This module was written by a medical student for other students who are curious about radiation dose and radiation planning.  It was designed to provide you with tools for reasoning about radiation dose in medicine, whether or not you want to be a radiation oncologist.  It also introduces concepts that you will encounter on your radiation oncology rotation, so that you will have a framework for understanding radiation planning.  

We aim to address the following objectives that are listed by the 2015 Canadian Oncology Goals and Objectives for Medical Students (by the Canadian Oncology Group):  

1. Demonstrate an understanding of the general principles of how radiation is used to treat cancer and different types of radiation (e.g. external beam, brachytherapy, stereotactic radiation). 
2. Describe the role of various medical and allied health professionals in multidisciplinary cancer treatment teams and know the services offered by a typical outpatient cancer center.

It’s clear that radiation oncology involves high doses of radiation.  But exactly how much radiation are we talking about?  

If you’ve ever looked into radiation treatment, you’ve probably come across phrases like “60 Gy in 30 fractions”.  What is a Gy (Gray) anyways?  To make things more confusing, you may come across other units like Sv (Seivert) or even others like Bequerel (Bq).  Why do we need more than one type of unit to describe the same process?

When ionizing radiation moves through something, it deposits energy.  This happens no matter what type of radiation we use, although the process looks different in each case.  For example, the photons we use in radiation oncology actually knock electrons out of their orbitals, which bounce around and wreak havoc.   For more information on this process, see the Radiation Oncology Basics section.  

If you take the energy that radiation deposits (measured in joules) as it moves through an object, and divide it by the mass of that object (in kilograms), this gives you a measurement of absorbed dose within a tissue. This is measured in Gray (Joules/Kilogram) and is the primary measurement of absorbed radiation used in oncology.  

Note what the absorbed dose -does not- depend on.  We have made no assumptions about the type of tissue we are using, nor the type of radiation.  The absorbed dose only depends on how much energy is transferred from the radiation to the tissue.  

We now have a way of talking about energy transfer from radiation: the absorbed dose, which is measured in Gray.  

You may have heard that some tissues are more “radiosensitive” or vulnerable to radiation than others.  Why is this, and how can we communicate this in our dose calculation?

In 1970, Munro et al. discovered that placing a highly radioactive polonium needle near the cell nucleus- but not the cytoplasm or the cell membrane- killed the hamster cells they were experimenting on.  It is DNA damage that kills cells.  Thinking back to our liberated electrons wreaking havoc, each gray of ionizing photons causes about one thousand single strand DNA breaks and 20-40 double strand breaks in each cell.  Each cell has mechanisms to repair DNA damage, but occasionally irreparable damage will occur in a gene that is necessary for cell survival, and the cell will die.  

Through a series of experiments on rabbit testes, two early 20th century scientists (Bergonie and Tribondeau) discovered that the more rapidly a cell divides, the more vulnerable it is to cell death from radiation.  We now know that this is because of DNA damage.  Cells from rapidly dividing tissues (such as bone marrow, breast, and colon) are much more radiosensitive than more slowly dividing tissues like muscles and nerves.  By accounting for differences in cell division and differentiation, we can create a chart of tissue weighting factors:

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The sum of these tissue weighting factors is 1 because the amount of radiation each organ receives will add up to the radiation the whole body receives.  

We use tissue weighting factors to account for differences in tissues.  We similarly use radiation weighting factors to account for the biological effects of different types of radiation.  For the photons we use in radiation oncology, the radiation weighting factor is 1.

Once we account for the type of tissue and radiation being used, we have arrived at the concept of effective dose, which is the absorbed dose multiplied by the tissue weighting factor and the radiation weighting factor.  The effective dose is measured in sieverts (Sv).  If the body is not uniformly radiated, as in radiation oncology, we must use some fancy calculus because the absorbed dose varies along the body.  The principles, however, are the same.  The Sievert is an important concept in radiation safety, but you won’t hear it commonly referenced within the radiation oncology clinic, where the Gray remains the standard unit.

