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  • 1
    Online Resource
    Online Resource
    Data_Sheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-7)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-7)
    Abstract: Purpose: Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Materials and Methods: Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial. Clinical factors, including age, gender, ethnicity, smoking status, stage group, histology, Karnofsky Performance Status, equivalent dose at 2 Gy fractions (EQD2), and the use of chemotherapy, were first tested under the univariate Cox's proportional hazards model. All significant clinical predictors were combined as a group of predictors named “Clinical.” The significant SNPs under the Cox proportional hazards model were combined as a group of predictors named “SNP.” The predictive powers of models using Clinical and Clinical + SNP were compared with the cross-validation concordance index (C-index) of random forest models. Results: Age, gender, stage group, smoking, histology, and EQD2 were identified as significant clinical predictors: Clinical. Among 14 SNPs, BMP2:rs235756 (HR = 0.63; 95% CI:0.42–0.93; p = 0.022), SMAD9:rs7333607 (HR = 2.79; 95% CI 1.22–6.41; p = 0.015), SMAD3:rs12102171 (HR = 0.68; 95% CI: 0.46–1.00; p = 0.050), and SMAD4: rs12456284 (HR = 0.63; 95% CI: 0.43–0.92; p = 0.016) were identified as powerful predictors of SNP. After adding SNP, the C-index of the model increased from 84.1 to 87.6% at 24 months and from 79.4 to 84.4% at 36 months. Conclusion: Genetic variations in the TGF-β1 pathway have the potential to improve the prediction accuracy for OS in patients with NSCLC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.599719
    DOI: 10.3389/fonc.2021.599719.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
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    DataSheet_3.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-13)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-13)
    Abstract: It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5–19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan–Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups ( P & lt; 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.659538
    DOI: 10.3389/fonc.2021.659538.s001
    DOI: 10.3389/fonc.2021.659538.s002
    DOI: 10.3389/fonc.2021.659538.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Tumor control probability modeling for stereotactic body radiation therapy of early-stage lung cancer using multiple bio-physical models
    Elsevier BV ; 2017
    In:  Radiotherapy and Oncology Vol. 122, No. 2 ( 2017-02), p. 286-294
    Details
    In: Radiotherapy and Oncology, Elsevier BV, Vol. 122, No. 2 ( 2017-02), p. 286-294
    Type of Medium: Online Resource
    ISSN: 0167-8140
    URL: Article
    DOI: 10.1016/j.radonc.2016.11.006
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1500707-8
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  • 4
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    A Classifier for Improving Early Lung Cancer Diagnosis Incorporating Artificial Intelligence and Liquid Biopsy
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-2)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-2)
    Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans’ Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery. Clinical Trial Registration Number ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370 .
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.853801
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
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    Online Resource
    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
    Impact Journals, LLC ; 2017
    In:  Oncotarget Vol. 8, No. 67 ( 2017-12-19), p. 111309-111317
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 67 ( 2017-12-19), p. 111309-111317
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v8i67
    DOI: 10.18632/oncotarget.22785
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 6
    Online Resource
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    Risk factors for symptomatic radiation pneumonitis after stereotactic body radiation therapy (SBRT) in patients with non-small cell lung cancer
    Elsevier BV ; 2021
    In:  Radiotherapy and Oncology Vol. 156 ( 2021-03), p. 231-238
    Details
    In: Radiotherapy and Oncology, Elsevier BV, Vol. 156 ( 2021-03), p. 231-238
    Type of Medium: Online Resource
    ISSN: 0167-8140
    URL: Article
    DOI: 10.1016/j.radonc.2020.10.015
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1500707-8
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  • 7
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    Single-cell and spatial transcriptomics to analyze radiation therapy-induced tumor microenvironment reshaping in HPV- cervical cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e17528-e17528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17528-e17528
