W13/T&H15 Radiation oncology Flashcards
1
Q
1 Gy = __________
A
1 joule per kg of tissue
2
Q
________ is the predominant form of radiation used in veterinary medicine. Interaction with tissue is primarily by the ________, producing high energy ______ that cause ionization events.
A
- Megavoltage photons
- Compton effect
- electrons
3
Q
Ionization events produce _______ that result in biologic damage that may kill the cell or render it incapable of reproducing. This type of death is referred to as _______, and is due to chromosomal aberrations, primarily _______________.
A
- highly reactive free radicals
- mitotic catastrophe
- double stranded DNA breaks
4
Q
Most radiation damage is repaired by cells within ________.
A
6-24 hours
5
Q
Cells in _____ are most resistant to radiation.
A
late S phase
6
Q
Cells in ______ are most sensitive to radiation.
A
Late G2 or M phase
7
Q
Normoxic cells are up to ____- fold more sensitive to radiation than hypoxic tissues.
A
3-fold
8
Q
What is relative biologic effectiveness?
A
how effective one type of radiation is at causing damage compared to standard reference
9
Q
The RBE of 1 Gy of _____ and _____ is the same.
A
photons and electrons
10
Q
_____ have a slightly higher RBE than photons and electrons.
A
protons
11
Q
RBE compares the biologic difference between specific types of radiation relative to the effect of _______.
A
photons
12
Q
What is the most common and second most common forms of cell death from radiation?
A
- most common: mitotic catastrophe
- second common: apoptosis
13
Q
Apoptosis of endothelium from radiation primarily occurs when __________ fractions are administered.
A
high dose fractions
14
Q
Describe hyperfractionation.
A
schedules in which dose per fraction is reduced and the total dose is increased
15
Q
Describe accelerated RT.
A
overall time of treatment is reduced
16
Q
What is the purpose of fractionation?
A
- to spare normal tissues (normal tissues with slowly dividing cells can be spared relative to tumor tissue with rapidly dividing cell since slowly dividing tissues are less sensitive to small doses of radiation)
- cell cycle redistribution and reoxygenation can take place
17
Q
The length of time over which RT is administered is important because of _________ and because of __________.
A
- tumor repopulation
- rapidly proliferating normal tissues
18
Q
What are 4 possible causes of accelerated repopulation?
A
- reduction in cell cycle time
- increase in number of tumor cells that are actively dividing (growth fraction)
- reduction in number of tumor cells that normally die (cell loss factor)
- increase in number of tumor stem cells
19
Q
What tissues are not significantly affected by the length of time radiation is administered?
A
- non-proliferating (late responding) normal tissues
20
Q
Fractions should be separated by at least _____ to allow repair of DNA damage to normal tissues - cells in the _______ and _____ may require additional time for repair.
A
- 6 hours
- brain or spinal cord
21
Q
What type of tissue is not sensitive to change in dose per fraction?
A
rapidly dividing cells, including tumors
22
Q
Early-delayed radiation effects have been recognized only in _______ tissues. This may be due to _____ or from ______ - associated cytokine release with tumor cell death.
A
- neurologic
- demyelination
- cerebral-edema
23
Q
Late effects occur due to loss of normal _________ with concurrent radiation-induced vascular changes and inflammation.
A
tissue stem cells
24
Q
_______ is believed to play a critical role in radiation fibrosis.
A
TGFB
25
Radiation with high ______, such as _______, results in carcinogenesis at a higher frequency than MV photons.
- LET
- neutrons
26
Certain tissues, such as ___, are most prone to development of radiation-induced tumors.
thyroid gland
27
Name 4 criteria that must be met for a tumor to be considered radiation-induced.
1. Must arise within irradiation field
2. Sufficient latency (at least 1 year) must have elapsed between treatment and tumor development.
3. The original and new tumor must have different histologic diagnoses
4. The tissue in which the new tumor forms must have been previously normal before radiation exposure
28
The overall incidence of radiation-induced tumors is ___%.
2%
29
What are 3 criteria to define SRT?
