Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 122
Filtrar
1.
Thorac Cancer ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579111

RESUMO

BACKGROUND: Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross-sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China. METHODS: A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed. RESULTS: A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%). CONCLUSION: Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High-quality pain education for both patients and physicians is needed in the future.

2.
Clin Exp Immunol ; 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35262683

RESUMO

CD155 is an immune checkpoint protein expressed in tumor cells that interacts with its ligand TIGIT, and inhibition of this point presents a new and novel way for cancer therapy. At present, whether the expression of CD155 affects the response to anti(α)-PD1 treatment in non-small cell lung cancer (NSCLC) patients is unclear. This observational study characterizes the expression of CD155 in NSCLC patients and its responses to PD1 inhibitors. We retrospectively detected the expression of CD155 and tumor-infiltrated lymphocyte (TIL) TIGIT by immunohistochemistry in advanced NSCLC patients who had received αPD1 therapy. The patients with CD155 positive had a significantly worse response to αPD1 therapy compared to CD155 negative patients (ORR: 25.6% vs 54.8%, P<0.01; median PFS: 5.1 vs 7.1 months, HR=2.322; 95% CI 1.396-3.861, P=0.001). This effect is more prominent in PD-L1 positive patients. In PD-L1 positive patients, CD155 expression is associated with a poor response to αPD1 therapy in both LUAC (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma); meanwhile, the expression of CD155 was associated with a poor response to the first-line αPD1 therapy, posterior-line αPD1 therapy, and αPD1 combination therapy. Furthermore, the expression of TIGIT was not correlated with the therapeutic effect of αPD1. Our pilot study suggests that CD155 expression attenuates the therapeutic effect of αPD1 therapy and is associated with a higher risk of progression. The CD155 pathway may be a promising immunotherapeutic target and simultaneously targeting CD155/TIGIT and PD1/PD-L1 can improve the effect of immunotherapy.

3.
Cancer Lett ; 531: 83-97, 2022 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-35157971

RESUMO

Lung adenocarcinoma is the most common form of lung cancer, accounting for 60% of non-small cell lung cancer (NSCLC) cases in Asian patients. Importantly, nearly half of these patients have epithelial growth factor receptor (EGFR) mutations. Though EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line therapy for NSCLC patients, the development of resistance reduces their efficiency and limits their application. As the complicated and heterogeneous mechanism of acquired resistance among individuals, the efficiency of anti-angiogenesis therapy, immune checkpoint inhibitors, or chemo-radiotherapies is rather less promising. In this research, we investigated the role of the tumor stem cell marker DCLK1 in EGFR-TKI resistance of lung adenocarcinoma. We discovered that DCLK1 was critical in maintaining the stemness of tumor cells through the Wnt/ß-Catenin pathway, which was conducive to the development of EGFR-TKI resistance. Inhibiting DCLK1 activity restored the sensitivity of TKI-resistant tumor cells and organoids. Moreover, our study showed that DCLK1 inhibitor had a synergistic effect in controlling tumor growth when combined with EGFR-TKIs. Overall, our study provides new insights into EGFR-TKI resistant lung adenocarcinoma through inhibition of DCLK1 expression.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento/genética , beta Catenina/genética
4.
Signal Transduct Target Ther ; 7(1): 25, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35087031

RESUMO

WX-0593 (Iruplinalkib) is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor (TKI). In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate (ORR) assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities (DLTs) including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not reached. Overall, 140 of the 152 (92%) patients experienced treatment-related adverse events (TRAEs) and 35 of the 152 (23%) patients had TRAEs ≥grade 3. The overall ORR was 59.3% (32 of 54) for the dose-escalation phase and 56.6% (56 of 99) for the dose-expansion phase. For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% (17 of 21) in the dose-escalation phase and 76.3% (29 of 38) in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% (8 of 21) and 45.7% (21 of 46) for the two phases, respectively. For patients who were ROS1-rearranged, the ORR were 30.0% (3 of 10) in the dose-escalation phase and 44.4% (4 of 9) in the dose-expansion phase. WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.


