EFFECTS OF RADIATION

Biological Effects of Radiation and its Role in Radiation Therapy

• Radiation therapy uses high-energy beams to target and kill cancer cells.
• High-energy beams irradiate cancer cells, causing them to die.
• Radiation therapy is a common cancer treatment.
• About 50% of cancer patients receive radiation therapy at some point during their treatment.
• The global use of radiotherapy is increasing due to aging populations in developed nations.
• There is a corresponding need for increased education and training of personnel.

What is Radiation Therapy?

• Radiation therapy is a form of curative treatment that uses high-energy beams of radiation.
• High-energy beams of radiation are used to bombard cancer cells.
• Normal cells are also affected by radiation but high-energy beams preferentially damage cancer cells.

Importance of Radiotherapy in Cancer

• Radiation therapy is a consistently effective cancer treatment.
• Half of all cancer patients will use radiotherapy in the course of their treatment.

Importance of Radiotherapy in Cancer

• Radiotherapy is one of the most effective cancer treatments.
• Approximately 50% of patients receive radiation therapy in the course of their cancer treatment.
• The use of radiotherapy is increasing. The reasons cited for this increase are the global aging population, increased incidence of cancer diagnoses and the need for increased education and training to support the use of radiotherapy.
• Global radiotherapy market is projected to reach USD 8,654.95 million by 2027.

Importance of Radiotherapy in Cancer Treatment Options

• Surgery is a major treatment with a longer history than radiotherapy, also successful in treating many types of early-stage cancers.
• Radiotherapy is an alternative to surgical treatment for conditions such as lung cancer and others, that are often successful in achieving good long-term control.
• Chemotherapy is another widely used treatment, with multiple options aimed at killing cancer cells.
• Targeted cancer therapies are new treatments effective at killing cancer cells specifically.

Cancer Type and Percentage Receiving Radiotherapy

• Data provided presents the percentage of patients receiving radiotherapy for various cancer types.
• Specific percentages are listed for different tumor types.

Ionizing Radiation

• Ionizing radiation causes neutral atoms or molecules to become ions (electrically charged entities).
• Radiation used in cancer treatment include X-rays, gamma rays, and particle radiation.
• Ionizing radiation can cause direct or indirect damage.

Types of Radiation and Penetration

• Different types of radiation have varying degrees of penetration.
• Alpha particles: Low penetration, stopped by paper.
• Beta particles: Moderate penetration, stopped by aluminum.
• X-rays: High penetration, stopped by lead.
• Gamma rays: High penetration, stopped by concrete.
• Neutrons: High penetration, stopped by concrete.

Types of Radiation and Biological Effects

• Alpha particles have high linear energy transfer (LET), resulting in high ionization density.
• Beta particles have lower LET than alpha particles.
• Gamma rays and X-rays have very low LET and high penetrating power.
• Neutron beams have high LET resulting in greater biological damage.
• Ionization and density directly correlate to biological effects.

Ionizing Radiation

• Direct ionization is when a radiation beam (e.g., protons, alpha or beta particles) causes disruption to the structure of the atoms/molecules in tissue as it passes.
• Indirect ionization, such as electromagnetic waves and neutron beam, delivers energy to the tissue.
• This then causes the production of fast-moving particles which then damage tissue.
• One key biological damage is the break in the DNA molecule within the cell nuclei.

How Does Radiotherapy Work?

• Radiation therapy induces damage to tumor cell DNA causing cell death.
• DNA can be damaged instantly by radiation.
• Radiation can also form free radicals from water, which can damage DNA in cancer cells (indirect damage method).
• Direct ionization disrupts the tissue atomic/molecular structure.
• Indirect ionization impacts tissue by increasing the production of fast-moving particles, resulting in significant tissue damage.

Direct or Indirect Damage of DNA

• Ionizing radiation directly affects DNA causing single or double strand breaks.
• Indirect damage is caused by free radicals reacting with DNA.

Direct and Indirect Actions of Radiation

• Direct reaction: radiation interacts directly with DNA.
• Indirect reaction: radiation interacts with other molecules (particularly water) forming free radicals.
• Free radicals cause DNA damage.

Why is DNA the Main Target of Ionizing Radiation?

• Ionized molecules are highly reactive, harming cellular components.
• DNA only has two copies, is large, and essential to cell function.

