Accurate Description of Heterogeneous Tumors by Their Effective Radiation-Sensitive and -Resistant Cell Compartments

Brahme, Anders

doi:10.1016/b978-0-444-53632-7.00904-7

Comprehensive Biomedical Physics 2014

DOI: 10.1016/b978-0-444-53632-7.00904-7

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Accurate Description of Heterogeneous Tumors by Their Effective Radiation-Sensitive and -Resistant Cell Compartments

Anders Brahme

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2023

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“…The influence of tumor vasculature heterogeneity on the distribution of hypoxia was carefully calculated for key tumor types and showed good agreement with clinically measured Eppendorf distributions of hypoxia [62][63][64][65]. This clinically very useful dataset for treating common hypoxic tumors with low LET later showed that the optimal LET for treating them is only as low as 25 eV/nm [46,47,54,65].…”

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TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology

Brahme

2023

Cancers

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The new biological interaction cross-section-based repairable–homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized treatments using a few high tumor dose-intensity-modulated light ion beams, thereby avoiding secondary cancer risks and generating a real tumor cure without a caspase-3-induced accelerated tumor cell repopulation. Light ions with the lowest possible LET in normal tissues and high LET only in the tumor imply the use of the lightest ions, from lithium to boron. The high microscopic heterogeneity in the tumor will cause local microscopic cold spots; thus, in the last week of curative ion therapy, when there are few remaining viable tumor clonogens randomly spread in the target volume, the patient should preferably receive the last 10 GyE via low LET, ensuring perfect tumor coverage, a high cure probability, and a reduced risk for adverse normal tissue reactions. Interestingly, such an approach would also ensure a steeper rise in tumor cure probability and a higher complication-free cure, as the few remaining clonogens are often fairly well oxygenated, eliminating a shallower tumor response due to inherent ion beam heterogeneity. With the improved fractionation proposal, these approaches may improve the complication-free cure probability by about 10–25% or even more.

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confidence: 71%

TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology

Brahme

2023

Cancers

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Accurate Description of Heterogeneous Tumors by Their Effective Radiation-Sensitive and -Resistant Cell Compartments

Cited by 1 publication

References 34 publications

TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology

TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology

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