Assuntos
Quinase do Linfoma Anaplásico/genética , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas , Rearranjo Gênico , Neoplasias Pulmonares , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos
5.
Zhongguo Fei Ai Za Zhi ; 25(1): 46-53, 2022 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-35078285

RESUMO

Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia
6.
Cancer Med ; 10(23): 8328-8337, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34612594

RESUMO

BACKGROUND: There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M-cis-C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. METHODS: This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M-cis-C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib-based therapy, 23 patients received chemotherapy in combination of anti-angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs. RESULTS: Compared to other targeted therapy, brigatinib-based therapy (median progression-free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21-0.73, p = 0.001) and chemotherapy-based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06-0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib-based therapy and chemotherapy-based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57-2.67, p = 0.58). Chemotherapy combined with anti-angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11-0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06-0.54, p = 0.001), no matter they received brigatinib-based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01-0.96, p = 0.05) or chemotherapy-based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01-0.49, p < 0.001). CONCLUSION: Brigatinib-based therapy and chemotherapy plus anti-angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis-C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis-C797S mutation.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/administração & dosagem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Inibidores da Angiogênese/administração & dosagem , Compostos de Anilina/administração & dosagem , China , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Compostos Organofosforados/administração & dosagem , Pirimidinas/administração & dosagem , Estudos Retrospectivos
7.
Biochem Biophys Res Commun ; 571: 38-45, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34303194

RESUMO

AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR-mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Neoplasias Pulmonares/metabolismo , Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
8.
Neoplasma ; 68(4): 823-831, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34097427

RESUMO

Due to tumor heterogeneity, the consistency of programmed cell death-ligand 1 (PD-L1) expression between circulating tumor cells (CTCs) and tissue is controversial. This study aimed to establish a method for detecting CTC PD-L1 expression and exploring the impact of the same on the prognosis of lung cancer. In 32 patients with non-small cell lung cancer, lung cancer cells in the blood were enriched using CD326 immunomagnetic beads. Goat anti-mouse polyclonal CD326 antibody stained the epithelial lung cancer cells and anti-PD-L1 antibody was used to detect the expression of CTC PD-L1. The DAKO Link 48 automatic staining device detected the expression in lung cancer tissue. The consistency of PD-L1 expression was analyzed in lung cancer tissue and CTCs. The effect of plasma interferon gamma, tumor necrosis factor alpha, and interleukin-2 on PD-L1 expression and prognosis was analyzed. The number of CTCs detected in patients was 1-36, with a median of 2. There was no significant difference in PD-L1 expression fractions between CTCs and paired tumor tissue (p>0.05). The correlation coefficient was 0.20. Regardless of lung cancer tissue or CTCs, there was no statistically significant difference in the blood cytokine levels between the two groups with positive or negative PD-L1 expression (p>0.05). There was no correlation between CTCs and PD-L1 in 23 untreated patients. The expression of PD-L1 in CTCs and lung cancer tissue is heterogeneous and unaffected by the peripheral cytokines' levels. PD-L1 expression has no correlation between CTCs and tissues and is not related to prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Animais , Apoptose , Antígeno B7-H1 , Biomarcadores Tumorais , Humanos , Ligantes , Camundongos , Prognóstico
9.
Technol Cancer Res Treat ; 20: 1533033821995275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34032165

RESUMO

The CellSearch system is the only FDA approved and successful used detection technology for circulating tumor cells(CTCs). However, the process for identification of CTCs by CellSearch appear to damage the cells, which may adversely affects subsequent molecular biology assays. We aimed to explore and establish a membrane-preserving method for immunofluorescence identification of CTCs that keeping the isolated cells intact. 98 patients with lung cancer were enrolled, and the efficacy of clinical detection of CTCs was examined. Based on the CellSearch principle, we optimized an anti-EpCAM antibody and improved cell membrane rupture. A 5 ml peripheral blood sample was used to enrich CTCs with EpCAM immunomagnetic beads. Fluorescence signals were amplified with secondary antibodies against anti-EpCAM antibody attached on immunomagnetic beads. After identifying CTCs, single CTCs were isolated by micromanipulation. To confirm CTCs, genomic DNA was extracted and amplified at the single cell level to sequence 72 target genes of lung cancer and analyze the mutation copy number variations (CNVs) and gene mutations. A goat anti-mouse polyclonal antibody conjugated with Dylight 488 was selected to stain tumor cells. We identified CTCs based on EpCAM+ and CD45+ cells to exclude white blood cells. In the 98 lung cancer patients, the detection rate of CTCs (≥1 CTC) per 5 ml blood was 87.76%, the number of detections was 1-36, and the median was 2. By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Separação Celular/métodos , Neoplasias Pulmonares/patologia , Mutação , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Front Chem ; 9: 674271, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981676

