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1.
J Chin Med Assoc ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507056

RESUMO

BACKGROUND: Esophageal varices (EV) is common and is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). However, the outcomes between cirrhotic and non-cirrhotic HCC patients with EV is not well studied. The present study aimed to investigate the clinical manifestations and prognoses of HCC patients after surgical resection stratified by the cirrhosis status. METHODS: A total of 111 patients with HCC and EV, who underwent surgical resection, were retrospectively enrolled between July 2003 to July 2019. The diagnosis of liver cirrhosis was established using the Ishak fibrosis score F5 or F6 in the non-tumor part of liver specimens. Prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: There were 85 (76.6%) and 26 (23.4%) patients with and without cirrhosis, respectively. Compared with those without cirrhosis, there were more females, less seropositive rate of hepatitis B surface antigen (HBsAg), more seropositive rate of antibody against to hepatitis C virus (HCV), less albumin-bilirubin (ALBI) grade 1, lower platelet count, and more had tumor burden within the Milan criteria in cirrhotic patients. Cirrhotic patients had a higher risk of post hepatectomy decompensation compared to non-cirrhotic patients (hazard ratio 9.577, p=0.017). No difference was observed in overall survival and recurrence-free survival between patients with or without cirrhosis. CONCLUSION: Compared to patients without cirrhosis, cirrhotic patients with HCC and EV are vulnerable to post hepatectomy decompensation. However, cirrhosis is not a poor prognostic factor of overall survival and recurrence for HCC patients after surgical resection.

2.
J Chin Med Assoc ; 85(5): 554-565, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385417

RESUMO

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is significantly higher in men than women. Nonetheless, the impact of sex disparities on HCC outcomes remains unclear. We aimed to compare the clinical manifestations and prognoses between male and female patients with HCC. METHODS: This retrospective study enrolled 5337 consecutive patients (3976 men, 1361 women) who were diagnosed with HCC from 2007 to 2020. The prognostic factors were identified by the Cox proportional hazards model. RESULTS: Male patients were younger upon HCC diagnosis (median age 64 vs 69 years; p < 0.001) with more favorable hepatic functional reserves (39.0% vs 35.1% albumin-bilirubin grade 1; p = 0.025) but had greater tumor burdens than the female patients. Furthermore, fewer male patients underwent curative therapies for HCC compared with the female patients (49.0% vs 57.0%; p < 0.001). After a median follow-up of 20.1 months (interquartile range, 5.8-47.3 months), 3133 patients died. The cumulative 5-year overall survival rates were 37.1% and 41.9% for male and female patients, respectively (p < 0.001). From the multivariate analysis, male sex was not an independent factor predictive of poor overall survival in all patients and in the subgroup analysis stratified by treatment modalities. When stratified by age, the female sex was an independent factor associated with lower mortality in younger (≤50 years) patients but not in older patients with HCC. CONCLUSION: Sex was not an independent predictor of the outcome of patients with HCC, especially for those aged more than 50 years.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Bilirrubina , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
3.
Cancers (Basel) ; 14(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35454919

RESUMO

The predictors of response and survival in patients with hepatocellular carcinoma (HCC) receiving regorafenib remain unclear. This study aimed to delineate the determinants of response and survival after regorafenib and evaluate post-progression treatment and outcomes. We retrospectively enrolled 108 patients with unresectable HCC receiving regorafenib after sorafenib failure. Progression-free survival (PFS), overall survival (OS), post-progression survival (PPS) and post-progression treatments were evaluated. The median PFS, OS and PPS were 3.1, 13.1 and 10.3 months, respectively. Achieving disease control by prior sorafenib, early AFP reduction and hand-foot skin reaction (HFSR) were associated with significantly better radiologic responses. By multivariate analysis, the time to progression on prior sorafenib, HFSR and early AFP reduction were associated with PFS; ALBI grade, portal vein invasion, HFSR and early AFP reduction were associated with OS. ALBI grade at disease progression, main portal vein invasion, high tumor burden and next-line therapy were associated with PPS. The median PPS was 12 months in patients who received next-line therapy, and the PPS was comparable between patients who received next-line targeted agents and immunotherapy. In conclusion, survival outcomes of regorafenib for HCC have improved in the era of multi-line sequential therapy. Preserved liver function and next-line therapy are important prognostic factors after regorafenib failure.

