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  • 1
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    Online Resource
    A real-world study update: Efficacy and safety of anlotinib for advanced non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21106-e21106
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21106-e21106
    Abstract: e21106 Background: Anlotinib is an oral novel receptor tyrosine kinases (RTKs) inhibitor targeting multiple RTKs including VEGFR, PDGFR, FGFR, and c-kit. Due to its high efficacy and low side effects in ALTER 0303 trial, Anlotinib has been approved as a 3rd line therapy for pts with advanced non-small cell lung cancer (NSCLC) by NMPA in May 2018. The interim results of our real-world study suggested anlotinib substantially prolonged the progression-free survival (PFS) with manageable toxicity in later lines treatment of advanced NSCLC patients. Here, we update our latest results on the treatment experience in a broad NSCLC population. Methods: This is a multi-center, non-interventional, prospective real-world study. All registered data are collected from real-life clinical practice setting. Patients with advanced NSCLC treating with anlotinib were included. The primary endpoint was PFS, and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: As of January 2022, a total of 371 pts were enrolled, of whom 347 were evaluable, with a median age of 63 years, 232 males (66.9%). There were 40 pts (11.5%) with brain metastasis, 52 pts (15.0%) with bone metastasis, and 29 pts (8.4%) with liver metastasis at baseline. 109 pts (31.4%) received anlotinib as first/second line treatment, whereas 238 pts (68.6%) as third/later line treatment. In the overall population, DCR and ORR were 84.7% and 18.7% respectively. The mPFS was 6.3 months (95%CI, 5.7, 6.9) and the mOS was 12.2 months (95%CI, 9.5,14.9). Subgroup analysis showed more details. A trend towards better ORR (33.3%) was observed in the first line setting while a significantly better DCR (89.5%) was observed in the second line setting. The mPFS of first-/second-line treatment (6.9 months) was longer than that of the third-line or above treatment (5.8 months). The mOS of the first-/second- and third-line or above treatment were 10.4 (7.8,13) and 13.5 (8.9,18.1) months respectively. 52 pts (15%) had any grade of adverse events, of which 10 pts (2.9%) had grade 3 or above AEs. The most common AEs were hypoalbuminemia (3.5%), alanine aminotransferase reduction (1.4%), proteinuria (1.2%) and hyponatremia (1.2%). Conclusions: The updated results showed that anlotinib prolonged not only PFS but also OS significantly with a favorable safety profile, especially for OS benefits in third-line or later treatment. These data also indirectly revealed that anlotinib is a promising treatment option for patients with advanced NSCLC despite of treatment line in the real world.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e21106
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
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    A Multicenter, Prospective, Comparative Study of the Efficacy and Safety of Nimustine Hydrochloride (ACNU) With Concurrent Whole Brain Radiotherapy in Lung Cancer Patients With Brain Metastasis
    Elsevier BV ; 2011
    In:  Chest Vol. 140, No. 4 ( 2011-10), p. 1048A-
    Details
    In: Chest, Elsevier BV, Vol. 140, No. 4 ( 2011-10), p. 1048A-
    Type of Medium: Online Resource
    ISSN: 0012-3692
    URL: Article
    DOI: 10.1378/chest.1117219
    RVK:
    XA 36340
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2007244-2
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  • 3
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    Comparative efficacy and safety of immunotherapy for advanced NSCLC: A systematic review and network meta-analysis.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21028-e21028
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21028-e21028
    Abstract: e21028 Background: Advanced non-small cell lung cancer (NSCLC) patients responded differently to checkpoint inhibitors (ICIs) therapy, leading to the confuse of choosing the optimal regimens for patients. Therefore, we performed this network meta-analysis to compare different agents across clinical trials. Methods: We searched databases, including EMBASE, PubMed, ClinicalTrials and etc, for abstracts, full-text articles and minutes of the annual meetings published from database inception through Oct 01, 2021. Phase 3 randomized clinical trials (RCTs) of first-line immunotherapy or combinations for adcanced (stage III/IV or recurrent) NSCLC were included. We selected 26 trials evaluating