Biological radiation response modifiers

Proceedingsofthe32ndAnnualASTFiO

101

Meeting

210 CARCINOMA

OF THE ENOOMETRIUM

Perry W. Grigsby,

- DIAGNOSIS

AND MANAGEMENT

M.D.

Radiation Oncology Center, St. Louis, MO 63110

Mallinckrodt

Institute

of Radiology,

Washington

University

School

of Medicine,

Carcinoma of the endometrium is the most common invasive gynecologic malignancy in the United States. Patients present with post-menopausal bleeding and the diagnosis is readily established by D & C. Therefore, almost 75% of patients present with stage I disease. Our knowledge of the natural history of the disease has been greatly enhanced by the surgical staging studies of the Gynecologic Oncology Group. Staging of endometrial cancer has been recently altered by FIG0 to a surgical staging system rather than a clinical stage. Prognostic factors have now been re-defined based upon surgical stage. The following prognostic variables will be reviewed: patient age, tumor histology and grade, vascular space involvement, depth of myometrial invasion, uterine serosal involvement, lymph node status, extra-pelvic disease and peritoneal cytology. Results of therapy based upon the new FIG0 surgical staging system will be presented. Limitations and the implications for prognosis of the new staging system will be discussed. Treatment strategies for stage I and II disease including preoperative versus postoperative irradiation and intracavitary or external beam radiotherapy will be presented. Extended field, whole abdominal irradiation, P-32, or systemic therapy for advanced stage carcinoma of the endometrium will be reviewed. The final topic to be presented will be the management of recurrent endometrial carcinoma.

211 BIOLOGICAL Rupert Dept.

RADIATION

RESPONSE

Schmidt-Ullrich, of Radiation

MODIFIERS

M.D.

Oncology,

Medical

College

of Virginia,

MCV Station

Box 55, Richmond,

VA

23298-0058

There is increasing evidence that growth control of mammalian cells is under influence of positively This has been and negatively regulating growth promotors which may represent cytokines and/or hormones. demonstrated for cells of epithelial mesenchymal, and lymphoidlmyeloid origin. Physiological autocrine and paracrine response mechanisms are altered in neoplastic cells relative to their normal counterparts. Many of these cytokine-mediated growth regulatory mechanisms are altered when cells are exposed to ionizing radiation. In this review we will discuss (1) the modulating effects of radiation on the radiosensitivity of mammalian cells and (2) cellular responses to and the production of growth modulating cytokines after radiation exposure. The following biological components can exert sensitizing or de-sensitizing effects to ionizing radiation on normal and neoplastic cells with the ultimate result of altered relative radiosensitivity as listed under (1): (a) lymphokines effecting T- and B-lymphocytes; (b) growth factors acting on neoplastic epithelial and normal mesenchymal or myeloid cells; (c) hormones for hormone-dependent neoplastic cells; (d) altered expression of oncogenes encoding growth factor receptors; (e) changes in the levels of secondary messengers. Closely related to mechanisms listed under (1) are the responses of cells to radiation exposure as outlined under (2). Cells do respond to radiation exposure with altered gene expression which may change their radiosensitivity at subsequent exposures. Depending on the cell type, this may result in the production of (a) stress proteins, (b) radiation-induced differentiation and/or altered growth properties, and (c) altered production of lymphokines and growth factors with resulting altered proliferation control. Research towards improved understanding of the mechanisms underlying altered gene expression and cellular proliferation control requires integrated cell biological, biochemical, and molecular biological approaches with focus on the cells' repair capacity and the role of secondary messengers.