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  • American Society of Clinical Oncology (ASCO)  (6)
  • Papadimitrakopoulou, Vassiliki  (6)
  • 2015-2019  (6)
Materialart
Verlag/Herausgeber
  • American Society of Clinical Oncology (ASCO)  (6)
Person/Organisation
Sprache
Erscheinungszeitraum
  • 2015-2019  (6)
Jahr
Fachgebiete(RVK)
  • 1
    Online-Ressource
    Online-Ressource
    Genomic and transcriptomic landscape of oral pre-cancers (OPCs) and risk of oral cancer (OC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 6009-6009
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 6009-6009
    Kurzfassung: 6009 Background: The molecular landscape of OPCs and its association with neoplastic progression is largely unknown. We report the results of high throughput DNA/RNA profiling of OPCs from pts in the Erlotinib Prevention of Oral Cancer trial (EPOC), with long-term prospective follow-up. Methods: We performed next generation sequencing of 201 cancer genes (MD Anderson T200 platform) in 170 OPCs from EPOC, and RNA profiling using HTG EdgeSeq Oncology Biomarker Panel containing 2,560 transcripts in a subset of 141 OPCs. 73 pts developed invasive OC during a median follow up of 7.3 years, from whom 23 paired OCs were profiled to characterize the evolutionary trajectory from OPCs to OCs. OPC molecular features were correlated with OC-free survival. Results were compared with TCGA invasive OC DNA/RNA profiles and an independent set of 86 OPCs with RNA data. Results: Similar to TCGA, C 〉 T was the predominant substitution. The top mutated genes in OPCs were TP53 (29%), CDKN2A (15%), NOTCH1 (11%) and PIK3CA (7%), which were also frequently mutated (albeit at higher rates) in OCs from EPOC or TCGA. There was a progressive increase of tumor mutation burden (TMB, P 〈 0.05) and frequency of high-risk TP53 mutations (P = 0.02) from hyperplasia, to dysplasia, to invasive OCs (P 〈 0.05). Median TMB was higher in OPCs from pts who developed OC (2.45 mut/Mb) vs those who did not (1.22 mut/Mb) (P 〈 0.01). Pts with TP53 mutated OPCs had shorter OC-free survival compared to TP53 wild-type (HR 1.81, 95% CI 1.13-2.90, P = 0.01). A prognostic score was derived from a Cox regression model which identified 12 mRNA transcripts associated with OC risk (HR 4.72, 95% CI 2.51-8.86, P 〈 0.01), and which was validated in the independent set of 86 OPCs (HR 2.68, P 〈 0.01). This score was also associated with shorter overall survival when applied to invasive OCs from TCGA pts (HR 2.72, P 〈 0.01). Conclusions: This is the first large-scale cohort of OPC pts with long-term, prospective follow up and comprehensive RNA/DNA profiling. We demonstrated an association between TMB, TP53 mutations, a 12-gene RNA signature score in OPCs, and OC risk. This study may provide a framework for similar efforts of pre-cancer molecular profiling in the oral cavity and other sites, such as the PreCancer Atlas of the NCI.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.6009
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Interplay between immune infiltration and tumor progression and survival in non-small cell lung cancer: An analysis of institutional and public data.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 8538-8538
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 8538-8538
    Kurzfassung: 8538 Background: In many types of cancer, infiltration of tumor by immune cells, as a reflection of the immune response against the tumor, is thought to play a critical role in clinical outcome. Tumors, however, tend to evade the immune response as they progress. In this study, we characterize the interplay between immune infiltration and tumor progression and survival in non-small cell lung cancer (NSCLC). Methods: We performed histologic immune profiling and microarray expression analysis on primary tumor specimens from 275 NSCLC patients (PR: PROSPECT trial) as well as RNA-Seq expression analysis on biopsy specimens from 50 patients with advanced NSCLC (B2: BATTLE-2 trial). RNA-Seq data from the TCGA lung cancer project was also analyzed. Immune Infiltration Score (IIS) was computed from the expression data using the Estimate package in R. Immune Suppression Score (ISS) was defined as the difference between the mean of CD3, CD4, CD8, FOXP3, and PD1 counts in the periphery and core of the tumor. Results: Tumor IIS is correlated (all p 〈 0.0005) with tumor immune infiltration as measured by inflammatory cell count on frozen tumor or several immune marker counts in tumor core. IIS is positively associated with survival (p = 0.04) independently of age (p = 0.008) and stage (p = 8e-10). IIS in the top half is associated with higher median survival vs. bottom half (10.2 vs 2.2 months, p 〈 0.0001) in B2. In TCGA lung adenocarcinoma samples, IIS is higher in stage I/II disease vs stage III/IV (p = 0.003). For all immune markers in PR samples, periphery of the tumor on average has higher counts vs tumor core (p 〈 0.0011), and this difference (suppression score) is higher in stage III/IV samples vs stage I/II for CD3, CD4, and CD8 (all p 〈 0.04) and for FOXP3 and PD1 (p 〈 0.1). ISS is negatively associated with survival (p = 0.02) independently of age (p = 0.06) and stage (p 〈 0.0001). Conclusions: As NSCLC tumors progress, immune infiltration in the periphery of the tumor increases while infiltration in the core decreases, reflecting increasing immune suppression. Tumor immune infiltration and suppression, as measured by IIS and ISS, are significant predictors of survival, independently of age and stage.