Tumor Kinetics & Normal Tissues Responses Flashcards
1
Q
How does increasing radiation dose affect cataractogenesis?
A
decreases the latent period
2
Q
Can the lens eliminate damaged fibers
A
No
3
Q
What is the latent period for cataractogenesis after a dose of 2.5 - 6.5 Gy?
A
8 years
Mnemonic: 8 looks like a pair of eyes
4
Q
What is the threshold dose for cataract induction?
A
- 0.5 Gy
- Used to be 2 Gy, but many studies suggested that the threshold was much lower (or not exist at all).
5
Q
Do radiation-induced cataracts have pathognomonic characteristics?
A
Yes, they usually start in the posterior portion
6
Q
What is the risk of severe restrictive pulmonary disease in children receiving fractionated TBI?
A
1%
7
Q
What is the risk for cataract formation in children receiving fractionated TBI?
A
The majority will develop cataracts
8
Q
What is the main 2nd malignancy in children receiving fractionated TBI?
A
Thyroid Ca
9
Q
How is the risk of developing osteochondroma related to the age of a child at the time of TBI?
A
The younger the age, the more the risk
10
Q
How common is hypogonadism in children who receive TBI?
A
Quite common
11
Q
What stages of spermatogenesis are radiosensitive?
A
Spermatogonia
12
Q
What stages of spermatogenesis are radioresistant?
A
spermatozoa, spermatids
13
Q
How does the risk for sterility vary with fractionation?
A
Increases w/ fractionation
Because of the difference in radiosensitivity of the different stages of spermatogenesis (radiosensitive vs. radioresistant), each fraction kills off the radiosensitive cells. The radioresistant cells then reassort into the radiosensitive phase, and are killed off by the next fraction.
14
Q
What is the TD5 for male sterility?
A
Single fx: 2 Gy
Multi fx: 1 Gy
15
Q
What is the TD50 for male sterility?
A
- Single fx: 8 Gy
- Multi fx: 2 Gy
16
Q
How much time is required for a spermatogonial stem cell to turn into a mature spermatozoan?
A
69 days
17
Q
How long does full recovery of sperm count after irradiation w/ 6 MV XRs take?
A
2 yrs
18
Q
How soon after pelvic irradiation can diarrhea be expected?
A
3 wks
19
Q
What is the most common manifestation of radiation injury to the bowel?
A
Diarrhea
20
Q
What are late bowel reactions to radiation?
A
- MucosaI atrophy
- Stenosis
- Ulceration
- Obstruction
- Adhesions
- Perforation
21
Q
How long after radiation do bowel adhesions develop?
A
2-7 mos
22
Q
What are some late signs of CNS and spinal cord toxicity?
A
- Vascular changes (microinfarcts, microhemorrhage, moyamoya)
- Cognitive dysfunction
- Melopathy (cord)
- Necrosis (brain)
23
Q
What are some toxicity sx for the brain?
A
- Localized necrosis gen limited to white matter (focal coagulative necrosis and demyelination)
- Motor, sensory, speech deficits, seizures, sx of increased ICP
- Somnolence syndrome (1-6 mos)
- Diffuse, transient demyelination → General neurologic deterioration (3-6 mos)
24
Q
When does somnolence syndrome usually occur after CNS tox?
A
1-6 mos
25
Why does the kidney have a relatively low radiation tolerance?
Limited # of clonogens in each nephron
However, the cells of each FSU themselves are not radiosensitive!
26
Does the kidney exhibit sparing with fractionation?
Yes!
27
Does the kidney tolerate re-irradiation?
No
28
What's the timescale of the appearance of radiation nephropathy?
Many, many months
29
When does radiation-induced liver disease (RILD) occur?
2 wks - 3 mos
3-6 mos: other sources
30
What are the sx of radiation-induced liver disease (RILD)?
- Ascites
- Elevated liver enzymes
- Hepatomegaly
- **No** jaundice
RT does not turn you green
31
What pathologic changes are seen in radiation-induced liver disease (RILD)?
- Widespread inflammation
- Killing of vascular endothelial cells
- Marked venous congestion in the central portion of each lobule (veno-occlusive disease)
-- Atrophy of hepatocytes adjacent to the congested veins
- Sparing of the larger veins
32
Which drug has been shown to help with radiation fibrosis and osteoradionecrosis?
