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PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed. RESULTS: In all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival. CONCLUSION: A high number of concurrent medications was associated with poor clinical outcomes.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Immune Checkpoint Inhibitors/therapeutic use , Humans , Male , Female , Middle Aged , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Insurance, Health , Neoplasms/drug therapy , Urologic Neoplasms/drug therapy , Melanoma/drug therapy , Anti-Bacterial Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Proton Pump Inhibitors/therapeutic use , Analgesics, Opioid/therapeutic use , Retrospective Studies , Republic of Korea , Drug InteractionsABSTRACT
Despite the increasing number of female cancer survivors, uncertainty remains regarding potential adverse health outcomes for their offspring. Comprehensive population-based studies would be invaluable for female cancer survivors in making decisions about their future. This study uses the National Health Information Database to investigate perinatal and long-term outcomes of offspring born to mothers with a history of cancer. In a South Korean cohort of 95,264 women aged 15-40 diagnosed with cancer between 2007 and 2010, we evaluated the outcomes of 15,221 children born to 11,092, cancer survivors. We selected 147,727 women without a history of cancer and 201,444 children as a control group. Our study found that children of female cancer survivors have a significantly higher odds ratio of primary outcomes including preterm birth, low birth weight, neonatal intensive care unit admission, and death. While there was no difference in the rate of death within 1 year of birth between the two groups, the total death rate during the follow-up period was significantly higher in children born to mothers with cancer. After adjusting for gestational age and birth weight, there was no statistically significant increased hazard ratio of secondary outcomes including cancer, chromosomal abnormalities, cerebral palsy, delayed development, epilepsy, language disorder, or hearing impairment.
Subject(s)
Cancer Survivors , Neoplasms , Premature Birth , Pregnancy , Humans , Infant, Newborn , Female , Child , Premature Birth/epidemiology , Infant, Low Birth Weight , Birth Weight , Gestational Age , Neoplasms/epidemiologyABSTRACT
PURPOSE: In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea. MATERIALS AND METHODS: This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs. RESULTS: Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020. CONCLUSION: This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.
Subject(s)
Antineoplastic Agents , Lung Neoplasms , Humans , Retrospective Studies , Lung Neoplasms/drug therapy , Genetic Testing , Antineoplastic Agents/therapeutic use , High-Throughput Nucleotide SequencingABSTRACT
PURPOSE: Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. MATERIALS AND METHODS: This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (> 0.794) and low (≤ 0.794) CAR groups. RESULTS: After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04-7.86, p < 0.001) and OS (HR: 2.97, 95% CI: 1.33-6.64, p = 0.008). CONCLUSION: CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.
Subject(s)
Lymphoma, T-Cell, Peripheral , Humans , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/pathology , C-Reactive Protein , Retrospective Studies , Prognosis , Proportional Hazards ModelsABSTRACT
Background: Immune checkpoint inhibitors (ICIs) are one of the main pillars of cancer therapy. Since other studies such as clinical trial and retrospective study have limitations for detecting the immune-related adverse events (irAEs) characterized by unpredictable onset, nonspecific symptoms and wide clinical spectrum, we aimed to identify the incidence of irAEs and to detect and evaluate the signals using real-world data. Methods: Cancer patients treated with anticancer medications were analyzed using the nationwide health insurance claims database of South Korea from 2017 to 2019, and Clinical Data Warehouse (CDW) database of Asan Medical Center (AMC), a tertiary referral hospital, from 2012 to 2019. AEs of ICI users were compared with those of non-ICI anticancer medication users. PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab) were evaluated. We defined an AE as a newly added diagnosis after the ICI prescription using an ICD-10 diagnostic code. A signal was defined as an AE that was detected by any one of the four indices of data mining: hazard ratio (HR), proportional claims ratio (PCR), claims odds ratio (COR), or information component (IC). All detected signals were reviewed and classified into well-known or potential irAEs. Signal verification was performed for targeted AEs using CDW of AMC using diagnostic codes and text mining. Results: We identified 118 significant signals related to ICI use. We detected 31 well-known irAEs, most of which were endocrine diseases and skin diseases. We also detected 33 potential irAEs related to disorders in the nervous system, eye, circulatory system, digestive system, skin and subcutaneous tissues, and bones. Especially, portal vein thrombosis and bone disorders such as osteoporosis with pathological fracture and fracture of shoulder, upper arm, femur, and lower leg showed high HR in ICI users than in non-ICI users. The signals from hospital database were verified using diagnostic codes and text mining. Conclusion: This real-world data analysis demonstrated an efficient approach for signal detection and evaluation of ICI use. An effective real-world pharmacovigilance system of the nationwide claims database and the EMR could complement each other in detecting significant AE signals.
