High LET radiation

Goldman, M., An overview of high LET radiation effects in cells, in The Health Effects of Plutonium and Radium (W. S. S. Jee, ed.), pp. 751-766, J. W. Press, Salt Lake City, Utah (1976). 

First, we want to make a comment about possible local temperature rise due to energy absorption. An early theory of radiation effect s was based on the point-heat hypothesis (Dessauer, 1923). Later analysis showed that the temperature rise would be too feeble and too transient for low-LET radiation to cause any real change (see Mozumder, 1969). There is no experimental evidence for temperature rise for low-LET radiations. The case of high-LET radiations is still open, though. 

Although HO2 and its conjugate base are only significant primary radicals for high LET radiation, they are important secondary radicals in oxygenated solution where they are formed in reactions (55)-(58) ... 

Complex damage presents an increased challenge to the repair processes operating in the cell and is postulated to be largely responsible for the greater biological elfectiveness of high-LET radiations. 

Experiments have shown slower repair of double strand breaks by high-LET radiations [66,152,226]. 

For high-LET radiations, per unit dose fewer regions of genomes are hit, i.e., smaller number of tracks per unit dose (Table 1). 

For high-LET radiations, reaching -70% of all double strand breaks contain additional strand breaks, if base damage is included, this proportion increases to -90% [79,81]. 

Fast neutrons were the first nonconventional radiation used in cancer therapy. Fast neutrons (a high-LET radiation) were introduced for the following radiobiological reasons (1) a reduction of the OER with increasing LET (2) a reduction in the difference in radiosensitivity related to the position of the cells in the mitotic cycle (3) and less repair and thus less clinical relevance of the different repair mechanisms. The best and clinically proven indications for fast neutrons are salivary gland tumors, locally advanced prostatic adenocarcinomas, and slowly growing, well-differentiated sarcomas. 

Radiobiological issues, mainly related to the RBE of high-LET radiation, are discussed. 

Improving the radiobiological differential effect between the cancer and normal cell populations. This second approach is more complex and involves radiobiological considerations. New and different radiation qualities have been considered such as high-LET radiations. Some of the radiobiological issues involved in the use of high-LET radiation, in particular the RBE concept, are discussed in Sec. 3. 

Improving the radiobiological differential effect fast neutrons and other high-LET radiations... 

Among high-LET radiations, fast neutrons were first introduced to exploit a radiobiological differential effect no benefit is expected from the physical selectivity. 

HIGH-LET RADIATION AND RBE RADIOBIOLOGICAL CONCEPT AND CLINICAL APPLICATION... 

The radiobiological and clinical data obtained with fast neutrons are reviewed in the following section they deserve a detailed and careful analysis as they constitute the rationale of the clinical application of any high-LET radiation and, in particular, the justification of the modern heavy-ion therapy programs. 

The arguments for using high-LET radiation in cancer therapy are based on these well-established differences in energy distribution at the microscopic level and can be summarized as follows ... 

The radiobiological arguments discussed above indicate that the high-LET radiation could bring a benefit in the treatment of some cancer types. However, they also imply the need for the development of predictive tests, allowing the radiation oncologist to... 

In the following section, heavy ions include ions heavier than protons (and helium ions). They combine the advantages of an excellent physical selectivity comparable to that of protons with the radiobiological advantages of high-LET radiations for some types of tumors (as discussed for fast neutrons in Sec. 4.1.1). However, as carbon ions are, at the moment, the only type of heavy ions used in therapy, the next section will deal mainly with carbon ions. 

Repair Capacity. Finally, when fractionated treatment is applied, the high-LET radiation at the level of the SOBP (i.e., PTV) partly prevents or reduces cell repair. In contrast, the normal tissues irradiated at the level of the initial plateau are exposed to... 

Table 7 Comparison of Some Clinical Results Obtained with Neon Ions and Fast Neutrons (i.e., External Beam and High-LET Radiation)...

The third approach is the introduction of another type of radiation quality high-LET radiation. Clinical experience with neutrons has demonstrated that high-LET radiations are superior to low-LET radiations for some tumor types or sites. Fast neutrons were indeed the first high-LET radiations to be applied clinically (see Sec. 4.1). Although in the first studies they were applied in suboptimal conditions from a technical or dose distributions point of view, their advantage for some types of tumors is well established, particularly for slowly growing, well-differentiated tumors. Randomized trials have indeed shown their superiority over conventional photons for salivary gland tumors and prostatic adenocarcinomas. 

Heavy ions combine the benefit of the high physical selectivity of proton beams and the biological advantage of high-LET radiation for some tumor types. They appear today to be one of the most promising radiation therapy modalities when the clinical indication is correctly selected (some tumor types and/or localizations). 

Reliable criteria to identify the (individual) patients suitable for high-LET radiation therapy need to be developed. At present, the available criteria are derived (mainly) from the clinical fast neutron experience. It can be expected that novel approaches based on modern techniques involving molecular biology or gene identification may provide appropriate and still missing information. They may also provide information on the susceptibility or risk for secondary radio-induced cancer. 

Figure 28 Schematic presentation of the relative situation of the different types of radiations used in therapy. Two criteria are considered the physical selectivity and the LET (or radiobiological properties). For the low-LET radiations, the physical selectivity was improved from the historical 200-kV x-rays to cobalt-60 gamma rays and the modern linacs. Even with the linacs today, significant improvement is continuously achieved (IMRT, etc.). Among the low-LET radiation, the proton beams have the best physical characteristics, but one of the issues is the proportion of patients who will benefit from proton irradiation. A similar scale can be drawn for high-LET radiation the heavy-ion beams have a physical selectivity similar to protons. Selection between low- and high-LET radiation is a biological/medical problem it depends on the tumor characteristics, and reliable criteria still need to be established (see text). (From Ref 54.)...

Field S.B. Hornsey S. In High-LET Radiations in Clinical Radiotherapy, Barendsen, G.W., Broerse, J.J., Breur, K. Eds. Pergamon Press Oxford, 1979 181 pp. 

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