Vanderbilt-Ingram Cancer Center

The SPORE in Lung Cancer: Research

Cores

• Core A: Administrative Core
  David Carbone, M.D., Ph.D. (Director) and David Johnson, M.D. (Co-Director)
• Core B: Pathology and Tissue Resources Core
  Adriana Gonzalez, M.D. (Director).
• Core C: Clinical Resources Core
  Alan Sandler, M.D. (Director)
• Core D: Biostatistics Core
  Yu Shyr, Ph.D. (Director)

Administrative Core

The Administrative Core is responsible for managing the SPORE resources and facilitating communications between the SPORE components, other collaborators, and with other SPORES and the NCI. This is accomplished through a series of oversight committees, organized administrative and scientific meetings of SPORE investigators, institutional representatives and external reviewers.

Pathology and Tissue Resources Core

The specific aims of this proposal are:

1. To collect, process, bank, and distribute tissue removed from lung cancer patients with normal control lung as outlined in the appropriate research informed consent, and to preserve these tissues frozen, formalin-fixed and paraffin-embedded, and on cytologic preparations (cytospins or touch imprints) to support lung SPORE projects.
2. To maintain a centralized, computerized database of all specimens with basic demographic and pathologic information to permit the integration of findings by SPORE investigators through molecular assays and other laboratory studies with risk factor data and follow-up.
3. To maintain the confidentiality and integrity of the database through keyed numeric identifiers assigned by the tissue core for each specimen.
4. To provide high quality control of all well-characterized tissues in both human and murine with respect to preservation and histopathologic characterization.
5. To provide cytology expertise to lung SPORE projects.
6. To provide tissue microarray services to lung SPORE investigators.
7. To provide laser microdissection to the SPORE investigators
8. To provide expertise in developing, performing and evaluation of immunohistochemical stains and quantitation in both human and murine tissues.

The tissue core relies on support services already established at Vanderbilt University Medical Center (VUMC), including the Tissue Acquisition Shared Resource of the Vanderbilt-Ingram.

Clinical Resources Core

The role of the Clinical Trials Core is to provide expertise in the development, implementation and coordination of all translational clinical trials resultant from the other SPORE projects that will ultimately lead to a better understanding of the biology of lung cancer. This improved understanding will ultimately lead to improvements in the treatment of lung cancer. To achieve this goal, the major responsibilities of the Clinical Trials Core will be

1. Provide expertise in the development and implementation of translational clinical trials related to the other SPORE projects
2. Accrual of patients to participate in SPORE initiated trials,
3. Timely and accurate collection of data, and
4. Accessibility of data for analysis by the various SPORE researchers at Vanderbilt university as well as researchers at other Lung SPORE sites. During the first 1-2 years there will be 2 – 3 trials open for accrual.

These trials will serve to further the scientific knowledge regarding the role of 1) To identify proteomic signatures of lung tumors and serum samples predictive of response molecular targeted therapy i.e. EGFR-TKI’s and to chemotherapy., 2) To determine the efficacy of docetaxel plus a selective COX-2 inhibitor in recurrent NSCLC exhibiting “COX dependence”3) Determine the Effect of Pharmacologic Inhibitor as Single Agent in Patients with Advanced, Refractory Non-small Cell Lung Cancer. 4) To determine if SAHA inhibits HDAC activity in patients and to test candidate molecular profiles predictive of clinical response or lack of response to SAHA.

Over the five year course of the SPORE grant, trials will open and close. One of the goals of this SPORE is that the successful completion of these early pilot trials will ultimately lead on to larger scale, multi-institution trials for confirmation of our results. A second goal is that additional translational clinical trials will be designed based upon the results of the early pilot trials as well as the ongoing research of the participating SPORE investigators. The current pilot trials will thus serve as the template for further translational research in lung cancer.

Biostatistics Core

The purpose of the Biostatistics Core is to provide professional expertise in statistics for all Vanderbilt University Lung Cancer SPORE projects, investigators and participants. Functions provided by this core include development of experimental designs, data quality control, statistical analysis and interpretation of findings, and collaboration on presentation of results. To achieve these functions, the core director and core biostatisticians are constantly available to investigators, and are in regular contact with the project and core leaders.

The primary objectives of the Biostatistics Core are:

1. To provide study design and review all laboratory, animal and clinical studies including feasibility assessment, power analysis and sample size estimation.
2. To collaborate in projects data analysis, interpretation of results, and the writing of final study reports and manuscripts.
3. To work with Clinical Resources Core and Pathology and Tissue Resource Core in the development of research project database, to maintain data quality control and to ensure timely data capture.
4. To develop and evaluate statistical methods for experimental design and data analysis.

The Biostatistics Core support is required in all Lung Cancer SPORE studies. Core personnel have worked and will continue to work closely with project leaders for assuring that Core provides state-of-the-art statistical support.