152 Radiation Oncology ??Biology ??Physics October 1984, Volume 10, Sup. 2

supplemented with PHA-LCM and MO-cell conditioned medium as sources of colony stimulating factor. GM-CFUc colony formation was scored on day 14 with histochemical stains for nitro blue tetrazolium dye (NBT), specific and nonspecific esterase, and Wright's/Giemsa; then were scored for percent granulocyte (G), monocyte/macro- phage (M) and mixed (GM) colony formation. For fresh human marrow the Do averaged 106 rad and the ii extrapo- lation averaged 1.5 and did not vary with dose rate. Sixty percent of colonies were scored as positive for granulocyte formation and this did not vary with dose or dose rate. For nonadherent cells from long term human bone marrow cultures, the Do averaged 135 rad and the extrapolation number averaged 1.00 and these num- bers did not vary with radiation dose rate or age of the culture harvest. Sixty percent of colonies from these cultures were also scored positive for granulocyte formation and this did not vary with radiation dose, dose rate, or age of the culture. These results confirm the dose rate independent killing of human granulocyte- macrophage progenitor cells and also demonstrate that these cells show minimal capacity to repair sublethal x-ray damage.

GM-CFUc FRESH MARROW Day of Harvest

Dose Rate (Rad/m) 5 200 Dose Rate (Rad/m)

Do 103 109 Do

ii 1.59 1.49 ii

Plating d7 0.34% Plating d? Efficiency d14 0.20% Efficiency d14

1011

GM-CFUc CULTURED MARROW

9 16 23

5 200 5 200 5 200

134 138 138 134 136 135

1.17 1.15 .98 -95 .95 -96

0.80% 1.50% 1.70% 0.38% 0.45% 0.34%

EFFECTS OF INTERSTITIAL IRRADIATION ON NORMAL BRAIN TISSUE USING Cf-252 OR Cs-137 RADIOACTIVE sou~cxs

H.W. Chin, Y. Maruyama, W. Markesbery, H.N. Huang and L. Beach

Departments of Radiation Medicine and Neuropathology, University of Kentucky, Lexington, Kentucky 40536-0084, U.S.A.

To study the normal brain reaction to the intracerebral interstitial irradiation, Cf-252 Or Cs-137, brain brachytherapy was performed to the brain of normal dogs. As a control group, two dogs underwent implant applicator placement in the right frontal lobe but no radioactive sources were loaded in the applicator. received Cf-252 interstitial irradiation,

Using the same technique, two dogs and another two dogs had Cs-137 intracerebral

irradiation following a placement of removable implant applicator in the right frontal lobe. The dogs were under close observation for ten months and then sacrificed for neuropathological examination. During the observation period, serial CAT and NMR scans were obtained in 2-3 month intervals, and clinical evaluations were made to detect any possible changes in daily activity, behavior, performance and habit. There were no clinically detectable abnormal changes noted. On the CAT and NMR examinations, some evidences began to show unilateral ventricular enlargement between seven to ten months after interstitial implantation. No abnormal enhancements or parenchymal changes were apparent on CAT or NMR studies. macroscopic findings.

Postmortem examination revealed no significant abnormal The most prominent microscopic changes were seen in the vascular

system, such as acute hemorrhage, small vessel wall.

endothelial proliferation and fibrinoid changes of The details regarding neuropathological findings will be discussed

as well as clinical and radiological features.

*This investigation was supported in part by Biomedical Research Support Grant RR 05374 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, NIH

1012 MISONIDAZOLE SENSITIZATION OF THE KIDNEY

John E. Moulder and Brian L. Fish

Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226

Because of reports of radiosensitization and chemosensitization of some normal tissues by misonidazole (MIS) we have tested high dose MIS for it ability to sensitize the rat kidney to radiation and cis-diamine-

Proceedings of the 1st Annual ASTRO Meeting 153

dichloroplatinum (cis-Pt). We have seen no evidence of kidney radiosensitization, but we have demonstrated chemosensitization of cis-Pt nephrotoxicity.