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
3. A method of stereotactically verifying patient positioning
30
________ cannot account for efficacy of SRT or SRS.
Direct tumor cell death
31
_____ tumors cells must die to eradicate a 1-gram tumor.
10^8-9
32
SRT has been shown to cause _____, which leads to greater-than-expected tumor control (______ tumor cell death).
- vascular damage
- indirect
33
Recent publications demonstrate SRT produces comparable survival times in ______ and ______ tumors and improved outcome in the treatment of _______ when compared to conventionally fractionated protocols.
- nasal and brain
- feline acromegaly
34
_______ and ________ are less tolerant to effects of irradiation than muscle or bone.
brain and spinal cord
35
For many tumor locations, a ___% probability for late effects is tolerated. For structures such as the spinal cord where a late effect such as paralysis is unacceptable, a ___% probability of effect is used.
- 5%
- 1%
36
The _________ is the relationship between a dose of radiation and the surviving fraction of cells.
Linear quadratic equation
37
Mechanistically, the linear quadratic model corresponds _________ to __________.
radiation injury to chromosomal aberrations
38
Alpha in the linear quadratic model corresponds to cell death that increases ______ with dose.
linearly
39
Beta in the linear quadratic model corresponds to cell death that increases in proportion to the ___________.
square of the dose (quadratic component)
40
Define the alpha/beta ratio.
the dose in Gy when the cell kill from the linear and quadratic components of the cell survival cure are EQUAL
41
At LOW dose fractions, tissues or cells with LOW alpha/beat ratio are _______ compared with tissues with high alpha/beta ratios.
radiation resistant
42
Tissues and cells with ______ alpha/beta ratios have a greater capacity for repair of sublethal radiation damage.
low
43
Most early-responding tissues and tumors have ______ alpha/beta ratio, except for what tumors?
- high
- OSA, STS, melanoma, prostatic tumors, TCC, breast cancer
44
Late responding tissues tend to have a ______ alpha/beta ratio.
low
45
The _______ is used to predict how changes in dose may affect different cells or tissues based on their alpha/beta ratio.
BED
46
What is the BED equation?
BED = nd [1 + d / (alpha/beta)]
47
The BED does not account for differences in _________ or ______.
- overall length of time of RT protocol
- accelerated repopulation
48
What 2 scenarios is the BED useful?
- when considering hyperfractionating
- to adjust a protocol if there was an extensive delay
49
Why is the validity of BED for SRT unclear?
BED may overestimate tolerance of acutely-responding tissues because of shortened overall treatment time in SRT
50
___________ is radiation administered by an external source, also called "external beam RT"
Teletherapy
51
Megavoltage emits photons with an average energy ________.
greater than 1 MeV
52
Megavoltage photons must interact with _______, allowing the dose to build up before the maximum dose can be achieved. ______ receives a lower dose.
- tissues
-skin
53
Absorption of megavoltage photons is minimally dependent on _______ of the tissue - permits even distribution of the dose throughout the tissue.
composition
54
Orthovoltage produces ________ at what energy level?
low energy x-rays (150-500 kVp)
55
Orthovoltage photons distribute maximum dose to _____ and are preferentially absorbed by _____.
- skin
- bone
56
Proton-beam radiation deposits dose in targeted range and ____________, this is in contrast to photon therapy.
minimal dose exits tumor
57
_______ accounts for variation in size and shape relative to anatomic landscapes when planning for radiation.
PTV
58
What is the major advantage of 3D-CRT?
Dose volume histograms can be obtained for the tumor and normal tissue structures
59
________ is a form of IMRT that uses a helical delivery system to sculpt the beam.
tomotherapy
60
_______ uses inverse treatment planning.
IMRT
61
What is not applied in radiation planning for SRT?
CTV; GTV = CTV
62
A port film results in a radiographic image with a dark central area indicative of _____ with lighter exposure of ____________ for reference.
- treatment field
- surrounding anatomy
63
______ is a kV energy system that provides superior contrast to images generated from a mV linear accelerator beam.
on-board imager (OBI)
64
Tumor control with acanthomatous ameloblastoma with RT can be close to ___%.