To summarize: 

1. The amount of energy absorbed from ionizing radiation per kilogram of tissue is the absorbed dose and is measured in gray (Gy)
2. To better account for the variable biological effects of tissue and radiation type, we multiply the absorbed dose by the tissue and radiation weighting factors.  We call this the effective dose, which is measured in sieverts (Sv).   

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We might like to think of ionizing radiation as something that happens only in an X-Ray or a CT scan.  Living on earth actually provides an ambient level of radiation exposure called background radiation, which averages about 2.40 mSv (0.0024 sieverts) per year.  Depending on where in Canada you live, it can range anywhere from 1 to 4 mSv!  

This dose comes from various sources including radon exposure, radioactive isotopes, and small amounts in the form of high energy cosmic rays from space.  

Fun fact: when you eat a banana, you receive about 0.1μSv (0.0000001 Sv) from a radioactive potassium isotope (⁴⁰K).  

Let’s go over an example to see how the absorbed and effective doses are related.  

Alice is an astronaut who works in the International Space Station (ISS).  Flying over 27,000 km every hour, she lives and works in Low Earth Orbit, about 400 kilometers above the surface of the Earth.  As a scientist, she studies the effects of microgravity and radiation on small chips of human tissue grown in a lab.

For those of us on the Earth’s surface, the magnetic field deflects nearly all of the charged particles from the sun.  As our altitude increases, our average absorbed dose increases also.  Alice’s dosimeter on the International Space Station averages about 0.2 mGy per day.  

Because of the associated risks of radiation exposure, NASA has set limits to protect their astronauts.  These include a 600 mSv lifetime career maximum on effective dose from space flight radiation exposure.  

1. Suppose that Alice receives a uniform whole-body absorbed dose identical to her dosimeter’s average reading, 0.2 mGy per day.  The main source of Alice’s radiation exposure is protons, which have a radiation weighting factor of 2.  How many days could Alice spend in Low Earth Orbit in her career before reaching NASA’s effective dose maximum (600mSv)?

2. Like NASA’s regulations for astronauts, the International Commission for Radiological Protection (IRCP) sets guidelines for occupational radiation exposure.  The IRCP has proposed a threshold for radiation-induced cataract formation at an absorbed dose of 0.5 Gy.  Is Alice in danger of passing this threshold during her career?

3. Suppose that the effective dose for a CT Pulmonary Angiogram (CTPA) to the breasts is 4 mSv.  How many days in Low Earth Orbit would provide the same effective dose to this tissue?

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Answers:

1. Alice’s body is uniformly radiated, so we don’t need to use the tissue weighting factors.  If you use them you will still get the right answer, but it will be a lot more work.  Remember that the tissue weighting factors sum to 1.  

Effective dose = (Tissue weighting factor) * (Radiation weighting factor) * Absorbed Dose 

= (1)*(2)*(0.2 mGy per day)

= 0.4 mSv per day.  

600 mSv / (0.4 mSv per day) = 1500 days ≈ 4 years.  Alice can spend about 4 years in Low Earth Orbit before reaching NASA’s lifetime effective dose maximum.  

2. Based on the answer in question 1, Alice receives 0.2 mGy per day, and will be in low Earth orbit for up to 1500 days in her career. 

0.2mGy /day * 1500 days =  300 mGy.  

Alice’s absorbed dose would be about 0.3 Gy when she reaches NASA’s effective dose maximum, so we would not expect her to pass this cataract threshold in her career.  

3. Recall that the tissue weighting factor for breast is 0.12.  Each day, she will receive

Effective dose = (0.12)*(2)*(0.2 mGy per day)  = 0.048 mSv per day to breast tissue. 

4 mSv / (0.048 mSv per day) = 83 days. 

A CTPA provides a similar effective dose to breast as about 83 days in Low Earth Orbit.

Now that we are starting to get comfortable with radiation doses, let’s take a look at radiation planning.  You may remember from the Radiation Oncology Basics module that we introduced a patient with stage III non-small cell lung cancer.  They received a planning CT in a reproducible position to create a model for radiation planning.  The tumor was delineated with the help of prior imaging including a PET scan.  The radiation oncologist marked out on the CT scan where the gross tumor volume (GTV) is, and then added:

1. Margins for microscopic cancer cells not seen on the CT scan, known as the clinical tumor volume (CTV),
2. Further margins for imprecision during treatment, known as the planning tumor volume (PTV).

