Hall 28 - Hyperthermia

Question 1

How is hyperthermia dose response measured?

Answer 1

Surviving fraction as a function of duration of hyperthermia

High temps = dose-response like photons (initial shoulder)

Low temps = killing blunted with longer treatment (curve concave up)

Question 2

What point is the change in temperature (high to low)?

Answer 2

43 C

Target: protein

Question 3

What cell cycle phase is most sensitive to hyperthermia?

Answer 3

Late S
(opposite RT)

Question 4

Does hypoxia protect cells from hyperthermia?

Answer 4

No

Question 5

At what pH do cells have increased sensitivity to hyperthermia?

Answer 5

Low pH
(and with nutrient deprivation)

Question 6

How do normal tissues respond to hyperthermia?

Answer 6

Early (via apoptosis)
No latent period for dividing stem cells and differentiated cells (impacted equally)

Normal tissues are better perfused&raquo_space; heat dissipates more easily

Question 7

What is thermotolerance?

Answer 7

Induced rapidly during the heating period and protects cells from second heat exposure

Mediated by heat shock proteins (HSPs) - bind to partially unfolded proteins and prevent aggregation

Question 8

Where do heat shock proteins bind?

Answer 8

Non-stressed conditions: heat shock factor 1 (HSF1) - inhibited

Stressed conditions: unfolded proteins (dissociate from HSF1)
» HSF1 binds to heat shock response element&raquo_space; transcription of more HSPs

Question 9

What are cumulative equivalent minutes (CEM)?

Answer 9

At 43ºC
A way of intercomparing different heat regimens/durations (like BED for RT)

CEM 43ºC = t x R^(43-T)

t = duration of hyperthermia
T = average temp
R = 0.5 for T >43 or 0.25 for T <43

Question 10

How can hyperthermia and RT synergize?

Answer 10

• Heat increases tumor blood flow, oxygenation, radiosensitivity
• Heat increases antitumor immune response
• Heat inhibits SLD repair
• Radioresistant S phase and hypoxic cells are sensitive to heat

Question 11

What is the thermal enhancement ratio?

Answer 11

Ratio of RT dose required to produce a given level of damage without vs with hyperthermia (thermal radiosensitization)

Increases with increasing temps

Normal tissues: TER is ~2 at 43ºC
Tumor: TER is 1.4 at 41ºC, increasing to 4.3 at 43ºC

Question 12

What is the therapeutic gain factor?

Answer 12

= TER of tumor / TER of normal tissue

Question 13

How does hyperthermia interact with chemo?

Answer 13

Some chemo agents synergize with heat

Question 14

How can hyperthermia be induced?

Answer 14

• Water bath
• Microwaves (shallow)
• Ultrasound (penetrating)
• Thermal ablation