90%
65
Reported 3-year progression-free survival rate for T1 and T2 AAs is ___% whereas for T3 tumors it is ___%.
- T1 and T2: 86%
- T3: 30%
66
In a retrospective study of 57 dogs with acanthomatous ameloblastomas treated with RT, the overall time to first event was ____, the overall MST was ____. What were 2 positive prognostic factors and their respective MST?
- oTTE: 40mo
- oMST: 48mo
- dogs younger than 8 years and dogs that received RT dose > 40Gy had significantly longer survival times
- MST <8yrs: 6 years vs >8 yrs 3yrs
- MST >40Gy: 8 yrs vs. <40Gy 5 mo
67
What are positive and negative prognostic factors for dogs with oral SCC?
- rostral tumors = better
- tumors at base of tongue or tonsils are highly metastatic
68
A study of canine oral SCC treated with RT reported a progression-free survival rate at 1 year to be ___% and at 3 years ___%.
- PFS 1yr: 72%
- PFS 3 yr: 40%
69
A study evaluating fractionated RT (48-57 Gy in 3-4 fractions) in 14 dogs with oral SCC found a DFI of _____ and MST of _____.
- DFI: 12 mo
- MST: 15mo
70
Cats with oral SCC treated with curative-intent RT combined with etanidazole or mitoxantrone therapy resulted in MSTs of ____-____.
4-6 months
71
In a study of 7 cats with mandibular SCC treated with surgery and mandibular LN extirpation followed by RT reported a MST of ____.
MST 14mo
72
A study of 9 cats with oral SCC receiving accelerated RT (14 fractions of 3.5 Gy in 9 days) reported a MST of _____.
MST 3mo
73
A study of 18 cats with oral SCC treated with SRT (20Gy) reported a MST of ____ with ____ acute radiation effects.
- MST 4mo
- minimal
74
Oral FSA are less radiosensitive although tumor control probabilities have ranged from ___-___% at 1 year.
33-67%
75
In a study of canine oral FSA treated with RT, PFS at 1 year was ___% and ___% at 3 years.
PFS 1yr: 76%
PFS 3yrs: 55%
76
In a study of canine oral FSA that underwent cytoreductive surgery followed by RT, MST were reported to be _____ in 8 dogs.
MST 18mo
77
Malignant melanoma responds to higher doses of radiation per fraction, at least ___ Gy or above.
4 Gy
78
In a study of 38 dogs with non-metastatic oral MM treated with 48Gy delivered in 4 Gy fractions, the overall PFS was _____, the median PFS for T1 tumors was _____, T2 tumors was _____, and T3 tumors was ______.
- oPFS: 18mo
- PFS T1: 38mo
- PFS T2: 12mo
- PFS T3: 12mo
79
In a retrospective study of 140 dogs with oral melanoma and regional or distant metastasis treated with various RT +/- surgery +/- chemotherapy, median time to first event was ____, MST was ____, tumor recurrence occurred in ___% with new metastasis or death being the first event in the remainder of dogs.
- TTE: 5mo
- MST: 7mo
- 27% local recurrence
80
In a retrospective study of 39 dogs with incompletely excised oral MM treated with coarsely fractionated RT plus platinum-based therapy administered 1 hour prior to RT, the MST was ____, local recurrence occurred in ___%, and median time to metastasis was ____.
- MST: 12mo
- local recurrence: 15%
- time to met: 10mo
81
A study of 5 cats with oral MM treated with 8 Gy delivered on days 0, 7, and 21, the MST was _____ and ____% died from progressive disease.
- MST: 5mo
- 100%
82
Mucositis from RT typically begins during _______ week of therapy and reaches maximum severity during or shortly after _______ week of therapy.
- 2nd week
- last week
83
Most common chemotherapeutics associated with radiation recall?
gemcitabine, doxorubicin, taxanes
84
The _____ is the most susceptible bone for osteoradionecrosis.
mandible
85
Late complications from RT specific to oral cavity include _____, _____, and ______.
oronasal fistula, osteoradionecrosis, xerostomia
86
A study of 31 dogs with nasal tumors treated with IMRT compared to 26 historical controls treated with 2D planning reported a MST of ____ with IMRT and ____ with controls.
