Oncology-Radiobiology of Normal Tissues

I. Mechanisms of Radiation Damage:

• Apoptosis: Programmed cell death occurring within 24 hours of irradiation. Primarily affects specific cell types (e.g., some hematopoietic cells, salivary gland cells). Often clinically insignificant due to tissue redundancy and stem cell replacement.
• Loss of Reproductive Capacity: Reduces the ability of cells to proliferate. The timing of damage manifestation depends on the tissue's cell renewal rate, leading to the distinction between acute and late effects. This is the predominant mechanism in most tissues.

II. Radiosensitivity:

Radiosensitivity varies greatly between tissues (see Table 1).

Table 1: Radiosensitivity of Normal Tissues

III. Acute vs. Late Effects:

• Acute Effects (within 8 weeks of treatment): Primarily affect rapidly proliferating tissues (skin, mucosa, hematopoietic system). Predominantly caused by loss of reproductive capacity, impacting cell replacement. Severity depends on total dose and treatment duration. Complete recovery is usually expected with properly selected treatment doses. Examples include erythema, desquamation, mucositis. The speed of recovery depends on stem cell survival.
• Late Effects (months to years after treatment): Primarily affect slowly proliferating tissues (lung, kidney, heart, CNS, connective tissue). Severity depends on total dose and dose per fraction (smaller fractions offer protection). Recovery may be incomplete. Examples include fibrosis, telangiectasia, radiation pneumonitis, nephropathy, cardiomyopathy. Late effects are not always predictable from the severity of acute reactions.

IV. Specific Tissue Responses:

• Skin: Acute – erythema, desquamation, ulceration (if severe). Late – atrophy, fibrosis, telangiectasia.
• Oral Mucosa: Acute – erythema, ulceration. Late – dry mouth.
• Gastrointestinal Tract: Acute – mucositis (oesophagitis, nausea/vomiting, diarrhoea, tenesmus). Late – ulceration, fibrosis, obstruction, necrosis.
• Central Nervous System (CNS): No acute reaction. Late – demyelination (somnolence, Lhermitte's syndrome), radiation necrosis.
• Lung: Acute – airway obstruction (with large single doses). Late – pneumonitis, fibrosis.
• Kidney: No acute response. Late – nephropathy (proteinuria, hypertension, renal failure).
• Heart: Late – pericarditis, cardiomyopathy, conduction blocks.

V. Normal Tissue Tolerance to Retreatment:

Some tissues (e.g., CNS) show significant recovery from subclinical radiation injury, allowing safe retreatment in certain circumstances.

VI. Carcinogenesis:

Radiation-induced DNA damage can lead to secondary malignancies (leukemias, solid tumors) years after exposure. The thyroid and breast are particularly susceptible, especially in childhood/young adulthood. This risk must be weighed against the risk of cancer recurrence.

VII. DNA Repair:

The body can repair some radiation-induced DNA damage. A minimum 6-8 hour gap between radiotherapy fractions is necessary for sufficient repair to prevent excessive normal tissue damage. Hereditary DNA repair defects can significantly increase the risk of severe normal tissue reactions to radiotherapy.

VIII. Hypoxia:

Hypoxic (oxygen-deficient) cells are less sensitive to radiation. Tumor hypoxia is common and can be aggravated by anemia. Tumor response and subsequent reoxygenation during fractionated radiotherapy can enhance tumor cell kill.