Linear Energy Transfer (LET)

• LET measures the amount of energy deposited by ionizing radiation per unit length of tissue.
• Lower LET, like photons and electrons, have lower energy than protons and alpha particles.
• LET reflects its application in energy deposition at a subcellular level.

Linear Energy Transfer (LET)

• Neutrons, despite being uncharged, have high LET because they interact with atomic nuclei, not electrons.
• This indirect process produces high ionization density, resulting in considerable DNA damage and more pronounced biological effects.
• High LET radiation causes greater cell death than low LET radiation at the same dose.
• Higher LET values correlate to higher likelihood of producing cell death.

Relative Biological Effectiveness (RBE)

• RBE measures the ratio of radiation doses needed to achieve the same level of biological effects.
• A relative comparison can be drawn between different forms of ionizing radiation: lower LET (like photons) versus higher LET radiation (alpha particles).

Relative Biological Effectiveness (RBE)

• RBE is the ratio of radiation doses needed to cause same degree of biological damage.
• Comparing different types of ionizing radiation, higher LET radiation requires a lower dose compared to lower LET radiation.
• Peak kilovoltage, kVp, is the highest voltage produced during an exposure.

Relative Biological Effectiveness (RBE)

• Generally, RBE increases with higher LET but plateaus, as very high LET radiation results in cell death.
• Beyond a certain point, further increase in LET does not significantly increase cell killing, a waste of radiation energy.

Radiation Weighting Factor (WR)

• This factor accounts for different biological effects of different radiation types.
• Different types of radiation have different effects on tissue and this difference is accounted for by the weighting factor. For example, photons (X-rays and gamma rays) have a weighting factor of 1, whereas alpha particles have a weighting factor of 20.

Tissue Weighting Factor (WT)

• This factor accounts for varying tissue sensitivities to radiation damage.
• WT is used to calculate the 'effective dose' reflecting the risk of damage to a specific tissue relative to that of the entire body.

The Success of Radiotherapy

• The success of radiation therapy relies on the amount of dose administered specifically to the tumor area.

Tissue Weighting Factor (WT)

• Different tissues exhibit varied radiosensitivities.
• Cells with frequent division (hematopoietic cells) are more vulnerable to radiation than those which divide less frequently (connective and adipose tissue).
• Factors such as oxygen concentration in the exposed volume are also significant.

Important Terms (Absorbed, Equivalent, Effective Dose)

• Absorbed dose: Energy absorbed per unit mass of tissue.
• Equivalent dose: Accounts for differing harm from various radiation types (radiation weighting factor).
• Effective Dose: Accounts for variations in tissue sensitivity (tissue weighting factor) to radiation.

Radiation Dose (Biological Effect)

• Biological effects of radiation depend on intensity, energy, radiation type, exposure time, and the area/depth of the radiation.

Measurement of Absorbed Dose

• The absorbed dose is energy deposited in a kilogram of material.

Equivalent Dose

• The equivalent dose accounts for the different biological effects of different types of radiation using a radiation weighting factor (WR).

Effective Dose

• The effective dose accounts for different tissue sensitivities to radiation using a tissue weighting factor (WT).

Intensity-modulated Radiation Therapy (IMRT)

• Cancer cells are targeted with radiation from various angles causing less harm to healthy tissues.
• Computed tomography (CT) scans are used to visualize the tumor and to plan treatment plans.

Intensity-modulated Radiotherapy (IMRT)

• IMRT is a high-precision form of radiation therapy accurately delivering radiation doses to malignant tumors, minimizing harm to surrounding healthy tissues.

Intensity-modulated Radiotherapy (IMRT)

• Planning radiation treatment using IMRT, involves 3D visualization of the tumor.
• Computer programs calculate radiation delivery from various angles to target tumor cells effectively while protecting neighboring tissues.

Intensity-modulated Radiotherapy (IMRT)

• Cancer types commonly treated with IMRT include prostate, breast, head/neck, lungs, and brain tumors.
• Tumors located near vital organs benefit from IMRT's ability to precisely target the tumor while preserving surrounding healthy tissue.

Unit 1 Revision

• Radiotherapy is crucial in cancer treatment.
• Half of all cancer patients will use radiotherapy.
• Ionizing radiation damages DNA, a key step in cancer treatment.

Specific DNA Regions in relation to Radiotherapy

• There is no known specific region of DNA that makes a cell more sensitive to radiotherapy.
• Damage to any part of the DNA molecule plays a similar role in causing cell death.

