I am writing to inform you about the Radiation Therapy Oncology Group (RTOG) tissue banking activities which recently were awarded NCI funding. The RTOG is a national cooperative cancer study group which explores therapeutic options involving radiation therapy in combination with other modalities for cancer patients. Over 250 radiation oncology departments in North America are members of the RTOG. The RTOG tissue bank is a central fixed tumor tissue repository for the RTOG including tumor from all sites under study by the group as phase III clinical trials. We are collecting blocks on RTOG phase III trials for cancers of prostate, bladder, lung, head and neck, esophagus, and malignant glioma. In each of these sites, the protocols have been modified to provide specific information about tissue bank procedures. The RTOG principal investigator and research associate for your institution have this information. The tissue bank has been in existence since 1994 but has only recently received specific funding through a supplementary grant submitted last Spring. This grant supplement provides funds to pay for the tissue bank personnel to manage the tissue bank and to maintain a database indicating what tissues and slides are stored. Funds are also allocated for reimbursement of pathologists for providing blocks to be stored. One hundred dollars per case (with at least one block submitted to the tissue bank), is available to be reimbursed to cover the costs of evaluating the slides and choosing and sending the block to the tissue bank. Pathologists should submit their request for reimbursement to the institutional Principal Investigator of the RTOG grant. This letter is being provided to you by the RTOG investigator or research assistant who can help you ascertain the proper mechanism for reimbursement of these activities.

The tissue bank will permit the study of cases entered on RTOG clinical trials by any qualified investigator making an application to the group or to the bank via an Intergroup. This tissue resource will allow correlative studies to be performed on clinically homogeneous patient populations which will give us important information about prognostic factors, treatment selection factors and biologic behavior if we use it wisely. Pathologists are eligible to apply for use of this resource. Applications are reviewed semiannually by either an RTOG tissue banking or Intergroup tissue banking committee who will decide whether tissue can be allocated for the project proposed. The investigator must have NCI or other funds available to carry out the research project. Correlative studies are also funded as part of the clinical trial proposal. This mechanism has been used successfully in many sites, including head and neck, prostate and lung cancer. A bibliography of successfully completed projects is enclosed with this letter. Other studies are underway.

I am an anatomic pathologist practicing in a large community hospital. I am well aware of the feelings that many of you have concerning the removal of blocks from your institution because they are being removed from my institution as well. Let me try to anticipate your concerns and address them: 

1. Patient Consent: Each patient, as part of enrollment in RTOG studies signs a study-specific consent form requesting them to allow use of tumor tissues for research purposes. Thus, patients have given explicit permission for use of their tumor tissues in research studies. The tissues are used only by case number and are never identified by name or retrieved individually. No patient specific information can be obtained by the mechanisms we use. In fact, investigators performing the studies do not have access to the clinical information allowing patient identification and linkage to treatment or demographics. These are population based studies which look at population characteristics rather than individual patient related issues.

2. Access of Institution to Tissue Blocks and Requirement for Five years of Storage to Satisfy CAP Regulations: The tissue blocks are stored in a cool, dry place by accession number. The location of blocks and material disposition is available on a data base that is readily available. Institutions needing their blocks returned because of patient, physician or legal requirements can have their blocks returned overnight by faxing or e-mailing a request. This satisfies the CAP requirement because the blocks are stored in a manner making them available within 24 hours.

3. Ability of Pathologists in the Institution to Perform Scientific Studies: The storage of tissues centrally does not preclude investigation of those blocks by anyone. Any scientist with a scientifically valid proposal and the money and methods to investigate it can use the tissue bank. The bank makes it possible to study larger numbers of patients on which treatment is standardized and followup is available. By sharing our resources, we are much more likely to answer important scientific questions. Since the tissue bank will reimburse pathologists for supplying blocks, funds will be available in larger accruing institutions to carry out small pilot projects on various tumor types. Enrollment in clinical trials rarely involves more than 5% of patients of a particular tumor type and thus does not compromise the group of patients available for local studies in most cases. Pooling funds from reimbursement of many tumors will likely result in significant funds being available. If an institution put 20 cases on RTOG studies and was reimbursed for this activity, $2000 would be available to the pathology department to carry out independent projects. This is significantly more money for pathology projects than is usually available and represents a wonderful opportunity for institutional pathologists. I would welcome a conversation with you about the tissue bank. This NCI funded activity will promote more research on patients in cooperative cancer group trials in a valuable ancillary manner. Pathologists have successfully supported the tissue banking activities of pediatric tumor initiatives and important biologic results have occurred. Please help us make such advancements in the understanding of the common tumors of adults.

