Publications by authors named "Zhenyu Ding"

62 Publications

Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy.

Int J Biol Sci 2021 30;17(5):1339-1352. Epub 2021 Mar 30.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated No. 6 People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Treatment for spinal cord injury (SCI) remains a challenge worldwide, and inflammation is a major cause of secondary injury after SCI. Peripheral macrophages (PMs) have been verified as a key factor that exert anti-inflammatory effects after SCI, but the mechanism is unidentified. As local macrophages, microglia also exert significant effects after SCI, especially polarization. Exosomes show source cell-like biological functions to target cells and have been the subject of much research in recent years. Thus, we hypothesized the PM-derived exosomes (PM-Exos) play an important role in signal transmission with local microglia and can be used therapeutic agents for SCI in a series of and studies. For the experiment, three groups of Sprague-Dawley (SD) rats subjected to spinal cord contusion injury were injected with 200 µg/ml PM-Exos, 20 µg/ml PM-Exos or PBS via the tail vein. Recovery of the rats and of spinal cord function were observed. , we investigated the potential anti-inflammatory mechanism of PM-Exos and evaluated microglial autophagy, anti-inflammatory type microglia polarization and the upstream signaling pathway. The results showed that spinal cord function and recovery were better in the PM-Exo groups than the control group. In the study, microglial autophagy levels and the expression of anti-inflammatory type microglia were higher in the experimental groups than the control group. Moreover, the expression of proteins related to the PI3K/AKT/mTOR autophagic signaling pathway was suppressed in the PM-Exo groups. PM-Exos have a beneficial effect in SCI, and activation of microglial autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway, enhancing the polarization of anti-inflammatory type microglia, that may play a major role in the anti-inflammatory process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.54302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040463PMC
March 2021

Injectable composite hydrogel promotes osteogenesis and angiogenesis in spinal fusion by optimizing the bone marrow mesenchymal stem cell microenvironment and exosomes secretion.

Mater Sci Eng C Mater Biol Appl 2021 Apr 17;123:111782. Epub 2021 Feb 17.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated No.6 People's Hospital, 600 Yishan Road, Shanghai 200233, China. Electronic address:

With the development of tissue engineering, it is no longer a challenge to repair and reconstruct bone defects using bone substitutes. However, in spinal fusion surgery, high rates of fusion failure are difficult to avoid. In our study, we designed a new composite hydrogel and found that it has good osteogenesis and angiogenesis effects. We extracted exosomes produced by rBMSCs (rat bone marrow mesenchymal stem cells) cocultured with the hydrogel to investigate their effects on osteogenesis and angiogenesis. The results showed that the PG/TCP (PEGMC with β-TCP) promoted rapid osteogenesis, facilitated spinal fusion at a high rate and quality and had an indirect effect on angiogenesis. We found that PG/TCP affected the rBMSC microenvironment, thus changing the function of exosomes; in a further study, we found that PG/TCP-MSC-Exos played a significant role in osteogenesis, which was coupled to angiogenesis. Thus, PG/TCP showed excellent potential in bone regeneration, especially the PG/0.2TCP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2020.111782DOI Listing
April 2021

Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment.

Cell Prolif 2021 Apr 2;54(4):e13009. Epub 2021 Mar 2.

Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

The sites of targeted therapy are limited and need to be expanded. The FGF-FGFR signalling plays pivotal roles in the oncogenic process, and FGF/FGFR inhibitors are a promising method to treat FGFR-altered tumours. The VEGF-VEGFR signalling is the most crucial pathway to induce angiogenesis, and inhibiting this cascade has already got success in treating tumours. While both their efficacy and antitumour spectrum are limited, combining FGF/FGFR inhibitors with VEGF/VEGFR inhibitors are an excellent way to optimize the curative effect and expand the antitumour range because their combination can target both tumour cells and the tumour microenvironment. In addition, biomarkers need to be developed to predict the efficacy, and combination with immune checkpoint inhibitors is a promising direction in the future. The article will discuss the FGF-FGFR signalling pathway, the VEGF-VEGFR signalling pathway, the rationale of combining these two signalling pathways and recent small-molecule FGFR/VEGFR inhibitors based on clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.13009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016646PMC
April 2021

cIAP2 expression and clinical significance in pigmented villonodular synovitis.

J Mol Histol 2021 Apr 18;52(2):397-406. Epub 2021 Feb 18.

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Pigmented villonodular synovitis (PVNS) is a rare hyperplasia disease of the synovium with a predilection for the knee in either a localized (LPVNS) or a diffuse form (DPVNS). But the exact cause is not clear. The aim of this study was to explore the relationship between the expression of cellular inhibitor of apoptosis 2 (cIAP2) and proliferation, apoptosis, invasive growth and postoperative recurrence in PVNS. Clinical significance of cIAP2 expression in synovium from 63 patients' knee joints with PVNS (40 DPVNS; 23 LPVNS) were investigated with 20 normal subjects acting as controls. The cIAP2 gene was screened by Human Cancer Pathway Finder PCR Array and real-time polymerase chain reaction (RT-PCR). We also used immunohistochemistry to detect cIAP2 and proliferating cell nuclear antigen (PCNA) protein expression and analyzed their relationship with PVNS type, invasive growth, and postoperative recurrence. The expression of cIAP2, PCNA, caspase-8, caspase-9 and caspase-3 protein was tested in Western blot. Screening results of Human Cancer Pathway Finder PCR array and RT-PCR showed significantly more cIAP2 mRNA in DPVNS synovium than in normal or LPVNS synovium (P < 0.05). Immunohistochemistry and western blot showed that the cIAP2 protein expression level in DPVNS was significantly higher than in LPVNS tissue (P < 0.01). As cIAP2 expression increased, the expression of PCNA increased (P < 0.05) and expression of cleaved caspase-3, -8, -9 decreased (P < 0.01). cIAP2 and PCNA overexpression were found to be related to ligament and bone erosion in PVNS and to disease recurrence (P < 0.05). This study suggested that cIAP2 overexpression plays an important role in the anti-apoptotic, proliferative and invasive growth of PVNS, which may account for the recurrence and poor prognosis of DPVNS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10735-021-09961-5DOI Listing
April 2021