In radiosensitization trials, MIS was given at 1000 mg/kg 30 minutes prior to radiation. This is a schedule which gives tumor radiosensitization in excess of 1.60 in these animals. MIS had no significant effect on kidney tolerance. Renal lethality data showed that sensitization of greater than 1.09 could be excluded at the 95% level of confidence. Urine creatinine and BUN studies at 6 months after irradiation showed that sensitization of greater than 1.06 could be excluded at the 95% level of confidence.

In the chemosensitization trials, MIS was given ip at 1000 rag/kg 15 minutes prior to a 7.5 mg/kg ip dose of cis-Pt. Control arms consisted of animals treated with MIS or cis-Pt or no drugs. All animals were hydrated ip at 3 ml per 100 gram body weight 15 minutes prior to cis-Pt injection. Cis-Pt and nondrug- treated animals received their hydration as normal saline; MIS-treated animals received their hydration from the distilled water in which the MIS was injected. At eight days after treatment BUN values were normal in 13 nondrug-treated animals, 18 animals given MIS, and 13 animals given cis-Pt. All 6 animals receiving both MIS and cis-Pt had BUN levels 2 to 4 times higher than normal. A subset of animals were followed for mortality. No mortality was seen in 10 animals given cis-Pt alone or in 10 animals which received hydration alone; 2 of 15 animals given MIS alone died within 24 hours of treatment. All three animals treated with MIS and cis-Pt died lo-12 days after treatment.

Experiments are underway to determine the chemosensitization ratio for MIS, to determine the lowest dose of MIS at which sensitization can be detected, and to determine the duration of the chemosensitization.

This work was supported by grants CA27084 and CA24652 from the National Cancer Institute.

1013 BREAST RETRACTION ASSESSMENT: MULTI-VARIATE ANALYSIS OF FACTORS RESPONSIBLE FOR COSMETIC RETRACTION IN PATIENTS TREATED CONSERVATIVELY FOR STAGE I OR II BREAST CANCER

Richard D. Pezner, M.D.* Mary P. Patterson, R.N., M.S.* L. Robert Hill, KS.** Nayana Vora, M.D.* Kanta R. Desai, M.D.* John 0. Archambeau, M.D.* James A. Lipsett, M.D.*

Division of Radiation Oncology* and the Department of Biostatistics**, City of Hope National Medical Center, Duarte, CA.

Breast Retraction Assessment (BRA) is an objective evaluation of cosmetic outcome in patients treated conservatively for breast cancer. A clear lucite sheet is vertically supported and marked as a grid at one cm. intervals. The nipple of each breast is localized on x- and y- coordinates. BRA values are calculated by simple geometry and represent the amount of retraction of the treated breast in comparison to the untreated one. BRA was determined 5-41 months following the completion of radiation therapy in 32 patients. BRA values ranged from 0.0 to 8.5 cm. with a mean of 3.5 cm, Multi-variate analysis evaluated the relative contribution to retraction of tumor size, tumor location in the breast, bra cup size, extensiveness of primary resection, use of separate nodal radiation fields, local primary tumor radiation boost, and use of adjuvant systemic chemotherapy. Statistical evaluation of BRA revealed that extensiveness of resection was the major factor associated with retraction.

1014 PREPLANNING OF Ir-192 IMPLANTS FOR BOOST IRRADIATION TO THE BREAST

R. Schmidt-Ullrich, M.D., R. D. Zwicker, Ph.D., and B. Schiller, Ph. D.

Tufts-New England Medical Center, Boston, MA

The conservative therapeutic management of early stage breast cancer with tumor excision and irradiation of the breast is becoming increasingly accepted as an alternative to modified radical mastectomy. At many institutions the radiotherapy consists of 45 to 50 Gy delivered with external beam irradiation, followed by interstitial Ir-192 implantation to boost the site of tumor excision. The finding that the majority of tumor recurrences in the irradiated breast can be localized in the area of the tumor bed suggests that modification of the current implant techniques may help to further improve local control. We have employed clinical assessment, mammography, and pathological evaluation of excised tumor to determine the tissue volume that