4.
Invest New Drugs ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35477812

RESUMO

Lenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%, p = 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months, p = 0.05) and OS (22.9 vs. 10.3 months, p = 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5-12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1-9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1-0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted.

5.
Life (Basel) ; 12(4)2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35455057

RESUMO

Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.

6.
PLoS One ; 17(3): e0264641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35231071

RESUMO

Intracranial germinoma (IG) rarely occurs in adults. Its optimal treatment strategy is unclear. We evaluated the outcomes of radiotherapy in adults with intracranial germinoma. Data of 29 adult patients (age, 18-52 years; median age, 24.3 years) with IG treated with radiotherapy at Taipei Veterans General Hospital were retrospectively reviewed. They were followed up for a median time of 5.9 years (range, 1.0-12.8 years). We used the Kaplan-Meier method to estimate the progression-free survival (PFS) and overall survival (OS), and univariate and multivariate Cox proportional hazards regression models to identify the factors affecting PFS. PFS and OS were compared between adult and pediatric patients with IG. The 1-, 3-, and 5-year PFS rates were 96.6%, 85.8%, and 77.8%, respectively, in the adult patients, and the OS rate were all 100%. Seven patients (24.1%) experienced recurrence, and in six of them, salvage therapy successfully controlled the disease. Two patients (6.9%) died after 5 years of follow-up due to disease progression and central pontine myelinolysis. In the univariate and multivariate Cox analysis, bifocal lesions had a significantly lower PFS than those with single lesions (p = 0.008). Kaplan-Meier survival analysis showed that adult patients had a poorer PFS (p = 0.06) and OS (p = 0.025) than pediatric patients. Our study showed bifocal lesions were associated with lower PFS than a single lesion among adult IG patients, and adult IG patients tended to have poorer PFS and OS compared to pediatric IG patients. For adult patients with bifocal IG, we recommend treatment with craniospinal irradiation, whole ventricle irradiation (WVI) with chemotherapy, or frequent spine images follow-up for patients who received only WVI.


Assuntos
Neoplasias Encefálicas , Germinoma , Adolescente , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Criança , Irradiação Craniana/efeitos adversos , Intervalo Livre de Doença , Germinoma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Eur J Cancer ; 166: 208-218, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35306319

RESUMO

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. METHODS: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. RESULTS: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CONCLUSIONS: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.


Assuntos
Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/patologia , Humanos , Células Neoplásicas Circulantes/patologia , Organoides/metabolismo , Neoplasias Pancreáticas/patologia , Estudos Prospectivos
8.
J Cell Mol Med ; 26(7): 1955-1968, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35174623

RESUMO

Nab-paclitaxel (Abraxane), which is a nanoparticle form of albumin-bound paclitaxel, is one of the standard chemotherapies for pancreatic ductal adenocarcinoma (PDAC). This study determined the effect of Abraxane in combination with a fusion protein, hIL15-ABD, on subcutaneous Panc02 and orthotopic KPC C57BL/6 murine PDAC models. Abraxane combined with hIL15-ABD best suppressed tumour growth and produced a 40%-60% reduction in the tumour size for Panc02 and KPC, compared to the vehicle group. In the combination group, the active form of interferon-γ (IFN-γ)-secreting CD8+ T cells and CD11b+ CD86+ M1 macrophages in tumour infiltrating lymphocytes (TILs) were increased. In the tumour drainage lymph nodes (TDLNs) of the combination group, there was a 18% reduction in CD8+ IFN-γ+ T cells and a 0.47% reduction in CD4+ CD25+ FOXP3+ regulatory T cells, as opposed to 5.0% and 5.1% reductions, respectively, for the control group. Superior suppression of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) and the induction of M1 macrophages in the spleen and bone marrow of mice were found in the combination group. Abraxane and hIL15-ABD effectively suppressed NF-κB-mediated immune suppressive markers, including indoleamine 2,3-dioxygenase (IDO), Foxp3 and VEGF. In conclusion, Abraxane combined with hIL15-ABD stimulates the anticancer activity of effector cells, inhibits immunosuppressive cells within the tumour microenvironment (TME) of PDAC, and produces a greater inhibitory effect than individual monotherapies.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Paclitaxel Ligado a Albumina/farmacologia , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Animais , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Humanos , Interleucina-15 , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/patologia , Microambiente Tumoral
9.
BMC Cancer ; 22(1): 55, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016637

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. RESULTS: There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. CONCLUSIONS: This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas , Sorafenibe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Pontuação de Propensão , Estudos Retrospectivos
10.
Cancers (Basel) ; 14(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35008382

RESUMO

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers-microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein-Barr encoding region (EBER)-were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.

