the best-known predictive serum markers, playing a crucial role in cancer investigation and subsequent treatment. In most adult cells, the production of this marker is suppressed after embryogenesis. However, its increased level raises concerns about underlying malignant conditions, which provide a valuable diagnostic tool for medical professionals in oncology. The existing AFP-producing adenocarcinomas exhibit unique clinical characteristics, including high malignancy and early metastatic potential, which result in poorer outcomes. To illustrate these characteristics, we decided to describe a case report of a 70-year-old African American female with a significantly elevated level of AFP. Further pathology results confirmed a duodenal adenocarcinoma versus adenocarcinoma from the pancreas. While AFP-producing adenocarcinoma has multiple underlying molecular mechanisms that correlate with poor prognosis, definitive treatment based on molecular pathways has yet to be defined. Therefore, further research is needed for new therapeutic modalities.
PubMed: 38817451
DOI: 10.7759/cureus.59384 -
World Journal of Gastroenterology May 2024The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical... (Comparative Study)
Comparative Study
BACKGROUND
The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest.
AIM
To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis, tumor features, and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers.
METHODS
This prospective, diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital. Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer (BCLC) categorization. Demographics, HCC etiology, and HCC features were recorded. Biomarkers and the GALAD score were obtained at baseline. The performance of the GALAD score and biomarkers were prospectively assessed.
RESULTS
Exactly 115 individuals were diagnosed with HCC. The GALAD score increased with disease severity. Between BCLC-0/A and BCLC-B/C/D, the GALAD score predicted HCC staging with an area under the curve (AUC) of 0.868 (95%CI: 0.80-0.93). For identifying the curative HCC, the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein (AFP) (0.753) and Lens culinaris agglutinin-reactive fraction of AFP-L3 (0.706), and as good as that of Protein induced by vitamin K absence-II (PIVKA-II) (0.897). For detecting aggressive features, the GALAD score gave an AUC of 0.839 (95%CI: 0.75-0.92) and significantly outperformed compared to that of AFP (0.761) and AFP-L3 (0.697), with a trend of superiority to that of PIVKA-II (0.772). The performance to predict 1-year mortality of GALAD score (AUC: 0.711, 95%CI: 0.60-0.82) was better than that of AFP (0.541) and as good as that of PIVKA-II (0.736). The optimal cutoff value of GALAD score was ≥ 6.83, with a specificity of 72.63% for exhibiting substantial reduction in the 1-year mortality.
CONCLUSION
The GALAD model can diagnose HCC at the curative stage, including the characteristic of advanced disease, more than that by AFP and AFP-L3, but not PIVKA-II. The GALAD score can be used to predict the 1-year mortality of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Prospective Studies; Female; Middle Aged; Neoplasm Staging; Prognosis; Biomarkers, Tumor; Aged; alpha-Fetoproteins; Prothrombin; Protein Precursors; Adult; Early Detection of Cancer; Severity of Illness Index; Predictive Value of Tests; Biomarkers
PubMed: 38813057
DOI: 10.3748/wjg.v30.i17.2343 -
Frontiers in Oncology 2024Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of...
Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.
PubMed: 38812781
DOI: 10.3389/fonc.2024.1393074 -
BMC Cancer May 2024The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect...
BACKGROUND
The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method.
METHODS
Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method.
RESULTS
In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes.
CONCLUSION
This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.
Topics: Humans; Male; Female; Aged; Biomarkers, Tumor; China; Reference Values; Middle Aged; Aged, 80 and over; Prothrombin; Neoplasms; alpha-Fetoproteins; Ferritins; CA-19-9 Antigen; Carcinoembryonic Antigen; CA-125 Antigen; Phosphopyruvate Hydratase; Keratin-19; Protein Precursors; Biomarkers
PubMed: 38811867
DOI: 10.1186/s12885-024-12408-1 -
SAGE Open Medical Case Reports 2024Nature killer cell therapy has shown strong efficacy in the field of oncology in recent years and has been applied to patients with metastases with the aim of improving...