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Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5-21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Molecular Targeted Therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/etiology , Disease Progression , Drug Resistance, Neoplasm , Female , Humans , Immune Checkpoint Inhibitors/administration & dosage , Kaplan-Meier Estimate , Lung Neoplasms/diagnosis , Lung Neoplasms/etiology , Male , Middle Aged , Molecular Targeted Therapy/methods , Treatment Failure , Treatment OutcomeABSTRACT
The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p < 0.001), 3-year overall survival (OS) (68.3% vs. 96.2%; p < 0.0001), and 3-year progression-free survival (PFS) (53.5% vs. 88.0%; p < 0.0001). After adjusting for the International Prognostic Index components, a high CAR value independently predicted poor OS (HR: 6.02, 95% CI 1.19-30.38; p = 0.030) and PFS (HR: 3.62, 95% CI 1.40-9.36; p = 0.008). In an independent validation cohort (n = 50), patients with CAR > 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , C-Reactive Protein/metabolism , Lymphoma, Large B-Cell, Diffuse , Neoplasm Proteins/blood , Serum Albumin, Human/metabolism , Aged , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prednisone/administration & dosage , Retrospective Studies , Rituximab/administration & dosage , Survival Rate , Vincristine/administration & dosageABSTRACT
BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning. METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG. RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not. CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.
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BACKGROUND: Despite recent advances in treating non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs), their role in ALK-positive NSCLC patients is unclear. We investigated the efficacy of ICIs in patients with ALK-positive NSCLC. METHODS: Between 2011 and 2018, a total of 14 ALK-positive NSCLC patients treated with ICIs were evaluated retrospectively. Clinicopathologic features including age, PD-L1 expression, and treatment outcomes were analyzed. RNA expression level and cytolytic activity by ALK positivity were analyzed using The Cancer Genome Atlas (TCGA) and National Cancer Center Research Institute (NCCRI) data sets. RESULTS: A total of 13 patients (92.9%) received ALK inhibitors. Patients received a median of three (range 2-8) courses of therapy. The study included nine patients (64.3%) who were PD-L1-high (>50%) and four (28.6%) who were PD-L1-low (<50%). The objective response rate was 14.3% (2/14). The median progression-free survival time was 2.18 months (95% confidence interval [CI] 1.13 months-not reached [NR]). The median overall survival time was 5.67 months (95% CI 3.00 months-NR). RNA expression levels of CD274 were similar between the ALK-positive and negative groups in both TCGA and NCCRI datasets. RNA levels of CD8A in both TCGA and NCCRI data sets were nonsignificantly lower in the ALK-positive group. Cytolytic activity scores including interferon-γ-related response were lower in the ALK-positive group in the NCCRI but not TCGA dataset. CONCLUSIONS: Despite high PD-L1-positive rates, ICIs show limited efficacy in ALK-positive NSCLC. Decreased interferon-γ-related response may underlie these findings.
Subject(s)
Anaplastic Lymphoma Kinase/metabolism , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Nivolumab/therapeutic use , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Background/Aims: Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis. Methods: The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI-spleen diameter-to-platelet ratio scores (ASPS) were calculated. Results: The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×109/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047). Conclusions: ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.
