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  • Miao, Qian  (10)
  • English  (10)
  • 1
    Online Resource
    Online Resource
    CD8+ T Cell/Cancer-Associated Fibroblasts Ratio Stratifies Prognostic and Predictive Responses to Immunotherapy Across Multiple Cancer Types
    Elsevier BV ; 2022
    In:  SSRN Electronic Journal
    Details
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    URL: Article
    DOI: 10.2139/ssrn.4141239
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 2
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    Cerebrospinal fluid circulating tumor DNA for the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e21039-e21039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21039-e21039
    Abstract: e21039 Background: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. Methods: Patients with LM from NSCLC were retrospectively analyzed. Circulating tumor DNA (ctDNA) of CSFand pairedextracranial tissue or plasma were tested by ARMS or next-generation sequencing(NGS).Clinical outcomes were compared with Kaplan-Meier log-rank test and Coxproportional hazards methodologies. Results: We reviewed charts of 80 patients with LM treated atFujian Cancer Hospital. A total of 57 CSF and of which 30 contemporaneouslypaired extracranial samples tested by NGS were analyzed. Most interestingly, CSF ctDNA revealed EGFR mutations in 4 patients previously diagnosed as wild-type by extracranial specimens, and survival was extended by targeted therapy. In the gene map of paired samples, CSF showed more abundant cell-cycle regulatory genes and complex independent evolutionary. CDKN2A/2B CNVs-del was enriched threefold in CSF (~26.3%) with LM compared to extracranial specimens (~8.9%)in lung adenocarcinoma without LM. The median overall survival (OS) was 14.1 months [95% confidence interval (CI): 10.7–17.5 months]. Univariate analyses and multivariate Cox analyses demonstrated that patients with CDKN2A/CDKN2Bco-mutation had poor prognosis. Conclusions: CSF-based ctDNA testing contributes to the phenotypic detection and unique characterization of resistance mechanisms of LM in NSCLC. CDKN2A/2B mutation maybe a poor prognostic factor in LM patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e21039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
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    A novel parameter reflecting the interaction between CD8+ T cells and cancer-associated fibroblasts.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e20536-e20536
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e20536-e20536
    Abstract: e20536 Background: Accumulating evidence reveal complicated crosstalk amongst cancer-related fibroblasts (CAFs) and immune cells in tumor microenvironment (TME). However, interaction within CAFs and immune cells, and their relationship with clinical outcomes remain largely undetermined. Methods: Interaction between CAFs and immune cells was evaluated by the CD8+ T cells/CAFs ratio (CFR), denoting great difference within single-sample gene-set enrichment analysis (ssGSEA) scores. Association of CFR with survival was examined in TCGA/GEO lung cancer and TCGA pan-cancer cohorts. Correlation between CFR and immunotherapeutic efficacy was determined in five independent cohorts including melanoma, lung cancer and urothelial cancer. orrelations between CFR and objective response rates (ORR) reported in the literature following pembrolizumab monotherapy were calculated in 20 TCGA cancer cohorts. To translate the in silico findings into clinical use, immunohistochemically-detected CD8/α-SMA ratio was used as prognostic and immuno-therapeutically predictive biomarker in two lung cancer cohorts. Furthermore, correlation within CFR, TMB, PD-L1, and molecular/genomic characteristics of CFR subgroups was also evaluated. Results: A moderately positive correlation existed between CAFs and immune cells infiltration in various cancer types. Higher immune cells/CAFs ratios indicated favorable prognosis regardless of distinct immune cells. Higher CFR, an independent risk factor and complementary factor to PD-L1 and TMB, was strongly associated with improved survival in melanoma, lung cancer and urothelial cancer immunotherapy cohorts (log-rank test, P 〈 0.05). Moreover, CFR averages across cancer types provided a higher correlation coefficient with the ORR following pembrolizumab monotherapy when compared to PD-L1 expression and TMB, r = 0.65 versus 0.36 and 0.31, respectively. Finally, in the clinical setting, CD8/α-SMA ratio was validated as an independent prognostic and predictive biomarker of immunotherapy efficacy in non-small cell lung cancer (HR, 0.21, 95% CI, 0.12-0.37, P 〈 0.001; HR, 0.37; 95% CI, 0.19-0.75; P 〈 0.001). Low CFR was associated with upregulation of hypoxia, TGF-β signaling, epithelial-mesenchymal transition and angiogenesis. Conclusions: CFR was a promising biomarker in the prediction of immunotherapeutic efficacy across various malignancies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e20536
    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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    Online Resource
    Interaction between CAF and CD8+ T cells in non-small cell lung cancer affects prognosis and efficacy of immunotherapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9536-9536
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9536-9536
