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  • Medicine  (13)
  • XA 52760  (13)
  • 1
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    Characteristics of T-cell receptor repertoire between lung cancer patients and healthy people.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e20728-e20728
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e20728-e20728
    Abstract: e20728 Background: Deep sequencing studies on T cell receptor (TCR) repertoire have provided a wealth of information, such as immune status, virus infection history and so on. As we all known, the thymus begins to involute at the time of birth, so does the immune system. We can use TCR sequence to describe changes in human’s immune system with age, the difference between males and females and immune stat of cancers. Methods: We analyzed TCRβrepertoire in 334 healthy individuals without cancer, aged 2–83 years, and 207 lung cancers. In detail, genomic DNA was extracted from peripheral blood and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of individual T cell clones. Shannon’s entropy was calculated on the clonal abundance of all productive TCR sequences. The normalized Shannon’s entropy (Shannon index) was determined by dividing Shannon’s entropy by the natural logarithm of the number of unique productive TCR sequences. HEC was defined by a CDR3 aa clonotype clonal frequency exceeding 0.1%. Results: Analysis had been made to test the age relationship among a cluster of commonly used immune parameters, such as Shannon’s entropy, clonality and so on. Two outcomes, Shannon index and HEC, had showed a more closed correlation with age. Shannon indexs were significantly decreasing with age (p = 6.2×10 -11 ), while HECs increased with age (p = 5.3×10 -10 ) . Comparison of the peripheral blood T cell repertoire diversity between male and female, we found TCRβdiversity decreases more rapidly in 20 to 40 years for males than for females. No gender difference was observed in the youngest cohort and the oldest age cohort. Lung cancer patients has a lower T cell diversity compared with health people aged 40 years or more (6.43±1.30 vs 6.71±1.70, p = 6.3×10 -5 ). Conclusions: Our data suggest that the human peripheral blood TCR repertoire diversity decrease from young ( 〈 20 years) to middle-aged ( 20 to 65 years ) to elderly adults ( 〉 65 years). Moreover, TCR repertoire displays significant gender difference in the 20-40 years age group. Lung cancer patients suffer a poorer immune state than healthy people.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e20728
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Long-course targeted therapy with bevacizumab to predict better survival in patients with advanced colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e14704-e14704
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e14704-e14704
    Abstract: e14704 Background: Bevacizumab has been the standard treatment in first-line treatment of advanced colorectal cancer. This study explored whether the short-course and long-course use of bevacizumab could influence overall survival (OS). Methods: A total of 74 patients with advanced colorectal cancer who had received at least one cycle of bevacizumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of advanced colorectal cancer to death. Results: The P value among the median OS of initiating bevacizumab in first-line group (n = 47), in the second-line group (n = 18), and the third-or more-line group (n = 9) was not reached statistically significance(P = 0.349). In the first-line initiating bevacizumab group, the irinotecan arm showed a trend of better activity than the oxaliplatin arm, but the significance was not reached(P = 0.128). For patients in the first-line initiating bevacizumab group who had received at least four courses of bevacizumab (n = 36), the median PFS and OS was 11 m and 29m respectively and for those receiving less than four courses of bevacizumab (n = 10), it was 3.9 m (P = 0.005) and 13m (P=0.003) respectively. Conclusions: The delayed use of bevacizumab has no negative effect on the OS of patients with advanced colorectal cancer. Long-Course targeted therapy with bevacizumab favors better survival in patients with advanced colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e14704
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Fruquintinib combination with sintilimab in refractory metastatic colorectal cancer patients in China.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 4028-4028
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 4028-4028
    Abstract: 4028 Background: Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is a new anti-cancer targeting drug independently developed in China for refractory metastatic colorectal cancer (mCRC). Because Regorafenib combined with nivolumab has a promising future in patients with refractory mCRC, we aim to evaluate the efficiency of combination of Fruquintinib with Sintilimab (a highly selective, fully human monoclonal antibody PD-1 mAb) in these patients. Methods: Fifty-two patients with refractory mCRC were given fruquintinib (3mg orally, once daily for 3 weeks, followed by 1 weeks off in 4 weeks cycles) and sintilimab (200mg intravenously, once every 3 weeks). Before treatment, peripheral blood samples were collected and next-generation sequencing was performed to detect the gene profile of patients. Results: The ORR was 15.38% (8/52), DCR was 57.6% (30/52), and mPFS was 108 days. The patients was divided into two groups according to their PFS: PFS ≥ 90 days and PFS 〈 90 days. PFS was significantly worse in patients with the following mutations: AMER1 ( p=0.0073), DNMT3A ( p=0.0075), ETV5 ( p=0.012), EWSR1 ( p=0.016), FANCA ( p=0.019), IKBKE ( p=0.0073), NOTCH1 ( p=0.015), STAG2 ( p=0.012) and TCF7L2 ( p=0.0073). It was also significantly worse in the patients had the abnormalities of complexity and coagulation cascades ( p = 0.026) and pancreatic cancer pathway ( p = 0.0098). Conclusions: Fruquintinib combined with Sintilimab seemed not resulted in a significant increase in ORR, DCR and OS in refractory mCRC. Certain mutational genes and abnormal pathway caused by some frameshift mutations may affect the efficacy. It is suggested that targeting these mutational genes and signaling pathway may be helpful to improve the efficacy of Fruquintinib combination with Sintilimab.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.4028