different ICIs (Atezolizuma (atezo), Pembrolizumab (pem), Nivolumab(nivo), Durvalumab (durva), Camrelizumab (camre), Tislelizumab (tisle), Sintilimab (sint), Sugemalimab (suge), Toripalimab (tori), Cemiplimab (cemip)) and combinations based on them. Primary outcomes of interests were overall survival (OS) and progression-free survival (PFS). Secondary outcomes of interests were objective response rate (ORR), and adverse events (AEs). Hazard ratio (HRs) and 95% confidence intervals (CI) were used to represent the results of OS and PFS. The subgroup analysis (pathological type, PD-L1 expression, gender, smoking history, ECOG score, metastasis status and ethnicity) was performed and the treatments were ranked in it and overall population. Results: In our study, all ICIs-based regimens had benefit in OS and PFS compared with chemotherapy. The network meta-analysis for OS showed the combination of Camre-Chemo ranked 1st in overall population, and most of dual ICIs-based regimens, except Nivo-Ipi-Chemo, showed minor improvement in OS while possess more safety concerns compared with other regimens. Atezo-Beva-Chemo (ranked 1st in PFS, 20th in safety), has shown good efficacy but was revealed with lower safety. Sint-Chemo demonstrated promising efficacy in PFS, but it remains to be seen whether the effectiveness could be transformed into OS benefit due to the lack of related data. Pem-Chemo (ranked 1st in ORR) demonstrated the best response to tumors in all treatments regardless of PD-L1 expression. In subgroup analysis, for patients with poor health conditions (≥65 years or with ECOG = 1), multi-drug combination regimens, such as Nivo-Ipi-Chemo and Atezo-Beva-Chemo, showed better benefits in PFS and OS compared with only chemo but had no significant advantages than any other treatments. Conclusions: In our study, we provide relative comprehensive results for latest researches of first-line ICIs. Overall, Care-Chemo, Pem-Chemo, Sint-Chemo, are prior to be recommended according to our study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e21028
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Safety and efficacy of repeated intra-hepatic artery and intravenous infusion of ET140202, a novel anti-AFP/MHC complex T-cell, in advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e14013-e14013
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14013-e14013
    Abstract: e14013 Background: Despite the success in hematological malignancies, immunotherapy of solid tumors using redirected T cells such as CAR-T remains challenging due to the lack of a unique tumor antigen, inefficient trafficking of CAR T cells to tumor sites and the presence of immunosuppressive tumor microenvironment. ET140202 is a novel T-cell platform that targets AFP/MHC complex with GPC3-guided co-stimulation aiming to improve the specificity and efficacy. Herein we report a case study of ET140202 for a subject with AFP+ recurrent HCC previous treated with surgery and 2 TACE therapies. Baseline imaging showed multiple nodules on segment 7 of right lobe with enlarged lymph nodes in hepatic hilar region. Methods: From 9/25/18 to 1/29/19 the subject first received 2 intra-hepatic artery infusions (i.a.) of ET140202 T cells at the dose of 3×10 6 cells/kg followed by 4 i.v. infusions at the dose of 6×10 6 cells/kg. No lymphodepleting chemotherapy was given prior to T-cell infusion. Vital signs, blood cell count, and blood chemistry were monitored on Days 1, 3, 7, and 14. Clinical responses were assessed at Month 1, 2, 3, 4, 6, 9, 12 and 24. Results: Vital signs are normal after each infusion. No treatment-related Grade 2 or higher AEs observed. Grade 1 events that were possibly attributable to therapy included transient elevation of AST and bilirubin 58 days post the 1 st infusion. Both events resolved in 4 days without treatment. The subject did not experience any clinical signs of CRS or neurotoxicity. Month 1, 2, and 3 follow-ups showed that the number and size of the liver nodules slowly increased overtime. Month 4 follow-up showed that the size of liver nodules decreased more than 50% of baseline and resulted in PR based on RECIST criteria. The AFP level elevated in the subject after infusion and reached the peak of 2097 ng/mL 55 days post 1 st infusion, gradually dropped to 905 ng/mL on day 67, elevated to the 2 nd peak of 2660 ng/mL and gradually decreased to 1235 ng/mL at the last follow-up on day 130. Conclusions: Repeated infusion of ET140202 T cells via i.a. and i.v. routes is safe and shows early sign of efficacy 4 months post initiation of the treatment in AFP+/HLA-A2+ HCC subject.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e14013