- MST IMRT: 14mo
- MST 2D planning: 14mo
87
In a study of 12 dogs with nasal tumors treated with IMRT with a dose commonly used for 2D or 3DCRT, MST was reported to be _____.
MST 15mo
88
A decrease in acute effects was profound with IMRT for nasal tumors compared to historical 2D/3DCRT with minimal grade II and III _____ and _____ toxicity. Although ipsilateral eye could not be spared, minima side effects were reported in contralateral eye.
- cutaneous and mucosal
89
SRT was evaluated in 29 dogs with solid nasal tumors (3 daily fractions of 10Gy). Clinical signs improved in ___% of dogs, acute side effects were _______, ~____% developed significant fistulas, MST was ____, 1 year survival was ___%, and 2 year survival was ____.
- clinical sign improvement: 100%
- minimal
- 10% fistulas
- MST 20mo
- 1yr survival: 69%
- 2yr survival: 22%
90
A study of cats with non-lymphoproliferative nasal tumors receiving 48Gy fractions in 4Gy over 4 weeks (fractionated RT), reported a 1-year survival of ___%, 2-year survival of ___%. _______ and _____ did not affect prognosis.
- 1-yr survival: 44%
- 2-yr survival: 17%
- histologic type and clinical stage did NOT affect prognosis
91
In a study of 9 dogs with recurrent nasal tumors previously treated with 3DCRT that were re-irradiated, overall MST from initial treatment was ____ with increased incidence of ________.
- MST 31mo
- increased incidence of late effects
92
Feline nasal planum SCC response to RT is affected by ______.
tumor stage
93
Feline nasal planum SCC treated with RT report 1-year survival rates of ____% and 5-year survival rates of __% for T1 tumors. MST for T1 tumors are ____.
T1:
1-year survival: 85%
5-year survival: 56%
MST: 53mo, median not reached
94
Tumor stage _____ for feline nasal planum SCC show less favorable response to RT.
- T2 or higher
95
Sr-90 emits a low-energy ____- particle.
beta
96
In a study of 49 cats with small SCC of nasal planum treated with 128Gy via Sr-90 in a single fraction, CR rate was reported to be ___% with median PFI of ____.
CR 88%
PFI: 4.7yrs
97
Long-term use of _______ and _____ are recommended to help mitigate RT effects in patients treated with SRT.
Pentoxifylline and vitamin E
98
What are acute ocular RT effects? Which may be temporary or permanent?
- blepharitis, blepharospasm, conjunctivitis, and KCS
- KCS - temp or permanent
99
What are late effects of RT to the eye?
vascular changes, cataracts, retinal degeneration
100
In a study of 46 dogs with brain tumors associated with neurologic disease treated with RT alone, MST was ____, which was superior to previous reports of _____. 1-year-survival was ___%, 2-year was ___%.
- MST: 23mo
- MST historical: 1 year
- 1-year survival: 69%
- 2-year survival: 47%
101
In a study of 31 dogs treated with 3DCRT for brain tumors, MST was ____.
MST 19mo
102
In a study of 31 dogs with meningioma treated with surgery +/- post-operative RT, the MST for surgery alone dogs was ______, and ______ for surgery + RT.
MST sx alone: 7mo
MST sx + RT: 17mo
103
In a study of 30 dogs with image-based diagnosed intracranial meningiomas treated with SRT using 24Gy divided into 3 fractions, overall MST for any cause of death was ____. Treatment was well tolerated.
MST 19mo
104
In a study of 39 dogs with image-based meningiomas treated with VMAT receiving 33Gy in 5 fractions, the 2-year survival rate was ___% and treatment was well tolerated.
2-year survival: 74%
105
In a study of 42 dogs with presumed gliomas treated with VMAT alone or in combination with Temodar, MST for RT alone was _____, for RT + Temodar was ____, and for control group treated only medically, the MST was ____.