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Online Resource
    MET kinase domain rearrangements across 10 cancer types.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3078-3078
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3078-3078
    Abstract: 3078 Background: MET is a transmembrane receptor tyrosine kinase and deregulated in many kinds of tumors by mutation, rearrangement and amplification. Since the first c onstitutively active MET rearrangement ( TPR-MET) was discovered, many other MET rearrangements have been identified in various tumor types. However, the frequency and characteristic of MET rearrangement in Chinese cancer patients is still unclear. Methods: Targeted sequencing using 1021-gene panel or 59-gene panel was performed on 3952 tissue samples and 5100 blood-based ctDNA samples from 9052 unique patients across 10 cancer types. All MET exons were sequenced, but MET intronic breakpoints were not specifically baited. Results: 24 (0.27%) MET kinase domain rearrangements (KDRE) were identified in 9052 patients. Specifically, 0.25% (16/6284) in non-small cell lung cancer (NSCLC), 0.69% (2/290) in gastric adenocarcinoma, 0.32% (2/897) in colorectal cancer, 0.33% (2/610) in breast cancer, 0.3% (1/330) in hepatocellular carcinoma and 0.69% (1/145) in ovarian cancer, none in 139 pancreatic cancer, 136 thyroid cancer, 111 renal cell carcinoma and 110 esophageal squamous cell carcinoma. Among all of the MET KDRE, 17 were fusions with 5’ identified partner, 3 were kinase domain duplication (KDD) and 4 were probable fusions with unidentified partner. The most common 5 ’partner gene was CAPZA2, followed by CD47 and TES. In the MET KDRE cases in NSCLC, 56.25% (9/16) did not found any clinical actionable variants referring to the NCCN guideline. In addition, MET amplification, EGFR L858R or exon 19 deletion and KRAS mutation co-occurred in 25% (4/16), 18.75% (3/16) and 12.5% (2/16) of NSCLC MET KDRE cases respectively. Conclusions: Our results, for the first time, illustrate the MET KDRE across 10 cancer types among Chinese population and might provide some novel targets to develop new therapies for patients with MET KDRE. MET KDRE across different tumor types. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3078
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Online Resource
    Using circulating tumor DNA analysis to depict genomic profiles and predict survival outcomes in patients with small-cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 8567-8567
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 8567-8567
    Abstract: 8567 Background: Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancers. Most patients have extensive-stage disease with widespread metastases and poor survival. Understanding the molecular mutation profile of each SCLC patient would allow precision treatment and improved clinical outcome. However, tumor tissues from surgery are not available for most SCLC patients and biopsy specimens are often have limited quantities. Several studies have provided evidence of circulating tumor DNA (ctDNA) in detecting somatic variants of multiple solid tumors. This study evaluated utility of ctDNA to depict genomic profiles and predict survival outcomes in SCLC patients. Methods: 22 Plasma samples were obtained before initial treatment from 22 patients with SCLC enrolled between 2012 and 2016. Targeted-capture deep sequencing was performed to identify somatic variants in 465 cancer-related genes. Genomic mutation profiles were described and the clinical implications were further analyzed. Results: Tumor DNA can be detected in all 22 plasma samples collected from patients with SCLC. In total, 340 variants were identified, and the mean and median mutation rate were 6.3 and 6.6 per Mb. TP53 and RB1 are the most frequently mutated genes, detected in 90.9% (20/22) and 59.1% (13/22) patients, respectively. Further analysis showed that high ctDNA fraction in cell-free DNA (cfDNA) was associated with heavy tumor burden (R = 0.7, p = 0.0017). Moreover, patients with high ctDNA fractions (ctDNA fraction 〉 = 18.3%) had poor progression free survival (PFS) (HR, 17.2; p = 0.0019). The median PFS of patients with high versus low ctDNA fractions was 5.2 months (95% CI 4.6 to 5.8 months) versus 10.0 months (95% CI 9.3 to 10.7 months), respectively. Conclusions: In this study, ctDNA analysis offers a promising way to depict the molecular profile in patients with SCLC. Moreover, these findings highlight the potential clinical utility of ctDNA to predicate clinical outcome in SCLC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.8567
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Discover BCL6 translocations partner gene in diffuse large b-cell lymphoma by target-captured next generation sequencing.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e19527-e19527
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e19527-e19527
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e19527
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Neoantigen-based vaccination as a practical measure for head and neck cancer treatment.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e18528-e18528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e18528-e18528