RESUMO

This study focuses on the recycling of a spent fluid catalytic cracking (FCC) catalyst to produce catalyst-based non-sintered bricks (CN-bricks) for the recovery of its aluminosilicate components and the solidification of heavy metals. The effects of the content of cement (10-20%), the proportion of FCC (10-40%), and the type of an activator (NaOH/Na2SiO3/Na2SO4) on the performance of a CN-brick were investigated in terms of the mechanical strength and leaching behavior. The results show that an optimal binder system of 20% cement + Na2SO4 could promote the compressive strength up to 42.3 MPa; the proportion of an optimal spent FCC catalyst of 20% could achieve the lowest porosity and water absorption. The microscopic mechanism of a cementitious process was analyzed by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), proving that C-S-H and ettringite (AFt) are the two main hydration products of a CN-brick. Na2SO4 is superior to NaOH or Na2SiO3 as an activator since Na2SO4 takes advantage of the aluminum-rich property of a spent FCC catalyst and specifically promote the formation of a needle-like AFt. Quantitative environmental risk assessment for the utilization of a CN-brick on roads was carried out based on the leaching test of a toxicity characteristic leaching procedure (TCLP), NEN 7371 maximum availability test, and the hazard Index (HI) identification, and a final HI 0.0045 (<1.0) indicates an acceptable risk for environment and nearby residents as CN-bricks are utilized on roads for 30 years.

11.
Front Oncol ; 11: 643199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842353

RESUMO

PURPOSE: Circulating cell-free DNA (cfDNA) level has been demonstrated to be associated with efficacy in first generation EGFR TKIs in non-small cell lung cancer (NSCLC). However, the role of dynamic cfDNA analysis using next-generation sequencing (NGS) in patients with subsequent third-generation EGFR TKIs remains unclear. METHODS: From 2016 to 2019, 81 NSCLC patients with EGFR T790M mutation either in tissue or plasma who received third-generation EGFR TKIs treatment were enrolled. CfDNA were sequenced by NGS with a 425-gene panel. The association of clinical characteristics, pretreatment, dynamic cfDNA and T790M level with outcomes in patients treated with the third-generation TKIs were analyzed. RESULTS: In univariate analysis, the median PFS of patients with undetectable cfDNA level during treatment was significantly longer than those with detectable cfDNA (16.97 vs. 6.10 months; HR 0.2109; P < 0.0001). The median PFS of patients with undetectable T790M level during treatment was significantly longer than those with detectable T790M (14.1 vs. 4.4 months; HR 0.2192; P < 0.001). Cox hazard proportion model showed that cfDNA clearance was an independent predictor for longer PFS (HR 0.3085; P < 0.001) and longer OS (HR 0.499; P = 0.034). The most common resistant mutations of the third-generation TKIs were EGFR C797S (24%). CDK6 CNV, GRIN2A, BRCA2, EGFR D761N, EGFR Q791H, EGFR V843I, and ERBB4 mutation genes may possibly be new resistant mechanisms. CONCLUSIONS: Patients with undetectable cfDNA during the third-generation EGFR TKI treatment have superior clinical outcomes, and dynamic cfDNA analysis by NGS is valuable to explore potential resistant mechanisms.

12.
Patient Prefer Adherence ; 15: 775-783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883885

RESUMO

BACKGROUND: Cancer treatment decision-making often needs to balance benefits, harms, and costs. This study sought to identify the differences in cancer treatment preference among oncologists, patients and their family members in China. METHODS: A semi-structured face-to-face qualitative interview was conducted among oncologists, patients and their family members recruited in four tertiary hospitals in China. The interview guide was developed based on literature review and expert consultation. Participants were asked to indicate their preferences when making lung cancer treatment decisions. All interviews were audio-taped, transcribed verbatim, and thematic analyzed. The preferences were compared among three groups of participants. RESULTS: A total of 17 participants (5 oncologists, 6 dyads of patients and family members) were interviewed between June and July 2019. Five themes, namely, survival benefit, adverse effect/symptom, treatment process, treatment cost, and the impact on daily life were identified. The oncologists and family members gave highest priority on survival benefit, while the patients are concerned most about treatment cost and quality of life. CONCLUSION: This study reveals different preferences for cancer treatment among oncologists, patients and their family members in China. Education is needed to empower patients and family members and promote share decision-making in this country.

