RESUMO
BACKGROUND: Quantitative data are limited on the natural course of liver fibrosis in patients with chronic HBV infection (CHB). AIMS: To estimate the prevalence of fibrosis status including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis throughout the natural course of CHB. METHODS: We searched Cochrane library, EMBASE, PubMed, SCOPUS, Web of Science, and ScienceDirect from January 1993 to November 2019 for studies with histologic data on liver fibrosis in CHB natural course. CHB course was defined based on current criteria for identifying infection phases as recommended by international clinical practice guidelines, including the HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases. Pooled prevalence rate of fibrosis status at each phase was obtained from random-effect meta-analyses. RESULTS: Thirty-three studies with 9,377 adult participants (23.8-49.0 age years; 45.5-88.6% males) were eligible and finally included. The estimated prevalence of non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis was, for HBeAg-positive immune-tolerant phase: 31.2% (95%CI 15.6-46.7), 16.9% (95%CI 7.8-26.1), 5.4% (95%CI 0.0-11.2), and 0.0% (95%CI 0.0-1.5); HBeAg-positive immune-active phase: 6.9% (95%CI 3.6-10.2), 50.6% (95%CI 39.2-61.9), 32.1% (95%CI 24.2-40.0), and 12.8% (95%CI 8.6-17.0); HBeAg-negative immune-inactive phase: 32.4% (95%CI 0.0-100.0), 24.8% (95%CI 4.5-45.1), 3.0% (95%CI 0.0-8.3), and 0.0% (95%CI 0.0-1.0); and HBeAg-negative immune-reactive phase: 6.3% (95%CI 3.5-9.2), 50.3% (95%CI 38.9-61.7), 30.3% (95%CI 20.9-39.6), and 10.0% (95%CI 6.6-13.5), respectively. There was only one study for HBsAg-negative phase, thus not allowing further meta-analyses. CONCLUSIONS: Fibrosis risk persists through CHB natural course. These data can support risk estimation in clinical practice and provide reference for noninvasive investigation.
Assuntos
Hepatite B Crônica , Adulto , DNA Viral , Feminino , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , MasculinoRESUMO
The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Terapia Neoadjuvante/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Mutação/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel/uso terapêutico , Carboplatina/uso terapêutico , Adulto , Resultado do Tratamento , DNA Tumoral Circulante/genética , AlbuminasRESUMO
OBJECTIVES: Neoadjuvant immunotherapy can be used to treat early-stage non-small-cell lung cancer; however, their effects on pulmonary lymphoepithelioma-like carcinomas (LELC) remain unclear. MATERIALS AND METHODS: Thirty-nine patients with stages I-III LELC were treated with chemotherapy (Chemo) or neoadjuvant immune-checkpoint inhibitors (ICIs) with or without chemo (IO) before radical-intent surgery. Short-term outcomes included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (PCR), and event-free survival. For comparison, we used IO to treat 63 patients with pulmonary squamous cell carcinomas (SQC) and 47 with adenocarcinomas (ADC). Propensity score matching was analyzed to minimize bias. RESULTS: ORRs of the LELC-IO and LELC-Chemo groups were 62.5% and 42.9%, respectively (odds ratio, 2.2, 95% confidence interval, 0.423-11.678, p = 0.346). Seven (21.9%) and zero patients in LELC-IO and LELC-Chemo groups, respectively, reached PCR. MPR was identified in five (15.6%) of the 32 patients with LELC-IO. The 1-year progression-free survival rates were 96.9% and 71.4% in IO and Chemo groups, respectively (p > 0.05). However, no difference was observed in ORR, PCR, and MPR between LELC and SQC groups (ORR, 63.2% vs. 68.4%, p > 0.05; PCR, 21.1% vs. 47.4, p > 0.05; MPR, 42.1% vs. 57.9%, p > 0.05) and LELC and ADC groups (ORR, 58.8% vs. 41.2%, p > 0.05; PCR, 17.6% vs. 23.5%, p = 0.672; MPR, 29.4% vs. 47.1%, p > 0.05). The plasma Epstein-Barr virus (EBV) DNA level in a patient was altered posttreatment. CONCLUSION: Patients with LELC could be benefit from neoadjuvant immunotherapy. Distinct histological subtypes demonstrated comparable efficacy with respect to neoadjuvant immunotherapy.