Pentoxifylline
33
What are the characteristics of radiation nephropathy?
- Proteinuria
- Anemia
- Hypertension
- Chronic, progressive decrease in renal function
34
Which drug(s) can treat or mitigate radiation nephropathy?
Any inhibitors of the RAAS pathway:
- ACE inhibitors (Captopril)
- Angiotensin receptor antagonists (Losartan)
They are effective at much lower doses than those required for BP control.
35
Can anti-hypertensive medications mitigate radiation nephropathy?
None, besides inhibitors of the RAAS pathway
36
Are B or T cells more radiosensitive?
B cells, which mature in the bone marrow, are more radiosensitive 2/2 the radiosensitivity of their progenitor cells.
37
Is Spleen radiosensitive?
Yes!
There is a marked decrease in the spleen size, fibrosis, capsule thickening, and obliteration of the sinusoids.
Remember, it is a treatment for splenomegaly!
38
What are the dose constraints for the parotid gland?
- One gland mean dose < 20 Gy
- Both glands mean dose < 25 Gy
39
Which cells are responsible for TGFβ-led fibrosis post-radiation?
- Fibroblasts
- Myofibroblasts
-- Both produce collagen → radiation fibrosis
40
Which pathway is the driver of the fibrosis process 2/2 radiation?
- TGFβ - Highly pro-inflammatory
41
Plasma levels of TGFβ have been extensively correlated with what kind of radiation injury?
Acute radiation lung injury
Levels can be used to predict which patients are at the highest risk for the injury.
42
Is salivary gland injury dependent on fx size?
No
43
Do bFGF or FGF2 protect against or enhance radiation-induced apoptosis?
Protect
44
What's the mnemonic for different ILs and their fxs?
- **H**ot **T-B**one st**EAK**
-- IL-1 → fever
-- IL-2 → stimulates T-cells
-- IL-3 → stimulates bone marrow
-- IL-4 → Produces IgE
-- IL-5 → Produces IgA
-- IL-6 → a**k**ute phase reactant (inflammatory)
- IL-8 → Neutrophil chemotactic
- IL-10 → At**TEN**uates inflammation
45
Which IL is a bone marrow radioprotector?
IL-1
46
How does hypoxia stimulate VEGF?
Hypoxia-inducible factor (HIF-1) binds to a hypoxia-responsive element (HRE) within the VEGF
the promoter, leading to VEGF transcription.
47
Which growth factors play a role in radiation-induced lung fibrosis?
- TGFβ1
- bFGF or FGF2
- CTGF
- PDGF
All the GFs!
48
What's the shape of the dose-response curve for the induction of late effects in normal tissues?
Sigmoidal
49
What happens to the majority of the patients who develop radiation pneumonitis?
They progress to pulmonary fibrosis
Almost all patients with pulmonary fibrosis have a history of pneumonitis. it may, however, have gone undetected or been subclinical.
50
What is the TD5/5 for whole lung?
-SIngle fx: 7 Gy
- Multi fx: 17.5 Gy
51
Does volume or fx have an effect on lung tolerance dose?
Both affect it
52
Is radiation pneumonitis limited to the radiation field?
No, instance of fibrosis outside the radiation field (abscopal effect) have been found.
53
Can FSU's be repopulated from clonogens that migrate from adjacent FSUs?
Yes!
54
Is the # of clonogens per FSU fixed?
Yes!
55
What dosimetric factor is critical for predicting lung complications after radiation?
V20 / V30
56
What is the dosimetric parameter that predicts the likelihood of rectal bleeding?
% volume of rectal wall that receives 40-50 Gy
57
What is the time period for focal necrosis after brian radiation?
6 mos - yrs
58
How does TGFβ affect epithelial cell proliferation?
It inhibits it.
59
How does TGFβ affect T cells?
Suppresses them!
60
How is TGFβ activated?
It is released as a homodimer complexed with latency-associated peptide (LAP). It is activated before it can exert its effects.
61
How does TGFβ affect granulocytes?
It is one of the strongest chemotactic factors for granulocytes.
62
Can the spinal cord tolerate re-irradiation?
Yes, granted at least 6 months have passed since the first course of radiation.
63
Can mouse lungs tolerate re-irradiation?
