**1.4. Technical history of local hyperthermia in oncology**

Despite the hyperthermia was among the very first medical treatments in human medicine, this approach has ambivalent evaluation as a therapy. While it is popular in households to "treat" many diseases like common cold, pain, various orthopedic problems, etc., it is on the periphery of the serious medical therapies. This frustration characterizes the complete history of hyperthermia in medicine, and explains why hyperthermia has no well- deserved place in the medical armory to treat various diseases.

At the end of the 19th century, energy delivery by electromagnetic fields became possible; but the real technical revolution of the heat therapies was when the modern microwave heating was developed, and applied in medicine from the middle of the 20th century. This focused, temperature-based deep heating became one of the line (focused local/regional heating), while the other was the whole body heating with various methods. In local heating, the paradigm is to reach the appropriate temperature locally.

Nevertheless, the intensive use of hyperthermia in oncology began in the last third of the 20th century. The first symposium on oncological hyperthermia was held in Washington DC, USA in 1975; and the second one in Essen, Germany in 1977. Both conferences were supported by the local scientific communities. We may consider the birth of the modern oncological hyperthermia from this time on, and take it as a strong candidate and a member of the acknowledged tumor therapies.

The original idea of the hyperthermia was the "fire by fire" concept: set a controlled contrafire depleting the possible fire-supply, blocking the coming large bush-fire endangering a house. The heated tumor is forced to higher metabolism; high metabolic rate of the cancer lesion is gained by elevated temperature. However, when the surrounding is intact, it delivers the same amount of nutrients as before, it does not deliver more glucose for the forced metabolism Figure **9**. The tumor very quickly deflates from nutrients, empties all its energies, suffers and burns away.

**Figure 9.** The focused local heating situation, expecting the locality for longer time

Indeed, there are many factors showing the validity of this assumption, but the breakthrough to accept the method widely hasn't been reached in the long historic period. The appropriate temperature selectively administered in the tumor still cannot be reached. This fact forms a lot of questions in the published literature:


10 Hyperthermia

ablation, [76]).

Herewith we do not discuss the extreme temperature facilities in local treatments, the ablative techniques with high temperature (heat-ablation, [75]) or low-temperature (cryo-

Despite the hyperthermia was among the very first medical treatments in human medicine, this approach has ambivalent evaluation as a therapy. While it is popular in households to "treat" many diseases like common cold, pain, various orthopedic problems, etc., it is on the periphery of the serious medical therapies. This frustration characterizes the complete history of hyperthermia in medicine, and explains why hyperthermia has no well- deserved

At the end of the 19th century, energy delivery by electromagnetic fields became possible; but the real technical revolution of the heat therapies was when the modern microwave heating was developed, and applied in medicine from the middle of the 20th century. This focused, temperature-based deep heating became one of the line (focused local/regional heating), while the other was the whole body heating with various methods. In local

Nevertheless, the intensive use of hyperthermia in oncology began in the last third of the 20th century. The first symposium on oncological hyperthermia was held in Washington DC, USA in 1975; and the second one in Essen, Germany in 1977. Both conferences were supported by the local scientific communities. We may consider the birth of the modern oncological hyperthermia from this time on, and take it as a strong candidate and a member

The original idea of the hyperthermia was the "fire by fire" concept: set a controlled contrafire depleting the possible fire-supply, blocking the coming large bush-fire endangering a house. The heated tumor is forced to higher metabolism; high metabolic rate of the cancer lesion is gained by elevated temperature. However, when the surrounding is intact, it delivers the same amount of nutrients as before, it does not deliver more glucose for the forced metabolism Figure **9**. The tumor very quickly deflates from nutrients, empties all its

**1.4. Technical history of local hyperthermia in oncology** 

heating, the paradigm is to reach the appropriate temperature locally.

**Figure 9.** The focused local heating situation, expecting the locality for longer time

place in the medical armory to treat various diseases.

of the acknowledged tumor therapies.

energies, suffers and burns away.


