H&N overview of radiation therapy

Question 1

Why might tumor cells exposed to an increased
concentration of growth factors, nutrients, and
oxygen be more susceptible to radiation and
chemotherapy?

Answer 1

A larger number will transition from G0 to G1 and enter the

cell cycle, during which their DNA is more susceptible to antineoplastic therapy.

Question 2

At what point during the cell cycle are cells most

radiosensitive? Radioresistant?

Answer 2

● Radiosensitive: M phase and G2
● Radioresistant: S phase
Note: The two most important checkpoints in relation to
radiation damage are G1 and G2.

Question 3

Does the proliferation rate of a tumor determine

its radiosensitivity?

Answer 3

Controversial. Both proliferating and nonproliferating tissues can be radiosensitive, but the effects in nonproliferating or slowly proliferating tissues are often delayed.
Radiosensitivity is unique to each tumor.

Question 4

How does radiation result in cell killing?

Answer 4

Radiation therapy produces intracellular ionization → breaks
chemical bonds, creates free radicals → DNA damage → cell
death. Double-strand breaks are the most important and
deadly injury imposed by radiation.

Question 5

What generally determines the maximum dose of

radiation that can safely be delivered to a tissue?

Answer 5

Ability of adjacent normal tissue to withstand the radiation

and effectively repair damage

Question 6

Although radiation can result in rapid cell death
(apoptosis), some cells do not die until they
attempt mitosis, and others continue to divide
several times before cell death. What is this
delayed cell killing called?

Answer 6

Mitotic cell death. This is why tumors do not shrink
immediately after radiation and may take weeks to demonstrate the full effects of radiation treatment (simplified explanation).

Question 7

Describe the basic principles involved in clinical
radiobiology, which is often described as the four
Rs of radiotherapy.

Answer 7

● Repair: Sublethal damage between fractions
● Redistribution: Into radiosensitive phases of the cell cycle
● Repopulation: With increased time between fractions
● Reoxygenation: Response to ionizing radiation is increased
1.5–3x in well-oxygenated cells; fractionation allows for
increased oxygen delivery to previously hypoxic cells.

Question 8

What is the unit used to describe the absorbed

radiation dose?

Answer 8

● Gray (Gy) = 1 Joule of energy per kilogram of material
● 1 Gy = 100 centigray (cGy) = 100 rads (old unit)
Note: The energy of radiation delivered determines the
depth of tissue penetration.

Question 9

What are the two general forms of ionizing

radiation?

Answer 9

● Particulate: Kinetic energy is carried by a particle that has
a resting mass, such as electrons, protons, or neutrons.
● Electromagnetic: Massless, chargeless packets of energy
(photon) that move through space at the speed of light,
including X-rays and gamma rays

Question 10

What are the three main radiotherapeutic modalities used clinically in head and neck cancer?

Answer 10

● Electrons: Produced by a linear accelerator; travel shorter
distances within tissue
● Photons/X-ray: Produced by linear accelerator; travel further within tissue; most widely used (e.g., intensity-
modulated radiation therapy, or IMRT)
● Protons: Produced by a cyclotron; charged particles;
pronounced peak of energy deposition with little dose
deposited beyond it (Bragg peak)
Note: Can use a mix of photons and electrons

Question 11

What device accelerates electrons to a high level of energy and then allows them to (1) exit the
machine as an electron or (2) collide with a specific target that results in the emission of photons
(both of which can be used for treatment)?

Answer 11

Linear accelerator

Question 12

In what type of radiation treatment is the radiation

source located outside the patient?

Answer 12

External-beam radiation therapy (EBRT)

Question 13

What radiation strategy attempts to match the target volume (defined by high-resolution imaging, such as CT or MRI) with a high dose of radiation while limiting the amount of radiation
given to adjacent normal tissue?

Answer 13

Conformal therapy (three-dimensional conformal radiation
therapy)
Note: IMRT is preferentially used to accomplish these goals
in the head and neck.

Question 14

What type of radiation therapy dynamically alters
the intensity of radiation across a field during
treatment delivery?

Answer 14

IMRT

Question 15

What type of radiation therapy delivers a full dose
of radiation in a single (or very few) fraction(s)
using photons generated by a cobalt-60 source or
by a linear accelerator?

Answer 15

Stereotactic radiation therapy, referred to as stereotactic

radiosurgery for intracranial and skull base applications

Question 16

What type of radiation therapy makes use of
radionuclides that decay within specific anatomical
subsites, resulting in very specific targeting?

Answer 16

Targeted radionuclide therapy (e.g., thyroid cancer and

iodine-131)

Question 17

Which form of radiation energy is better able to
deposit most of its energy at a specific target,
minimizing the dose to surrounding tissues based
on the Bragg peak?