Subject(s)
Elasticity Imaging Techniques/statistics & numerical data , Esophageal and Gastric Varices/diagnostic imaging , Gastrointestinal Hemorrhage/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Area Under Curve , Elasticity Imaging Techniques/methods , Esophageal and Gastric Varices/epidemiology , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/etiology , Humans , Incidence , Liver Cirrhosis/complications , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Assessment/methods , Spleen/diagnostic imagingABSTRACT
PURPOSE: Endoscopic bile duct decompression using bilateral self-expandable metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered a preferred procedure for malignant hilar biliary obstruction (MHBO). However, occlusion thereof occurs frequently. Here, we investigated stent patency duration and risk factors related to stent obstruction with bilateral SIS placement for MHBO at two large centers. MATERIALS AND METHODS: The present study reviewed data on patients with MHBO who underwent endoscopic biliary drainage using the SIS method. Clinical outcomes, including stent patency duration and patient overall survival, were analyzed. Factors associated with stent patency were evaluated using Cox proportional hazards models. RESULTS: Seventy patients with MHBO underwent endoscopic biliary drainage using the SIS method. Median age was 68 years old, and median follow-up duration was 140 days (interquartile range, 57-329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median stent patency duration with the SIS method was 108 days according to Kaplan-Meier curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days. Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as an independent risk factor related to stent patency (p<0.05). CONCLUSION: In endoscopic biliary decompression using SEMS placed with the SIS method, obstructive jaundice was a risk factor for stent patency. The SIS method for high-grade MHBO showed short stent patency.
Subject(s)
Bile Duct Neoplasms/complications , Carcinoma/complications , Cholestasis/therapy , Endoscopy, Digestive System/methods , Prosthesis Implantation/methods , Self Expandable Metallic Stents , Adult , Aged , Bile Duct Neoplasms/surgery , Carcinoma/surgery , Cholestasis/etiology , Drainage/methods , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Stents/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: Liver stiffness (LS) was assessed using transient elastography, and the enhanced liver fibrosis (ELF) test was performed to accurately assess fibrotic burden. We validated the LS-ELF algorithm and investigated whether the sequential LS-ELF algorithm performs better than concurrent combination of these analyses in chronic hepatitis B (CHB) patients. METHODS: Between 2009 and 2013, 222 CHB patients who underwent liver biopsy (LB), as well as LS measurement and the ELF test, were enrolled. RESULTS: Advanced fibrosis (≥F3) and cirrhosis (F4) were identified in 141 (63.6%) and 118 (53.2%) patients, respectively. Areas under receiver operating characteristic curve for LS predictions of ≥F3 (0.887 vs 0.703) and F4 (0.853 vs 0.706) were significantly higher than the ELF test (all pï¼0.001). Based on the LS-ELF algorithm, 60.4% to 71.6% and 55.7% to 66.3% of patients could have avoided LB to exclude ≥F3 and F4, respectively, whereas 68.0% to 78.7% and 63.5% to 66.1% of patients could have avoided LB to confirm ≥F3 and F4, respectively. When confirmation and exclusion strategies were applied simultaneously, 69.4% to 72.5% and 60.8% to 65.3% of patients could have avoided LB and been diagnosed as ≥F3 and F4, respectively. The proportion of patients who correctly avoided LB for the prediction of ≥F3 (69.4% to 72.5% vs 42.3% to 59.0%) and F4 (60.8% to 65.3% vs 23.9% to 49.5%) based on the sequential LS-ELF algorithm was significantly higher than the concurrent combination (all pï¼0.05). CONCLUSIONS: The sequential LS-ELF algorithm conferred a greater probability of avoiding LB in CHB patients to diagnose advanced fibrosis and cirrhosis, and this test performed significantly better than the concurrent combination.