    Abstract: 9536 Background: Cancer-related fibroblasts (CAFs) are important components of the tumor microenvironment (TME) and play a key role in tumor progression. There is growing evidence that CAF levels in tumors are highly correlated with treatment response and prognosis. However, the effect of CAFs on immunotherapy response remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The SVA package ComBat function was used to remove batch effects. The ssGSEA algorithm was used to assess the level of cell infiltration in each sample. OS (overall survival) and DFS (disease free survival) were analyzed using the Kaplan–Meier method. GO enrichment analysis was used to assess the biological processes of subgroup differential genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. The prognosis according to CD8+ T cells was not strong, but CD8+ T cells / fibroblasts (CFR) were significant protective prognostic factors [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.56–0.78; P 〈 0.001]. Multivariate analysis revealed that the CFR was an independent prognostic biomarker. The TCGA pan-cancer cohort confirmed the widespread presence of CMIRP in cancer. We further defined the CFR high and CFR low subgroups. CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β, epithelial-mesenchymal transition, and angiogenesis pathways. Finally, we combined TIDE and submap to speculate that CFR is a potential prognostic marker of immunotherapy for NSCLC. Conclusions: We proposed the term “CMIRP” to shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9536
    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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  • 5
    Online Resource
    Online Resource
    Intrapulmonic Cavity or Necrosis on Baseline CT Scan Serves as an Efficacy Predictor of Anti-PD-(L)1 Inhibitor in Advanced Lung Squamous Cell Carcinoma
    Informa UK Limited ; 2021
    In:  Cancer Management and Research Vol. Volume 13 ( 2021-07), p. 5931-5939
    Details
    In: Cancer Management and Research, Informa UK Limited, Vol. Volume 13 ( 2021-07), p. 5931-5939
    Type of Medium: Online Resource
    ISSN: 1179-1322
    URL: Article
    DOI: 10.2147/CMAR.S319480
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2508013-1
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  • 6
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    Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer
    Elsevier BV ; 2023
    In:  European Journal of Cancer Vol. 188 ( 2023-07), p. 81-89
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 188 ( 2023-07), p. 81-89
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2023.04.009
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 7
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    Tumor response heterogeneity, a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21146-e21146
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21146-e21146
    Abstract: e21146 Background: Tumor response heterogeneity (TRH) to treatment is common across different foci within the same cancer patient. However, the effect of heterogeneity on clinical outcome remains unclear. Here, we developed a quantitative assessment of TRH and explored the correlation of TRH with the clinical outcome. Methods: In this retrospective study, the main eligibility criteria were: patients with advanced lung adenocarcinoma, 3-10 measured foci, ECOG 0-1 and received first-line chemotherapy or targeted therapy. Percent change of the longest diameter in each measurable lesion were quantified with RECIST1.1. TRH score was the absolute value of the dispersion coefficient of the percentage value of each target lesion. Patients were randomly divided into a learning and a validation set. The optimal cutoff value of TRH score was identified according to progression free survival information in the discovery cohort. Then, we confirmed and analyzed the correlation of TRH scores with clinicopathological features in the validation cohort. The Next-generation sequencing was performed for mechanism exploration. Results: Between January 2016 and December 2020, 174 patients were enrolled, 101 (58.0%) treated with platinum-based doublet chemotherapy and 73 (42.0%) with targeted therapy. Median follow-up was 19.8 months (95% CI, 14.5 to 25.0). In the discovery cohort (n = 85), 0.46 was defined as the optimal cut-off point of TRH score. Patients with high TRH score had poor PFS (median PFS 4.5 months vs. 15.8 months, HR 4.43; 95% CI 2.14 to 9.16; P 〈 0.001) compared to those with low TRH score. In validation cohort (n = 89), high TRH score was confirmed to be associated with significantly shorter PFS (median PFS 5.1 months vs. 12.9 months, HR 2.69; 95% CI 1.59 to 4.55; P 〈 0.001). The median value of TRH score followed the order of PD, SD and PR ( P 〈 0.001). Patients with high TRH score had poor ORR (30.0% vs. 68.0%; Fisher's exact test, P 〈 0.001) compared with those with low TRH score. In all population, high TRH score was further confirmed as an independent biomarker for PFS by univariate and multivariate analysis. Moreover, TRH score were able to further distinguish the outcomes in PR and SD subgroup. In PR, high TRH score was associated with significantly shorter PFS in PR subgroup (HR 2.79; 95% CI 1.24 to 6.29; P 〈 0.001) and SD subgroup (HR 2.55; 95% CI 1.44 to 4.49; P = 0.002), respectively. Compared with low TRH score, high TRH score was associated with higher tumor mutation burden and high frequency variation of cell cycle signal pathway. Conclusions: TRH score, a novel parameter for evaluating tumor response heterogeneity, was a powerful independent predictor of outcome in advanced lung adenocarcinoma. The TRHscore further stratifies patients with the same RECIST assessment results and is a useful addition to the RECIST assessment system. Further prospective studies are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e21146
