Radiation Therapy

Question 1

1 Gy = ?

Answer 1

Gray (Gy); 1 Gy equals one joule absorbed per kilogram of tissue

Question 2

Ionizing radiation kills cells by?

Answer 2

damaging critical molecules in the cell, primarily deoxyribonucleic acid (DNA), which eventually leads to cell death

Question 3

What is Compton effect?

What are the 2 effects?

What is mitotic catastrophe?

Answer 3

Producing high energy electrons

1) Ionization events either to critical molecules (direct action). 2) Form water molecules located within nanometers of critical molecules (indirect action).

Is due to chromosomal aberrations, primarily from double strand breaks

Question 4

MOST RESISTANT CELLS = ___ PHASE

MOST SENSITIVE CELLS = _____PHASE

Answer 4

S-phase

Late G2-M phase

Question 5

Normoxic cells are up to _____ to radiation than hypoxic cells

Answer 5

three-fold more sensitive

Question 6

What are the 4 R’s of radiation?

SLOW DIVIDING CELLS

Sensitive?

Less sensitive?

RAPIDLY DIVIDING CELLS

Sensisitve?

Less sensitive?

Answer 6

“Four Rs” of RT:

• repair of DNA damage,
• redistribution of cells in the cell cycle,
• reoxygenation of tumor cells, and
• repopulation of tumor and normal tissues.
• radiosensitivity

SLOW DIVIDING CELLS

• Sensitive=HIGH DOSES
• Less sensitive=LOW DOSES

RAPIDLY DIVIDING CELLS

• Sensitive=LOW DOSES
• Less sensitive=HIGH DOSES

Question 7

If smaller doses per fraction are used, normal tissues with ____ dividing cells can be spared relative to tumor tissues with _____ dividing cells

Answer 7

slowly, rapidly

Question 8

Accelerated repopulation.

It is believed that after approximately _____ of therapy, tumors repopulate more rapidly than initially.

(1) a reduction in the cell cycle time
(2) an increase in the number of tumor cells that are actively dividing (growth fraction)
(3) a reduction in the number of tumor cells that normally die (cell loss factor)
(4) an increase in the number of tumor stem cells.

Answer 8

4 weeks

Question 9

Repopulation of rapidly proliferating (also known as acutely responding) normal tissues is also affected by time.

The same total dose of radiation administered over a short period results in somewhat more ______ than if administered over a longer course.

Nonproliferating (late responding) normal tissues are not significantly affected by the _____ over which therapy is administered=they are more affected by _____ and _____.

Answer 9

severe acute effects

length of time, dose per fraction, total dose

Question 10

Fractions should be separated by at least ____ to allow repair of DNA damage to normal tissues.

Answer 10

6 hours

Brain and spinal cord may need more time

Question 11

Benefits of protocols that use small doses per fraction are:

Allow a ____ dose to be administered without increasing the probability of damage to ____ normal tissues.

Answer 11

higher total, late-responding

Question 12

Early delayed radiation effects have been recognized only in ____ tissues. Occurring between ____ after treatment, they may take several forms.

_____ may develop in patients receiving whole brain irradiation

May simulate tumor recurrence or may cause neurologic signs not previously associated with the tumor, and so careful imaging evaluation is necessary.

Early delayed effects may be due to ____ or from _____ –associated cytokine release with tumor cell death.

Early delayed effects will generally respond to corticosteroid administration and supportive care

When late effects occur, they may be quite severe, resulting in fibrosis, necrosis, loss of function, and even death

These changes are multifactorial, but the cytokine ______ is believed to play a critical role in radiation fibrosis

Answer 12

neurologic, 2 weeks and 4 months

Somnolence

demyelination, cerebral edema

transforming growth factor beta (TGFβ)

Question 13

For a tumor to be considered radiation induced, the following criteria must be met:

The malignancy must arise within the irradiated field.

Sufficient latency must have elapsed between the time of irradiation and development of the tumor (typically at least 1 year).

The original tumor and the new tumor must have different histologic diagnoses.

The tissue in which the new tumor forms must have been previously normal before radiation exposure.

The overall incidence of radiation-induced tumors=up to 2%

Question 15

SRT

Although generally associated with hypofractionated protocols, the technology can be used for administration of traditionally fractionated RT.

definition, requires:

(1) a tumor for targeting (not microscopic disease)
(2) treatment planning and administration that will provide a dramatic dose drop off between the tumor and the surrounding normal tissue structures;
(3) a method of stereotactically verifying patient positioning

The result is that normal late-responding tissue structures are spared through dose avoidance rather than by administering small doses per fraction.

the total dose to normal tissue structures is lower than what is typical for fractionated

Question 16

The relationship between a dose of radiation and the surviving fraction of cells is commonly described by the linear quadratic equation:

S(D) = e–(αD + βD2), where S is the surviving fraction at a dose (D)

Alpha (α) and beta (β) are constants that vary according to the tissue,

α =corresponding to the cell death that increases _____ with dose,

β =corresponding to the cell death that increases in ____ of the dose (also known as the quadratic component).