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.

Signal Transduct Target Ther 2021 Jan 20;6(1):26. Epub 2021 Jan 20.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3-14 doses/person). In total, 12-30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-020-00448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817684PMC
January 2021

Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer.

Int Immunopharmacol 2021 Feb 23;91:107296. Epub 2020 Dec 23.

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood.

Materials And Methods: We conducted a single center, retrospective study of advanced NSCLC patients who were treated with PD-1 inhibitors between 10 October 2016 and 1 April 2020. TFA was characterized as new onset subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism. Frequency of development of TFA-irAEs, and its relationship with overall survival (OS) and progression free survival (PFS) were evaluated.

Results: In our study, 191 patients were treated with PD-1 inhibitors. Among them, forty patients (20.9%) developed TFA, of whom 10 (5.2%) presented with subclinical hypothyroidism, 15 (7.9%) with overt hypothyroidism, 6 (3.1%) with subclinical hyperthyroidism and 9 (4.7%) with overt hyperthyroidism. Survival analysis showed that the OS (16.8 months vs. 11.1 months, p < 0.001) and PFS (10.4 months vs. 5.5 months, p < 0.001) were significantly longer in patients with TFA-irAEs than in those without TFA-irAEs. In subgroup analysis of hypothyroidism and hyperthyroidism groups, similar trends were also obtained for both OS and PFS. After adjusting for potential confounding variables, patients with TFA-irAEs had a lower mortality risk (HR 0.334, 95%CI 0.196-0.571) than those without TFA-irAEs.

Conclusions: TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.107296DOI Listing
February 2021

Nomogram Personalizes and Visualizes the Overall Survival of Patients with Triple-Negative Breast Cancer Based on the Immune Genome.

Biomed Res Int 2020 24;2020:4029062. Epub 2020 Nov 24.

Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.

Background: Triple-negative breast cancer (TNBC) is usually poorly differentiated, highly invasive, susceptible to distant metastasis, and less responsive to endocrine and targeted therapy. However, immunotherapy is a promising treatment for TNBC patients recently.

Methods: The prognostic value of immune-related genes (IRGs) was explored by using RNA sequencing and microarray data of 123 and 107 TNBC patients from TCGA and GEO databases, respectively.

Results: In TCGA database, GO and KEGG pathway analysis of 119 differential IRGs indicated that they actively participate in the interaction of cytokines and receptors. A nomogram model constructed by the prognosis-related CCL25, IL29, TDGF3, GPR44, and GREM2 in the IRGs could personalize and visualize the 1-, 2-, 3-, 4-, and 5-year overall survival (OS) of TNBC patients. Moreover, TNBC patients could be defined as low-risk (risk score < 194) or high-risk (risk score ≥ 194) cohorts based on the risk score derived from the nomogram model. The results could be validated by the GSE58812 dataset. Furthermore, the risk score was an independent risk factor for TNBC patients (HR = 1.019, 95% CI 1.012-1.027, < 0.001) and was positively related to stage ( = 0.017). Interestingly, the risk score could reflect the infiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, and neutrophils.

Conclusion: These findings provided a reference for personalized OS prediction in TNBC patients and might be potential immune biomarkers for designing novel therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4029062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709499PMC
May 2021

DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine.

J Control Release 2020 12 27;328:210-221. Epub 2020 Aug 27.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. Electronic address:

To date, many clinical trials have been carried out with neoantigen-specific mRNA vaccines, and positive results have been achieved. However, further improvements in the efficiency of the intracellular delivery of mRNA and the production of a stronger immune response are still worth studying. In this study, we used the cholesterol-modified cationic peptide DP7 (VQWRIRVAVIRK), which was developed in our previous study, with a transmembrane structure and immunoadjuvant function to modify DOTAP liposomes to create a common mRNA delivery system. This system was intended to improve the efficiency of the delivery of mRNA encoding individualized neoantigens to dendritic cells (DCs) and enhance the activation of DCs. The system serves dual functions as a carrier and as an immunoadjuvant. As a carrier of mRNA, DP7-C-modified DOTAP liposomes (DOTAP/DP7-C) could transfer mRNA efficiently into different type of DCs in vitro. As an immunoadjuvant, DOTAP/DP7-C liposomes were shown to be more efficacious in stimulating DC maturation, CD103 DC (contributing to antigen presentation) production and proinflammatory cytokine secretion than DOTAP liposomes both in vitro and in vivo. In animal studies, the subcutaneous administration of DOTAP/DP7-C/LL2 neoantigen-encoding mRNA complexes significantly inhibited the growth of LL2 in situ and the growth of subcutaneous tumors and stimulated the production of antigen-specific lymphocyte reactions, which were superior to the DOTAP/LL2 neoantigen-encoding mRNA complex group. In conclusion, DOTAP/DP7-C liposomes may serve as a potential universal mRNA delivery system, providing a simple method to increase the efficiency of intracellular mRNA delivery and the immunostimulatory activity of DCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2020.08.023DOI Listing
December 2020

Anlotinib-induced acute myocardial infarction: A case report and literature review.