Sincerely,

Elizabeth H.Hammond M.D.
Vice Chair of RTOG
Director, RTOG tissue bank
(801) 321-1029
fax (801) 321-5020
e-mail: ldehammo@ihc.com

1. Crissman, J.D., Pajak, T.F., Zarbo, R.J., Marcial, V.A., Al-Sarraf, M.: Improved response and survival to combined cisplatin and radiation in non-keratinizing squamous cell carcinomas of the head and neck. An RTOG study of 114 advanced-stage tumors. Cancer 59:1391-1397, 1987.

2. Fischbach, A.J., Martz, K.L., Nelson, J.S., Nelson, D.F., Griffin, T.W., Chang, C.H., Horton, J.: Long-term survival in treated anaplastic astrocytomas: A report of combined RTOG studies. Am J Clin Oncol 14:365-370, 1991.

3. Fu, K.K., Hammond, E., Pajak, T.F., Clery, M., Doggett, R., Byhardt, R.W., McDonald, S.: Flow cytometric quantification of proliferation associated nuclear antigen p105 and DNA content in advanced head & neck cancers: Results of RTOG 91-08. Int J Radiat Oncol Biol Phys 29:661-671, 1994.

4. Grignon, D., Caplan, R., Sarkar, F., Lawton, C., Hammond, E., Forman, J., Mesic, J., Fu, K., Abrams, R., Shipley, W., Cox, J.: p53 suppressor gene status as a predictor of outcome in patients with locally advanced prostatic adenocarcinoma treated by radiation therapy with and without neoadjuvant androgen ablation: A study based on RTOG 8610. J Natl Cancer Inst, 89(2):158-165, 1997.

5. Grignon, D., Won, M., Hammond, E.H., Dolan, P., Lawton, C., Mesic, J., Fu, K., Porter, A., Abrams, R., Shipley, W.: DNA content as a prognostic indicator in prostate cancer: A study based on RTOG protocol 8610. United States-Canadian Academy of Pathology, Washington, DC, Mod Path, 9(1): 74A, [419], 1996.

6. Grignon, D.J., Abdel-Malek, M., Mertens, W., Koster, J., Keeney, M., Sakr, W., Shepherd, R.R.: Prognostic significance of cellular proliferation in renal cell carcinoma: A comparison of S-phase fraction and PCNA index. Mod Pathol 8:18-24, 1995.

7. Grignon, D.J., Caplan, R., Sakr, W., Porter, A.T., Doggett, R.L.S., John, M.J., Lawton, C.: Neuroendocrine (NE) differentiation as a prognostic indicator in locally advanced prostate cancer: A study based on RTOG protocol 8610. Mod Pathol 8:76A, 1995.

8. Grignon, D.J., Caplan, R., Sarkar, F., Foreman, J., Mesic, J., Fu, K.K., Abrams, R., Lawton, C.: p53 suppressor gene mutations predict for failure following combined neoadjuvant total androgen ablation and external beam radiation therapy for locally advanced prostate cancer: A study based on RTOG Protocol 8610. J Urol 153:293A, 1995.

9. Grignon, D.J., Caplan, R., Sarkar, F., Forman, J., Mesic, J., Fu, K.K., Abrams, R., Lawton, C.: p53 suppressor gene status as a predictor of outcome in patients with locally advanced prostatic adenocarcinoma (PCA) treated by radiation therapy with and without androgen ablation pretreatment: A study based on RTOG protocol 8610. Mod Pathol 8:77A, 1995.