11.
J Chin Med Assoc ; 85(1): 42-50, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34759212

RESUMO

BACKGROUND: Nanoliposomal irinotecan (nal-IRI), accompanied by 5-fluorouracil (5-FU) and leucovorin (LV), is an effective and safe therapy for patients in whom metastatic pancreatic ductal adenocarcinoma has progressed after gemcitabine-based chemotherapy. Our aim was to evaluate the effectiveness and safety of a nal-IRI + 5-FU/LV regimen for patients with metastatic pancreatic cancer and gemcitabine-based treatment failure in the real world. METHODS: We retrospectively collected the baseline characteristics, treatment courses and dosage, treatment response, overall survival (OS), progression-free survival (PFS), and adverse effects of patients treated with the nal-IRI-based regimen at Taipei Veterans General Hospital. RESULTS: Sixty-seven patients who received the nal-IRI + 5-FU/LV regimen from August 2018 to June 2019 were identified. Their median age was 65 years and 52% were male. Most patients had an Eastern Cooperative Oncology Group performance status of 0 to 1, but patients with an Eastern Cooperative Oncology Group performance status of 2 to 4 before initiation of the nal-IRI regimen were also enrolled (31%). The median dose intensity was 40.4 mg/m2 and the median treatment duration was 8.3 weeks (range: 5 days-75.7 weeks). Objective response and disease control rates were 10.4% and 38.8%, respectively. The median OS)was 7.9 months (95% confidence interval [CI]: 5.6-10.1 months) and the median PFS was 2.9 months (95% CI: 1.6-4.1 months). Elevated total bilirubin (hazard ratio [HR]: 4.31, 95% CI: 1.21-15.30, p = 0.024), carcinomatosis (HR: 3.75, 95% CI: 1.46-9.66, p = 0.006), and previous treatment with irinotecan (HR: 4.86, 95% CI: 1.67-14.10, p = 0.004) were associated with a worse OS. Previous treatment with irinotecan (HR: 3.03, 95% CI: 1.22-7.49, p = 0.02) was associated with a worse PFS. The most common all-grade adverse effects were anemia (73.9%), nausea (66.2%), and fatigue (61.5%). The most common grade 3-4 adverse effects were neutropenia (21.5%), anemia (18.5%), and diarrhea (15.4%). CONCLUSION: Clinically, nal-IRI + 5-FU/LV is effective and tolerable at reduced doses in patients with metastatic pancreatic adenocarcinoma that has progressed after gemcitabine-based therapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Irinotecano/administração & dosagem , Metástase Neoplásica/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores da Topoisomerase I/administração & dosagem , Idoso , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan
12.
Gastric Cancer ; 25(1): 207-217, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480657

RESUMO

BACKGROUND: The phase 3 ATTRACTION-2 study demonstrated that nivolumab monotherapy was superior to placebo for patients with pretreated advanced gastric or gastroesophageal junction cancer, but early progression of tumors in some patients was of concern. METHODS: This post hoc analysis statistically explored the baseline characteristics of the ATTRACTION-2 patients and extracted a single-factor and double-factor combinations associated with early disease progression or early death. In the extracted patient subgroups, the 3-year restricted mean survival times of progression-free survival and overall survival were compared between the nivolumab and placebo arms. RESULTS: Two single factors (age and peritoneal metastasis) were extracted as independent predictors of early progression, but none of them, as a single factor, stratified patients into two subgroups with significant differences in restricted mean survival time. In contrast, two double-factor combinations (serum sodium level and white blood cell count; serum sodium level and neutrophil-lymphocyte ratio) stratifying patients into two subgroups with significant differences in the restricted mean survival time were extracted. Additional exploratory analysis of a triple-factor combination showed that patients aged < 60 years with peritoneal metastasis and low serum sodium levels (approximately 7% of all patients) might receive less benefit from nivolumab, and patients aged ≥ 60 years with no peritoneal metastasis and normal serum sodium levels might receive higher benefit. CONCLUSIONS: A combination of age, peritoneal metastasis, and serum sodium level might predict benefit from nivolumab as salvage therapy in advanced gastric or gastroesophageal junction cancer patients, especially less benefit for patients having all three risk factors.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Esofágicas , Neoplasias Gástricas , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Humanos , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Neoplasias Gástricas/patologia
13.
Am J Cancer Res ; 11(11): 5526-5542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34873477