Why are these radiation planning terms necessary, and how do they fit into our understanding of dose?

During radiotherapy, random and systematic error is necessarily introduced at many stages.  The appearance of the tumor on CT scan will only match the presence of disease as well as the resolution of the instrument used.  There may be microscopic disease that reaches beyond the area that we would consider to be the tumor volume based on imaging alone.  There are also limitations for how reproducibly we can place the patient in the same position relative to the scanner- and limitations on how well they can stay still.  And how about physiological movement- breathing, peristalsis, internal movement of organs?

As the dose delivered to the tumor increases, the likelihood of local recurrence decreases.  However, as we increase the dose, the adverse effects of radiotherapy to nearby organs also increases.  Hence the goal should be to irradiate the smallest volume necessary to account for the tumor, extent of microscopic disease, and error inherent to its measurement.   These are the gross tumor volume (GTV), clinical tumor volume (CTV), and planning tumor volume (PTV), respectively.  

Since the CTV is accounting for spread of microscopic disease, it may or may not have a uniform margin.  In some cases, we understand how a particular cancer spreads and can shape our CTV accordingly.  We may create clinical tumor volumes for regional lymph nodes.  We may also use anatomical boundaries, such as the skull or the surface of the patient.  Since the PTV, on the other hand, depends on geometric uncertainties, it often extends beyond anatomical boundaries.  

Dose constraints are introduced using these volumetric terms.  For instance, it may be necessary to provide at least 95% of the prescribed dose to at least 98% of the planning tumor volume (Represented as V95% > 98%).  

In the same way that it is necessary to introduce dose-volume constraints to describe the minimum amount of coverage for tumor control, it is also necessary to limit radiation delivery to organs that are sensitive to radiation.  We call these organs at risk (OAR).  The relevant organs at risk will depend on the location of the tumor.  For the thoracic cavity, for example, they may include the heart, esophagus, lungs, trachea, and spine. 

These constraints have two parts: both dose and volume.  For example, a set of constraints for the esophagus may look like:

1. D_max < 80 Gy, 
2. V70 < 20%
3. V50 < 40%, 
4. Mean dose < 34 Gy.

Which in plain English would be: 

1. The maximum dose that any part of the esophagus receives should be less than 80 Gray.
2. The volume of the esophagus that receives 70 Gray or more should be less than 20% of the total volume of the esophagus.  
3. The volume of the esophagus that receives 50 Gray or more should be less than 40% of the total volume of the esophagus.  
4. The mean (average) dose that the esophagus receives should be less than 34 Gray.  

Limiting the dose to organs at risk minimizes the risks of side effects of radiation.  We discuss these further in the “Side Effects” chapter of the Radiation Oncology Basics module on the LearnOncology website.

Once the radiation oncologist has contoured the target volumes and the organs at risk, they will work with a dosimetrist to create an optimal treatment plan.  A dosimetrist is a specialist who uses their knowledge of physics and radiobiology to evaluate how radiation will be delivered and interact with tissue.  They work with patient imaging data for dose calculations, create immobilization molds when necessary, and have a role in determining treatment settings.  Computer software is used to best meet all of the constraints introduced in radiation planning.  We discuss the types of external beam radiation therapy in the Radiation Oncology Basics module.  

Another specialist involved in creating the radiation plan is the radiation physicist. They are involved in key quality assurance activities in the planning process and review almost all plans prior to treatment. Radiation physicists are key to the day-to-day function of the radiation department and are involved in such activities as setting up new radiation machines (commissioning), regular ongoing quality assurance/maintenance activities, and new program development.

In summary, radiation oncology requires a team of experts working together to ensure that each patient receives the best possible treatment.  It is important to have a framework for understanding dose in order to reason about the role of radiation in medicine, both in radiation oncology and more broadly. 

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