Exp Ther Med 2020 Oct 24;20(4):3203-3207. Epub 2020 Jul 24.

Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Anlotinib hydrochloride is a multi-target tyrosine kinase inhibitor, which has been recently approved for the treatment of advanced non-small cell lung cancer in China. One of its mechanisms of action is the inhibition of angiogenesis and it is similar to other anti-angiogenesis drugs, as it has cardiovascular toxicity, which may damage vascular endothelial cells and result in hypertension and hyperlipidemia. All of the aforementioned factors are considered risk factors for coronary heart disease; however, the risk of developing acute myocardial infarction (AMI) has not been assessed by any previous clinical trials and subsequent research. The present case study, to the best of our knowledge, was the first to report on a patient who developed hypertension, hyperlipidemia and angina pectoris, and eventually experienced AMI, following treatment with anlotinib. This indicates that patients receiving anlotinib may require further observation and monitoring during use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.9041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444427PMC
October 2020

Enhanced Photovoltaic Performances of La-Doped Bismuth Ferrite/Zinc Oxide Heterojunction by Coupling Piezo-Phototronic Effect and Ferroelectricity.

ACS Nano 2020 Aug 11;14(8):10723-10732. Epub 2020 Aug 11.

Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 100083, P.R. China.

Ferroelectric materials have drawn widespread attention due to their switchable spontaneous polarization and anomalous photovoltaic effect. The coupling between ferroelectricity and the piezo-phototronic effect may lead to the design of distinctive photoelectric devices with multifunctional features. Here, we report an enhancement of the photovoltaic performances in the ferroelectric -type La-doped bismuth ferrite film (BLFO)/-type zinc oxide (ZnO) nanowire array heterojunction by rationally coupling the strain-induced piezoelectricity in ZnO nanowires and the ferroelectricity in BLFO. Under a compressive strain of -2.3% and a 10 V upward poling of the BLFO, the open-circuit voltage () and short-circuit current density ) of the device increase by 8.4% and 54.7%, respectively. Meanwhile, the rise (/decay) time is modulated from 153.7 (/108.8) to 61.28 (/74.86) ms. Systematical band diagram analysis reveals that the promotion of photogenerated carriers and boost of the photovoltaic performances of the device can be attributed to the modulated carrier transport behaviors at the BLFO/ZnO interface and the superposed driving forces arising from the adding up of the piezoelectric potential and ferroelectric polarization. In addition, COMSOL simulation results of piezopotential distribution in ZnO nanowire arrays and the energy band structure change of the heterojunction further confirm the mechanisms. This work not only presents an approach to design high-performance ferroelectric photovoltaic devices but also further broadens the research scope of piezo-phototronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c05398DOI Listing
August 2020

Publisher Correction: Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.

Nat Med 2020 Jul;26(7):1149

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-020-0973-6DOI Listing
July 2020

Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.

Nat Med 2020 05 27;26(5):732-740. Epub 2020 Apr 27.

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 editing of immune checkpoint genes could improve the efficacy of T cell therapy, but the first necessary undertaking is to understand the safety and feasibility. Here, we report results from a first-in-human phase I clinical trial of CRISPR-Cas9 PD-1-edited T cells in patients with advanced non-small-cell lung cancer (ClinicalTrials.gov NCT02793856). Primary endpoints were safety and feasibility, and the secondary endpoint was efficacy. The exploratory objectives included tracking of edited T cells. All prespecified endpoints were met. PD-1-edited T cells were manufactured ex vivo by cotransfection using electroporation of Cas9 and single guide RNA plasmids. A total of 22 patients were enrolled; 17 had sufficient edited T cells for infusion, and 12 were able to receive treatment. All treatment-related adverse events were grade 1/2. Edited T cells were detectable in peripheral blood after infusion. The median progression-free survival was 7.7 weeks (95% confidence interval, 6.9 to 8.5 weeks) and median overall survival was 42.6 weeks (95% confidence interval, 10.3-74.9 weeks). The median mutation frequency of off-target events was 0.05% (range, 0-0.25%) at 18 candidate sites by next generation sequencing. We conclude that clinical application of CRISPR-Cas9 gene-edited T cells is generally safe and feasible. Future trials should use superior gene editing approaches to improve therapeutic efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-020-0840-5DOI Listing
May 2020

Cholesterol-modified DP7 enhances the effect of individualized cancer immunotherapy based on neoantigens.