- MST RT alone: 13mo
- MST RT + Temodar: 14mo
- MST medical alone: 3mo
106
Dogs with pituitary tumor treated with fractionated RT have a MST reported to be ____-____.
1-2 years
107
In a study comparing 19 dogs with pituitary tumors receiving RT (48Gy in 16 daily fractions) to untreated dogs, the RT group survival rates for 1-year was ___%, 2-year ___%, and 3-year ___% compared to untreated dogs for 1-year ___%, 2-year ___%, 3-year ___%.
RT treated dogs:
- 1-year: 93%
- 2-year: 87%
- 3-year: 55%
Untreated survival:
- 1-year: 45%
- 2-year: 32%
- 3-year: 25%
108
In a study of 53 cats with functional pituitary adenomas associated with acromegaly treated with SRT, the MST was ____, ___% experienced a decrease in required insulin dose, ___% achieved diabetic remission, and ___% developed hypothyroidism.
- MST 36mo
- 95% decrease insulin
- 32% diabetic remission
- 14% hypothyroidism
109
Trigeminal nerve sheath tumors in dogs have been treated with SRT in 2 studies. MST ranged from ____-____.
MST 15mo - 25mo
110
For many brain tumors, IMRT will or will not provide an improved dose distribution compared to 3d-CRT?
will NOT
111
Radiation tolerance is ____ when the entire brain is treated.
LOWER
112
_______ may be an important factor when radiating brain and spinal lesions.
volume
113
Early-delayed effects can occur in ___-___ after treatment. ___% of humans have been reported to develop these effects after brain RT.
1-3 months
40%
114
In a study of SRT for canine meningiomas, ___% of dogs showed mild to moderate exacerbation of neurologic signs 3-16 weeks after treatment.
37%
115
Late RT effects from brain generally occur at least _____ after treatment with _____ being the most common late effect.
- 6 months
- brain necrosis
116
In a study of 83 dogs with brain masses treated with hypofractionated RT, brain necrosis was confirmed or suspected in ___%.
14%
117
It is prudent to obtain a CT or MRI _____ after treatment for brain tumors to serve as a reference if clinical signs develop in future.
6 months
118
In a study of 48 dogs with STS treated with cytoreduction followed by RT, ___% developed tumor recurrence and 5-year survival rate was ___%.
- 16%
- 78%
119
In a study of 33 cats with ISS treated with RT followed by surgery, the DFI was ______ and the MST was _____.
DFI: 13mo
MST: 20mo
120
In a study of 25 cats with ISS with subclinical disease after surgery treated with RT +/- chemotherapy, the MST was ____ and local recurrence occurred in ___% with the majority being in the RT field.
- MST 23mo
- 29% local recurrence
121
In a study of 78 cats with ISS treated with surgical cytoreduction followed by RT, cats that underwent ____ surgery before RT had a lower recurrence rate than cats that had more than ___ surgery.
- 1
- >1
122
In a study of 79 cats treated with either pre- or post-operative RT for ISS, a PCV ___% was associated with a better outcome of ____ compared to _____ if PCV was ___%.
MST PCV >25%: 25mo
MST PCV <25%: 10mo
123
In a study of 37 dogs with grade II MCTs treated with cytoreduction and RT, tumor control at 1 and 2 years was ___%
90%
124
In a study of 56 dogs with incompletely excised MCTs treated with RT, the median DFI was ____.
DFI 33mo
125
In a study of 64 dogs with incompletely excised MCTs treated with adjuvant RT, the recurrence rate was ___% and the MST was _____. For dogs that did not receive RT, the recurrence rate was ___% and the MST was _____.
RT
- recurrence rate: 8%
- MST: 8 years
No RT
- recurrence rate: 38%
- MST: 24mo
126
In a study of 19 dogs with MCT and regional LN involvement treated with surgical cytoreduction of the primary site followed by radiation to the primary site and LN and prednisone therapy, the DFS was ____.