    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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    Coronavirus Disease 2019 Infection Among Medical Staff in Wuhan
    Elsevier BV ; 2020
    In:  Chest Vol. 158, No. 4 ( 2020-10), p. 1409-1412
    Details
    In: Chest, Elsevier BV, Vol. 158, No. 4 ( 2020-10), p. 1409-1412
    Type of Medium: Online Resource
    ISSN: 0012-3692
    URL: Article
    DOI: 10.1016/j.chest.2020.05.529
    RVK:
    XA 36340
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2007244-2
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  • 6
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    A pan-cancer analysis of the granzyme family based on the TCGA database and single-cell RNA sequencing data.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e14580-e14580
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e14580-e14580
    Abstract: e14580 Background: Human Granzymes (GZMs) are mainly regarded as protective cytotoxic proteases that block the development of cancer. This study aimed to systematically analyze the expression signature, immune infiltration pattern, predictive values of prognosis and immune response, and the biological process associated with GZMs in different cancers. Methods: We estimated the predictive values of GZMs in prognosis and drug sensitivities by Cox regression analysis, immunophenoscore (IPS) algorithm, etc. We identified potential factors associated with the expression of GZMs, involving the somatic mutation and copy number variation of driver genes. We further investigate the distributions of GZMs and their discrepancy in single-cell resolution. The package CellChat and SCENIC were used for cell-cell communications and regulatory network reconstruction respectively. The ssGSEA algorithm was used to calculate the GZMs score for a gene set of five granzymes and the enrichment score (ES) of regulons based on the bulk-seq data. We chose the specific regulons to cluster patients in pan-cancer. Results: In the immunotherapy context, the higher GZMs score was associated with better overall survival (OS) in urothelial carcinoma (HR = 0.31, p 〈 0.01). In melanoma, the pooled HR value calculated by meta-analysis assay was 0.33 (95%CI: 0.189-0.58). In the single-cell resolution, we found the three patterns of GZMs expression in CD8+T/NK cells. Furthermore, we analyzed the discrepancy among different GZMs subtype cells in functions, cell-cell communications, and cell-type-specific regulons. In CD8+ Effector memory T cells, cluster 1 (GZMB+) and cluster 2 (GZMK+) exhibited different enriched pathways in adhesion, anti-bacteria, chemotaxis, migration, and metabolism. In the cell-cell communications analysis, the IFNG − (IFNGR1+IFNGR2) between CD8+ T cells and malignant cells was only significant in the C1 and C2 clusters. Pan-cancer patients were divided into five regulons clusters based on the regulons. Cluster 5 had the worst OS (HR = 8.49, 95%CI = 6.67-10.81, p 〈 0.01) compared to cluster 1 which had the best prognosis. Cluster 5 had higher ES of regulons including Myb, Hmgb2, E2f7, E2f8, and lower ES of Egr3. Conclusions: In conclusion, the expressions of GZMs, GZMs score, and the specific regulons identified in this study were associated with the prognosis in pan-cancer patients. GZMs score was a valuable biomarker that can predict the response to immunotherapy. The patients who belong to different regulons subtypes have specific transcription factors, which may be potential targets for the precision medicine of anti-tumor strategies in pan-cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e14580
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Pan-Cancer Analysis of Microbiome Quantitative Trait Loci
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 19 ( 2022-10-04), p. 3449-3456
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 19 ( 2022-10-04), p. 3449-3456
    Abstract: Microorganisms are commonly detected in tumor tissues, and the species and abundance have been reported to affect cancer initiation, progression, and therapy. Host genetics have been associated with gut microbial abundances, while the relationships between genetic variants and the cancer microbiome still require systematic interrogation. Therefore, identification of cancer microbiome quantitative trait loci (mbQTL) across cancer types might elucidate the contributions of genetic variants to tumor development. Using genotype data from The Cancer Genome Atlas and microbial abundance levels from Kraken-derived data, we developed a computational pipeline to identify mbQTLs in 32 cancer types. This study systematically