A7 Radiotherapy

Topic

Radiotherapy uses ionizing radiation—photons, electrons, protons, or heavy ions—to destroy tumor cells by damaging their DNA, specifically causing double-strand breaks. If a cell fails to repair this damage before dividing, it loses its reproductive capacity. Cell survival depends on two components of the damage: a direct component, which increases in proportion to the dose, and a component associated with the interaction between less severe lesions, the significance of which increases roughly with the square of the dose.

The relationship between these two components varies across tissue types and determines their sensitivity to the size of individual doses. Late-responding tissues—such as the spinal cord, lung, or kidney—are particularly sensitive to large doses per session, whereas many tumors and rapidly responding tissues are relatively less dependent on the size of each fraction. This difference forms the basis of conventional fractionation: dividing the total dose into numerous small sessions allows for better protection of healthy late-responding tissues while maintaining the cumulative effect on the tumor.

Some tumors exhibit a different sensitivity to fractionation. Prostate cancer, for example, may behave more like a late-responding tissue than a typical tumor. This allows for the use of hypofractionated regimens—involving fewer sessions and higher doses per session—aiming for a tumor-killing effect equivalent to that of longer conventional treatments without sacrificing the relative protection of healthy tissues.

The goal is not simply to destroy the bulk of the tumor. A single surviving clonogenic cell can retain the ability to reproduce and regenerate the tumor mass. Therefore, the probability of tumor control increases when the dose reduces the expected number of surviving clonogenic cells to extremely low levels. However, increasing the dose also raises the likelihood of complications in the irradiated healthy tissues. Treatment planning therefore seeks to maximize the probability of tumor control while keeping the risk of complications in nearby organs within acceptable limits.

Radiation efficacy also depends on oxygen availability. Oxygen stabilizes some of the radiation-induced DNA damage, hindering its repair. Consequently, hypoxic regions within a tumor can be significantly more resistant than well-oxygenated areas, requiring higher doses to achieve a comparable effect. To overcome this resistance, strategies include using substances that mimic oxygen's sensitizing effect, employing different fractionation schemes, or using radiation types—such as heavy ions—whose effects are less dependent on tissue oxygenation.

Delivering the required dose to the tumor without exceeding the tolerance of healthy tissues necessitates calculating how energy is deposited throughout the irradiated volume. Modern treatment planning systems combine anatomical data with the physical characteristics of the radiation beams, modulating beam intensity from various angles. This allows the dose to be concentrated on the tumor volume while simultaneously limiting the dose received by organs at risk.

Anatomy does not remain static throughout the course of treatment; the position and shape of the tumor and surrounding tissues can shift between sessions. Therefore, modern techniques utilize images acquired prior to or during irradiation to verify anatomy and correct for deviations before the planned dose is delivered.

In summary, radiotherapy integrates radiobiological and physical principles to strike a balance between tumor destruction and the protection of healthy tissue. Dose distribution is determined by the nature of the DNA damage and sensitivity to fraction size; the likelihood of tumor control depends on the number of surviving clonogenic cells; the dose that can be administered is limited by the tolerance of nearby organs; and tumor resistance can be heightened by hypoxia. Dosimetric planning and image-based verification allow these factors to be integrated for precise radiation delivery, aiming to destroy the tumor effectively without causing unacceptable damage to surrounding tissues.

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