Nature killer cell therapy has shown strong efficacy in the field of oncology in recent years and has been applied to patients with metastases with the aim of improving the prognosis of advanced gastric cancer. A 59-year-old male with gastric adenocarcinoma with pancreatic metastasis (T4N0M1) who underwent radical surgery for gastric cancer with tumor metastasis was treated with oxaliplatin and tegafur combined with cellular reinfusion in stages. Computed tomograpy scan and serum tumor markers were monitored continuously after the treatment course. After five courses of combined treatment, the patient was in disease control with no significant side effects. At the last follow-up, the alpha fetoprotein had returned to its normal value with a poor display of low-density shadows in the body of the pancreas. Pancreatic cancer is insidious in origin and has a high mortality rate. The report provides clinical evidence for cell therapy of pancreatic metastatic cancer with improved quality of life.
PubMed: 38803362
DOI: 10.1177/2050313X241254743 -
Technology in Cancer Research &... 2024To scrutinize the therapeutic efficiency and safety profile of lenvatinib, accompanied by the programmed cell death protein-1 (PD-1) monoclonal antibody, and...
Efficacy of Lenvatinib in Combination With PD-1 Monoclonal Antibody and Interventional Treatment for Intermediate-Stage Hepatocellular Carcinoma: Impact on Serum Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Levels: A Retrospective Study.
To scrutinize the therapeutic efficiency and safety profile of lenvatinib, accompanied by the programmed cell death protein-1 (PD-1) monoclonal antibody, and interventional treatment in managing intermediate-stage hepatocellular carcinoma. Retrospective analysis was performed on clinical data from 93 patients suffering from intermediate to advanced hepatocellular carcinoma, treated at our institution from May 2018 to April 2020. Patients were divided based on the therapeutic regimen: 43 cases constituted the control group receiving lenvatinib plus transhepatic artery chemoembolization (TACE), while the remaining 50 cases in the study group were managed with lenvatinib, PD-1 monoclonal antibody, and TACE. Outcome measures included therapeutic efficacy, tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP], α-L-fucosidase [AFU], carbohydrate antigen 199 [CA199]), immune response indices (CD3+, CD4+, CD8+, CD4+/CD8+ ratio), pertinent cytokine levels (vascular endothelial growth factor [VEGF], matrix metalloproteinase-9 [MMP-9], basic fibroblast growth factor [aFGF], acidic fibroblast growth factor [bFGF]), quality of life (as per Quality of Life Assessment Scale for Cancer Patients [QOL-LC] scores), adverse effects, and survival rates. The study group exhibited a significantly enhanced total effective rate compared to the control group (74.00% vs 53.49%, < .05). Post-treatment levels of CEA, AFP, AFU, CA199, CD8+, VEGF, MMP-9, aFGF, and bFGF were notably lower in both groups, particularly in the study group. Contrastingly, CD3+, CD4+, CD4+/CD8+ratios, and QOL-LC scores were substantially elevated in the study group ( < .05). Adverse reaction prevalence was analogous between 2 groups (27.91% vs 26.00%; > .05). Moreover, the study group reported significantly higher 1-, 2-, and 3-year survival rates than the control group ( < .05). The combined use of lenvatinib, PD-1 monoclonal antibody, and interventional treatment for intermediate to advanced hepatocellular carcinoma may have a definitive therapeutic efficacy. This regimen is effective in reducing tumor marker levels, enhancing immune function, modulating VEGF, MMP-9, and other related cytokine levels, and improving patients' quality of life without significantly augmenting adverse effects. This treatment paradigm also contributes to increased survival rates and promises favorable prognosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Quinolines; Female; Phenylurea Compounds; Middle Aged; Vascular Endothelial Growth Factor A; Retrospective Studies; Programmed Cell Death 1 Receptor; Matrix Metalloproteinase 9; Aged; Biomarkers, Tumor; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Chemoembolization, Therapeutic; Adult; Antibodies, Monoclonal; Combined Modality Therapy
PubMed: 38802996
DOI: 10.1177/15330338241256812