10. Grignon, D.J., Pajak, T., Hammond, E., Byhardt, R., Mesic, J., Gallagher, M., Roach, M., Hanks, G., Sause, W.: Application of the Gleason grading system: A comparison of institutional and central review grading using RTOG Protocols 8531 and 8610. United States-Canadian Academy of Pathology, Washington, DC, Mod Path, 9(1): 73A, [418], 1996.

11. Hammond, M.E., Sause, W.T., Martz, K.L., Pilepich, M.V., Asbell, S.O., Rubin, P., Myers, R.P., Farrow, G.M.: Correlation of prostate-specific acid phosphatase immunohistochemistry with survival in prostate carcinoma. Cancer 63:461-466, 1989.

12. Kindblom, L.G., Nelson, J.S., Meis-Kindblom, J.M.: Comparison of Ki-67, PCNA and p53 expression in pleomorphic xanthoastrocytoma (PXA) and glioblastoma multiforme (GBM). Lab Invest 72:136A, 1995.

13. Meis, J.M., Ho, K.L., Nelson, J.S.: Gliosarcoma: A histologic and immunohistochemical reaffirmation. Mod Pathol 3:19-24, 1990.

14. Meis, J.M., Martz, K.L., Nelson, J.S.: Mixed glioblastoma multiforme and sarcoma: A clinicopathologic study of 26 RTOG cases. Cancer 67:2342-2349, 1991.

15. Nelson, D.F., Nelson, J.S., Davis, D.R., Chang, C.H., Griffin, T.W., Pajak, T.F.: Survival and prognosis of patients with astrocytoma with atypical or anaplastic features. J Neurooncol 3:99-103, 1985.

16. Nelson, J.S., Petito, C.K., Scott, C.B., Rotman, M., Asbell, S., Murray, K.: Glioblastoma with oligodendroglial features (GBM-OL): Report from Radiation Therapy Oncology Group (RTOG) 8302. Proceedings of the U.S.-Canadian Academy of Pathology, 1996.

17. Nelson, J.S., Schoenfeld, D., Tsukada, Y., Fulling, K., Lamarche, J., Peress, N.: Necrosis as a prognostic criterion in malignant, supratentorial astrocytic gliomas. Cancer 52:550-554, 1983.

18. Scott, C.B., Nelson, J.S., Farnan, N.C., Curran, W.J., Murray, K.J., Fischbach, A.J., Gaspar, L.E., Nelson, D.F.: Central pathology review in clinical trials for patients with malignant glioma: A report of Radiation Therapy Oncology Group 83-02. Cancer 76:307-313, 1995.

19. Tester, W., Porter, A., Asbell, S., Coughlin, C., Heaney, J., Krall, J., Martz, K., Venner, P., Hammond, E.: Combined modality program with possible organ preservation for invasive bladder carcinoma: Results of RTOG Protocol 8512. Int J Radiat Oncol Biol Phys 25:783-790, 1993.

20. Yesner, R., Seydel, G.H., Asbell, S.O., Cox, J.D., Bauer, M., Shin, K.H., Byhardt, R., Perez, C.: Biopsies of non-small cell lung cancer: Central review in cooperative studies of the Radiation Therapy Oncology Group. Mod Pathol 4:432-435, l991.

21. Yesner, R.: Pathologic review of bronchial biopsies in non-small cell lung carcinoma. Fifth World Conference on Lung Cancer. Interlaken, Switzerland, August 1988.

22. Zhou, R., Sause, W.T., Hammond E.H., Rubin, P., Perez, C., Pilepich, M.V., Asbell, S.D., Parker, D.L.: Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using image analysis: A preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07. Int J Radiat Oncol Biol Phys 33:823-829, 1995.

23. Zhou, R., Hammond, E.H., Parker, D.L.: Determination of the PAP stain mass in tissue section by dual wavelength method. Analytical Cytometry 14:73, l992.

24. Zhou, R., Hammond, E.H., Sause, W.T., Rubin, W.T., Emami, B., Pilepich, M.V., Asbell, S.O., Parker, D.L.: Quantitation of prostate-specific acid phosphatase in prostate cancer: Reproducibility and correlation with subjective grade. Mod Pathol 7:440-448, 1994.