Biomaterials 2020 05 11;241:119852. Epub 2020 Feb 11.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Personalized cancer vaccines based on neoantigens have become an important research direction in cancer immunotherapy. However, their therapeutic effects are limited by the efficiency of antigen uptake and presentation by antigen presenting cells. Here, the low-toxicity cholesterol-modified antimicrobial peptide (AMP) DP7 (DP7-C), which has dual functions as a carrier and an immune adjuvant, improved the dendritic cell (DC)-based vaccine efficacy. As a delivery carrier, DP7-C can efficiently delivery various antigen peptides into 75-95% of DCs via caveolin- and clathrin-dependent pathways. As an immune adjuvant, DP7-C can induce DC maturation and proinflammatory cytokine release via the TLR2-MyD88-NF-κB pathway and effectively increase antigen presentation efficiency. In addition, DP7-C enhanced the efficacy of DC-based individualized cancer immunotherapy and achieved excellent antitumor effects on mouse tumor models using the OVA antigen peptides and LL2-neoantigens. Excitingly, after DP7-C stimulation, the antigen uptake efficiency of monocytes-derived DCs (MoDCs) in patients with advanced lung cancer increased from 14-40% to 88-98%, the presentation efficiency increased from approximately 15% to approximately 65%, and the proportion of mature MoDCs increased from approximately 20% to approximately 60%. These findings suggest that our approach may be a potentially alternative strategy to produce cancer vaccines designed for individual patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.119852DOI Listing
May 2020

Crizotinib versus chemotherapy: a real-world cost-effectiveness study in China.

J Comp Eff Res 2020 01 21;9(2):93-102. Epub 2020 Jan 21.

Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

To assess the cost-effectiveness of crizotinib verses platinum-based doublet chemotherapy as the first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in the real-world setting. Data from 163 advanced ALK positive NSCLC patients were collected from West China Hospital, Sichuan University (Chengdu, China). They were categorized into two groups as treated with crizotinib (n = 83) or chemotherapy (n = 80) as a first-line therapy. The progression-free survival (PFS) as the primary clinical outcome, and the direct medical costs were collected from hospital information systems. Incremental cost-effectiveness ratio (ICER) was calculated with costs, quality-adjusted life-years, as well as the costs discounted at 3% annually. Additionally, two different kinds of medical insurance (MI) for pharma-economic assessment were considered. Crizotinib improved PFS versus chemotherapy in ALK positive patients (median PFS 19.67 m vs 5.47 m; p < 0.001). Moreover, crizotinib obtained an ICER of US$36,285.39 before the end of 2016, when crizotinib, pemetrexed and anti-angiogenesis drugs were not MI covered. This is more than the willingness to pay threshold (three-times of gross domestic product per capita in mainland China or Sichuan Province). However, ICER was US$7321.16, which is less than willingness to pay, when crizotinib and all chemotherapy drugs were covered by MI from the end of 2016. Sensitivity analysis demonstrated a 99.7% probability for crizotinib to be more cost-effective than chemotherapy, when crizotinib and all anticancer drugs were MI covered. One-way sensitivity analysis for the reimbursement ratio of crizotinib indicated that cost-effective tendency for crizotinib increased as reimbursement ratio increased. Crizotinib could be an effective, and cost-effective first-line treatment for ALK positive advanced NSCLC with the MI coverage currently available in Chengdu, Sichuan Province, China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/cer-2019-0075DOI Listing
January 2020

Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models.

Cancer Immunol Immunother 2020 Jan 5;69(1):135-145. Epub 2019 Dec 5.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, No. 17, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, Sichuan, China.

Development of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used. Therefore, it is necessary to choose a more effective neoantigen vaccination method. In this study, we compared the differences in immune and anti-tumor effects between neoantigen-pulsed DC vaccines and neoantigen-adjuvant vaccines using murine lung carcinoma (LL2) candidate neoantigens. The enzyme-linked immunospot (ELISPOT) assay showed that 4/6 of the neoantigen-adjuvant vaccines and 6/6 of the neoantigen-pulsed DC vaccines induced strong T-cell immune responses. Also, 2/6 of the neoantigen-adjuvant vaccines and 5/6 of the neoantigen-pulsed DC vaccines exhibited potent anti-tumor effects. The results indicated that the neoantigen-pulsed DC vaccines were superior to the neoantigen-adjuvant vaccines in both activating immune responses and inhibiting tumor growth. Our fundings provide an experimental basis for the selection of immune modalities for the use of neoantigens in individualized tumor immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-019-02448-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949210PMC
January 2020

A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC.

Invest New Drugs 2020 04 24;38(2):478-484. Epub 2019 Jun 24.

Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China.

Objective Apatinib is an oral small molecule anti-angiogenic drug. This phase I study aimed to establish the feasible dose of apatinib in combination with pemetrexed plus carboplatin as first-line therapy for epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) negative stage IV non-squamous non-small cell lung cancer (NSCLC). Methods Using a 3 + 3 dose-reduction design, patients received oral apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day two weeks on/one week off schedule (500 mg schedule 2/1) or 250 mg qd. Pemetrexed (500 mg/m) plus carboplatin (AUG = 5) was administered every three weeks. Maintenance therapy by apatinib or pemetrexed could be carried on until disease progression or unacceptable toxicity. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. Result A total of twelve patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd dosage of apatinib (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events (AEs) were hematological toxicity, hypertension, hand-foot syndrome, and hepatic transaminases elevation. Partial response was observed in four patients of eleven evaluable patients (objective response rate 36.4%), and six patients exhibited stable disease (disease control rate 90.9%). Conclusion In patients with advanced non-squamous NSCLC, the feasible dose of apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-019-00811-6DOI Listing
April 2020

Pulmonary metastases of fibrosarcomatous dermatofibrosarcoma protuberans respond to apatinib-based angiogenesis and chemotherapy: a case report.