DFS 3.4yrs
127
In a study of 21 dogs with grade II, stage II MCTs treated with surgery and adjuvant chemotherapy, the addition of RT was assessed. The MST for adjuvant RT was _____ compared to without RT of ______.
MST sx+ chemo + RT: 5.6 yrs
MST sx + chemo and no RT: 3 yrs
128
In a study of 46 dogs with appendicular OSA treated with SRT +/- chemotherapy, the MST was ____. The pathologic fracture rate at 3 months was ___%, 6 months ___%, and 9 months ___%. The area of the bone was prognostic. _______ involvement was associated with higher risk of fracture with median time to fracture at _____ compared to no involvement at _____. Occasional grade II and late skin toxicity particularly for tumors involving the ______ was seen.
- MST 10mo
Fracture rates:
- 3 mo: 27%
- 6 mo: 56%
- 9 mo: 62%
Subchondral bone involvement
- fracture time for involvement: 4 months
- fracture time without involvement: 16 months
- radius
129
In a study of 10 cats with extranodal lymphoma (nasal, retrobulbar, mediastinum, SC, oral) treated with mV RT +/- chemotherapy found a CR rate of ___%, PR rate of ___%, and median remission time for cats in CR at ____. ___% developed disease outside of the RT field, suggesting adjuvant chemotherapy may improve control.
- CR 80%
- PR 20%
- CR remission duration: 26mo
- 30%
130
A ____ Gy dose to lymphoma cells reduces surviving fraction to _____.
- 8Gy
0.005
131
In a study of 11 cats with relapsed or resistant alimentary LSA (small, large, LGL) treated with whole abdomen RT (4Gy on 2 consecutive days) , ___% had either partial or complete clinical remission, _____ acute effects, and the post-RT MST was _____.
- 90%
- minimal acute effects
- Post-RT MST: 7 mo
132
For autologous bone marrow transplantation, after treatment with standard CHOP-based chemotherapy, dogs are given high-dose ___, followed by 2 weeks later with progenitor cell mobilization using 5 days of _________. PBMCs are then harvested and _______ cells are enumerated with goal of obtaining _________. The next day, ___-___ Gy of total body RT is administered over 2 days, and the harvested cells are immediately infused IV once RT is completed. In a toxicity study of 10 dogs, 100% experienced grade IV ________, ______, and _____. Neutrophils recovered to at least 500 by _____, and ________ often persisted for weeks.
- Cytoxan
- Neupogen
- CD34+ cells
- 2 million/kg CD34+ cells
- 10-12 Gy
- neutropenia, lymphopenia, and thrombocytopenia
- day 12
- thrombocytopenia
133
In a study of 24 dogs with high-grade B cell LSA treated with autologous bone marrow transplantation following standard CHOP, high dose Cytoxan, and TBI, the median DFI was ____, the MST was ___, and ___% of dogs lived greater than 2 years.
- DFI: 9mo
- MST: 15mo
- 33%
134
In a study of dogs with high grade B-cell LSA treated with allogeneic bone marrow transplantation, the cure rate was ___% and ___% developed graft host disease.
- 89%
- 20%
135
In a study using autologous bone marrow transplant in 13 dogs with high grade T cell LSA in first remission, the DFI was ___, MST was ___, and ___% of dogs were long-term survivors.
- DFI: 6mo
- MST: 8mo
- 15%
136
In a retrospective study of multomodal therapy for axial OSAs, dogs treated with curative-intent RT protocols reported a MST of ____ compared to palliative SRT at _____.
- MST curative-intent: 9mo
- MST palliative SRT: 3mo
137
In a study of 9 dogs with primary or secondary vertebral OSA treated with SRT, ___% had improved pain control, and the MST was ___.
83%
MST 5mo
138
Name 4 ways RT can ameliorate pain for bone tumors.
1. decreases intra-tumoral pressure
2. local anti-inflammatory effects
3. tumor cell apoptosis
4. cytotoxicity to osteoclasts
139
In a study of 58 dogs with OSA receiving 8Gy administered over 2 consecutive days, pain relief was observed within ____ in ____% of patients.
