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Part II

Chapter 8

Introduction

What is TBI?

Early Use of TBI for Radioresistant Tumors: The Manhattan Project Experiments on Patients and the Subsequent AEC Review

Renewed Interest in Total-Body Irradiation

Postwar TBI-Effects Experimentation: Continued Reliance on Sick Patients in Place of Healthy "Normals"

AEC-Sponsored TBI at Oak Ridge

Conclusion

Chapter 8: What is TBI?

Medically administered total-body irradiation, also known as whole-body radiation, involves the use of external radiation sources that produce penetrating rays of energy to deliver a relatively uniform amount of radiation to the entire body. Total-body irradiation was used as a medical treatment long before the 1944-1974 experiments, and it continues to be used today. Soon after doctors began to experiment with radiation, they recognized that radiation had different effects on different types of cancers. They thus began to distinguish between radiosensitive cancers, which generally responded to the radiation treatment, and radioresistant cancers, which most often did not respond. By the 1940s, TBI was recognized as an acceptable treatment for certain radiosensitive cancers that are widely disseminated throughout the body, such as leukemia and lymphoma (a cancer whose origin is in the lymphoid tissue). By the late 1950s, TBI was also being used to assist in conjunction with research on bone marrow transplantations for radiosensitive cancers. During this period, TBI was also explored as a possible palliative treatment (providing relief, but not cure) for disseminated radioresistant cancers, such as carcinomas of the breast, lung, colon, and other organs (carcinoma is a cancer that originates from the cells lining these organs).[6] However, TBI alone did not prove to be of value in treating these cancers because, without support measures to maintain bone marrow function, the doses needed to significantly shrink the tumors were potentially lethal to the patient.

In the 1950s, there were few effective methods for treating radioresistant cancers. Chemotherapy was just being developed; it was risky to use and only marginally effective. With no better alternatives, interest in TBI continued. In addition, the development in the 1950s of high-energy sources of radiation--cobalt 60, cesium 137, and megavolt x-ray sources--represented a significant advance in technology. These new teletherapy units allowed high-energy radiation to penetrate deeper into the body without damaging the overlying skin and soft tissues; thus higher absorbed marrow doses (in rad) could be delivered than with previous equipment. The advent of this new teletherapy encouraged researchers to retest TBI on patients with radioresistant cancers even though prior TBI techniques with older x-ray therapy machines had failed. By the late 1960s, however, chemotherapy began to be recognized as more effective, and interest in TBI waned. During the 1970s, researchers explored the effectiveness of administering TBI without bone marrow transplant through multiple exposures at lower doses (e.g., 10 to 30 rad), known as "fractionated radiation," to achieve cumulative total body doses of 150 to 300 rad, rather than single exposures of an equivalent total body dose.[7] They also focused much more extensively on partial-body irradiation, because the risk of patient bone marrow failure was lower. Since the 1980s, TBI has again been used to treat certain widely disseminated, radioresistant carcinomas at doses as high as 1,575 rad in conjunction with effective bone marrow transplantation, which became routinely available in the late 1970s.[8]

TBI can cause acute health effects during the first six weeks following an acute (single) exposure. The type and severity of the effects depend, among other things, on the dose, the dose rate, and the individual’s sensitivity to radiation.[9] The most serious side effects seen during this period are related to radiation-induced depression of the bone marrow, which can cause a decrease in the number of circulating platelets and white blood cells, which in turn can result in small hemorrhages and infections, possibly leading to death. Moderate bone marrow depression results with doses of about 125 rad. The following table describes the general acute effects that are likely to occur to healthy persons from a single exposure;[10] these effects can be exaggerated and prolonged for people who are ill or have had prior radiation treatments. As with an ordinary diagnostic x ray, the patient feels nothing during the radiation exposure itself. In addition, TBI, like most other forms of radiation exposure, can potentially have long-term effects such as cancer induction; however, most patients who receive TBI do not live long enough to experience most long-term effects.

Midline Tissue Dose Symptoms Percentage Time Postexposure
50-100 rad nausea 5-30 3-20 hours
100-200 rad nausea 30-70 4-30 hours
vomiting 20-50 6-24 hours
death[11] <5 5-6 weeks
200-350 rad nausea 70-90 1-48 hours
vomiting 50-80 3-24 hours
death 5-50 4-6 weeks
350-500 rad nausea 90-100 1-72 hours
vomiting 80-100 3-24 hours
death 50-99 4-6 weeks
550-750 rad death 100 2-3 weeks
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