    Abstract: e17528 Background: Radiotherapy (RT) is the most widely used conventional first-line treatment in cervical cancer (CC). However, the treatment response rate was only 10%-40%, and even lower in HPV- negative CC (HPV- CC). So far, previous knowledge of radiotherapy on tumor and tumor immune microenvironment (TME) remodeling is still insufficient. In this study, we aimed to comprehensively understand the dynamic change of tumor and TME of HPV- CC at the single-cell level. Methods: The single-cell and spatial transcriptome sequencing (STRNAseq) were used to analyze the TME of newly diagnosed HPV- CC tumor tissues, including pre-radiotherapy and 3 weeks after radiotherapy. Tissue samples were split into two parts, the freshly lysed single-cell suspension for 10X single-cell sequencing, and another part that was immediately processed into frozen and embedded for STRNAseq. Cell clustering, annotation and Single-cell sequencing and spatial transcriptome integration were analyzed by Seurat 4.0. The CNV of epithelial cells (ECs) was estimated by InferCNV. Results: A total of 14000 cells were obtained from paired HPV-CC patient samples (pre-RT and 3 weeks after RT) and clustered into 21 cell subsets. Six EC subsets, four fibroblast subsets, three macrophage subsets, two T cell subsets, two B cell subsets, one mast cell cluster, and an endothelial cell cluster were discovered. CNV analysis revealed that all ECs were malignantly proliferating tumor cells. Tumor cells accounted for 90% of the total tumor tissue prior to RT, but only less than 1% of tumor cells remain after RT. Fibroblasts and myeloid cells, which make up 60% of tumor tissue, increase significantly after radiotherapy, with myeloid cells accounting for nearly 50% of the total. Furthermore, we found a population of cells in the Post-RT sample that were both highly expressed CD14 and CD68 (macrophage biomarkers) and highly expressed COL1A2 (fibroblast biomarker). Differential analysis showed that this group of cells was down-regulated in Focal adhesion and ECM-receptor interaction pathways, while up-regulated in cytokine secretion and phagosome pathways, indicating that this group of cells might remodel the intercellular matrix and interacted with other cells to regulate the immune microenvironment. Integrating single-cell and spatial transcriptome data, fibroblasts and myeloid cells formed a tight co-distribution in tissues after radiotherapy, implying that their interaction is critical for the formation of the tumor immune microenvironment. Conclusions: This study comprehensively analyzed the dynamic change of tumor and TME of HPV- CC treated with RT at the single-cell transcriptional scale. After radiotherapy, fibroblasts and myeloid cells significantly increased and were highly heterogeneous, and the interaction between them is critical in forming a tumor ecosystem for radiotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e17528
    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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  • 8
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    Preliminary results of sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy using single tremelimumab regular interval durvalumab in locally advanced, unresectable hepatocellular carcinoma (START-FIT using STRIDE): A single-arm, phase II study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4124-4124
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4124-4124
    Abstract: 4124 Background: Sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy (IO) (START-FIT) using anti-PD-L1 has demonstrated promising efficacy in locally advanced HCC (laHCC). We aimed to evaluate START-FIT activity using anti-PD-L1 and anti-CTLA-4 IO backbone. Methods: Adult patients with laHCC not suitable for curative resections were recruited. Each with tumor at least 5cm, maximum three tumors, and child-Pugh A5-B7 liver function. Patients had single TACE, 5-SBRT 28 days after, then single Tremelimumab (300mg) and regular 4-week interval Durvalumab (1500mg) at 7 days upon SBRT completion. Primary endpoint was overall response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST); secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related (TR) adverse event (AE) [NCT04988945]. Results: During 11 Dec, 20 and 3 Oct, 22, 16 patients were enrolled with median age 66 (range (r): 51–84 years), 14 (87.5%) were male, the lesion(s) diameter median sum was 11.2 cm (r: 5.8–15cm), and 11 (68.8%) had macrovascular invasion (n=6, hepatic vein, n=4, branched portal vein, n=1 both). With median 11.3 months (r: 3.7–24.5 months) follow-up time, the best ORR was 81.3% (95% CI: 54.4–96.0%) (Complete response CR: n=7, 43.8%; partial response PR: n=6, 37.5%; static disease SD + progressive disease PD: n=3, 18.7%). The 6 and 12-month PFS rates was 86.7% (95% CI: 69.3–100%) and 58.7% (95% CI: 33.6–84.4%), while 6 and 12-month OS rates was 100% (95% CI: 91.7–100%) and 83.3% (95% CI: 62.2–100%) respectively. The 12-month OS with CR vs. PR vs. SD+PD was 100%, 75%, and 50% respectively. Four (25%) and one patient (6.3%) experienced TRAEs and immune-related AE of grade 3 or worse respectively. Conclusions: START-FIT using STRIDE is safe and effective in unresectable laHCC resulted in 43.8% CR rate and promising survival. Clinical trial information: NCT04988945 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.4124