Subject(s)
Hepatitis B, Chronic/complications , Liver Cirrhosis , Liver , Adult , Algorithms , Biopsy/methods , Elasticity Imaging Techniques/methods , Female , Hepatitis B, Chronic/epidemiology , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Liver Function Tests/methods , Male , Middle Aged , Reproducibility of Results , Republic of Korea/epidemiology , Retrospective Studies , Severity of Illness IndexABSTRACT
BACKGROUND/AIMS: Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. METHODS: Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. RESULTS: In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the ß regression coefficient of each factor, we established the NEXT score (Survival after Stopping Nexavar Treatment), allocating 1 point each for an Eastern Cooperative Oncology Group score ≥2, Child-Pugh class B or C, serum sodium ≤135 mEq/L, and α-fetoprotein ã400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (pï¼0.05, log-rank test). CONCLUSIONS: In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new "NEXT score" may help predict survival and prognosis even in patients who discontinue sorafenib treatment.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Niacinamide/analogs & derivatives , Phenylurea Compounds , Severity of Illness Index , Withholding Treatment/statistics & numerical data , Aged , Area Under Curve , Carcinoma, Hepatocellular/drug therapy , Female , Humans , Liver Neoplasms/drug therapy , Male , Middle Aged , ROC Curve , Retrospective Studies , Risk Factors , Sorafenib , Survival RateABSTRACT
BACKGROUND AND AIMS: The risk of developing hepatocellular carcinoma (HCC) varies, even in the context of cirrhosis. We investigated the relationship between liver stiffness (LS) in subcirrhotic range, assessed via transient elastography (TE), and risk of HCC development in patients with chronic hepatitis B (CHB)-related cirrhosis. METHODS: Data on 540 patients presenting with clinically evident CHB-related cirrhosis between April 2006 and December 2014 were reviewed retrospectively. Subcirrhotic range of LS was defined by TE values ≤13 kPa. RESULTS: Of the study population, 214 (39.6%) had LS values in the subcirrhotic range. During follow-up (median 54.1 months), 81 patients (15.0%) developed HCC. In conjunction with age, male gender, and diabetes mellitus, subcirrhotic LS value (hazard ratio = 0.462) was an independent predictor of HCC development on multivariate analysis (all p < 0.05). Cumulative HCC incidence was significantly lower for patients in subcirrhotic (versus cirrhotic) LS range (log-rank test, p < 0.05). In our cohort, the modified REACH-B score performed better than other prediction models, namely REACH-B, CU-HCC, and LSM-HCC scoring systems (area under receiver operating characteristic curve: 0.717 versus 0.669, 0.578, and 0.624, respectively, for 7-year HCC risk). CONCLUSIONS: A significant association between subcirrhotic range of LS value and lower risk of HCC development was identified in patients with clinically evident CHB-related cirrhosis. Thus, different TE-based HCC surveillance strategies may be required even in patients with identical liver cirrhosis disease category.
Subject(s)
Carcinoma, Hepatocellular/complications , Elasticity Imaging Techniques/methods , Hepatitis B, Chronic/complications , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/complications , Liver/diagnostic imaging , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/pathology , Humans , Incidence , Liver/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Republic of Korea/epidemiology , Retrospective Studies , RiskABSTRACT
Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).
Subject(s)
Malnutrition/diagnosis , Nutrition Assessment , Pancreatic Neoplasms/diagnosis , Aged , Body Mass Index , Disease-Free Survival , Endpoint Determination , Female , Follow-Up Studies , Humans , Lymphocyte Count , Male , Malnutrition/etiology , Middle Aged , Nutritional Status , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/therapy , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Factors , Serum Albumin/metabolismABSTRACT
BACKGROUND AND AIM: Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) can evaluate the degree of liver fibrosis. We investigated whether GPR can predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. METHODS: We retrospectively evaluated 1109 CHB patients that were enrolled between 2006 and 2012, and all patients had available data for the assessment of GPR at enrollment. Three risk groups were defined according to tertile stratification: GPR < 0.05, low-risk (n = 370 [33.4%]); GPR 0.05-0.24, intermediate-risk (n = 370 [33.4%]); and GPR > 0.24, high-risk (n = 369 [33.2%]). The predictive accuracy of GPR, fibrosis-4 (FIB-4), and aspartate transaminase-to-platelet ratio index (APRI) in predicting HCC development was tested. RESULTS: The median age of the study population (746 men and 363 women) was 50 years. During the follow-up period (median, 32 months; interquartile range, 19-57 months), 69 (6.2%) patients developed HCC. Together with age, male gender, diabetes mellitus, antiviral therapy, serum albumin, and alpha-fetoprotein, the relative risk of HCC development significantly increased from low-risk to high-risk GPR groups (hazard ratio [HR], up to 29.5; adjusted HR, up to 10.6; all P < 0.05). In addition, FIB-4 was calculated to be a significantly high relative risk of HCC development (HR, up to 20.1; adjusted HR, up to 7.3; all P < 0.05), whereas APRI was not (P = 0.168). The cumulative incidence of HCC development was significantly different among three risk groups (P < 0.001, log-rank test). CONCLUSIONS: This study suggests that GPR can be used as a noninvasive marker to assess the risk of HCC development in CHB patients.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/etiology , Hepatitis B, Chronic/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/etiology , Platelet Count , gamma-Glutamyltransferase/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Time FactorsABSTRACT
BACKGROUND & AIMS: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+ -M2BP) can be used to assess the degree of liver fibrosis, but few studies have investigated its prognostic utility. We evaluated whether serum WFA+ -M2BP can predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. METHODS: A total of 1323 CHB patients with WFA+ -M2BP test results between 2009 and 2011 were included in this retrospective analysis. RESULTS: The mean age of patients (793 men) was 51.0 years. During the follow-up period (median 60.3 months), 52 (3.9%) patients developed HCC. Age, the proportion of male gender, the presence of diabetes and cirrhosis, and levels of aspartate aminotransferase, alpha-foetoprotein, and WFA+ -M2BP were significantly greater in patients with HCC than in those without HCC, whereas serum albumin levels and platelet counts were significantly lower in patients with HCC than in those without HCC (all P<.05). In multivariate analysis, WFA+ -M2BP level was an independent predictor of HCC development (adjusted hazard ratio 1.143, 95% CI: 1.139-1.829), along with male gender and diabetes (all P<.05). In patients without cirrhosis (n=1087), WFA+ -M2BP levels ≥1.8 were associated with a higher risk of HCC development (P<.001 by log-rank test), whereas WFA+ -M2BP levels ≥1.8 tended to be associated with a higher risk of HCC development in patients with cirrhosis (n=236) (P=.073 by log-rank test). CONCLUSIONS: WFA+ -M2BP level can independently predict HCC development. Further studies should investigate whether WFA+ -M2BP level could be incorporated into surveillance strategies for CHB patients.
Subject(s)
Antigens, Neoplasm/blood , Carcinoma, Hepatocellular/blood , Hepatitis B, Chronic/complications , Liver Cirrhosis/complications , Liver Neoplasms/blood , Membrane Glycoproteins/blood , Plant Lectins/blood , Receptors, N-Acetylglucosamine/blood , Adult , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/epidemiology , Elasticity Imaging Techniques , Female , Humans , Kaplan-Meier Estimate , Liver/diagnostic imaging , Liver/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/epidemiology , Male , Middle Aged , Multivariate Analysis , Prognosis , Republic of Korea/epidemiology , Retrospective StudiesABSTRACT
Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA-M2BP) is a serologic marker corresponding with degree of hepatic fibrosis. We evaluated its accuracy in assessing hepatic fibrosis and in predicting the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).In a 5-year period (2009-2013), a total of 95 CHB patients with available serum WFA-M2BP assay and transient elastography assessment [to assess liver stiffness (LS)] who had undergone liver biopsy were recruited for retrospective analysis.Areas under the receiver operating characteristic curve for predicting fibrosis stages via serum WFA-M2BP level were as follows: ≥F2, 0.688; ≥F3, 0.694; and F4, 0.704 (all Pâ<â0.05). During the follow-up period (median, 45 months), HCC developed in 7 patients (7.4%). In patients with HCC, age, use of antiviral therapy, test parameters (HBV DNA, WFA-M2BP, and LS determinations), and histologic stage of fibrosis were all significantly greater than in those free of HCC, whereas platelet count was significantly lower (all Pâ<â0.05). On multivariate analysis, WFA-M2BP was found independently predictive of emergent HCC [hazard ratio (HR)â=â2.375; Pâ=â0.036], although LS and histologic stage of fibrosis were not (Pâ>â0.05). Risk of developing HCC was significantly greater in patients with high WFA-M2BP levels (≥1.8) (adjusted HRâ=â11.5; Pâ=â0.025). Cumulative incidence rates of HCC were also significantly higher in patients with high (vs. low) levels of WFA-M2BP (log-rank test, Pâ=â0.016).WFA-M2BP determination significantly reflected degree/extent of hepatic fibrosis and independently predicted the risk of developing HCC in patients with CHB.