Yes, depending on the total dose they received during the first course. The more dose received, the less the tolerance, and vice versa.
64
How does the TD5 for the spinal cord vary with length?
It **decreases** with increasing cord length and then remains relatively constant.
The more length of the spinal cord you irradiate, the more the chance that you will damage one of the serial FSUs, leading to more of a chance of damage.
65
What is TD5/5?
It is the dose that will result in a 5% risk of severe complications 5 yrs post-radiation
66
What are the steps in wound healing?
1. Inflammation
2. Proliferation
3. Remodelling
67
How is the inflammation state of wound healing governed on a molecular level?
Pro-inflammatory cytokines stimulate angiogenesis, fibroblast activation, keratinocyte activation, and wound contraction
68
How is the proliferation state of wound healing governed on a cellular level?
Fibroblasts migrate to the wound, form granulation tissue, and deposit collagen
69
How is the remodeling state of wound healing governed on a cellular level?
Regression of capillaries
Collagen degeneration
70
Under what condition is radiation-induced cardiomyopathy observed during or shortly after radiation?
When RT is given concurrently with anthracycline (Adriamycin) chemotherapy.
71
What's the probability of RT-induced valvular disease in someone receiving ≥ 35 Gy to the heart?
> 80%
72
Are patients who received mediastinal radiotherapy for Hodgkin's disease or those who received RT for breast cancer at risk for heart disease?
Yes, they are at statistically significant risk for fatal myocardial events, especially 2/2 myocardial infarction
73
What is the risk of myocardial infarction in Japanese atomic bomb survivors?
Survivors who received doses as little as 1-2 Gy are at an increased risk of MIs more than 40 yrs after the bombing.
74
What is the most common manifestation of heart injury?
- Acute pericarditis 1-2 yrs after treatment (historical)
- Not so common these days
75
What is the critical structure/tissue within the heart responsible for RT-induced heart disease?
Endothelial lining of blood vessels
76
How does the endothelial lining of blood vessels contribute to RT-induced heart disease?
It starts a pro-inflammatory cascade that enhances arteriosclerosis and microvascular dysfunction
77
Can bone marrow failure occur after focal, high-dose RT to a small segment of a bone?
No, because there is compensation from the unirradiated marrow.
78
What are some complications seen with RT-induced bone injury?
- Osteoradionecrosis
- Stress Fractures
- Growth retardation after epiphyseal plate irradiation in children
- RT-induced bone sarcomas
79
Which drug class can prevent RT-induced esophagitis?
NSAIDs
80
Which drugs can prevent or reduce the risk of radiation-induced fibrosis in breast cancer patients?
- Pentoxifylline
- Vitamin E
81
What commonly causes mandibular radionecrosis?
Tooth extraction 2/2 poor dentition after radiotherapy
82
What blood test can be used to estimate accidental radiation exposure?
Serial blood counts
83
When is radiation pneumonitis usually seen after lung RT?
2-3 mos
84
How does the gradient (steepness) of the dose-response curve for lungs change with fraction size?
Relatively stable (steepness does not change)
85
Which cell types are involved in pulmonary late effects?
- Alveolar macrophages
- Vascular endothelial cells
- Type II pneumocytes
86
Why are patients at risk for dental caries post-radiation?
Death of saliva-secreting cells → xerostomia → Increased risk for caries
87
Which heart cell type is most radiosensitive?
Vascular endothelial cells, NOT cardiomyocytes
88
Which heart cell type is most radioresistant?
Cardiac myocytes
89
Which sex and age groups are most at risk for radiation-induced heart disease?
- Females > Males
- Age > 65 yrs (elderly)
90
How does damage to the parietal pericardium present?
An increased thickness of the fibrous layer
91
Is veno-occlusive liver disease an acute or a late effect?
Late (90 days)
92
How do Kupffer cells change during veno-occlusive liver disease post-radiation?
Kupffer cells are hepatic phagocytes, which consume the RBCs that lead from the damaged vasculature. They contain a lot of hemosiderin, the pigment from the breakdown of hemoglobin.
93
Does radiation cause selective damage to the grey matter?
Usually not
94
Which cells are considered the primary targets for radiation damage in the CNS?
- Vascular endothelial cells
- Oligodendrocytes
- Glial cells
95
Are there any pathognomonic characteristics of radiation damage in the CNS?