Ann Transl Med 2019 Apr;7(7):149

Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Dermatofibrosarcoma protuberans (DFSP) is soft tissue malignancy which is locally aggressive, slow-growth, rarely metastasizing but recurs frequently after surgical excision. Fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) is a variant of DFSP with a higher risk of recurrence and metastasis. For treatment of metastatic DFSP, antiangiogenesis therapy is an important therapeutic option, which is beneficial in increasing the efficacy of chemotherapy. Apatinib is a novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor and revealed potential anti-tumor efficacy in some types of sarcomas. However, there is still no report of apatinib as an angiogenesis therapy for metastatic DFSP to date. Herein we first describe a case of FS-DFSP relapsed and metastasized post multiple surgeries and adjuvant radiotherapy responded to apatinib in combination with chemotherapy, indicating apatinib may be a potential therapeutic option for metastatic DFSP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.02.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511556PMC
April 2019

Author Reply to "Regarding 'The Superior Glenohumeral Joint Capsule Alone Does Not Prevent Superior Translation of the Humeral Head: An In Vitro Biomechanical Study'".

Arthroscopy 2019 05;35(5):1301-1303.e1

Department of Sports Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2019.03.005DOI Listing
May 2019

Progression of Central Nervous System Metastases in Advanced Nonsmall Cell Lung Cancer Patients Effectively Treated with First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor.

Cancer Biother Radiopharm 2018 Dec;33(10):421-426

1 Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China .

Central nervous system (CNS) progression is frequently detected in patients with favorable initial responses to first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), but data are incomplete with respect to clinical features and prognostic factors of CNS failure in this population. We retrospectively evaluated 420 advanced nonsmall cell lung cancer (NSCLC) patients treated with first-generation EGFR-TKI for over 3 months. We analyzed CNS progression of these patients, defining as newly developed CNS metastases or progression of preexisting brain lesions after EGFR-TKI treatment. Of the 420 patients, 99 (23.6%) with CNS progression after EGFR-TKI initiation were identified. The median time to CNS progression was 12 months (95% confidence interval [CI] 10.5-13.5). Patients with L858R mutation were more likely to experience CNS failure than those with exon 19 deletion ( = 0.008). For patients with previous brain metastases (BM), the median time to CNS progression of patients with EGFR-TKI and local CNS therapy was significantly longer than those treated with EGFR-TKI alone (14.0 months vs. 11.2 months;  = 0.016). The median survival time after CNS progression was 11.2 months (95% CI 8.8-13.5). L858R mutation, multiple BM progression and CNS with other site failures were negative prognostic factor, while localized CNS therapy was the only significant favorable prognostic factor for overall survival after CNS progression. For advanced NSCLC patients treated successfully with first-generation EGFR-TKI, careful monitoring for CNS progression should be considered, especially for those with L858R mutation. Localized CNS therapy should be considered for CNS progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cbr.2018.2493DOI Listing
December 2018

Predicting severe acute radiation pneumonitis in patients with non-small cell lung cancer receiving postoperative radiotherapy: Development and internal validation of a nomogram based on the clinical and dose-volume histogram parameters.

Radiother Oncol 2019 03 29;132:197-203. Epub 2018 Oct 29.

Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address:

Background And Purpose: Postoperative radiotherapy (PORT) can potentially lead to radiation pneumonitis. We aim to develop a nomogram predicting the severe acute radiation pneumonitis (SARP, grade ≥3) in patients with non-small cell lung cancer (NSCLC) receiving PORT.

Materials And Methods: Clinical and dose-volume histogram (DVH) factors were collected from 109 patients between 2006 and 2017. The endpoint was the development of SARP within 3 months after PORT. Logistic regression was used to evaluate the prognostic value of each factor in predicting SARP. Nomogram was generated based on multivariate regression coefficients. Area under the ROC curve (AUC), calibration curves, and decision curve analyses (DCA) were conducted to validate the model.

Results: Univariate and multivariate analysis indicated that total lung mean dose (tlMD) (OR: 1.003, 95%CI: 1.001-1.006, p = 0.013), percentage of ipsilateral lung volume receiving ≥5 Gy (ilV) (OR: 1.084, 95%CI: 1.020-1.151, p = 0.009), and concurrent chemoradiotherapy (CCRT) (OR: 4.091, 95%CI: 1.331-12.572, p = 0.014) were independent prognosticators of SARP and were included in the nomogram. ROC curves revealed the AUC of the nomogram was 0.842, which was much higher than any factor alone (tlMD: 0.769; ilV: 0.744; CCRT: 0.661). Calibration curves showed favorable consistency between the predicted SARP and the actual observation. DCA showed satisfactory positive net benefits of the model among most of the threshold probabilities, indicating great clinical effect.

Conclusion: We identified that the tlMD (>10.8 Gy), ilV (>64.9%), and CCRT could predict SARP among patients with NSCLC receiving PORT. Combining clinical and DVH parameters, a nomogram was first built and validated, showing its potential value in practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.10.016DOI Listing
March 2019

A Novel Nomogram and Risk Classification System Predicting the Cancer-Specific Survival of Patients with Initially Diagnosed Metastatic Esophageal Cancer: A SEER-Based Study.