    Abstract: e18528 Background: The view that neoantigens serve as potential vaccine targets has arisen in the last decade. Clinical and computational efforts have been done to increase the practicality of its application in real world. With these advances, we conducted a retrospective study on a Chinese population to explore the clinical feasibility of neoantigen-based vaccines for head and neck cancer treatment. Methods: Tumor and normal samples were profiled using a 1021-gene panel. Sequencing data were pre-analyzed according to our in-house standard procedures. Class I HLA typing was completed using OptiType v1.0. Curated somatic mutations in coding regions (SNVs and non-frameshift Indels with an allele frequency ≥ 5%) were collected and altered peptides produced by these mutations were analyzed using NetMHCpan v4.0. Peptides with an IC 50 〈 500 nM were considered potential binders, and especially, those with an IC 50 〈 50 nM were considered strong binders. An altered peptide was considered a neoantigen if IC 50 altere d is 〈 IC 50 wildtype . Results: We analyzed a total of 243 patients and detected 114 unique HLA alleles. By carrier percentage, the top three alleles are C*01:02 (44%), B*46:01 (36%), and A*11:01 (33%). In total, 743 mutations were deemed eligible for neoantigen prediction and 223 unique neoantigens were found. Of these neoantigens, 67 (carried by 21% of patients) were strong binders, among which 26 (carried by 9% patients) exhibited a great fold change (≥ 5 folds) of binding affinity. Moreover, the neoantigens in these patients are unique, as only two neoantigens were shared. A search for shared neoantigens revealed a combination of mutation PIK3CA p.E542K and HLA A*11:01, which was detected in 0.54% of all patients. Additionally, 43.6% (106/243) of patients were diagnosed with nasopharyngeal carcinoma, among whom 42% (44/106) possessed predicted neoantigens, including 15 patients with strong-binder neoantigens. Conclusions: (1) Neoantigen-based vaccination is a practical measure to treat patients with head and neck cancer, as indicated by the percentage of patients harboring strong-binder neoantigens. (2) Off-the-shelf neoantigen vaccines may not be practical, given the result that the most common combination of a neoantigen-producing mutation and the corresponding HLA was only found in 0.54% of all patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e18528
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    Using target capture sequencing detect microsatellite instability(MSI), tumor mutational burden(TMB) and POLE/POLD1 mutations in colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e15012-e15012
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e15012-e15012
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e15012
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 9
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    The prevalence of HLA LOH across 10 cancer types in Chinese patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 3124-3124
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3124-3124
    Abstract: 3124 Background: Recognition of tumor neoantigen is the key to generating immune response. The expression and integrity of human leukocyte antigen (HLA) are the prerequisites for neoantigen presentation, and loss of heterozygosity in HLA (HLA LOH) may facilitate immune evasion. However, the incidence of HLA LOH in Chinese cancer patients is unknown. Methods: In this study, 45 samples sequenced with both 1021-gene panel and whole-exome sequencing(WES) were used to evaluate the consistency of HLA LOH in the two testing strategies. The prevalence of HLA LOH analysis was performed in 1546 advanced patients across 10 diverse cancer types and 114 early-stage lung cancer patients who had undergone tumor profiling using 1021-gene panel. Exon 2, exon 3 and bilateral introns of HLA-A/B/C genes were well covered in 1021-gene panel. HLA LOH were analysis using LOHHLA algorithm (McGranahan, et al. 2017). Results: In the HLA LOH analysis of 45 samples, the consistency of 1021-gene panel and WES was 95.6% (43/45). Among the 1660 samples, 1.3% (21) were detected as HLA homozygous at all of the three site. HLA LOH was found in 45.1%(697/1546) of all the advanced patients, range from 24.1% to 59.7%. In colorectal cancer, the HLA LOH ratio of MSS samples was significantly higher than that of MSI-H samples (46.2%, 61/132 vs 16.7%, 3/18 p =0.0214). For NSCLC, the proportion of HLALOH in early-stage (I-IIIa) lung adenocarcinoma and lung squamous cell carcinoma was 25.7% (18/70) and 65.9% (29/44), respectively, consistent with the report. However, advanced (IIIa-IV) lung adenocarcinoma and lung squamous cell carcinoma were 49.4%(168/340) and 58.7%(179/305), respectively. The reason for the difference between early-stage lung adenocarcinoma and advanced lung adenocarcinoma needs further study. In 43.8% of cases (326/744), LOH occurred simultaneously in HLA-A, B and C,suggesting that the Class I locus was often lost together. Conclusions: We can use multi-gene panel for HLA LOH analysis, provided that the relevant regions are well captured. The prevalenceof HLA LOHpresent differences among cancer types.Understanding these distributions may provide more information for immunotherapy research. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.3124
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Online Resource
    Identification and characterization of germline pathogenic variants using matched tumor-normal next-generation sequencing in 7363 pan-cancer patients in China.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 1545-1545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 1545-1545
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.1545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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