Journal ClubDept. Of Medical Physics

Faculty of Medicine Iran Uni. Of Medical Sciences

Hyperthermia

SR Mahdavi1395/07/27

Article:OverviewHyperthermia: a Potent Enhancer of Radiotherapy

Clinical Oncology (2007) 19: 418 - 426

M. R. Horsman, J. OvergaardDepartment of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark

Importance of Hyperthermia topic

Extensive preclinical data showing that hyperthermia (HT) combination with radiation is one of the most effective radiation sensitizers.

Selection Criteria: 1. HT as a complementary medicine, 2. Established technique in developed countries 3. Wide research area; HT+RT/Ch.T 4. A branch of Clinical application of Medical Physics 5. Research design in the physics of HT (QA, thermometry,…..) 6. This facility is now present in Iran

Search strategy

This article was an internet research product in the field of HT Explain.

I know Prof. Michael Horsman well. He is PhD in radiation biology in Department of Clinical Medicine - Department of Experimental Clinical Oncology, Aarhus University Hospital.

Research methodology: Purpose

Authors try to say that: 1. Although hyperthermia per se is probably only useful in palliative situations and has no role

to play in the curative treatment of human tumours. But;

2. There is definitive evidence that when hyperthermia is combined with other treatments, such as Radiation, significant improvements in clinical outcome are possible.

.

In fact hyperthermia is probably one of the most effective radiation sensitizers known.

Research methodology (cont’d): Combining Heat and Radiationin vitro and in vivo

Interaction between heat and radiation is dependent on a number of factors. These include heating temperature, heating time, and sequence and time interval between the two modalities, as illustrated in Fig. 1.

Combination of heat and radiation in vitro

The exact mechanism by which heatsensitizes cells to radiation is not known, but most evidence suggests that heat primarily interferes with the cells’ ability to deal with radiation-induced DNA damage

Combination of heat and radiation in vivo

In vivo; the heat-induced enhancement of radiation damage generally result of two mechanisms:

1. Direct radio-sensitization as in vitro 2. Indirect mechanism (HT toxicity): heat kills the radio-resistant hypoxic cell

population.

Tumour’s vascular supply is structurally and functionally abnormal.

This results in the development of areas that are nutrient deprived, low in oxygen, and highly acidic.

Cells under hypoxic conditions are more sensitive to the lethal effects of hyperthermia than cells in a well-oxygenated environment.

Combination of heat and radiation in vivo

Factors Influencing the Responseto Single Treatments

1. Generally, for tumours the thermal enhancement ratio (TER) of the radiation response is greatest when the radiation and heat are administered simultaneously (Fig. 2).

2. The larger TER pre-radiation heating is may beindicative of a persistent thermosensitization (direct) mechanism.

3. Post-radiation heating enhancement can be due to HT radio-resistant cell killing (indirect) effect.

Findings

For simultaneous treatment no therapeuticadvantage is to be expected.

Sequential treatment has little or no effect innormal tissues means that there is a substantial therapeutic benefit with it.

Thermotolerance: Depends on the cell type, temperature, duration, and the interval between successive heat treatments.

Tissue temperature fluctuation: Step-down heating (SDH) and SUH.

With SUH the tumour response is the result of an additive effect of the two heat treatments, whereas with SDH not only is there additional cell killing from the higher temperature, but significant sensitization to the second heat treatment is also observed.

Findings

Other findings discussed in this paper

Role of the Tumour Vasculature Tumour micro-environmental changes Effect of heat on the tumour vasculature

Findings, cont’d:Clinical Trials with Heat and Radiation

Results show loco-regional control, which is the most relevant end point for locally applied treatments, and show significant heatinduced improvements in a number of distinct sites,including chest wall, cervix, rectum, bladder, melanoma, and head and neck.

Table 1 . Meta analysis of all clinical trials in which patients were randomised to receive radiation alone or radiation with hyperthermia*

Critical appraisal

Type of heat generating method Radiofrequency and Capacitive HT Difficulties in adequately and effectively heating

tumours in patients (Physics and technical issues) These types of studies can have important role in

improvement of HT methodology and clinical application.

Conclusion

So, how can we change the current thinking about the application of hyperthermia and radiation? Clearly, with so many randomised trials showing obvious benefits it is unlikely that carrying out additional trials would be the answer. What is needed are improvements in the physics and biology so that preferential tumour heating becomes easier.

Group discussion

Opening clinical trials with emphasis on physics and biology

Treatment planning Phantom design for thermal mapping and

measurement

متشکرم بسیار

Methods to increase tumour temperature