Answer 17

Protons

Question 18

You are planning to treat a patient with a superficial head and neck cancer using photon radiation. To ensure that sufficient dose is deposited superficially, you create a material with a similar density to skin to place over the tumor.
What is this called?

Answer 18

Bolus

Question 19

What type of fractionation schedule uses radiation
given in multiple daily doses without changing the
overall treatment time compared with traditional
daily radiotherapy, and why does this potentially
result in decreased late morbidity despite a higher
total dose?

Answer 19

Hyperfractionation. Normal tissue is more sensitive to the
size of each individual dose. Therefore, if you decrease the
size of each individual dose while increasing the total dose
given over the entire course, there should be increase
tumor cell killing and decreased impact on normal tissues.

Question 20

What type of fractionation schedule relies on
multiple daily treatments using larger doses of
radiation and a shorter overall treatment time
compared with standard daily radiation therapy?

Answer 20

Accelerated fractionation

Question 21

What are the three primary radiosensitizing

strategies currently available?

Answer 21

● Decreasing hypoxemia (due to increased interstitial pressure within the tumor or comorbid anemia): Hyper-
baric oxygen therapy*, inhaled carbogen, hypoxic cell sensitizers (nimorazole, tirapazamine), recombinant hu-
man erythropoietin**
● Concomitant chemotherapy: Additive (kills micrometa-
stasis, toxicity profiles do not overlap) vs. synergistic
effect (increased cytotoxic activity)
● Targeted therapy: Goal is to decrease side effects and
improve radiation efficacy; monoclonal antibody against
EGFR (cetuximab).
* No change in 5-year outcomes
**Worse locoregional control and overall survival

Question 22

What are the five basic steps involved in radiation

treatment?

Answer 22

● Simulation
● Treatment planning (defining target volumes, imaging,
dose, schedule)
● Verification
● Dose delivery
● Quality assurance

Question 23

Imaging the patient to delineate targets and
treatment volumes is done using CT or MRI. Is this
typically done before or after the patient is
immobilized?

Answer 23

After. It allows for better accuracy of treatment.

Question 24

When planning radiation targets, what three

volumes must be considered?

Answer 24

● Gross tumor volume: Delineates tumor boundaries
● Clinical target volume: Identifies regions at high risk for
harboring microscopic disease
● Planning target volume: Includes a “margin” to allow and
fraction to fraction variability in patient positioning

Question 25

What types of tissues are at risk for acute radiation

related toxicity? Delayed toxicity?

Answer 25

● Acute: Rapidly dividing cells; skin, mucous membranes,
bone marrow, tumor cells. Related to total treatment time,
dose per fraction, total dose, time between treatments
● Delayed: More slowly dividing cells; neural and connec-
tive tissue. Related to total dose and dose per fraction

Question 26

Acute radiation toxicity occurs over days to weeks
following treatment. What are some of the most
common toxicities associated with treatment of
the head and neck?

Answer 26

● Mucositis
● Dermatitis
● Xerostomia
● Hoarseness
● Odynophagia
● Dysphagia
● Weight loss

Question 27

Delayed or late radiation toxicity occurs months to
years after treatment. What are the most common
toxicities?

Answer 27

● Xerostomia
● Dental caries/decay
● Osteoradionecrosis, chondronecrosis
● Fibrosis
● Hypothyroidism
● Neurologic damage

Question 28

Compared with two- or three-dimensional con-
formal techniques, intensity-modulated radiation therapy may spare what organs within the head
and neck?

Answer 28

● Salivary glands
● Pharyngeal musculature
● Otic structures
● Optic structures
● Temporomandibular joints (TMJs)
● Brain

Question 29

In an effort to reduce the incidence of osteoradio-

necrosis, when should decayed and nonrestorable teeth be extracted in relation to radiation therapy?

Answer 29

Before radiation

Question 30

What are the theoretical advantages to preopera-

tive radiation therapy?

Answer 30

● Reduction of unresectable tumors to the point of resectability
● Reduces the extent of necessary surgery
● Microscopic disease is usually more radiosensitive pre-operatively because it has a better blood supply.
● Cells disseminated during the course of surgery may be
less viable after radiation therapy.
● Requisite treatment volumes are smaller preoperatively
than postoperatively.

Question 31

What are the theoretical advantages to postoperative radiation therapy?

Answer 31

● Surgery allows for definition of the extent of tumor.
● Surgery is easier before radiation.
● Dosing can be adjusted depending on residual tumor
after surgery.
● Fewer wound-related complications

Question 32

What type of fractionation regimen has been
shown to result in better local control and overall survival compared with conventionally fractionated radiation therapy?

Answer 32

Hyperfractionated
Note: With concurrent chemoradiation therapy, there is no
benefit. This is a complex issue.