Virtual Library

Start Your Search

R. Bueno



Author of

  • +

    OA19 - Translational Research in Early Stage NSCLC (ID 402)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Early Stage NSCLC
    • Presentations: 1
    • Now Available
    • +

      OA19.01 - A Standardized and Validation of Prognostic Gene Expression Signatures for Squamous Cell Lung Carcinoma by the SPECS Lung Consortium (Now Available) (ID 4329)

      R. Bueno

      • Abstract
      • Presentation
      • Slides

      Background:
      High-throughput gene expression profiling led to proposal of multiple expression-based prognostic signatures for squamous cell lung carcinoma (SCC), but none has been validated. A multi-institutional squamous lung cancer consortium of investigators is developing prognostic signatures through the US NCI Lung SPECS (Strategic Partnership for Evaluation of Cancer Signatures) program. Six institutions contributed tumor specimens and published/unpublished expression-based prognostic signatures for validation using standardized sample cohorts (a primary validation cohort comprising institutional cases, and additional validation cohorts from two prospective cooperative group studies) and quality controlled assessment in independent laboratory and statistical cores. Here, we report the results of the primary validation.

      Methods:
      Cases of primary SCC (by central pathology review) meeting clinical (Stage I-II; surgical treatment only; 3-year followup) and specimen quality criteria (Tumor cellularity >= 50%; necrosis <= 20%) were submitted. Clinical, pathological and outcome data were uploaded to a central database. Frozen tumor samples underwent centralized mRNA extraction (Qiagen Symphony), quality control (RIN >= 6.0) and microarray profiling (Affymetrix U133) in core labs. An independent statistical core assessed validation of 7 pre-existing mRNA signatures and generated new models using MCP clustering.

      Results:
      Among 250 cases meeting entry criteria, median age was 70 (43-92), 161 (65%) were male, and most were former (70%) or current (28%) smokers. Surgery was pneumonectomy: 5%; bilobectomy: 2%; lobectomy: 74%; sublobar: 18%. Pathologic staging was T1: 49%; T2: 50%; T3: 1%; N0: 88%; N1: 12%, and grade was G1: 4%; G2: 50%; G3: 44%. At followup, 148 (59%) were deceased. Three mRNA signatures demonstrated significant univariable association with OS and added independent prognostic value (see Figure) to a multivariable model accounting for age, sex and stage (c-index = 0.641).

      Conclusion:
      The validated signatures, along with two novel signatures generated from the current dataset, are currently undergoing further validation studies using two prospective co-operative group cohorts. Figure 1



      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.05 - Poster Session with Presenters Present (ID 457)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 2
    • +

      P1.05-001 - Creation and Early Validation of Prognostic miRNA Signatures for Squamous Cell Lung Carcinoma by the SPECS Lung Consortium (ID 6088)

      R. Bueno

      • Abstract

      Background:
      Despite overall favorable prognosis for operable early stage non-small cell lung cancer, predicting outcome for individual patients has remained challenging. Small retrospective studies have reported potential non-coding micro(mi)RNAs that might have prognostic significance; however, these studies lacked statistical power and validation. To refine these initial findings to clinical application, the investigators have undertaken a collaborative, structured evaluation of multiple signatures putatively prognostic for lung squamous cell carcinoma (SCC) under a NCI/SPECS (Strategic Partnerships fo Evaluating Cancer Signatures) award. The study design specifies a primary validation cohort comprising institutional cases, and additional validation cohorts of Cooperative Group cases, all profiled via a common pipeline.

      Methods:
      Completely resected SCC (confirmed by central pathology review) meeting clinical (Stage I-II; complete 3-year follow-up) and specimen quality criteria (Tumor cellularity ≥ 50%;necrosis ≤ 20%) were submitted by 6 institutions. Clinical, pathological and outcome data were uploaded to a central database. Lysates from 5 um sections of FFPE SSC tumor samples were run on the HTG EdgeSeq Processor (HTG Molecular Diagnostics, Tucson, AZ) using the miRNA whole transcriptome assay in which an excess of nuclease protection probes (NPPs) complimentary to each miRNA hybridize to their target. S1 nuclease then removes un-hybridized probes and RNA leaving behind only NPPs hybridized to their targets in a 1-to-1 ratio. Samples were individually barcoded (using a 16-cycle PCR reaction to add adapters and molecular barcodes), individually purified using AMPure XP beads (Beckman Coulter, Brea, CA) and quantitated using a KAPA Library Quantification kit (KAPA Biosystems, Wilmington, MA). Libraries were sequenced on the Illumina HiSeq platform (Illumina, San Diego, CA) for quantification. Standardization and normalization was provided to the project statistical core for validation of two pre-existing signatures and generation of new models (MCP clustering).

      Results:
      Among 224 cases with miRNA data, median age was 70 (43-92), 143 (64%) male, with 67% former (67%) and current (26%) smokers. All patients were completely resected stage I or II. . At follow-up, 59 (26%) had documented recurrence and 129 (58%) were deceased. To date, we have been unable to validate the previous models, but have created a novel signature of three miRNAs (see Figure) that is being validated in the second phase of the project using an independent, blinded multi-institutional cohort.