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.8538
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2017
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 30 ( 2016-10-20), p. 3638-3647
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 30 ( 2016-10-20), p. 3638-3647
    Kurzfassung: By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non–small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients and Methods Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling–targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Results Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib (n = 61). In all, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm 1, 32%; arm 2, 50%; arm 3, 53%; and arm 4, 46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P = .04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P = .03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P = .02). Conclusion Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2015.66.0084
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2016
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Immune profiling of oral pre-malignant lesions (OPLs): An Erlotinib Prevention of Oral Cancer (EPOC) study biobank analysis.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 1545-1545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1545-1545
    Kurzfassung: 1545 Background: We previously demonstrated that high-risk loss of heterozygosity (LOH) profiles (i.e., 3p14/9p21 LOH) and EGFR gene copy number gain (CNG) in OPLs were associated with inferior oral cancer-free survival (OCFS) in patients enrolled in the randomized EPOC trial. Herein, we performed comprehensive immune profiling of OPLs and correlated the findings with molecular features and outcomes, using the prospectively collected and clinically annotated EPOC biobank. Methods: We evaluated OPL specimens by multiplex immunofluorescence using the Opal 7-color fIHC Kit and the Vectra multispectral microscope / inForm Cell Analysis software. Markers included AE1/AE3 pancytokeratins, PD-L1 (clone E1L3N), CD3, CD8, and CD68. Wilcoxon rank-sum and Fisher’s exact tests were used to assess the associations between binary markers and continuous and categorical variables, respectively. Cox model was used to investigate associations of markers with OCFS. Results: The cohort included 188 OPL patients with hyperkeratosis/hyperplasia (18%), mild/moderate (44%), or severe dysplasia (5%); 65% had high-risk LOH profiles. The 5-year OCFS was 72.3% (median follow-up of 50 months). PD-L1 expression in 〉 1% of epithelial cells occurred in 28% of OPLs. Intraepithelial CD3+, CD3+/CD8+, CD68+, and CD68+/PD-L1+ cells were detected in 100%, 88%, 88%, and 54% of the samples, respectively. OPLs with high-risk LOH profiles had increased epithelial PD-L1 expression (P = 0.007), intraepithelial CD68+/PD-L1+ cells (P = 0.002), and a trend towards more CD3+/CD8+ cells in the stroma (P = 0.06) but not in the epithelium (P = 0.97), compared with low-risk LOH OPLs. Increased epithelial PD-L1 expression was associated with inferior OCFS on univariate (P = 0.023), and multivariate analysis including LOH status and EGFR CNG as co-variates (P = 0.018). Conclusions: High-risk OPLs defined by LOH profiles had increased PD-L1 expression in epithelial cells and intraepithelial macrophages, as well as stromal CD3+/CD8+ immune infiltration. Higher PD-L1 expression was associated with increased oral cancer risk. The findings may support evaluation of (PD-1-targeted) immunoprevention strategies in high-risk OPLs.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.1545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2017
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    Spatial and temporal heterogeneity of PD-L1 and its impact on benefit from immune checkpoint blockade in non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 9017-9017
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9017-9017
