Hall Book Ch 19 (Dose-Response Relationships for Model Normal Tissues)

Question 1

The relationship between dose and incidence is ( ) for both tumor control and normal tissue damage.

The ratio of tumor response to normal tissue damage is called the ( ).

Answer 1

sigmoid, therapeutic ratio or therapeutic index

Question 2

The therapeutic index can be manipulated by ( ) or by the use of ( ) that preferentially increase tumor response.

Answer 2

dose fractionation, drugs

Question 3

After irradiation, most cells die as mitotic death; that is, they die in ( ). In some tissues, cells die by ( ), which is a programmed cell death.

Answer 3

attempting the next or a later mitosis, apoptosis

Question 4

Systems involving clonogenic end points (i.e., cell survival) for cells of normal tissues include some in which cells regrow in situ and some in which cells are transplanted to another site.

In situ regrowth techniques include skin colonies, crypts in the jejunum, testes stem cells, and kidney tubules.

Single-dose experiments can yield the slope (D0) of the dose–response curve over a range of high doses.

Multifraction
experiments allow the whole dose–response curve to be reconstructed.
Systems in which cell survival is assessed by transplantation into another site
include bone marrow stem cells, thyroid cells, and mammary cells.
A dose–response curve for bone marrow stem cells can be obtained by
allowing cells from the donor animal to lodge and grow in the spleens of
recipient animals. These are very sensitive cells with a D0 close to 1 Gy, with
little or no shoulder.
Dose–response curves for mammary and thyroid cells can be obtained by
transplanting them into fat pads of recipient animals.
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The radiosensitivity of cells from normal tissues varies widely. The width of
the shoulder of the curve is the principal variable. Jejunal crypt cells have a
very large shoulder; bone marrow stem cells have little, if any, shoulder. Most other cell types studied in clonogenic assays fall in between.
Dose–response curves for functional end points, distinct from cell survival, can
be obtained as follows:
1. Pig skin and rodent skin—by measuring skin reactions
2. Early and late response of the lung—by measuring breathing rate
3. Spinal cord—by observing myelopathy:
a. Paralysis develops after a latency of months to years.
b. Early lesions are limited to white matter; late delayed injury may have
a vascular basis.
c. Spinal cord damage is very sensitive to fractionation—α/β of about
1.5 Gy.
d. Sublethal damage repair probably has “fast” and “slow” components.
e. If multiple fractions per day are used, the interfraction interval should
be at least 6 to 8 hours.
f. FSUs are arranged serially like links in a chain.
g. For short lengths of cord, tolerance dose varies markedly with cord
length irradiated; for cord lengths greater than a few centimeters,
tolerance dose is virtually independent of cord length.
The shape of the dose–response relationship for functional end points, obtained
from multifraction experiments, is more pertinent to radiotherapy than
clonogenic assays.
The ratio α/β (the dose at which the linear and quadratic components of
radiation damage are equal) may be inferred from multifraction experiments
in systems scoring nonclonogenic end points.