Mednotes

L8 Cancer Principles of radiation treatment of cancer (changed 7_7)

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tagscancer, lecture
aliasesL8 Cancer Principles of radiation treatment of cancer (changed 7_7)

11 min read

Overview

This lecture introduces radiotherapy (RT) as a mainstream cancer treatment tool: why it matters and how common it is, its history and the discovery of radiation’s biological effects, how a treatment machine is built and physically works, the biological mechanism by which radiation kills cells, the practical patient pathway from planning to delivery, and the side effects radiation causes in normal tissue.

Why Radiotherapy Matters

  • Radiotherapy should be thought of as a tool like any other in medicine (alongside surgery, chemotherapy, antibiotics); the difficulty for learners is simply unfamiliarity with what radiation “looks like,” not any special conceptual difficulty (“it has nothing to do with physics”).
  • About 50% of all cancer patients receive radiotherapy at some point during their illness, and radiotherapy contributes to around 40% of curative cancer treatment (Baskar et al., Int J Med Sci 2012;9(3):193-199).
  • It is a highly cost-effective single-modality treatment, accounting for only about 5% of the total cost of cancer care.
  • Global cancer deaths have risen steadily from 1990 to 2016 (Our World in Data / IHME), with tracheal/bronchus/lung cancer forming the largest single contributing category.

An early slide shows a dense, unexplained figure (no title given) illustrating the complexity of RT physics: a radiotherapy bunker shielding schematic (primary/secondary barriers, primary/leakage/scattered radiation), a radiative-transport equation, biologically effective dose (BED) comparisons between an original, applied and new treatment schedule (BED3 ratio = 106.7%), and IMPT vs VMAT planning scans with isodose levels (41.4-18.0 Gy). The transcript records these elements as visible but does not interpret them, since the slide itself gives no explanatory text.

History and Understanding of Radiation Effects

  • Radiation and radioactivity were discovered by Wilhelm Röntgen, Henri Becquerel and Marie Curie.
  • An early X-ray photograph of a hand wearing a ring, captioned “I have seen my death!”, illustrates the first public reactions to seeing inside the living body.

    The handwritten annotation and stamp on this historic photograph were too small/faint to transcribe accurately.

  • Radium-dial painters, who hand-painted watch and clock dials using fine brushes and radium-based paint, are used historically to illustrate radiation’s harmful biological effects from occupational exposure.
  • Study of Hiroshima and Nagasaki atomic bomb survivors, mapping radiation exposure zones (by gray dose) against total vs partial building destruction around the hypocenter, has been used to build understanding of radiation’s impact on humans.
  • The attributable fraction of cancer deaths due to radiation increases with dose: roughly 57% at doses >2 Gy, 35% at 1-2 Gy, 25% at 0.5-1 Gy, 13% at 0.2-0.5 Gy, 6% at 0.1-0.2 Gy, and about 1% at 0.005-0.1 Gy.
  • Comparative radiation exposure levels (approximate, in mSv, with Gy equivalents where given): 10,000 mSv (~10 Gy) is fatal within weeks; 6,000 mSv was the typical dose recorded in Chernobyl workers who died within a month; 5,000 mSv is the single dose that would kill half of those exposed within a month; 1,000 mSv (~1 Gy) can cause radiation sickness/nausea but not death; 400 mSv/hr was the max level recorded at Fukushima (14 March); 350 mSv was the exposure of relocated Chernobyl residents; 100 mSv is the recommended five-year limit for radiation workers; 10 mSv is the dose from a full-body CT scan; 9 mSv is the annual dose for airline crew flying the NYC-Tokyo polar route; 2 mSv is average annual natural background radiation; 1.02 mSv/hr was detected at the Fukushima site (12 March); 0.4 mSv is a mammogram; 0.1 mSv is a chest X-ray; 0.01 mSv is a dental X-ray.

Dose, Units and Treatment Aims

  • Radiation dose is measured in Gray (Gy).
  • Treatment courses are either curative or palliative: curative courses typically deliver 50-75 Gy; palliative courses deliver 4-30 Gy; both are delivered over 1-35 fractions (#).
  • Example schedules: breast cancer 26 Gy in 5#; radical head and neck cancer 70 Gy in 35#; rectal cancer 50 Gy in 25#.
  • Stereotactic Ablative Radiotherapy (SABR) uses a high dose per fraction with a low number of fractions (1-5#, totalling 15-55 Gy) and high-precision targeting, in contrast to conventional fractionation. (The transcript names “volume effect” and “fractionation” as related concepts on the same slide but does not elaborate on them further.) [slide does not elaborate]
  • Aims of RT treatment:
    • Cure — if the cancer has not spread, is sensitive to RT, and the patient is well enough for treatment.
    • Extension of life expectancy/quality.
    • Palliation — if the disease has spread, is resistant to RT, or the patient is frail.
    • Uncertain — the pros and cons must be discussed with the patient.