13.
Zhongguo Fei Ai Za Zhi ; 24(4): 254-264, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33910273

RESUMO

BACKGROUND: Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers. METHODS: Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis. RESULTS: The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006). CONCLUSIONS: In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Memória Imunológica , Antígenos Comuns de Leucócito , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
14.
Lancet Respir Med ; 9(8): 829-839, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33780662

RESUMO

BACKGROUND: Furmonertinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both sensitising EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to assess the efficacy and safety of furmonertinib in patients with EGFR T790M mutated advanced non-small-cell lung cancer (NSCLC). METHODS: This study was a single-arm, open-label, phase 2b study at 46 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumour tissue who progressed after first or second generation EGFR TKIs or with primary EGFR T790M mutations received furmonertinib 80 mg orally once daily. The primary endpoint was objective response rate. Efficacy was assessed by blinded independent central review as per the Response Evaluation Criteria in Solid Tumors (version 1.1) in all patients who had measurable disease at baseline and received at least one dose of furmonertinib. Safety was assessed as per the Common Terminology Criteria for Adverse Events (version 4.03) in all patients who received at least one dose of furmonertinib with at least one safety assessment during follow-up. This study is registered with ClinicalTrials.gov (NCT03452592) and is ongoing for survival follow-up. FINDINGS: From Jun 4, 2018, to Dec 8, 2018, 220 patients received furmonertinib treatment. All 220 patients were included in the efficacy and safety analyses. At the data cutoff point of Jan 29, 2020, 71 (32%) patients remained on treatment. The median duration of follow-up was 9·6 months (range 0·7-19·4). The objective response rate was 74% (163 of 220 [95% CI 68-80]). Grade 3 or higher adverse events occurred in 58 (26%) patients and treatment-related grade 3 or higher adverse events occurred in 25 (11%) patients. The most common all-cause grade 3 or higher adverse events were increased γ-glutamyltransferase (five; 2%), increased aspartate aminotransferase, increased alanine aminotransferase, hyponatraemia, hypertension, pulmonary infection, hypermagnesaemia, and pericardial effusion (three each; 1%). Treatment-related diarrhoea was reported in ten (5%) patients and rashes were reported in 16 (7%) patients, all grade 1-2. Serious adverse events were reported in 52 (24%) patients, of which 12 (5%) were possibly treatment-related as evaluated by the investigator. INTERPRETATION: Furmonertinib has promising efficacy and an acceptable safety profile for the treatment of patients with EGFR T790M mutated NSCLC. Furmonertinib is expected to become a new treatment option after first or second generation EGFR TKIs in the Chinese population. FUNDING: Shanghai Allist Pharmaceutical Technology, Ministry of Science and Technology of the People's Republic of China, and Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China , Receptores ErbB/genética , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos
15.
Thorac Cancer ; 12(7): 1106-1114, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33565277

RESUMO

BACKGROUND: ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. METHODS: We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK-rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). RESULTS: The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second-line therapy. One patient had stable disease (SD) and progression-free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non-smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first- or second-line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. CONCLUSIONS: Patients with ALK-rearranged SCC obtained clinical benefit from ALK-inhibitor therapy, especially those who were non-smokers and whose tumors had been identified by IHC+/FISH+.


Assuntos
Quinase do Linfoma Anaplásico/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
16.
J Thorac Oncol ; 16(5): 827-839, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33588113

RESUMO

INTRODUCTION: By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC. METHODS: In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel. RESULTS: A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation. CONCLUSIONS: Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.


Assuntos
DNA Tumoral Circulante , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , DNA Tumoral Circulante/genética , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Piperazinas , Inibidores de Proteínas Quinases/farmacologia , Piridazinas
17.
Zhongguo Fei Ai Za Zhi ; 24(2): 78-87, 2021 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-33478196

RESUMO

BACKGROUND: Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring. METHODS: The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy. RESULTS: Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months. CONCLUSIONS: The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Estudos Retrospectivos
18.
Foot Ankle Int ; 42(4): 458-463, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33179533