      Conclusion:
      The Squamous Lung Cancer SPECS Consortium has established well-annotated and quality-controlled resources for validation of prognostic miRNA signatures. A new candidate 3-miRNA signature has been identified for further development as a clinically useful biomarker.

    • +

      P1.05-027 - Novel Prognostic Gene Expression Signatures for Squamous Cell Lung Carcinoma: A Study by the SPECS Lung Consortium (ID 4490)

      R. Bueno

      • Abstract

      Background:
      A multi-institutional squamous lung cancer consortium of investigators is developing prognostic signatures through the US NCI Lung SPECS (Strategic Partnership for Evaluation of Cancer Signatures) program. Six institutions contributed tumor specimens and published/unpublished expression-based prognostic signatures for validation using standardized sample cohorts (a primary validation cohort comprising institutional cases, and additional validation cohorts from two prospective cooperative group studies) and quality controlled assessment in independent laboratory and statistical cores. Here, we report on de novo prognostic signatures derived using the pooled institutional dataset.

      Methods:
      Highly quality-controlled cases of primary SCC from the pooled cohort (N=249) were analyzed to generate de novo prognostic signatures from among the 147 genes comprising pre-existing signatures, and from among all profiled genes. Minimax Concave Penalty (MCP) selection and Ward’s minimum variance clustering yielded survival analyses with 2 clusters that were evaluated using Cox regression and bootstrap cross validation (bCV; 500 iterations).

      Results:
      Two significantly prognostic models were generated (see Figure): Pooled Model A (PMA) was the optimal 2-cluster model using probesets representing 6 genes selected from components of pre-existing signatures: CASP8, MDM2, SEL1L3, RILPL1, LRR1, COPZ2. Pooled Model B (PMB) was the optimal 2-cluster model using probesets representing 6 genes selected from among all those profiled: SSX1, DIAPH3, LOC619427, CASP8, EIF2S1, HSPA13. PMA and PMB each remained independently prognostic in multivariable analyses incorporating an a priori baseline model (age, sex, stage; c-index = 0.641).

      Conclusion:
      Two de novo prognostic signatures were derived using a pooled multi-institutional cohort of SCC assembled for validation of pre-existing signatures. PMA and PMB were each found to be independently prognostic, accounting for established clinical predictors. Both now move forward, along with validated pre-existing signatures, to additional assessment of discrimination, calibration and clinical usefulness using additional independent prospective US co-operative group cohorts of cases. Figure 1



  • +

    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      P2.03a-050 - Elevated Expression of CCP Genes is Associated with Absolute Chemotherapy Benefit in Early Stage Lung Adenocarcinoma Patients (ID 4204)

      R. Bueno

      • Abstract

      Background:
      A validated RNA molecular expression signature based on cell cycle progression (CCP) genes [CCP score] and a molecular Prognostic Score [(mPS) combination of CCP score and pathological stage] are significant prognostic markers of cancer-specific mortality in patients with early stage lung adenocarcinoma. Additionally, preliminary data suggest a significant association between CCP score and absolute benefit with platinum-based adjuvant chemotherapy in early stage lung adenocarcinoma patients. The aim of this study is to further demonstrate the effectiveness of CCP score and mPS in predicting platinum-based chemotherapy benefit in a large, multi-institutional cohort of stage IB and IIA lung adenocarcinoma patients who underwent definitive surgical resection with and without adjuvant chemotherapy.

      Methods:
      Formalin-fixed paraffin-embedded surgical tumor samples from approximately 1000 patients diagnosed with stage IB and II adenocarcinoma who underwent definitive surgical treatment with adjuvant platinum-based chemotherapy (n = 400) and without (n = 600) will be analyzed for 31 proliferation genes by quantitative RT-PCR. The associations of CCP score and mPS with absolute benefit from platinum-based chemotherapy will be separately examined using Cox proportional hazards regression with an outcome of 5-year lung cancer survival.

      Results:
      To date, lung tumor samples have been accrued from 388 patients treated with a platinum-based chemotherapy and 590 untreated patients. We hypothesized that the absolute treatment benefit will increase as CCP score or mPS increases. Results will be shown for continuous CCP score and mPS as well as pre-defined binary CCP score and binary mPS.

      Conclusion:
      This study will determine the abilities of CCP score and mPS as predictive tools for absolute chemotherapy benefit and 5-year lung cancer survival in patients with early stage lung adenocarcinoma thereby furthering the clinical utility for these signatures to identify patients with high risk disease who should receive adjuvant chemotherapy.

  • +

    SC06 - Novel Therapies in Malignant Pleural Mesothelioma and Thymic Malignancies (ID 330)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
    • +

      SC06.01 - Comprehensive Genomic Analysis of Malignant Pleural Mesothelioma (Now Available) (ID 6621)

      R. Bueno

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    WS04 - Mesothelioma Workshop (Ticketed Session) (ID 416)

    • Event: WCLC 2016
    • Type: Workshop
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 12/04/2016, 08:00 AM - 11:00 AM, Stolz 2
    • +

      WS04.01 - Debate - Extrapleural Pneumonectomies Should be Performed for Pleural Mesothelioma (Now Available) (ID 6981)

      R. Bueno

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.