Ann Surg Oncol 2019 Feb 24;26(2):321-328. Epub 2018 Oct 24.

Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Metastatic esophageal cancer (mEC) is the end stage of esophageal cancer. We aimed to construct a predictive model predicting the cancer-specific survival (CSS) of mEC patients.

Methods: Data from 1917 patients with initially diagnosed mEC were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Patients were randomly divided into the training and validation cohorts (7:3). Cox regression was conducted to select the predictors of CSS. The validation of the nomogram was performed using concordance index (C-index), calibration curves, and decision curve analyses (DCAs).

Results: Cancer-specific death occurred in 1559/1917 (81.3%) cases. Multivariate Cox regression indicated that factors including age, sex, grade at diagnosis, number of metastatic organs at diagnosis, pathological type, local treatment, and chemotherapy were independent predictors of CSS. Based on these factors, a predictive model was built and virtualized by nomogram. The C-index of the nomogram was 0.762. The calibration curves showed good consistency of CSS between the actual observation and the nomogram prediction, and the DCA showed great clinical usefulness of the nomogram. A risk classification system was built that could perfectly classify mEC patients into three risk groups. In the total cohort, the median CSS of patients in the low-, intermediate- and high-risk groups was 11.0 months (95% confidence interval [CI] 10.1-11.9), 8.0 months (95% CI 7.3-8.7), and 2.0 months (95% CI 1.8-2.2), respectively.

Conclusions: We constructed a nomogram and a corresponding risk classification system predicting the CSS of patients with initially diagnosed mEC. These tools can assist in patient counseling and guiding treatment decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-018-6929-0DOI Listing
February 2019

The Superior Glenohumeral Joint Capsule Alone Does Not Prevent Superior Translation of the Humeral Head: An In Vitro Biomechanical Study.

Arthroscopy 2018 11 22;34(11):2962-2970. Epub 2018 Sep 22.

Department of Sports Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China. Electronic address:

Purpose: To answer 2 questions: What is the main structure that prevents the superior translation of the humeral head, the supraspinatus or the superior capsule (SC)? And what mechanism does the principal structure rely on to prevent the superior translation of the humeral head, the spacer effect or the tensional hammock effect?

Methods: Eight shoulder specimens were assessed using a custom biomechanical testing system. Glenohumeral superior translation and subacromial peak pressure were compared using 6 models: the intact joint model, supraspinatus dysfunction model, supraspinatus defect model, SC tear model, SC defect model, and irreparable rotator cuff tear (IRCT) model.

Results: Compared with the intact joint model, the supraspinatus defect model significantly increased the superior translation (by 2.6 mm; P < .001) and subacromial peak pressure (by 0.43 MPa; P = .013) at 0° glenohumeral abduction, while the SC defect model unremarkably altered the superior translation at 0° (by 0.6 mm; P = .582) and 45° (by 0.3 mm; P = .867) of glenohumeral abduction and the subacromial peak pressure at 0° (by 0.11 MPa; P = .961), 30° (by -0.03 MPa; P = .997), and 45° (by -0.33 MPa; P = .485) of glenohumeral abduction. The supraspinatus dysfunction model significantly increased the superior translation at 0° (by 1.7 mm; P < .001), 30° (by 1.2 mm; P = .005), and 45° (by 0.8 mm; P = .026) of glenohumeral abduction, but not the subacromial peak pressure compared with the intact joint model. However, no significant differences were found between the supraspinatus defect model and the supraspinatus dysfunction model with respect to the superior translation or subacromial peak pressure (all P > .05).

Conclusions: The anatomic SC has a negligible role in preventing the superior translation of the humeral head.

Clinical Relevance: SC reconstruction is not a simple anatomic reconstruction, and its promising clinical outcome may be due to tensional fixation technique and choice of graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2018.06.025DOI Listing
November 2018

A first-principles study of the effect of vacancy defects on the electronic structures of greigite (FeS).

Sci Rep 2018 Jul 30;8(1):11408. Epub 2018 Jul 30.

College of Mechanical Engineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.

Greigite (FeS) is a ferrimagnetic mineral with an inverse spinel structure. Besides its importance in the bio-geochemical cycle, it also has great potential applications for its unique properties such as its half metallic electronic structure at ambient condition. However, it has been challenging to get high purity and crystallinity samples of greigite in experiment, and the defect effect on the electronic structure of greigite was not clear. In the present study, first-principles calculations have been performed to investigate the ground state electronic structure of greigite with monovacancy. It is found that, with an vacancy concentration lower than 3.6%, the greigite with an Fe vacancy is an insulator with charge orderings, while the greigite with a S vacancy becomes a half-metal and has a magnetic moment of <4.0 μB per formula unit. The present result helps to understand the absence of the Verwey transition and the magnetic property of greigite measured in experiment. The understanding of the electronic structure of defective greigite could also be utilized to manipulate the properties of greigite for spintronic applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-29176-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065442PMC
July 2018

Well-controlled pleural effusion indicated pseudoprogression after immunotherapy in lung cancer: A case report.

Thorac Cancer 2018 09 6;9(9):1190-1193. Epub 2018 Jul 6.

