HC20: Radiation oncology

Radiation oncology

Radiation oncology is a separate discipline in oncology where ionizing radiation is used to treat cancer. It is not the same as radiology or nuclear medicine:

• Radiation oncology uses as much radiation as possible, radiology uses as little radiation as possible
• Nuclear medicine is done with the use of soluble radionuclides, radiation oncology uses linear accelerators and fixed sources

50% of cancer patients are irradiated. Radiotherapy can be a form of curative or palliative treatment. Together with other treatments, it increases the numbers of long survivors.

Ionizing radiation

There are several types of ionizing radiation:

• α-radiation
  • Low penetrance
    • Can be stopped by a piece of paper → not often used
  • Sometimes used with cell cultures to measure
• β-radiation
  • Often used
• γ-radiation
  • Most used
• H⁺-radiation (protons)
  • Sometimes used
• Electrons
  • Sometimes used
  • Low penetrance
    • Ideal for superficial tumors (skin cancers) → doesn’t affect deeper laying tissues

External beam radiotherapy:

External beam radiotherapy uses the photons of γ-rays. A linear accelerator can be turned on or off. This is a form of local treatment → there only is radioactivity when the linear accelerator is on. Afterwards, patients won’t be radioactive anymore.

Mechanism of action

Radiation oncology has the following mechanism of action:

1. Radiation causes DNA-strand breaks
   • This can happen due to direct photon-DNA interaction, but mostly due to indirect interaction: photons activate oxygen radicals → cause DNA damage
   • Double strand breaks, single strand breaks and other kinds of DNA damage are being caused
2. Normal cells recognize and repair most of the damage
3. Cancer cells have less regenerative capacity and die at cell division

The aim is to kill the tumor. The side effects of the therapy are determined by the slow down of cell division in surrounding healthy tissues. This causes both acute and late cell side effects.

Dose severity

A higher dose does not always give more tumor control → the likelihood of tumor control isn’t a linear line but is S-shaped. The higher the dose, the higher the toxicity to both tumor and normal cells. The aim of radiotherapy is to kill the tumor without normal cell damage.

Therapeutic window:

The therapeutic window or safety window refers to a range of doses which optimize between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity. It is the space between the tumor control curve and toxicity curve.

There are ways to increase the therapeutic window:

• Make the tumor more sensitive to radiotherapy
  • The tumor responds much faster than the normal healthy cells
  • The therapeutic window becomes bigger → more tumor control with the same amount of radiation
• Make the healthy tissue more resistant to radiation
  • A bigger therapeutic index

Increasing the therapeutic window enhances the sensitivity.

Side effects

Radiation therapy has early, late and chronic side effects:

• Early
  • Dryness of the skin
  • Mucositis
    • Swallowing problems
    • Passage problems
    • Nausea
    • Diarrhea
  • Pneumonitis
  • Alopecia
• Late
  • Proctitis
  • Myelopathy
  • Secondary tumors
• Chronic
  • Fibrosis

Tolerance of normal tissue:

Some tissues are more sensitive to radiotherapy than others:

• Bone marrow: can handle 2-3 Gy → develops aplasia when a higher dose is administered
• Lungs: can handle 16 Gy → develop pneumonitis when a higher dose is administered
• Spinal cord: can handle 50 Gy → develops necrosis when a higher dose is administered

Fractionation

Not all tumor cells will be eradicated after 1 dose → multiple smaller doses are given. While normal cells can repair DNA and recover, cancer cells have malfunctioning DNA repair mechanisms which cause less recovery. This causes the cancer cells to die after multiple doses.

Fractionation schedules:

Fractionation schedules show the doses which are needed to cure different types of cancer. Not all tumor cells are similar in radiation sensitivity → both fractionation doses and total doses vary.

Possibilities to improve the outcome

The outcome can be improved by increasing the therapeutic window. This can be done via:

• Fractionation of the total dose
• Lowering the dose to normal tissue → decreases the toxicity
• Enhancing the sensitivity of tumors → increases the tumor control

Lowering the dose to normal tissue:

There are multiple ways to lower the dose to normal tissues:

• Irradiate from multiple directions → only a small portion (where all the beams meet) is exposed to highly concentrated radiation
  • From 3D to IMRT to VMAT
  • All organs at risk are delineated
  • Patient movement needs to be taken into account
    • Breathing, bowel movements, bladder filling, etc.
• Shield healthy tissues: lead leaves are put over the normal tissue → shields healthy tissues from toxic radiation
• Image guided therapy: used to locate the tumor

Brachytherapy

Brachytherapy consists of a radioisotope close to the tumor. This makes giving very high, local doses to the tumor possible. This can be done by application of:

• An iridium-192 wire
  • Gynaecological, esophageal or rectal tumors
  • Duration: minutes-hours
• Iodine-125 seeds
  • Prostate cancer
• Ruthnium-106 plaques
  • Melanoma of the eye
  • Duration: days
• Cesium-137