Lecture 57- Radiation Oncology

What is radiation therapy?

The use of ionizing energy to kill cancer cells

What forms of energy provide radiation therapy?

Photons, electrons, and other particles

How does ionizing radiation damage tissues?

Direct tissue damage or generation of secondary charged particles (usually electrons) that damage tissue

What determines the type and severity of radiation damage?

Energy of the incident photon

What type of interaction occurs with low-energy photons?

Photoelectric effect

What characterizes the photoelectric effect?

Low energy and atomic mass related

What type of interaction occurs with intermediate-energy photons?

Compton scattering

What characterizes Compton scattering?

Intermediate energy and non-atomic mass related

What type of interaction occurs with high-energy photons?

Pair production

What characterizes pair production?

High energy and increased with atomic mass

How do ionizing particles and free radicals cause cell death?

Break chemical bonds, damage lipid membranes, and cause DNA strand breaks

Is radiation-induced cellular damage distributed uniformly?

No, damage is random

Is resultant cellular death predictable?

No, cellular death is also random

What are the 4 R's of radiobiology?

Repair, Reoxygenation, Redistribution, Repopulation

What determines the cellular lethality of radiation?

The 4 R's of radiobiology

What is repair of sublethal injury?

Cellular repair following sparse ionization damage

How long do most normal tissues require to repair sublethal injury?

Approximately 3-24 hours

How do tumor tissues compare with normal tissues in DNA repair?

Tumors repair slowly or lack repair capacity

Why is radiation fractionated?

To allow normal tissue repair between treatments

What is a disadvantage of excessive treatment delays?

Tumor tissue may recover and repair

How does oxygen influence radiation therapy?

Oxygen stabilizes free radicals and increases cell kill

How do hypoxic cells respond to radiation?

They require more radiation to kill

Why are large tumors often radiation resistant?

They contain hypoxic regions

How does tumor shrinkage improve radiation effectiveness?

Decreases hypoxic areas

How does fractionation improve tumor oxygenation?

Allows reperfusion and reoxygenation between treatments

What phase of the cell cycle is most sensitive to radiation?

G2/M phase

How does fractionation affect cell-cycle sensitivity?

Allows redistribution of cells into more sensitive phases

Which tissues contain many rapidly cycling cells?

Mucosa and skin

Why are rapidly cycling tissues more sensitive to radiation?

Higher percentage of cells are in G2/M phase

Which tissues are relatively spared by redistribution effects?

Connective tissue and brain

How does repopulation influence radiation therapy?

Rapidly proliferating tumors regenerate faster

What factors determine the impact of repopulation?

Tumor repair capacity and redistribution effects

Why can rapidly proliferating tumors sometimes respond well to radiation?

Deficient repair capacity and redistribution into sensitive cell-cycle phases

What factors influence radiation control probability?

Tumor size, radiation dose, and tumor histologic type

What tumor characteristics create favorable response curves?

Small, well-vascularized, homogeneous tumors

What tumor characteristics create unfavorable response curves?

Large, bulky, hypoxic, heterogeneous tumors

Why is radiation administered in fractions?

To improve outcome and reduce toxicity

What unit describes radiation dose per treatment?

Gray (Gy)

What happens when dose per fraction increases?

Side effects increase

What is the advantage of lower dose fractions?

Fewer side effects and ability to give higher cumulative doses

What determines optimal dose per fraction?

Tumor-specific 4 R's

What determines total number of fractions?

Tumor-specific and site-specific considerations

What determines side-effect severity?

Dose per treatment and cumulative dose

Describe a conventional radiation protocol.

2.0-3.0 Gy given 5 times/week for 4-6 weeks

What is the goal of conventional fractionation?

Minimize long-term side effects

Describe a palliative radiation protocol.

4.0-8.0 Gy given daily to weekly

How does total dose compare in palliative protocols?

Lower than conventional protocols

What is the goal of palliative fractionation?