RESUMO

Whether direct-acting antivirals (DAA) provide comparable survival benefit with interferon (IFN)-based therapy remains unclear. The aim of this study was to compare the outcomes after achieving SVR by IFN-based and DAA therapy after resection of HCV-related hepatocellular carcinoma (HCC). Consecutive 285 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 103 (36.1%) and 69 (24.2%) patients with IFN-based and DAA therapy, respectively. Factors associated with recurrence, overall survival (OS) and hepatic decompensation-free survival were evaluated. The SVR rate of DAA was 95.7% in HCC patients. During a median follow-up period of 49.6 months, 102 (35.8%) patients died and 63 (24%) developed hepatic decompensation. By multivariate analysis, SVR by DAA or IFN-based therapy was not associated with early or late HCC recurrence. Achieving SVR (by IFN-based therapy: HR=0.321, P<0.001; by DAA: HR=0.396, P=0.011), BCLC stage B-C (HR=1.914, P=0.024), FIB-4 score >3.25 (HR=1.664, P=0.016) and microvascular invasion (HR=1.603, P=0.048) were independent predictors of OS. Achieving SVR (by IFN-based therapy: HR=0.295, P<0.001; by DAA: HR=0.193, P=0.002), BCLC stage B-C (HR=2.975, P=0.001), GGT >70 U/L (HR=1.931, P=0.015) and cirrhosis (HR=2.035, P=0.007) were independent predictors of decompensation-free survival. The benefit of achieving SVR was consistently observed in cirrhotic and non-cirrhotic patients, and in patients with and without HCC recurrence. In conclusion, achieving SVR by either DAA or IFN-based therapy provide comparable and significant reduction of mortality and hepatic decompensation after surgical resection of HCV-related HCC. DAA therapy should be prescribed for all HCC patients after curative surgical resection.

14.
Sci Rep ; 11(1): 23142, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848751

RESUMO

Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/tratamento farmacológico , Idoso , Antineoplásicos/farmacologia , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Taiwan/epidemiologia , Resultado do Tratamento
15.
Liver Cancer ; 10(6): 572-582, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34950180

RESUMO

BACKGROUND AND AIMS: Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection. METHODS: Consecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery. RESULTS: A total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only. CONCLUSION: The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.

16.
Liver Cancer ; 10(6): 629-640, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34950185

RESUMO

BACKGROUND AND AIMS: For patients with intermediate-stage hepatocellular carcinoma (HCC), the definition of high tumor burden remains controversial. This study aimed to compare the prognostic value of different criteria of tumor burden in patients with intermediate-stage HCC undergoing transarterial chemoembolization (TACE). METHODS: From 2007 to 2019, 632 treatment-naive patients with intermediate-stage HCC undergoing TACE were retrospectively enrolled. We compared different criteria of tumor burden in discriminating radiologic response and survival, including up-to-7, up-to-11, 5-7, 7 lesions criteria, and newly proposed 7-11 criteria. RESULTS: The proportions of patients classified as high tumor burden were varied by different criteria. Among the 5 criteria, 7-11 criteria have the best performance to discriminate complete response (CR) and overall survival (OS) after TACE. In patients with low, intermediate, and high tumor burden classified by 7-11 criteria, the CR rate was 21, 12, and 2.5%, respectively (p < 0.001), and the median OS was 33.1, 22.3, and 11.9 months, respectively (p < 0.001). By multivariate analysis, 7-11 criteria were significantly associated with CR (intermediate vs. high burden, odds ratio = 4.617, p = 0.002; low vs. high burden, odds ratio = 8.675, p < 0.001) and OS (intermediate vs. high burden, hazard ratio = 0.650, p < 0.001; low vs. high burden, hazard ratio = 0.520, p < 0.001). Seven to 11 criteria also had the lowest corrected Akaike information criteria, highest homogeneity value, and highest area under the receiver operating characteristic curve in predicting 1-, 2-, and 3-year mortality among all criteria. CONCLUSION: Conventional definitions of tumor burden were not optimal for patients with intermediate HCC. The new 7-11 criteria had the best discriminative power in predicting radiologic response and survival in patients with intermediate-stage HCC undergoing TACE.