Effect of Radiation on Tumors

• Tumors have a specific microenvironment composed of tumor cells and other supportive cells, which impacts treatment effectiveness.

Hypoxia (Low Oxygen)

• Hypoxia is a condition where tissues have insufficient oxygen supply, usually due to poor blood supply.
• This condition is common in solid tumors.
• Hypoxic cells have a decreased radiosensitivity; radiation might have less of an effect.

Hypoxia and the Microenvironment of a Tumor

• Tumor-associated cells influence the tumor microenvironment and this influence varies with different cell types.
• Cells in the tumor microenvironment support tumor growth.
• Connective tissues within tumors prevent anticancer drug delivery.

Hypoxia and Radiotherapy

• Hypoxic conditions in tumors decrease the effectiveness of radiotherapy in some cases.
• The cause of this phenomenon is that hypoxic cells have already developed adaptations to survive in poor oxygen conditions.
• Hypoxic cancer cells can potentially withstand radiation damage better.

Effects of Ionizing Radiation on the Tumor Microenvironment

• Ionizing radiation affects the tumor microenvironment.
• Radiotherapy causes both beneficial and adverse effects, as it can cause immune cell death, but it also enhances anti-tumor immune responses.

Dose Fractionation

• Dividing the radiation dose into smaller, repeated fractions over several weeks improves treatment effects while reducing damage to healthy tissues (re-oxygenation and repair).

Dose Fractionation and Redistribution

• Cancer cell radiosensitivity varies based on cell cycle phase (most sensitive during mitosis and second growth phase).
• Cancer cells that are not in their most sensitive phase gain the opportunity to repair some of the radiation damage between treatment fractions.

Dose Fractionation: Re-oxygenation

• Dividing the total radiation dose into multiple fractions maximizes the ability for cells that lack oxygen supply within the tumor (hypoxic cells) to recover sufficient oxygen supply.
• These hypoxic cells become more sensitive to radiation.

Dose Fractionation: Repair

• Partitioning the total radiation dose into multiple fractions provides opportunities for healthy cells to repair any radiation damage.
• Meanwhile, malignant cancer cells may not have the same DNA repair capabilities and are less able to repair the damage.

Combining Radiotherapy With Drugs

• Drugs that interfere with DNA repair mechanisms can increase the effectiveness of radiotherapy treatments.
• The drugs target the cancer cells' DNA repair molecules potentially making them unable to fix the damage and improving treatment efficacy.

Important Points

• Normal tissue is impacted by radiation and needs to be factored into treatment parameters.
• Radiotherapy treatments have both early and chronic effects, with some adverse effects.

Early vs Chronic Effects of Radiotherapy

• Early side effects are observed shortly after treatment, in organs with high proliferative activity, such as bone marrow, skin, or intestinal mucosa.
• These effects are typically reversible.
• Chronic effects can appear months or years after treatment, and these can include infertility, immune system damage, and the development of cancer.

Effect of Radiotherapy on Blood Cells

• Radiotherapy affects all types of blood cells, particularly WBCs, RBCs and platelets in blood.
• This can lead to infections, anemia, and bleeding problems in the patient caused by decreased numbers of these blood cells.
• Infections may be caused by a shortage of neutrophils in WBCs, anemia due to low RBC or low hemoglobin count in red blood cells and bleeding problems caused by low platelets.

Acute Radiation Syndrome (ARS)

• ARS is a severe reaction to high doses of radiation.
• It can cause various issues depending on the organs/tissues.

Chernobyl Nuclear Accident

• The 1986 Chernobyl accident resulted in widespread radiation exposure.
• Widespread health issues and cancers occurred in those exposed.

Radiation-Induced Secondary Cancer

• Patients undergoing radiotherapy or chemotherapy have an increased risk of developing secondary cancers later in life.

Photon and Proton Radiotherapy

• Photon therapy has higher incidence of developing secondary cancers later in life compared with proton therapy.
• Protons deliver more highly concentrated radiation doses, causing less severe radiation damage to the surrounding healthy tissue compared with photon therapy.

Acute Radiation Syndrome (ARS)

• Radiation sickness, associated with high doses of radiation in a short time, typically presenting with acute effects (minutes to hours) in exposed organ systems.

Important Points

• The type of radiation influences resulting cancers.
• Important terms for radiation measurements include absorbed dose, equivalent dose, and effective dose. Radiation-induced secondary cancers are a possible outcome.
• Radiotherapy may have chronic effects due to the effect of the radiation on the patient's health.