    Kurzfassung: 9017 Background: Temporal and spatial heterogeneity of PD-L1 has been reported. However, its impact on clinical benefit from immune checkpoint inhibitor (ICI) has not been clearly defined. Methods: We queried the MD Anderson Lung Cancer GEMINI database and compared PD-L1 expression (tumor proportion score by immunohistochemistry using FDA-approved antibodies) in NSCLC specimens from different organs at different time points. We assessed the predictive value of PD-L1 for benefit from ICIs in patients with metastatic NSCLC. Results: In 1398 NSCLC patients, PD-L1 level was significantly associated with biopsy sites (p = 0.007). Adrenal and liver metastases had the highest PD-L1 level and positive rate (by 1% or 50% cutoff) while PD-L1 was the lowest in bone and brain biopsies. In addition, PD-L1 was significantly higher in fresh tissues (PD-L1 staining at 〈 90 days after biopsy) than archival tissues (PD-L1 staining at 〉 90 days after biopsy), in squamous cell carcinoma than adenocarcinoma, in EGFR wild-type ( WT ) than EGFR mutant, in MET amplified than MET WT , and in STK11 WT than mutant (p 〈 0.01). Among 112 patients with longitudinal specimens tested, 55 (49%) had major changes with PD-L1 at different time points falling into different clinically relevant categories ( 〈 1%, 1-49%, 〉 50%). ICIs were associated with significant decrease in PD-L1 level compared to treatment-naïve counterparts (p = 0.019). Furthermore, 398 patients with EGFR/ALK WT metastatic NSCLC who received ICIs were divided into three groups based on biopsy sites including lung (n = 252); lymph node (LN, n = 85) and distant metastasis (n = 61). Higher PD-L1 level in biopsies from lung or distant metastasis was associated with significantly higher response rate, disease control rate and significantly longer progression free survival and overall survival using either 1% or 50% cutoff. However, the PD-L1 expression from LN biopsies was not associated with either response or survival in this cohort of patients. These findings remained constant in multivariate analyses. Conclusions: PD-L1 expression varies substantially across different anatomic sites and changes during clinical courses. PD-L1 in LN biopsies may not be reliable to predict clinical benefit for ICIs in NSCLC. Repeat biopsy and PD-L1 staining should be considered if only remote tissues, particularly, LN biopsies are available.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.9017
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 6
    Online-Ressource
    Online-Ressource
    Local consolidation therapy (LCT) after first line tyrosine kinase inhibitor (TKI) for patients with EGFR mutant metastatic non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e20654-e20654
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e20654-e20654
    Kurzfassung: e20654 Background: Although most NSCLC patients with sensitizing EGFR mutations (L858R, Exon 19 deletion) have an impressive initial response, the vast majority develop acquired resistance after 9-14 months of EGFR TKI therapy. Clearly, more effective strategies to prevent resistance emergence are needed. We recently reported a randomized phase 2 trial that showed that LCT with surgery or radiation, for molecularly unselected patients with oligometastatic NSCLC who did not progress after initial systemic therapy, improved progression-free survival (PFS) compared to maintenance therapy alone (Gomez, et al., 2016). Herein, we aim to determine the outcomes of LCT after first line TKI in patients with metastatic EGFR mutant NSCLC. Methods: This is a post-hoc analysis of our recently published phase 2 clinical trial and a retrospective review of MD Anderson Cancer Center GEMINI database. Eligible patients had metastatic EGFR mutant NSCLC, had first line TKI without progression followed by LCT with surgery or radiation. Results:In GEMINI database, 129 EGFR (L858R/Exon 19 deletion) mutant NSCLC patients were treated with first line TKI (erlotinib, gefitinib or afatinib) and 12 were treated with TKI followed by LCT (3 treated within our published clinical trial and 9 at the discretion of their physician). Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤3 metastases) and 4 patients had 〉 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for one patient. Patients treated with TKI followed by LCT had a significantly longer PFS (36 months) compared to patients treated with first line TKI alone (PFS 14 months, p = 0.0024, log-rank). Conclusions:Our retrospective data suggests that first line TKI plus LCT is a promising therapeutic strategy that led to a significant outcome improvement for patients with EGFR mutant NSCLC. A multicenter phase 2 clinical trial comparing TKI plus LCT to TKI alone is planned.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e20654
    RVK:
    XA 52760
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2017
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
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