17.
Biochem Biophys Res Commun ; 582: 137-143, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34710829

RESUMO

Overexpression of HER2 is associated with cancer phenotypes, such as proliferation, survival, metastasis and angiogenesis, and has been validated as a therapeutic target. However, only a portion of patients benefited from anti-HER2 treatments, and many would develop resistance. A more effective HER2 targeted therapeutics is needed. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and a HER2-targeting scaffold protein, ZHER2:2891, fused with yeast cytosine deaminase (Fcy) to target HER2-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned the coding gene of ZHER2:2891 and fused with those of ABD (albumin-binding domain) and Fcy. The purified ZHER2:2891-ABD-Fcy fusion protein specifically binds to HER2 with a Kd value of 1.6 nM ZHER2:2891-ABD-Fcy binds to MDA-MB-468, SKOV-3, BT474, and MC38-HER2 cells, which overexpress HER2, whereas with a lower affinity to HER2 non-expresser, MC38. Correspondingly, the viability of HER2-expressing cells was suppressed by relative low concentrations of ZHER2:2891-ABD-Fcy in the presence of 5-FC, and the IC50 values of ZHER2:2891-ABD-Fcy for HER2 high-expresser cells were approximately 10-1000 fold lower than those of non-HER2-targeting Fcy, and ABD-Fcy. This novel prodrug system, ZHER2:2891-ABD-Fcy/5-FC, might become a promising addition to the existing class of therapeutics specifically target HER2-expressing cancers.


Assuntos
Antineoplásicos/farmacologia , Citosina Desaminase/genética , Pró-Fármacos/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Proteínas Recombinantes de Fusão/genética , Proteínas de Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Antineoplásicos/química , Biotransformação , Linhagem Celular Tumoral , Citosina Desaminase/metabolismo , Flucitosina/metabolismo , Fluoruracila/metabolismo , Fluoruracila/farmacologia , Expressão Gênica , Humanos , Concentração Inibidora 50 , Terapia de Alvo Molecular , Pró-Fármacos/química , Ligação Proteica , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
18.
J Chin Med Assoc ; 84(10): 917-922, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613941

RESUMO

BACKGROUND: The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients. METHODS: A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV. RESULTS: Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient's survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001). CONCLUSION: Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.


Assuntos
Varizes Esofágicas e Gástricas/fisiopatologia , Neoplasias Pancreáticas/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Análise de Sobrevida
19.
Cancers (Basel) ; 13(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34503135

RESUMO

Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration.

20.
Am J Cancer Res ; 11(7): 3711-3725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354870

RESUMO

The recurrence rate remains high even under nucleos(t)ide analogues (NUCs) therapy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after resection. The aim of this study is to evaluate the prognostic role of HBsAg in patients undergoing surgical resection for HBV-related HCC in NUCs era. Consecutive 522 patients undergoing surgical resection for HBV-related HCC were retrospectively enrolled. Factors associated with early (within 2 years), late (year 2 to 5), very late (beyond 5 years) recurrence and early or late mortality (within or beyond 5 years) were evaluated. During a median follow-up period of 59 months, 308 (59%), and 146 (28%) patients developed recurrence and mortality, respectively. HBsAg level did not correlate with early recurrence and mortality. By multivariate analyses, HBsAg >200 IU/mL (hazard ratio (HR)=1.778, P=0.037) and presence of cirrhosis (HR=2.157, P=0.001) were independent predictors of late recurrence, while HBsAg >50 IU/mL (HR=4.658, P=0.038), body mass index >25 kg/m2 (HR=2.720, P=0.013) and significant hepatic fibrosis (HR=2.509, P=0.039) were independent predictors of very late recurrence. HBsAg >50 IU/mL (HR=11.427, P=0.017), age >60 years (HR=2.688, P=0.006), albumin ≤3.5 g/dL (HR=4.739, P<0.001) and presence of cirrhosis (HR=2.781, P=0.006) were independent predictors of late mortality beyond 5 years. Combining these factors could well predict patients with minimal risk of long-term recurrence and mortality. In conclusion, tumor factors, liver function surrogate markers, metabolic factors and serum HBsAg levels play distinct roles in recurrence and survival at different time intervals after surgical resection for HBV-related HCC. Pre-operative HBsAg level is an important predictor of long-term recurrence and survival in patients with HBV-related HCC undergoing surgical resection.

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