- within 2 days
- 91%
140
In a study of 15 dogs with appendicular bone tumors treated with palliative RT, ___% had improved limb function and the MST was ____.
80%
MST 4mo
141
In a study of 95 dogs with appendicular OSA treated with either 3 fractions of 10Gy or 2 fractions of 8Gy, ___% experienced pain relief for a median duration of ___. Which protocol was superior?
- 74%
- 2 months
- no difference in response between protocols
142
In a study of dogs with thyroid carcinoma treated with fractionated RT (total dose 48Gy), the 1-year PFS was __% and 3-year PFS was ___%.
- 1-year PFS: 80%
- 3-year PFS: 72%
143
In a study of 7 cats with thymoma treated with RT, MST were close to ___.
2 years
144
In a study of 18 dogs with urogenital cancer treated with IMRT (54-58Gy for 20 daily fractions) and majority also received concurrent NSAIDs and chemotherapy, the MST was ______.
MST 22mo
145
In a study of 28 dogs with locoregionally advanced (Stage IIIb) AGASACA treated with either surgery or RT, the PFS for IMRT dogs was ____, and the PFS for surgery dogs was ____.
- PFS IMRT: 15mo
- PFS sx: 6 mo
146
_______ is a common acute effect during RT for colorectal tumors.
Colitis
147
In a study of 9 dogs with adrenocortical tumors with vascular invasion treated with SRT, MST was ____, _____ toxicity was observed, and the endocrine panels in ___ of ___ dogs with cortisol-secreting tumors normalized.
- MST 34mo
- minimal
- 2 of 3 dogs
148
6 dogs with heart base tumors that received SRT reported a MST of ___. What were 3 treatment-related complications?
- MST not reached
- CHF, tachyarrhythmias, coughing
149
Describe the Compton effect.
energy transfer process that involves a collision between the photon and outer orbital election of an atom, with partial energy transfer to electron and scattering of photon in new direction
150
ROS generated by ionizing radiation can interact with proteins in cell membranes, some of which may be involved in signal transduction and lead to apoptosis of certain cell types by activation of a ___________ pathway.
ceramide-sphingomyelin pathway
151
Chromosomal vs. chromatid rearrangments reflect cell-cycle phase at time of irradiation. Name the chromosome types that are seen if damage from radiation occurs in G1 or early S phase, and name the chromatid types that are seen if damage from radiation occurs in S and G2 phases.
G1 or early S phase chromosome aberrations:
- dicentrics
- reciprocal translocations (symmetrical interchange)
- acentric fragments
- terminal deletion
- interstitial deletion (asymmetrical interchange)
S and G2 chromatid aberrations:
- asymmetrical/symmetrical interchanges
- chromatid deletion
- triradials
152
Mitotic catastrophe occurs when lethally damaged cells undergo ______ abortive mitotic cycles and then lysis.
<4
153
What cells die in an apoptotic cell death when irradiated?
lymphocytes, spermatocytes, thymocytes, salivary gland epithelium, endothelial cells
154
In hematopoietic cells, radiation can lead to upregulation of genes _____, _____, _____, which facilitate apoptosis.
caspase 3, Fas, Bax
155
Ionizing radiation can initiate a __________ signaling pathway within the cell membrane, which induces apoptosis in absence of DNA damage. ________ is generated from sphingomyelin by _______ or by de novo synthesis via _________. In endothelial, lymphoid, and hematopoietic cells, _____ mediates apoptosis. In other cells, it may play no role in death response. This pathway can be inhibited by _______ or by genetic mutation of ______.
- sphingomyelin-dependent
- Ceramide
- acid sphingomyelinase (ASM)
- ceramide synthase
- ceramide
- bFGF
- ASM
156
Damaged and surviving cells cease to enter mitosis, while cells already in mitosis continue to G1 and eventually ___________. The time after which this occurs is known as _________.
- reenter mitosis
- mitotic delay
157
The _____ protein plays a role in initiating checkpoint pathways in all 3 cell-cycle phases.