No
96
Does the severity of early reactions predict the severity of late reactions?
No, because early reactions occur due to cell killing, while late usually manifest from vascular damage.
97
What causes skin pigment changes after radiation? How long does it take for this to happen?
- Proliferation of melanocytes → pigment changes
- Occurs weeks to months after RT 2/2 low proliferation rate of melanocytes
98
What is the TD5/5 of ureter?
70 GY
99
What is the TD5/5 of kidney?
23 Gy
Mnemonic: You have **2** kidneys, not **3**
100
What is TD5/5 of colon?
45 GY
101
What is TD5/5 of stomach?
50 Gy
102
What is TD5/5 of liver?
30 Gy
103
What is the dose threshold and timeline for temporary erythema?
- 2Gy
- 1d
- When questions talk about erythema, they refer to the **main** erythema reaction, which occurs at 6 Gy in 1.5 weeks.
104
What is the dose threshold and timeline for main erythema reaction?
- 6 Gy
- 1.5-3 wks
105
What is the dose threshold and timeline for temporary epilation?
- 3 Gy
- 3 wks
106
What is the dose threshold and timeline for permanent epilation?
- 7 Gy
- 3 wks
107
What is the dose threshold and timeline for dry desquamation?
- 14 Gy
- 4 wks
108
What is the TD5/5 for lungs?
- Single dose: 7 GY
- Conventional fx: 17.5 Gy
109
What is the dose threshold and timeline for moist desquamation?
- 18 Gy
- 4/5 wks
110
What is the dose threshold and timeline for secondary ulceration?
- 24 Gy
- > 6 wks
111
What is the dose threshold and timeline for ischemic dermal necrosis?
- 18 Gy
- > 10 wks
112
What is the dose threshold and timeline for dermal atrophy (1st phase)?
- 10 Gy
- >12 wks
113
What is the dose threshold and timeline for dermal atrophy (2nd phase)?
- 10 Gy
- > 52 wks
114
What is the dose threshold and timeline for telangiectasias?
- 10 Gy
- > 52 wks
115
What is the dose threshold and timeline for late erythema?
- 15 Gy
- 8-10 wks
116
What is the dose threshold and timeline for delayed necrosis?
- 12 Gy
- > 52 wks (following trauma)
117
What is the dose threshold and timeline for skin cancer?
Dose unknown, > 15 yrs
118
How does the infection that leads to mortality in GI syndrome develop?
- Increased permeability of the GI mucosa
- Altered immunity 2/2 RT effects on lymphoreticular system
119
What is an effector molecule that works downstream of TGFβ that plays a role in radiation fibrosis?
Connective Tissue Growth Factor
120
Are serous glands affected by fraction size?
No, serous glands like the one found in the parotid glands, would not be affected by fraction size.
121
What molecule is a bone marrow radioprotector?
IL 1
122
Are the esophagus, rectum, and spinal cord serially arranged or parallel?
Serial
123
Does the length of the esophagus radiated predict the severity of esophagitis?
No!
124
What is the main anti-inflammatory cytokine?
IL 10
125
What are the main inflammatory cytokines?
- IL1
- IL8
- IL6
- TNFα
126
What is the purpose of giving probiotics after radiation?
Prevents radiation-induced enteritis
127
How do PARP inhibitors affect recovery after radiation?
They potentiate radiation damage.
128
Are late effects irreversible?
No, new data suggests that interruption of the cascade of events that leads to late effects can potentially reduce the late effects.
129
How are late effects and wound healing related?
They occur through common mechanisms.
130
What leads to the latency period in early-responding tissues?
The latency period is defined by cell turnover in early responding tissues, which is FIXED. It does not depend on dose.
131
How is the severity of the reaction of early responding tissue related to the dose?
The severity increases with increasing doses.
132
What cell types are considered the primary targets for radiation injury to the salivary glands?
The serous acinar cells
133
How do the serous acinar cells die?
They die by apoptosis!
134
Are serous or mucous cells more radioresistant?
Mucous cells are more radioresistant
135
Can we spare cells with pro-apoptotic tendencies with fractionation?
No!
136
Which signal transducers are involved in TGFβ-induced fibrosis?