RESUMO

BACKGROUND: The treatment of plantar fasciitis may require surgical intervention in patients with ineffective response to conservative treatment. There is a lack of evidence regarding the differences in clinical outcomes between the endoscopic and the mini-open procedures. The purpose of this study was to compare the clinical outcomes of the endoscopic partial plantar fasciotomy via 2 medial portals with mini-open partial plantar fasciotomy for treating refractory plantar fasciitis. METHODS: A retrospective analysis was carried out on 62 patients with refractory plantar fasciitis from January 2015 to July 2017. Thirty-three patients received endoscopic partial plantar fasciotomy, while the other 29 received mini-open procedure by patient preference. Two medial portals were used in the endoscopic group while single mini-medial method was used in the open group. All patients were followed up for 24 months. The pain visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, the calcaneodynia score (CS), and the 36-item Short Form Health Survey questionnaire (SF-36) were employed to evaluate the clinical outcomes of the 2 groups. RESULTS: There was increase in the functional scores (eg, VAS, AOFAS, CS, and SF-36) in both groups recorded at 3 months, 6 months, 1 year, and 2 years after surgery. The patients in the endoscopic group had better VAS, AOFAS, CS, and SF-36 scores at 3 months after the surgery compared with those of the open group. During the 6-month follow-up, although the 2 groups showed similar VAS and AOFAS, the CS and SF-36 scores of the endoscopic group were significantly higher than those of the open group. During the 1-year and 2-year follow-ups, the endoscopic group gained equivalent VAS, AOFAS, CS, and SF-36 scores compared with those of the open group. The recurrence rate was similar in both groups. Moreover, the patients in the endoscopic group achieved earlier recovery in comparison to those in the open group. CONCLUSION: For refractory plantar fasciitis, endoscopic partial plantar fasciotomy via 2 medial portals produced better short-term and equivalent long-term subjective outcomes than the mini-open surgery. LEVEL OF EVIDENCE: Level II, comparative study.


Assuntos
Fasciíte Plantar , Fasciíte Plantar/cirurgia , Fasciotomia , Humanos , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento
19.
Ther Adv Med Oncol ; 12: 1758835920965849, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281949

RESUMO

BACKGROUND: Carboxyamidotriazole (CAI), a calcium channel blocker, inhibits tumor cell proliferation, metastasis, and angiogenesis. This trial aimed to determine whether CAI combined with conventional chemotherapy could prolong progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients. METHODS: Patients were assigned into groups (3:1 ratio) to receive either chemotherapy + CAI or chemotherapy alone. Cisplatin (25 mg/m2) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m2) on days 1 and 8 of each 3-week cycle for four cycles. CAI was administered at 100 mg daily with concomitant chemotherapy; this treatment was continued after chemotherapy was ceased until serious toxicity or disease progression had occurred. PFS was the primary endpoint, and the secondary endpoints were objective response rate (ORR), disease control rate, overall survival (OS), and quality of life. RESULTS: In total, 495 patients were enrolled in the trial: 378 in the chemotherapy + CAI group and 117 in the chemotherapy + placebo group. PFS was significantly greater in the chemotherapy + CAI [median, 134 days; 95% confidence interval (CI) 127-139] than in the chemotherapy + placebo (median, 98 days; 95% CI: 88-125) group, with a hazard ratio of 0.690 (95% CI: 0.539-0.883; p = 0.003). There was no difference in the OS rates of both groups. The ORR was greater in the chemotherapy + CAI group than in the chemotherapy + placebo group (34.6% versus 25.0%, p = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) versus 64 (55.2%); p = 0.014]. CONCLUSION: CAI + platinum-based chemotherapy prolonged PFS and could be a useful therapeutic option to treat NSCLC. CLINICAL TRIAL REGISTRATION: chinadrugtrials.org.cn identifier: CTR20160395.

20.
Front Oncol ; 10: 1162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850330

RESUMO

HER2 mutations have emerged as oncogenic driver gene mutations in non-small cell lung cancer (NSCLC), which have not been described in detail like other driver gene mutations. Here, 295 patients with advanced lung adenocarcinoma were retrospectively screened for HER2 mutations using next-generation sequencing (NGS), and the positive cases were validated by Sanger sequencing. We identified five cases with HER2 exon 20 insertions, representing 1.7% of 295 lung adenocarcinomas. Among them, four different subtypes of HER2 exon 20 insertions were identified, including a rare subtype G778_S779insCPG never reported before with a partial response (PR) to pyrotinib and progression-free survival (PFS) of 12.8 months. Our findings reveal that HER2 exon 20 insertion mutations were detected in a small subset of lung adenocarcinomas. Given the different drug sensitivities, determining the mutation subtype by next-generation sequencing at the time of diagnosis might make sense.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...