Many of the researchers evaluating the capabilities of oncological hyperthermia share the opinion expressed in the editorial comment of the European Journal of Cancer in 2001: the biological effects are impressive, but physically the heat delivery is problematic. The hectic results are repulsive for the medical community. The opinion, to blame the "physics" (means technical insufficiency) for inadequate treatments is general in the field of oncological hyperthermia, formulated the following statement: "The biology is with us, the physics are against us [82]. In the latest oncological hyperthermia consensus meeting the physics was less problematic. However, in accordance with the many complex physiological effects, a modification was proposed: "The biology and the physics are with us, but the physiology is against us" [88].

The most problematic issues have always been technical: how to heat in depth, locally focused, being selective for malignant cells, and the other side: how to control it and how to measure the efficacy of the treatment? Even when the local treatment is focused well, the temperature by its way tends to be equalized; the focus is extended by time, due to the very effective heat-exchanger – the blood-stream. The heated tumor strongly exchanges its heat with its healthy surrounding, extending the focus gradually and increasing the local bloodflow. This unwanted effect has some problematic consequences:


the alkaline blood delivers more oxygen to the volume, by positive feedback mechanism,

Local Hyperthermia in Oncology – To Choose or not to Choose? 13

Pumping the same energy into identical volumes, but having different surfaces, the temperature increase will be definitely different, because the volume is differently cooled down by the environmental conditions. Furthermore, the heat can make structural or other rearrangement in the material, it could be transformed into work without temperature increase of the system. For example: melting the ice absorbs energy without temperature increase, still it is completely transformed into liquid. The heat, which is pumped in to the system at this phase transition does not increase the temperature; its energy is used

Other clear example is the Sun radiation to the Earth. A huge part of the energy of the Sun's radiation is converted to the meteorology (like wind or rain), their mechanical effects (like waves in the ocean, like distortion of the rocks). The Sun's energy is the solely energy-source of the life processes, and this energy of the Sun makes our oil reserves, allowing us to use this energy for various applications in our everyday life. So the simple electromagnetic radiation (the spectrum of the Sun) is converted to the various kinds of energies in the Earth.

Other simple example is the human energy-intake: a female adult eats ~1600 kcal/day. When she takes more energy a day, it will not change her body temperature at all. However, when she gets this energy from radiation, she will starve, despite of the fact that she gets more

When there are so serious differences between the heat and temperature, why do we confuse them? The main reason is: we fix our attention to simple situations when we heat such materials which distribute the energy immediately all over the system, making thermal equilibrium without internal work (reactions, dilatation, etc.) in the system. In such cases, of course, all the heat energy increases the internal energy of the system, and so it is

When we fix our attention to such systems, like heating water in its liquid form, the applied heat and temperature are strictly proportional in a certain interval (when the water is definitely liquid). However, we have a problem even in this simple system. When a phasetransition occurs, we lose this proportionality completely. At the/a study of hyperthermia in living systems, we have to well distinguish the overall energy, the heat energy and the

"The use of thermodynamics in biology has a long history rich in confusion." [91]. The main complication is the fact that life cannot be studied isolated from its environment, and so the energetically open system could lead to numerous uncertainties, leading sometimes to

The idea of the local heating effect to burn-out the energy sources of the malignancy has dominated the hyperthermia applications from the time of Hippocrates. Its operation measured by modern methods [92], shows definite decrease of ATP and increase of lactic

completely to change the structure of the material from solid to liquid.

Only a fraction of the radiation is realized as heat and rising temperature.

distributed in it, and proportionally increases its temperature.

temperature (which is not energy) from each other.

mystification as well.

**2.1. The heating paradigm** 

energy than she could take from nutrients.


These technical challenges are definitely complex, and can make the actual hyperthermia treatment uncontrolled. This branch of problems could be the reason for some controversial results and the weak acceptance of the conventional hyperthermia among medical experts.