Minimize short-term side effects

What is a potential disadvantage of palliative protocols?

Lower tumor control rates

What equipment comprises modern external beam radiation units?

Electron gun, water coolant, tungsten target

How are photons generated in external beam therapy?

Accelerated electrons strike a tungsten target

What photon energies are typically generated?

>1 MeV

Can electrons be used directly for therapy?

Yes

How do photons and electrons differ?

They have markedly different depth-dose distributions

Why are different particle types and energies selected?

To optimize tumor dose while minimizing normal tissue dose

How is external beam radiation focused on tumors?

Collimators and multiple radiation fields

What is the purpose of multiple fields?

Improve tumor dosing while sparing normal tissue

What is brachytherapy?

Placement of radioactive source within or near a tumor

What is the major advantage of brachytherapy?

High tumor dose with normal tissue sparing

What radioactive sources may be used in brachytherapy?

Seeds, wires, pellets, capsules, intralesional electronic sources

What radionuclide is commonly used for feline hyperthyroidism?

I-131

What type of emission does I-131 produce?

Beta emission

What is the energy of I-131 emissions?

0.19 MeV

What radionuclide is used for intralesional therapy and radioembolization?

Yttrium-90

What type of emission does Yttrium-90 produce?

Beta emission

What is the energy of Yttrium-90 emissions?

0.94 MeV

How does tumor size influence radiation outcomes?

Larger tumors have worse outcomes

Why do large tumors respond poorly to radiation?

Hypoxia and decreased radiation sensitivity

When is radiation most effective?

For microscopic disease

How can treatment limitations be overcome?

Combining treatment modalities

What normal tissue factors may limit radiation success?

Proximity to sensitive tissues

Why is patient condition important for radiation planning?

Must tolerate anesthesia or sedation

What practical consideration affects treatment choice?

Cost

What are the two major categories of radiation toxicity?

Acute and late tissue reactions

What tissues typically develop acute toxicity?

Rapidly dividing tissues

What tissues typically develop late toxicity?

Slowly responding tissues

What examples of unacceptable radiation toxicity were listed?

Non-healing skin wounds and secondary tumor formation

What approximate incidence of unacceptable side effects is accepted?

~5%

What are characteristics of acute radiation toxicity?

Typically reversible and occurs during/immediately after therapy

Which tissues are most affected by acute toxicity?

Rapidly dividing tissues

What are common acute toxicities?

Mucositis, moist desquamation, erythema

What usually limits total radiation dose?

Late toxicity, not acute toxicity

What is an exception to late toxicity being dose-limiting?

Palliative therapy

What are characteristics of late radiation toxicity?

Permanent injury developing months to years later

Which tissues are most susceptible to late toxicity?

Fibroblasts, neurons, muscle, bone

What are common examples of late toxicity?

Xerostomia, KCS, fibrosis, soft-tissue necrosis, nerve damage

What factors influence late toxicity?

Cumulative dose and dose per fraction

How does increasing dose per fraction affect late toxicity?

Makes toxicity worse

How common are cutaneous squamous cell carcinomas among skin tumors?

Approximately 5%

Where are cutaneous SCCs most common?

Unpigmented regions

What major risk factor causes many SCCs?

Solar exposure

What percentage of cutaneous SCCs are multifocal?

Approximately 30%

What is the metastatic potential of cutaneous SCC?

Low

How do bulky SCCs respond to radiation?

Poorly responsive

What is the disease-free interval for T3 SCC tumors?

Approximately 3-9 months

What is the disease-free interval for T1 SCC tumors?

Approximately 5 years

What is the most common histology of canine nasal tumors?

Adenocarcinoma

Rank common nasal tumor histologies from most to least common.

Adenocarcinoma > SCC > Sarcoma

What prognostic factors are important for nasal tumors?

Histology and tumor stage

Which nasal tumor histology has the best prognosis?

Adenocarcinoma