[CANCER RESEARCH (SUPPL.) 52, 2766s, May 1, 1992] Diagnostic Research: Breakout Group Report1 James L. Mulshine and Melvyn S. Tockman Biomarkers and Prevention Research Branch, DCPC, National Cancer Institute, Rockville, Maryland 20850 [J. L. M.J, and Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205 ¡M.S. TJ In considering applications of biomarkers for preventive ap proaches for the control of lung cancer, a critical step is to specifically define the nature of the biomarker application. The potential uses of markers include risk assessment, exposure, early detection, intermediate end point, prognosis, or diagnosis. Each of these applications imposes different requirements with regard to formal validation. Since one of the principal objectives of the Workshop was early detection, considerable discussion focused on the unique resource requirements for this type of research. All conventional diagnostic tools detect lung cancer when métastaseshave already occurred. If one is to validate a detection tool that detects lung cancer at an earlier stage, then an archive of serially obtained specimens from high risk popu lations (including a reasonable number of specimens from sub jects who developed cancer during the period of the study) is an absolute requirement. An example of such an archive is the stored sputum serially acquired during the Johns Hopkins' participation over the last decade in the National Cancer Insti tute-sponsored lung cancer early detection trial. In addition to serially obtained sputum specimens acquired during the 8-year trial, the clinical follow-up of the study subjects allowed for unequivocal designation of who did or did not go on to develop lung cancer. The Johns Hopkins' archive was acquired as part of a trial to ask a prospective question. The workshop participants agreed that having a motivated study group setting up such an archive as part of a primary investigation was to be preferred over having a vendor develop an archive as an end in itself. A number of methodological issues were discussed including the appropriate end point for an early detection trial. The most definitive end point was the frequency of developing cancer. Cancer-free survival was a parameter that was potentially sub ject to lead-time bias. The efficiency and economy of this type of research would be improved by concentrating on very high risk populations and it was observed that Stage I resected non-small cell lung cancer patients comprised such a population. This population is also attractive for intervention trials. Studies of early detection tools generally should be evaluated separately from intervention trials to minimize complicating design issues. As more investigators recognize the unique opportunity provided by this study popu lation then special provisions will have to be made to ensure optimal conservation of this clinical trial resource. An important goal for early detection research to help define the range of potentially useful markers for early detection research is to establish which markers are expressed in the 1Report from the NCI Workshop "Investigational Strategies for Detection and Intervention in Early Lung Cancer," April 21-24, 1991, Annapolis, MD. injured bronchial epithelium that comprises the field of carci- nogenesis. A partial list would include markers of proliferation, cell surface structures, differentiation, carbohydrates, onco- genes, ploidy status, growth factors or their receptors, and cell adhesion structures. The markers which define the biology of the field of carcinogenesis would be likely to have utility both as early detection markers and as intermediate end point mark ers. As mentioned before, however, even if a particular marker is used for multiple prevention-oriented applications, each spe cific application needs to be validated independently. As the lung cancer early detection research matures, it is going to stimulate rational intervention research because con ventional lung cancer treatments including surgery may not be the ultimate modality to appropriately manage the very early lung cancer lesions. An effective early detection tool for lung cancer mandates the parallel effort to develop more appropriate intervention tools. The better the intervention tool performs, especially if the side effects of the intervention are mild, the less is the demand for precision associated with the application of the early detection tool. Summary of Priorities Resource support to permit the systematic acquisition of appropriate clinical material to develop tissue archives from individuals with high risk of developing cancer needs to be identified. Long term clinical follow-up should be conducted to permit classification of true cancer status through time. Quality control standards for the clinical data and the analyses need to be very rigorous. Investigator participation with the acquisition of the clinical specimen archive should allow an archive resource with sufficient quality to expedite the evaluation of new candi date early detection markers, which were not necessarily envi sioned as part of the original study design. Quality control standards need to be defined for a range of parameters including the optimal format for obtaining early detection specimens including sputum, urine, blood, and tissue to maximize the yield of information from those specimen analyses. A wide range of specimens could be obtained to enable marker research including any specimen acquired as a part of a clinically indicated procedure as long as the high risk subject has provided concurrence. Invasive procedures to obtain tissue for early detection research should be generally restricted to defined high risk populations and generally avoid general anesthesia-requir ing procedures. The ability to quantitate an end point for early detection research is highly desirable. Incentives to accelerate the tempo of such targeted research need to identified. 2766s on July 17, 2021. © 1992 American Association for Cancer Research. cancerres.aacrjournals.org Downloaded from