Radiobiology and Cancer Terminology

Radiobiology

• Radiobiology is the study of radiation on living things.

Terminology

• DNA carries genetic information for development and function.
• Tumors are abnormal cell growths (benign or malignant).
• Cancer is a disease of abnormal cells that infiltrate and destroy normal tissue.

The Nature of Cancer

• Carcinogenesis is the process of cancer formation, taking years.
• Normal cells (10-20 microns) undergo genomic alterations, leading to uncontrolled replication and tumor formation (radiologically detectable at 2mm³).
• Benign tumors stay localized and usually don't return after removal.
• Malignant tumors are mobile (metastasize), show angiogenesis, and exhibit uncontrolled proliferation, with loss of growth suppressors.
• Carcinoma (80-90%): a type of cancer affecting glands and organs (e.g., adenocarcinoma).
• Squamous Cell Carcinoma: affects squamous epithelium.
• Sarcoma: affects connective tissue.
• Myeloma: affects plasma cells in bone marrow.
• Leukemia: affects blood cells in bone marrow ("liquid/blood cancer").
• Lymphoma: affects lymph cells.
• Hodgkin's and Non-Hodgkin's are types of lymphoma.
• Mixed types of cancer include combinations.

Epidemiology

• Epidemiology is the study of the distribution and determinants of disease.
• Incidence is the number of new cases in a population over a specific time.
• Prevalence is the number of existing cases (previous and new) in a population.
• Mortality is the death rate, often disease-related.

Etiology

• Etiology is the study of causation.
• Risk factors are variables linked to the likelihood of a specific endpoint (e.g., cancer).
  • Intrinsic risks are those that cannot be changed, such as random errors during DNA replication or biological aging.
  • Non-intrinsic risks are those that can be changed, such as exposure to radiation, chemical carcinogens, and infections (viruses).

Screening

• Screening is a mechanism for detecting undiagnosed diseases.
• Effective screening tests should have high sensitivity (detecting disease in those who have it) and specificity (correctly identifying those without disease).
• Screening tests should be acceptable to the target population.
• Screening strategies include breast, colorectal, lung, and prostate screenings, which may include non-invasive and invasive tests.

Radiation Physics

• Radiation physics encompasses electromagnetic radiation (e.g., light, radio waves, X-rays) and particle radiation (fast-moving particles with energy and mass).
• Ionizing radiation loses energy upon interaction with matter.
• Interactions, such as photoelectric effect, Compton scattering, and pair production, can occur with inner or outer-shell electrons.
• Stopping power is the average rate of energy loss of a charged particle per unit length.
• Linear Energy Transfer (LET) is the energy transferred by radiation per unit length. Higher LET corresponds to more energy deposition in a smaller area.

Relative Biological Effectiveness (RBE)

• RBE is a measure of the amount of radiation required to achieve a particular biological effect, expressed in Gray (Gy).
• Equal doses of different radiation types do not have equivalent biological effects.
• RBE is used to compare the effectiveness of different radiation types.

Radiation Chemistry

• Radiolysis is the breakdown of a molecule, causing free radicals/ions to form via ionization.
• Chemical interactions of radicals or ions with other molecules, and energy transfer can occur.
• Water is a primary target for indirect effects, and these processes may lead to long-term biological consequences.

Cell Cycle

• The cell cycle includes stages when DNA is replicated (S phase) and duplicated/separated (M).
• Stages are G1, S, G2, and M to regulate cell growth.
• Checkpoints control transitions between phases.

Chromosome damage

• Chromosomes can be damaged by radiation.
• This results in different types of chromosome abnormalities.

Cell Death

• Apoptosis and necrosis are two types of cellular death.
• Apoptosis is programmed cell death, involving controlled processes at the cellular level.
• Necrosis is uncontrolled cell death, often due to injury or damage.

DNA Repair

• Various mechanisms exist for DNA repair.
• Base excision repair (BER) targets single-strand damage.
• Nucleotide excision repair (NER) corrects larger distortions in DNA strands.
• Homologous recombination repair (HR) repairs double-strand breaks using a homologous template.
• Non-homologous end joining (NHEJ) joins broken ends directly, less accurate.
• Mismatch repair (MMR) corrects base mismatches.

Survival curves

• Survival curves show the relationship between the dose of radiation and the proportion of surviving cells.
• The D0 value is the dose required to reduce survival by 37%.
• D37: the dose required to reduce survival to a 63% level.

In-vitro assays/mouse tumour models

• In-vivo studies are used to observe effects in living organisms.
• In-vitro studies use lab techniques to investigate biological effects.
• Mouse assays are common methods for modelling cancer and radiation damage in vivo/in-vitro conditions.

Other important concepts

• Radiation induces chromosomal aberrations.
• Risk of radiation comes from several factors (e.g., quality/type of radiation, amount).
• Stochastic damage: no threshold of radiation dose for harmful effect.
• Deterministic damage: a threshold dose above which tissue damage is observed.
• OER = oxygen enhancement ratio: measures how much increased effect of radiation there is when oxygen levels are higher.
• RBE = relative biological effectiveness: measures the amount of different types of radiation that can produce a certain effect.