Division of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Squamous cancer (SqCC) of the lung has a poor prognosis. With the advent of immunotherapy, prognosis has tended to improve; however, pseudoprogression poses a challenge to the management of immunotherapy. Herein, we discuss the case of a 47-year-old heavy smoker with advanced SqCC. The patient had recurrent disease after initial successful control of the tumor by concurrent radiochemotherapy, together with ample pleural effusion. Pleural effusion was well controlled with systematic nivolumab and intra-thoracic recombinant endostatin; however with simultaneous deterioration of performance and tumor progression. Nivolumab was maintained with the addition of nab-paclitaxel. The combination soon led to a partial response and rapid improvement of the patient's performance. During treatment of this case, we advocated the early control of pleural effusion as an indicator for pseudoprogression. Our experience might be helpful to identify pseudoprogression for the clinical management of immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.12799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119617PMC
September 2018

Association of the independent polymorphisms in CDKN2A with susceptibility of acute lymphoblastic leukemia.

Biosci Rep 2018 06 27;38(3). Epub 2018 Jun 27.

Department of Clinical Laboratory, Core Facility, Quzhou People's Hospital, Quzhou, Zhejiang 324000, China

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and alterations in were considered to play an important role on leukemogenesis. Two single nucleotide polymorphisms (SNPs) at locus were identified to impact on ALL susceptibility via genome wide association studies, and followed by multiple subsequent replication studies at the specific hits. Here, we conducted a systematic review and meta-analysis to re-evaluate the association of both SNPs (rs3731217 and rs3731249) with ALL susceptibility by gathering the data from 24 independent studies, totally containing 7922 cases/21503 controls for rs3731217 and 6295 cases/24191 controls for rs3731249. Both SNPs were significantly associated with ALL risk (odds ratio [OR] = 0.72 and 2.26 respectively), however, exhibit race-specific pattern. In summary, our meta-analysis indicated that two SNPs at locus are associated with ALL susceptibility independently mainly in Caucasians. Future large-scale studies are required to validate the associations in other ethnicities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20180331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019384PMC
June 2018

Assessment of programmed cell death ligand-1 expression with multiple immunohistochemistry antibody clones in non-small cell lung cancer.

J Thorac Dis 2018 Feb;10(2):816-824

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610021, China.

Background: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with PD-L1 as a potential predictive biomarker. However, a specific antibody for PD-L1 expression is an immediate requirement. Meanwhile, the clinicopathological identification of patients with positive PD-L1 remains unclear.

Methods: The present study adopted three anti-PD-L1 IHC antibodies, SP142, SP263, and UMAB228 to test PD-L1 expression in 84 non-small cell lung cancer (NSCLC) specimens. The concordance among antibodies was examined by analytical comparison, and the association between PD-L1 expression and clinicopathological factors was assessed.

Results: The samples from 41 (48.8%), 51 (60.7%), and 50 (59.5%) patients were detected as PD-L1 positive evaluated by antibody SP142, SP263, and UMAB228, respectively. The kappa coefficient was 0.53, 0.58, and 0.46 for SP263 SP142, SP263 UMAB228, and SP142 UMAB228, respectively. On the other hand, the univariate analysis of consensus cases indicated that the PD-L1 expression was significantly correlated with tobacco use (χ=4.25, P=0.04).

Conclusions: The analytical comparison showed moderate concordance between SP142, SP263 and UMAB228, whereas SP263 exhibited higher overall positive rate. Moreover, PD-L1 positive rate was significantly higher in patients with smoking history, which might help in identifying patients who would benefit from PD-1/PD-L1 checkpoint inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2018.01.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864642PMC
February 2018

Comparison of chemotherapy plus bevacizumab vs. chemotherapy alone as third-line treatment or beyond for advanced non-small cell lung cancer: A propensity score-matched analysis.

Oncol Lett 2018 Apr 15;15(4):5671-5679. Epub 2018 Feb 15.

Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

The addition of bevacizumab to chemotherapy has demonstrated efficacy as a first-line treatment for non-small cell lung cancer (NSCLC). Whether this combination is effective as a salvage treatment for patients with NSCLC remains unclear. The present retrospective study was designed to compare the efficacy and safety of chemotherapy plus bevacizumab with chemotherapy alone as a third-line, or continuing, treatment for patients with NSCLC. Between January 2011 and June 2016, a total of 38 patients with stage IV NSCLC who had received chemotherapy plus bevacizumab subsequent to failure of ≥2 prior regimens were matched with 38 patients who had received chemotherapy alone using propensity score matching from a dataset of 165 patients. The variables that were analyzed included age, sex, smoking history, histology, epithelial growth factor receptor mutation status, number of prior regimens and type of chemotherapy regimen. Univariate and multivariate analyses were used to evaluate the prognostic factors for survival outcomes and tumor response, and toxicity analyses were performed. The objective response rate (ORR) and disease control rate (DCR) were improved in patients who underwent chemotherapy-bevacizumab treatment compared with chemotherapy alone (ORR, 23.7 vs. 5.3%, P<0.001; DCR, 65.8 vs. 31.6%, P<0.001). Progression-free survival was prolonged in the chemotherapy-bevacizumab group compared with the chemotherapy-alone group (median, 3.9 vs. 2.2 months; HR, 0.54; 95% CI, 0.32-0.89, P=0.014). Incidence of ≥grade 3 adverse events was low and similar across the groups. The combination of chemotherapy and bevacizumab is a potentially effective and safe alternative salvage treatment for patients with NSCLC who have not received bevacizumab treatment previously.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2018.8064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844063PMC
April 2018

Concurrent brain radiotherapy and EGFR-TKI may improve intracranial metastases control in non-small cell lung cancer and have survival benefit in patients with low DS-GPA score.

