Understanding the Theory of Radiotherapy: Effects and Mechanisms
Radiotherapy, a cornerstone in the treatment of cancer, operates on a fundamental understanding of how radiation interacts with normal tissues and malignant cells. This intricate interplay is governed by several mechanisms and is vital to comprehending the theory of radiotherapy.
Radiation Effects on Tissues
The effects of radiation on tissues primarily manifest through two mechanisms:
1. Apoptosis: This is a form of programmed cell death, typically occurring within 24 hours of irradiation. Radiation can trigger apoptosis, leading to the loss of mature functional cells.
2. Loss of Cellular Reproductive Capacity: Radiation can impair the ability of cells to reproduce. This loss of reproductive capacity is another key effect, and its severity increases with higher radiation doses.
The impact of radiation is dose-dependent, meaning that increasing radiation doses result in greater cell loss. However, different types of cells exhibit varying sensitivities to these mechanisms. For instance, some cells of the haemopoietic lineage and salivary glands are more prone to apoptosis. Importantly, most tissues possess redundant functional cells, enabling them to tolerate a significant loss of cells through apoptosis without clinical impairment. Often, lost cells are replaced through the proliferation of surviving stem cells or progenitor cells. These replacement cells can originate from within the irradiated tissue or migrate from adjacent unirradiated areas.
Radiosensitivity of Normal Tissues
The sensitivity of different tissues to radiation varies widely:
- Highly Sensitive: Lymphocytes and germ cells are among the most sensitive to radiation.
- Moderately Sensitive: Epithelial cells display moderate sensitivity.
- Resistant: Certain tissues, such as the central nervous system (CNS) and connective tissues, are relatively resistant to radiation.
The nature of cell loss, whether through apoptosis or loss of reproductive capacity, depends on the specific tissue and the radiation dose applied.
Acute Effects of Radiation
Acute effects of radiation predominantly impact tissues with rapid cellular turnover. These include the skin, mucosal linings, and the haemopoietic system. While apoptosis may play a role, the primary effect is the loss of cellular reproductive capacity, which impedes the replacement of lost cells.
The timing of acute radiation effects is influenced by the rate of radiation dose administration or fractionation. For example, the mucosal lining of the intestinal tract may be depleted within days after a single high dose, but it may take several weeks during a fractionated course with smaller daily doses.
The speed of recovery from acute reactions varies depending on the extent of stem cell depletion. Severe epithelial damage may persist as a chronic ulcer if the number of surviving stem cells is too low.
Late Effects of Radiation
Late radiation effects primarily affect slowly proliferating tissues like the lung, kidney, heart, liver, and CNS. However, late effects are not limited to these tissues. These effects become apparent only after a considerable time post-irradiation and are not always predictable based on the severity of acute reactions. The total radiation dose and dose per fraction significantly influence the development of late radiation effects.
**Normal Tissue Tolerance to Retreatment**
Recent research has shown that some tissues have a substantial capacity to recover from subclinical radiation injury. This allows for the safe retreatment of previously irradiated areas, particularly in the CNS, offering new treatment possibilities.
Carcinogenesis
Radiation-induced DNA damage can contribute to the development of secondary cancers (2° malignancies). These cancers may surface years after radiation exposure, with leukaemias typically appearing within 6-8 years and solid cancers emerging after 10-30 years.
Repair of Radiation-Induced DNA Damage
Some radiation-induced DNA lesions can be repaired. A minimum gap between fractions is essential to allow for DNA repair when using multiple fractions of radiotherapy.
Hypoxia
Hypoxic cells, often found in cancerous tissues due to abnormal blood supply, are less sensitive to radiation than oxygenated cells. During fractionated radiotherapy, cancer response may lead to the reoxygenation of initially hypoxic areas, enhancing tumor cell kill.
Understanding these mechanisms and effects is crucial in optimizing radiation therapy for cancer treatment, ensuring the balance between eradicating cancer cells and preserving healthy tissues.