ATM
158
What are the least sensitive cells to ionizing radiation? (ie, not resistant, just least sensitive)
- normal cells
- Li-Fraumeni cells
- patients with defects not involved in DSB repair (Xeroderma pigmentosum)
159
Cells derived from people with Cockayne syndrome or xeroderma pigmentosum patients with_____ defects are extremely sensitive to ____.
- NER defects
- UV irradiation
160
_________ and ________ are repaired by HR and NHEJ whereas ______ and ______ are repaired by NER.
- DNA DSBs and single-strand breaks
- cyclobutene pyrimidine dimers and 6-4PPs
161
Name cells with increased sensitivity to ionizing radiation and cells with most sensitivity.
Increased sensitivity
- defects in HR or in mediators proteins (ie, BRCA mutations, Fanconi Anemia)
Most sensitivity
- defects in NHEJ and mutations in NBS1, ATM, or DNA ligase IV genes
162
_____ is a small molecular inhibitor is linked to inhibition of DNA repair protein RAD51 and may be considered to be a radiosensitizer.
imatinib
163
Inhibiting repair of DNA base damage and single-strand breaks with inhibitors of ____ lead to radiosensitization.
PARP
164
What signaling pathways are linked to tumor radioresistance?
- RAF/MEK/ERK
- PI3K-AKT/PKB
- TGFB
- NF-kB
165
Activation of PI3K-AKT/PKB pathway is associated with what 3 major mechanisms of tumor radioresistance? This pathway can be caused by stimulation of RTK, such as ____. AKT can stimulate accumulation of _____ at DNA-DSBs and promote its activity during NHEJ and has been shown to bind to DSBs itself in vitro following irradiation. Interest in ____ inhibitors as radiosensitizers especially given its overexpression in may tumors.
1. Intrinsic radioresistance
2. Tumor-cell proliferation
3. Hypoxia
- EGFR
- DNA-PKcs
- AKT inhibitors
166
Tyrosine kinase activity of ___ is increased following exposure to radiation and addition of exogenous ___ to cell culture renders cells radioresistant.
- EGFR
- EGF
167
A phase III study demonstrated _____ given with RT for head and neck cancer in humans improved locoregional control and overall survival without increasing mucosal toxicity. The use of these type of inhibitors are thought to combat _____ during RT as basis for improved therapeutic ratio.
- EGFR inhibitor cetuximab
- tumor cell repopulation
168
How does TGFB lead to radioresistance?
by targeting ATM, leading to increased DNA repair
169
X-rays and gamma rays are part of the electromagnetic spectrum that are made up of packets of energy called _____.
photons
170
Define ionizing radiation. Explain the two general categories of ionizing radiation and give examples of each.
- ionizing radiation: any electromagnetic or particulate radiation capable of producing ion pairs by interaction with matter
particulate: subatomic particles with mass (electrons, alpha and beta particles, protons, neutrons)
- Examples: I-131 (beta), Sr-90 (beta), electron beams
electromagnetic (waves): no mass or charge (x-rays or gamma rays)
- Examples: external beam therapy using linear accelerator (high-energy x-rays), Cobalt (gamma rays produced by radioactive decay)
171
X-rays are produced when electrons are accelerated and hit a _____ target. As they decelerate they emit a spectrum of _________ radiation. When x-rays interact with tissue they give up energy by one of three processes. Name the three processes in order from lowest to highest energy. For the lowest and middle energy process, describe where in clinical practice these are used.
- tungsten
- Bremsstrahlung
- photoelectric effect < Compton effect < pair production
- photoelectric effect - radiography
- Compton effect - radiation therapy
172
What range of RT is Compton Effect?
100 keV to 25 MeV
173
Name a thiol containing drug used as a radioprotectant.
amifostine
174
Which of alpha and beta correlates with repairable damage and which with non-repairable damage?
- alpha: non-repairable damage
- beta: repairable damage
175
What is the major mechanism underlying observations that a larger total dose can be tolerated when radiation dose is fractionated?
repair of sublethal cellular damage between radiation doses
176
Explain the shoulder of the cell survival curve.
shoulder of curve represent accumulation of sublethal damage that can be repaired
177