How a Linear Accelerator Works

  • Radiotherapy machines have evolved from orthovoltage machines (1940s/50s, a large cylindrical tube head on an articulated arm) to modern linear accelerators (Linear accelerators, e.g. Elekta).
  • In a linear accelerator (LINAC): an electron gun generates an electron beam; the beam is accelerated along the accelerating waveguide (powered by an RF power generator); it passes through the electron beam transport system and strikes an X-ray target, producing the treatment X-ray beam; the gantry (rotating about the gantry axis, supported by the stand) directs this beam at the isocentre, where the patient lies on the treatment couch (positioned along the couch axis).

Mechanism of Cell Killing

  • The electromagnetic spectrum runs from non-ionizing radiation (safe and beneficial in appropriate dosage at low frequencies such as radiofrequencies, microwaves, infra-red, visible and, at higher frequency, low-danger to dangerous, e.g. ultraviolet) to ionizing radiation (X-rays and gamma rays), which is extremely harmful.
  • Ionizing radiation damages DNA by two mechanisms:
    • Direct action: a photon ejects an electron that directly strikes and damages the DNA strand.
    • Indirect action: a photon ejects an electron from a water molecule (H₂O), producing a hydroxyl free radical (OH), which then damages the DNA strand; this action operates over a range of about 20 Å.
  • Biological response pathway: radiation strikes both normal and cancer cells, causing DNA damage in the form of double-strand breaks (DSB) and single-strand breaks (SSB). These activate the sensor kinases ATM, ATR and DNA-PK, which in turn activate p53 (also inducing Bax and Puma) and drive a G1 halt with repair via p21. The downstream outcomes are apoptosis, growth arrest, or proliferation. Apoptosis kills cancer cells; growth arrest and proliferation rescue normal cells.

Patient Pathway

  • Planning begins with a CT planning/simulation scan (e.g. on a Siemens Somatom Definition AS scanner).
  • Immobilisation devices are used to ensure reproducible positioning: e.g. the “BreastSTEP” board with arm/hand rests and a wedge for breast cases, or a mesh thermoplastic mask for head and neck cases, aligned at setup using projected laser crosshairs.

    One slide in this sequence shows only an uncaptioned close-up photograph of a hand and wrist, with no slide title or label; the transcript notes that the teaching point of this image is not stated on the slide.

  • Some treatment rooms use a patient visual-feedback system comprising a pico projector, an adjustable table mount, a curved radiolucent screen, and a flexible screen attachment around the patient’s waist; the slide labels these four components but does not state their purpose. [slide does not elaborate]
  • Planning CT images are contoured in treatment-planning software to define target volumes and organs at risk, recorded in a structures table listing each structure’s colour, volume (cm³) and type (e.g. Target, External).
  • Treatment is delivered on a linear accelerator (e.g. an Elekta Versa HD) in the treatment room.

Side Effects

  • General mechanism of side effects: inflammation and reduced function of the irradiated tissue/organ region, illustrated across body regions including CNS, head and neck, breast/chest, abdomen and pelvis.
  • Late side effects: loss of cell numbers (atrophy), reduced blood flow, and fibrosis of muscles and subcutaneous tissues.

One slide shows an uncaptioned collage of roughly 17 web-search-style thumbnail images on the theme of radiotherapy side effects (skin reactions such as erythema and blistering, body diagrams, and article graphics from various non-academic websites). Individual thumbnail captions and sources were too small to transcribe reliably; this appears to be an unattributed image collage rather than a single sourced figure.

The lecture ends with an “Examples” section-divider slide; the transcript records no further content slides for it.

Self-test

  1. What proportion of cancer patients receive radiotherapy during their illness, and how much does radiotherapy contribute to curative cancer treatment?
  2. Why is radiotherapy considered a cost-effective treatment modality?
  3. Trace the historical discoveries that shaped understanding of radiation’s biological effects, from Röntgen’s early X-rays to the atomic bomb survivor data.
  4. Describe how the attributable fraction of cancer deaths due to radiation changes with dose.
  5. What unit measures radiotherapy dose, and what are the typical dose ranges for curative versus palliative treatment?
  6. Give three examples of dose/fractionation schedules used for specific cancers.
  7. Distinguish SABR from standard fractionated radiotherapy schedules.
  8. List the possible aims of radiotherapy treatment and the criteria that determine which applies.
  9. Describe the steps of X-ray beam generation in a linear accelerator, from the electron gun to the isocentre.
  10. Distinguish the direct and indirect actions by which radiation damages DNA.
  11. Describe the cell-signalling pathway triggered after radiation-induced DNA damage, from strand breaks to the possible cellular outcomes.
  12. Why can radiation kill cancer cells while normal cells can be “rescued”?
  13. Describe the steps of the patient pathway from CT planning to treatment delivery, including the role of immobilisation devices.
  14. Distinguish the early/acute side effects of radiotherapy from its late side effects, giving examples of each.
  15. Integrative: explain how the biological mechanism of radiation-induced DNA damage underlies both radiotherapy’s therapeutic effect and its side effects.

Answers

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