identified 38,660 mbQTLs across cancers, ranging 50 in endometrial carcinoma to 3,133 in thyroid carcinoma. Furthermore, a strong enrichment of mbQTLs was observed among transcription factor binding sites and chromatin regulatory elements, such as H3K27ac. Notably, mbQTLs were significantly enriched in cancer genome-wide association studies (GWAS) loci and explained an average of 2% for cancer heritability, indicating that mbQTLs could provide additional insights into cancer etiology. Correspondingly, 24,443 mbQTLs overlapping with GWAS linkage disequilibrium regions were identified. Survival analyses identified 318 mbQTLs associated with patient overall survival. Moreover, we uncovered 135,248 microbiome–immune infiltration associations and 166,603 microbiome–drug response associations that might provide clues for microbiome-based biomarkers. Finally, a user-friendly database, Cancer-mbQTL (http://canmbqtl.whu.edu.cn/#/), was constructed for users to browse, search, and download data of interest. This study provides a valuable resource for investigating the roles of genetics and microorganisms in human cancer. Significance: This study provides insights into the host–microbiome interactions for multiple cancer types, which could help the research community understand the effects of inherited variants in tumorigenesis and development.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-22-1854
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    Abstract 1903: Cancer stem cell vaccine significantly reduces local tumor relapse and prolongs survival in the adjuvant setting
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1903-1903
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1903-1903
    Abstract: Although surgical resection has been a standard treatment for solid malignancies, therapeutic efficacy is limited by both local and distant recurrence. Effectively preventing local tumor recurrence remains a significant challenge. The existence of micro metastasis at the time of tumor resection represents an even greater therapeutic challenge, since 90% of tumor deaths are due to tumor metastasis. There is increasing evidence that many cancers are driven and maintained by a subpopulation of cells that display stem cell properties. Cancer stem cells (CSCs) can self-renew, mediate tumor growth and contribute to tumor recurrence and metastasis. Targeting CSCs may thus increase the therapeutic efficacy of current cancer treatment. We previously described a strategy to target CSCs using CSC-dendritic cell (DC) vaccination. However, the efficacy of CSC targeted therapeutics may be greatest when they are deployed in the adjuvant setting. In this study, two mouse models were utilized: SCC7 subcutaneous (s.c.) tumors, and a D5 melanoma model. Established s.c. SCC7 tumors were surgically removed from mice followed by treatment using ALDHhigh SCC7 CSC-DC vaccine, which significantly reduced local tumor relapse and prolonged animal survival. This effect was significantly augmented by simultaneous administration of anti-PD-L1 mAb. In the minimal disease setting of D5, ALDHhigh CSC-DC vaccination significantly inhibited tumor growth, reduced spontaneous lung metastases resulting in increased survival. CCR10 and its ligands were down-regulated on ALDHhigh D5 CSCs and in lung tissues respectively in animals subjected to ALDHhigh D5 CSC-DC vaccination. Down-regulation of CCR10 by siRNA significantly blocked tumor cell migration in vitro and metastasis in vivo. T cells harvested from ALDHhigh D5 CSC-DC vaccinated animals selectively killed the ALDHhigh D5 CSCs. There was also evidence of humoral immunological targeting of CSCs. As a result, CSC-DC vaccination significantly decreased the percentage of ALDHhigh cells in residual tumors. These data indicate that, when used in an adjuvant setting, ALDHhigh CSC-DC vaccines effectively inhibit local tumor recurrence, reduce spontaneous lung metastasis, and prolong animal survival; compared with traditional DC vaccines and that simultaneous PD-L1 blockade can significantly enhance this effect. Citation Format: Fei Liao, Yang yang Hu, Xin Chen, Alfed E Chang, Robert E Hollingsworth, Elaine Hurt, John Owen, Jeffrey S Moyer, Mark E.P Prince, Joel Whitfield, Yuxin Chu, Qibin Song, Max S Wicha, Qiao Li. Cancer stem cell vaccine significantly reduces local tumor relapse and prolongs survival in the adjuvant setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1903. doi:10.1158/1538-7445.AM2017-1903
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-1903
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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