Lac-5 Radiobiology .pdf

Radiobiology Lecture -5 Severity of Radiation effects ,Tumor Response of radation Assist. Lec.Sura Alaa Al Rafidain University College Radiation effects on human health can be broadly categorized into three types: sub-acute, acute, and chr...

Radiobiology Lecture -5 Severity of Radiation effects ,Tumor Response of radation Assist. Lec.Sura Alaa Al Rafidain University College Radiation effects on human health can be broadly categorized into three types: sub-acute, acute, and chronic. Each type of effect has different severity and characteristics: 1. Sub-Acute Effects Sub-acute radiation effects occur in the period between acute and chronic effects. These effects typically manifest within weeks to a few months after exposure. They can include: Hematopoietic Syndrome: Damage to bone marrow, resulting in decreased blood cell production, which can lead to infections, anemia, and bleeding. Gastrointestinal Syndrome: Damage to the lining of the gastrointestinal tract, leading to nausea, vomiting, diarrhea, and severe dehydration. 2. Acute Effects Acute radiation effects, also known as Acute Radiation Syndrome (ARS), occur within hours to days of exposure to high levels of radiation. The severity depends on the dose received: Mild Exposure (1-2 Gy) : Nausea, vomiting, and fatigue. Moderate Exposure (2-6 Gy): More severe nausea and vomiting, hair loss, and damage to the bone marrow leading to infections and bleeding.  Severe Exposure (6-10 Gy): Severe gastrointestinal symptoms, significant bone marrow damage, and a high risk of infections and bleeding. Without medical treatment, survival is unlikely. Very High Exposure (above 10 Gy): Severe damage to internal organs and tissues, often resulting in death within days to weeks. 3. Chronic Effects Chronic radiation effects emerge months to years after exposure and can result from lower doses of radiation over extended periods. These effects include: Cancer : Increased risk of various types of cancer, such as leukemia, thyroid cancer, and solid tumors, due to DNA damage and mutations. Cataracts: Radiation-induced damage to the lens of the eye, leading to clouding and vision impairment. Cardiovascular Diseases: Increased risk of heart disease and stroke due to damage to blood vessels and heart tissues. Fibrosis: Tissue scarring and loss of function in organs such as the lungs and liver. Tumor Response to Radiation Radiation therapy targets cancer cells by damaging their DNA, which disrupts their ability to replicate and survive. This process can be broken down into several key factors: DNA Damage and Repair: Radiation causes breaks in DNA strands. Cancer cells, often less efficient at repairing DNA than normal cells, are more likely to die as a result. Cell Cycle Sensitivity: Cells are most sensitive to radiation during certain phases of the cell cycle, particularly the G2 and M phases. Radiation therapy can be timed or fractionated to exploit this sensitivity. Hypoxia: Tumor cells in low-oxygen environments (hypoxic conditions) are more resistant to radiation. Strategies such as hyperbaric oxygen therapy or hypoxia-activated prodrugs can help overcome this resistance. Fractionation: Delivering radiation in smaller, multiple doses allows normal cells time to repair between treatments while maintaining the pressure on tumor cells, which have a diminished repair capability. Therapeutic Index (Combined Radiation and Drug Treatments) The therapeutic index (TI) is a measure of the balance between the therapeutic effect of a treatment and its toxic side effects. In the context of combined radiation and drug treatments: Enhanced Efficacy: Drugs can enhance the effect of radiation on tumor cells. For example, chemotherapy drugs can make cancer cells more susceptible to radiation by inhibiting their DNA repair mechanisms or synchronizing their cell cycles to more sensitive phases. Radio protectors: Some agents can protect normal tissues from radiation damage. These drugs selectively protect healthy cells without shielding cancer cells, thereby widening the therapeutic index. Radio sensitizers: Drugs that make cancer cells more sensitive to radiation. This means lower doses of radiation can be used to achieve the same effect, reducing side effects. Synergistic Effects: The combination of radiation and drugs can have a greater effect than either treatment alone. For instance, some chemotherapy agents can induce DNA damage that is further exacerbated by radiation. Tumor Control Probability (TCP) Tumor control probability (TCP) is the likelihood that a given treatment regimen will completely eradicate a tumor. Dose-Response Relationship: TCP increases with higher doses of radiation, up to a point. The goal is to deliver a dose sufficient to kill all cancer cells while sparing normal tissues. Heterogeneity: Tumor cells can vary widely in their sensitivity to radiation. Factors like genetic mutations, the microenvironment, and cell cycle status all contribute to this variability. Hypoxia: As mentioned earlier, hypoxic tumor cells are more resistant to radiation. Techniques like oxygenation therapy or hypoxia-targeted drugs can improve TCP by making these cells more susceptible to treatment. Biomarkers: Identifying biomarkers that predict tumor response to radiation can help personalize treatment, aiming to maximize TCP for individual patients. Normal Tissue Complication Probability (NTCP) Normal tissue complication probability (NTCP) estimates the risk of damage to healthy tissues from radiation therapy. Dose Constraints: Limits are set on the maximum dose that normal tissues can receive to minimize the risk of complications. These constraints are based on clinical data and models predicting NTCP. Volume Effects: The amount of normal tissue exposed to radiation affects NTCP. Larger volumes receiving high doses are more likely to suffer complications. Fractionation: By spreading the total radiation dose over several sessions, the risk to normal tissues is reduced. This allows for some recovery between treatments, lowering NTCP. Individual Sensitivity: Genetic differences can affect how patients react to radiation. Some individuals have a higher inherent sensitivity to radiation, which can be factored into treatment planning to reduce NTCP.