Hall Book Ch 28 (Hyperthermia)

Question 1

Hyperthermia at Cytotoxic Temperatures ( )

Survival curves for heat are similar in shape to those for radiation except that time at the elevated temperature replaces ( ) dose.

No consistent difference in inherent sensitivity exists between ( ) cells.

Answer 1

42° to 45° C, absorbed, normal and malignant

Question 2

The inactivation energy is different above and below a break temperature of
about 43° C.

The inactivation energy suggests that the target for heat toxicity may be
protein.
The age-response function for heat complements that for x-rays. S phase cells
that are resistant to x-rays are sensitive to heat.
Hypoxia does not protect cells from heat as it does from x-rays. Hyperthermia
may be very effective at reversing hypoxia through its effects on vascular
perfusion. This may be an important mechanism of radiosensitization by
hyperthermia.
Cells at low pH and nutritionally deprived (more likely to be in tumors) are
more sensitive to heat, although cells can adapt to pH changes and lose their
sensitivity to heat.
Thermotolerance is the induced resistance to a second heat exposure by prior
heating and may be monitored by the appearance of HSPs.
Heat damage in normal tissues is expressed more rapidly than x-ray damage
because heat kills differentiated as well as dividing cells and because cells
can die in interphase rather than at the next (or subsequent) mitosis, as is the
case for x-rays.
The TER is the ratio of radiation doses with and without heat to produce the
same biologic effects. TER values of 2 to 4 can be obtained in tumors and
normal tissues in experimental animals.
951
Hyperthermia at Modest Temperatures that Can Be
Achieved in Human Tumors
Hyperthermia at modest temperatures that can be achieved in human tumors
results in little cytotoxicity but has been shown to result in reoxygenation in
animal and human tumors.
There is some evidence that hyperthermia at temperatures that result in little
cytotoxicity can induce an immune response that may account for some of
the benefits of combining hyperthermia with radiation. This remains to be
proven.
Several phase III randomized trials now demonstrate a clear and significant
benefit for the addition of hyperthermia to standard RT and/or chemotherapy.
The cancer types tested include cervical cancer, superficial localized breast
cancer, recurrent or metastatic malignant melanoma, nodal metastases from
head and neck cancer, glioma, esophageal cancer, and high-risk sarcoma.
The TER is the ratio of radiation doses with and without heat to produce the
same biologic effects. TER values of between 1.15 and 1.5 have been
reported in clinical analyses.
Temperature measurement in vivo is difficult but improving. Progress toward
noninvasive thermometry includes the use of magnetic resonance imaging.
Novel applications of heat include enhanced targeted delivery of chemotherapy
by thermosensitive liposomes.
Thermal ablation refers to the destruction of tissue by extreme hyperthermia
(more than 60° C) delivered by needle-type RF or microwave applicators
implanted directly into the tumor under CT or ultrasound guidance.