Biological mechanisms of normal tissue damage: Importance for the design of NTCP models

Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice

“…It was conceivable that nonthymic tissue damage caused by irradiation also may have remotely affected homing of progenitors to the thymus. 38 Using a lead block to shield either the upper half or lower half of the recipients, we found that 900 cGy of irradiation of the upper half of the mouse blocked homing of progenitors, whereas irradiation of the lower half did not ( Figure 3A), indicating that irradiation of nonthymic tissues was not sufficient to impair thymic settling. To ensure that the homing defect resulted from thymic irradiation, we used computed tomography scans to guide a collimator and direct a beam of irradiation 1.1 cm in diameter at the recipient thymus.…”

Why RBE must be a variable and not a constant in proton therapy

“…In contrast, the late reaction depends on chronic inflammatory processes, with latedeveloping vascular insufficiency along with the development of progressive fibrosis resulting in tissue dysfunction, and which typically occur at intervals of at least 6 months to many years after treatment. 21,22 Late reactions are important since they determine the long-term quality of life in patients cured of cancer; they are highly fraction sensitive, with low radiosensitivity and a/b values, with a high repair capacity, so that RBE values are expected to be higher on the basis of the statements made above.…”

“…The most pertinent consideration is that the increased clustering of ionization events with increasing LET produces a higher proportion of unrepairable damage, which confers greater radiosensitivity and reduced fraction sensitivity than that with lower LET radiation. Another potentially misleading aspect is the definition of the boundary between "low" and "high" LET, which can be misleading in the case of protons where elevations in RBE can occur at what are deemed to be low LET values (from 1 to 10 keV mm 21 ). 12,13 In the present article, high LET will refer to any LET which exceeds the control low LET value which should be in the 0.5-1.5 keV mm 21 range, since there is a steep increase in RBE beyond this value, and more so in the case of protons than other ions 12,13 where the gradient of RBE with LET is less marked.…”

Spätfolgen nach Radiotherapie

“…Zudem ist das Immunsystem beteiligt. Späte Strahleneffekte stellen somit eine komplexe Reaktion dar [1,5,10,25,28]. Sie sind mit wenigen Ausnahmen irreversibel und im Schweregrad fortschreitend.…”