    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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  • 9
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    An investigation on acquired mutations after TKI treatment in Chinese lung cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e21162-e21162
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e21162-e21162
    Abstract: e21162 Background: Targeted therapy has greatly extended the survival of certain molecular selected cancer patients. However, lots of them would eventually develop drug resistance and required alternative treatment. Research on the genomic changes before and after treatment allows us to understand the mechanism of drug resistance and to develop new treatment strategies. Methods: A total of 143 patients were enrolled and their specimens were sequenced with a panel of 680 cancer-related genes in this study. Briefly, tumor FFPE samples before treatment (T1) were collected and underwent deep sequencing (2000X), and blood samples after treatment (T2) were collected, cell-free DNA (cfDNA) was isolated and sequenced (20000X). Patients with positive EGFR mutations at T1 received TKIs afterwards. Results: A total of 160 mutations were identified in T1 and 206 mutations were found in T2 samples, while 90 of them were shared in both time points. EGFR mutations were found in 95 (66.4%) patients at T1 and 101 (70.6%) patients at T2. ERBB2 mutations were found in 9 (6.3%) patients at T1 and 19 (13.3%) patients at T2. Among them, one patient had ERBB2 amplification at T1, and new ERBB2 amplifications were found in 11 patients at T2. Conclusions: ERBB2 amplifications are associated with TKI treatment, and are likely to be involved with disease progression and TKI drug resistance.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e21162
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Association between genetic variations in transforming growth factor beta pathway and overall survival in patients with non-small cell lung cancer treated with definitive radiotherapy.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e17530-e17530
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17530-e17530
    Abstract: e17530 Background: The transforming growth factor beta (TGFβ) pathway, an important regulator in cellular metabolic process, has been reported for significant association with cancer prognosis. This study was to exam the association between single nucleotide polymorphisms (SNPs) of TGFβ pathway and overall survival (OS) in subjects with non-small cell lung cancer (NSCLC). Methods: Patients with stage I-III NSCLC received definitive radiotherapy with/without chemotherapy were eligible to this prospective study. The primary endpoint was OS which was calculated from radiation treatment start to death or censored. DNA samples for genotyping were extracted from buffy-coat which was collected before commencement of treatment. 19 SNPs in 10 genes (BMP1, BMP2, INHBC, SMAD1, SMAD3, SMAD4, SMAD6, SMAD7, SMAD8, TGFβ1), which was reported to have significant correlation with OS of lung cancer, were selected. MassArray System (Sequenom Company) was used for genotyping. Cox regression was performed for multivariate analysis to examine the effects of genotypes on OS using dominant and recessive genetic model. Results: 126 consecutive patients, 91% of them were Caucasian, were recruited in this study. All SNPs call rates were over 90%. Assay reproducibility was over 99% by random double-blinding duplicate or triplicate genotyping. Among clinical factors analyzed, radiation dose was only significant independent factor predicting OS (P=0.001). Genotypic association study showed that 7 SNPs (rs235756, rs11939979, rs12102171, rs6494633, rs12456284, rs12906898 and rs4803455) were significantly associated with OS, adjusted for age, gender, smoking, histology, clinical stage, tumor volume, Karnofsky Performance Status, radiotherapy dose, and chemotherapy. The strongest association was in SMAD3: rs12102171 (P=0.004, HR=2.28, 95%CI, 1.26-4.15). Conclusions: This study partly validated findings from previous studies that genetic variations in the TGFβ pathway are significant predictors of overall survival in NSCLC patients treated with definitive radiotherapy with/without chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e17530
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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