Oncotarget 2017 Dec 30;8(67):111309-111317. Epub 2017 Nov 30.

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has intracranial activity in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). The optimal timing of brain radiotherapy (RT) and appropriate patients who need early brain RT remains undetermined. This is a retrospective study of EGFR-mutant NSCLC patients with newly diagnosed brain metastases (BMs) before EGFR-TKI initiation. Intra-cranial progression free survival (IC-PFS) and overall survival (OS) were measured from the date of EGFR-TKI treatment. A total of 113 patients were eligible, 49 received concurrent early brain RT with EGFR-TKI and 64 were treated with EGFR-TKI alone as initial therapy, including 27 with salvage RT upon BM progression. The patients with early brain RT had superior IC-PFS than those without early brain RT (21.4 vs 15.0 months, P=0.001), which remained significant in multivariate analysis (HR 0.30, P<0.001). The median overall survival (OS) for early RT, EGFR-TKI alone and salvage RT groups was 28.1, 24.5, and 24.6 months, respectively (P=0.604). Similar IC-PFS (23.6 vs 21.4 months, P=0.253) and OS (24.6 vs 28.1 months, P=0.385) were observed between salvage RT and early RT groups. For patients with Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) score of 0 to 2, early brain RT was the independent factor for improved OS (HR 0.33, P=0.025). In conclusion, concurrent early brain RT with EGFR-TKI may improve intracranial disease control in EGFR-mutant NSCLC with BM and have survival benefit in patients with low DS-GPA score. Salvage brain RT upon BM progression may be acceptable in some patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.22785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762323PMC
December 2017

Monitoring the estimated glomerular filtration rate (eGFR) in patients with small-cell lung cancer during chemotherapy: equations based on serum creatinine or cystatin C?

Int J Clin Oncol 2018 Apr 4;23(2):258-265. Epub 2017 Nov 4.

Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: This study compared the differences between the estimated glomerular filtration rate (eGFR) calculated by several equations based on serum creatinine (Scr) and cystatin C (CysC) concentrations for monitoring renal function in patients with small-cell lung cancer (SCLC) during chemotherapy.

Methods: Seventy-one patients with SCLC were retrospectively analyzed. The eGFR before and after each chemotherapy cycle was calculated by the following equations: the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, the modification of diet in renal disease (MDRD) equation, the Cockcroft-Gault (CG) equation, and five CysC-based equations. The patients were compared among the different eGFR groups.

Results: The mean decreases in eGFR (-2.25 ± 9.89 ml/min/1.73 m) between each treatment cycle were more significant than the decreases in eGFR (-0.46 ± 10.17 ml/min/1.73 m), eGFR (-0.48 ± 9.79 ml/min/1.73 m), and five calculated eGFR (p < 0.05). Single-/multiparameter analyses showed that patients with a higher body mass index (BMI >23) and receiving more treatment cycles (>3) were at increased risk for developing renal impairment with an eGFR less than 60 ml/min/1.73 m during chemotherapy.

Conclusions: The eGFR calculated by the CKD-EPI equation changed more significantly between each chemotherapy cycle than did the eGFR from the other equations based on Scr or CysC in patients with SCLC. Oncologists should pay more attention to the renal function of specific patient groups during treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-017-1206-yDOI Listing
April 2018

Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for lung squamous carcinomas harboring EGFR mutation: A multicenter study and pooled analysis of published reports.

Oncotarget 2017 Jul;8(30):49680-49688

Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinoma (ADC) but rare in squamous cell carcinoma (SQC). The efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for SQC with EGFR mutations is unclear. The aim of this study was to evaluate the efficacy of EGFR-TKIs for these patients. We performed a retrospective matched-pair case-control study from 3 cancer centers, including 44 SQC and 44 ADC patients with EGFR mutation who were treated with EGFR-TKI. Subsequently, we performed a pooled analysis on the efficacy of EGFR-TKIs for EGFR-mutant SQC in 115 patients, including 71 patients selected from 25 published reports. In our multicenter study, EGFR-mutant SQC and ADC patients had similar objective response rate (ORR) (43.2% vs. 54.5%, p = 0.290), but SQC patients had lower disease control rate (DCR) (71.3% vs. 100%, p = 0.001), significant shorter median progression free survival (PFS) (5.1 vs. 13.0 months, p = 0.000) and median overall survival (OS) (17.2 vs. 23.6 months, p = 0.027). In pooled analysis, the ORR, DCR, PFS and OS of SQC patients were 39.1%, 71.3%, 5.6 months and 15.0 months, respectively. Performance status was the only independent predictor of PFS and erlotinib treatment was associated with a better survival. In conclusion, EGFR-TKI was less effective in EGFR-mutant SQC than in ADC but still has clinical benefit for SQC patients. Further study is need to evaluate the using of EGFR-TKIs in these SQC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.17915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564798PMC
July 2017