Answer 16

linearly

proportion to the square

Question 17

Higher α/β ratio have a more ____ appearance

Low α/β ratio have a _____ shape.

Answer 17

Linear

Parabolic

Question 18

The α/β ratio is also an important description of the radiosensitivity of a cell

Low α/β ratio are relatively ______ compared with tissues or cells with high α/β ratio

suggested that tissues and cells with low α/β ratios have a greater capacity for repair of _____

Most early-responding tissues and tumors have a ____ α/β ratio

Late-responding tissues have a ___ α/β ratio

Lower α/β ratio tumors include?

Sublethal radiation damage is defined as damage that can become lethal if it interacts with additional damage

is the reason that cell survival increases when a radiation dose is split into two fractions separated by a time interval

Answer 18

Radiation resistant

Sublethal radiation damage

High

Low

Melanoma, prostatic tumors, soft tissue sarcomas, transitional cell carcinomas, and OSA

Question 19

Megavoltage radiation has excellent ____ capabilities

Orthovoltage x-rays, which have ___ energy, distribute maximum doses to the _____

Orthovoltage radiation is preferentially absorbed by ___

Bolus

This allows the dose buildup to occur before reaching the skin so that the skin and associated tumor can receive the maximum dose of radiation

Answer 19

tissue-penetrating

low, skin surface

bone

Question 20

ORAL TUMORS

AAs are very radiation responsive. Tumor control with RT can be close to 90%

The reported 3 year PFS for AA

• PFS: T1 tumors (less than 2 cm) and T2 tumors (2–4 cm) =86%;
• PFS: it is only about 30% = T3 tumors (over 4 cm).

In a retrospective study of 57 dogs with AAs that were treated with RT overall median time to first event = 1210 days, median survival time (MST) = 1441 days, respectively

Younger dogs had SIG LONGER MSTs

• Younger than 8.3 years old=2322 days
• Older than 8.3 years old=1106 days

Dogs receiving more than 40 Gy had SIG LONGER MST

• Received >40 Gy MST= 2994 days
• Recevied <40 Gy MST=143 days

Question 21

SCC

Canine oral SCCs are responsive to radiation

• prognosis is site dependent, with tumors located more rostrally having better probability of control.
• Tumors at the base of the tongue or tonsil are highly metastatic and are likely to recur locally or regionally.

In one study of oral SCC for all Tumor stages treated with RT

• PFS 1 year=72%
• PFS 3 year=40%

Another study of fractionated RT (48–57 Gy in 3–4 Gy fractions) in 14 dogs with oral SCC,

• median disease-free interval (DFI)=365 days
• MST=450 days

Question 22

In cats, oral SCC has a poor prognosis.

• Although many cats show an initial response and may even show dramatic reductions in tumor size, tumor recurrence is common.
• Combining curative- intent RT with etanidazole or mitoxantrone therapy has resulted in MSTs of 116 to 170 days.
• Seven cats with mandibular SCC were treated with hemimandibulectomy and mandibular node excision followed by RT; the MST was 420 days, but some cats do not adapt to bilateral mandibulectomies.
• Nine cats with oral SCC received accelerated RT (14 fractions of 3.5 Gy in 9 days), which resulted in an MST of 86 days.
• In a different approach, SRT (20 Gy) was delivered to 18 cats with oral SCC.
  
  • Acute radiation effects were minimal and initially cats improved clinically,
  • MST was only 106 days.

Question 23

FSA

• Oral fibrosarcomas (FSAs) are unlikely to metastasize but can be difficult to control locally.
• Oral FSAs are less radiosensitive than AAs and SCCs, although
• tumor control probabilities ranging from 33% to 67% at 1 year=ORAL FSAs
• In one study of oral FSAs treated with RT,
  
  • PFS at 1 year =76%
  • PFS at 3 years=55%
• Surgical cytoreduction improves the probability of tumor control by RT
• An MST of 540 days was reported in eight dogs with oral sarcomas treated with surgery followed by RT.

Question 24

MM

Malignant melanoma (MM)

• Higher doses of radiation per fraction (4 Gy and above) are believed to improve response rates for melanoma.
• In one study, 38 dogs with nonmetastatic oral MM were treated with 48 Gy delivered in 4 Gy fractions on a Monday-Wednesday- Friday schedule.
• The overall median PFS was 17.8 months, Median PFS
  
  • T1=38 months
  • T2=11.7 months
  • T3=12.0 months.