    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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  • 8
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    Tumour response heterogeneity as a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma: a retrospective analysis
    Elsevier BV ; 2022
    In:  The Lancet Oncology Vol. 23 ( 2022-07), p. S13-
    Details
    In: The Lancet Oncology, Elsevier BV, Vol. 23 ( 2022-07), p. S13-
    Type of Medium: Online Resource
    ISSN: 1470-2045
    URL: Article
    DOI: 10.1016/S1470-2045(22)00412-0
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2049730-1
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  • 9
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    Effect of intrathecal pemetrexed on survival in patients with lung adenocarcinoma with leptomeningeal metastasis: A propensity score matching analysis.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e21048-e21048
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21048-e21048
    Abstract: e21048 Background: The effect of intrathecal chemotherapy (ITC) on the survival of leptomeningeal metastasis (LM) from lung adenocarcinoma (LUAC) has not yet been clearly defined. Methods: LUAC patients with cytologically or radiographically proven LM and receiving systemic pharmacotherapy after LM diagnosed were collected at the Fujian Cancer Hospital from July 2018 to March 2022. Patients were divided into intrathecal pemetrexed (IP) or non-IP groups and then propensity matched 1:1 into two groups. Among the matched cohort, the log-rank tests and multivariable Cox proportional hazards regression models were performed to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results: A total of 165 patients with LM were included; 83 were in the IP group and 82 were in the non-IP group. After PSM, 114 patients were identified in the matched cohort. There were no statistically significant differences between IP and non-IP groups in median overall survival (13.2 months versus 10.1 months; hazard ratio 0.84, 95% CI: 0.53 - 1.33; p = 0.49). In the multivariable Cox regression analysis, only ECOG PS was confirmed as an independent prognostic factor for overall survival in the matched cohort (hazard ratio 1.83, 95% CI: 1.04 - 3.23; p = 0.037). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (14.3 months versus 1.6 months; p = 0.002), but not in patients with good ECOG PS (12.8 months versus 12.6 months; p = 0.884). Conclusions: Our results indicated that IP may not bring survival benefit to all LUAC patients with LM, but may improve survival in patients with poor ECOG PS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e21048
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Tumor necrosis or cavity on baseline CT scan as a negative predictive biomarker for immune checkpoint inhibitors in advanced lung squamous cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e20556-e20556
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e20556-e20556
    Abstract: e20556 Background: Current predictive biomarker for immune checkpoint inhibitors (ICIs) does not distinct according to histologic subtype. We hypothesize that necrosis or cavity on baseline CT scan in lung squamous cell carcinoma (LSCC) is predictive of treatment for ICIs. Methods: This was a multicenter retrospective analysis of patients with advanced LSCC. All eligible patients must had received either first-line chemotherapy only (chemotherapy group), or ICIs as monotherapy or combined with chemotherapy (ICIs group). Radiotherapy to thorax was not allowed. Baseline contrast-enhanced CT were reviewed by independent radiologist in each center. Radiologic finding was correlated with outcomes. Results: Total of 538 patients were eligible with 270 patients in the chemotherapy group and 268 patients in ICIs group. Baseline characteristics were well balanced. Tumor necrosis or cavity was identified in 111 (41.1%) in chemotherapy group and 99 (36.9%) in ICIs group. In chemotherapy group, there was no difference in PFS between patients with or without necrosis or cavity (5.33 vs 4.97 months, Hazard Ratio (HR) 1.05, 95% confidence interval (CI), 0.81-1.36, p= 0.726). In contrast, there was significant difference in PFS in ICIs group favoring patients without tumor necrosis or cavity (8.7 vs 6.5 months, HR 0.67, 95% CI 0.42–0.63, p 〈 0.001). Multivariate Cox analysis confirmed necrosis or cavity as an independent unfavorable predictive factor for PFS (HR 0.68; 95% CI, 0.51-0.9; p= 0.007). Conclusions: Tumor necrosis or cavity on baseline chest CT scan is a promising predictive biomarker for ICIs in LSCC, and this observation warrant further investigation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e20556
    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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