- SMAD proteins
- They modulate the transcription of genes related to TGFβ receptors and other pro-fibrotic entities
137
Does fibrosis increase or decrease the therapeutic ratio?
It decreases it (more normal tissue injury!)
138
Which tissue is least likely to develop fibrosis after radiation?
Bone marrow!
139
How does bone marrow change after radiation?
It is replaced with fatty cells.
140
Which cytokine family mediates collagen deposition?
Fibrogenic cytokines, including TGF β
141
Can we predict the severity of radiation fibrosis?
Usually not, as it can vary not only in individual organs but also between individuals
142
Damage to which area of the brain is responsible for radiation-induced cognitive defects?
Hippocampus, hence we do hippocampal sparing WBRT!
143
What's the mechanism behind acute radiation effects in the brain?
- Rapid bust of apoptotic cell death, including endothelial cells
- Loss of BB barrier → edema
144
Which patients are most at risk for radiation-induced tissue changes within the brain?
Those with AVM
145
What are the acute effects of CNS radiation?
- Occur days to weeks after RT
- Brain edema
146
What are the early delayed effects of CNS radiation?
- Occur 1-6 mos
- 2/2 transient demyelination
-- Somnolence syndrome: Extreme drowsiness, clumsiness, lethargy, and slow mental processing.
-- Lhermite sign: An electric shock-like sensation that occurs on flexion of the
147
What are the late delayed effects of CNS radiation?
- Occur ≥ 6 mos
- Vascular changes (microinfarcts, microhemorrhage, moyamoya)
- Cognitive dysfunction
- Melopathy (cord)
- White matter necrosis (brain)
148
What are some biological/lifestyle risk factors of osteoradionecrosis?
- Age
- Sex
- Nutrition Status
- EtOH and tobacco use
149
What is the threshold dose for radiation retinopathy?
40 Gy
150
What is the risk of radiation nephropathy for a dose of 70 Gy?
100%
151
What is the incidence of conjunctivitis sicca (dry eyes) for doses > 55 Gy?
100%
152
Does fraction size affect the propensity for optic nerve lesions?
Yes
153
What is the incidence of optic nerve lesions for 1 Gy fx size?
5%
154
What is the incidence of optic nerve lesions for 1.9 Gy fx size?
40%
155
How is α/β related to fraction size and the impact of total tx time?
The lower the α/β ratio, the more the impact of fx size and less the impact of tx time.
156
What is α/β for late-responding tissues?
Low (≤ 3 Gy)
157
What is α/β for early-responding tissues?
High (≥ 10)
158
What dose would cause permanent arrest of endocrine function in testes?
20 Gy
159
What single and fx doses to the testes can cause permanent sterility in males?
- Single: 6 Gy
- Fx: 2 Gy
Mnemonic: DP capacity is lower than just one
160
How does fractionation impact tolerance dose for sterility in testes?
Fx decreases the tolerance dose
161
If sterility isn't resolved by this time after radiation, it will likely not resolve.
3 years
162
How is the probability of the development of late effects related to treatment time in H&N cancers?
The shorter the time, the more the possibility of late effects
163
How does lymphatic size change after radiation?
Increases
164
How is mucosal thickness impacted by radiation?
atrophy
165
How many monkeys developed myeloparesis after re-irradiation with 55.6-66 Gy given 3 years after the first round of RT (44 Gy in 2Gy/fx)?
4/45 (< 10%)
166
What is the volume effect?
It says that the total dose you can tolerate depends on the volume of the tissue irradiated.
167
What is a strong volume effect?
When low dose to a large volume can be hazardous
But a high dose to a small volume may be innocuous
168
What are hierarchical (H) type tissues?
Tissues that have unlimited proliferation, and have a hierarchy of stem cells → differentiated cells
169
What are Flexible (F) type tissues?
These are tissues that rarely divide but can be triggered to do so after damage or stress.
170
What are reverting postmitotic cells?
Nondividing, functional cells that have the potential to revert and divide, if needed.
171
What are differentiating intermitotic cells?
All cell stages b/w stem cells and fully differentiated cells
172
What are vegetative inter-mitotic cells?
- They divide constantly without differentiation.
- Includes basal epithelial cells (skin, intestinal crypts, etc), undifferentiated hematopoietic cells, and germ cells.
- **Most** radiosensitive.
173
What is the damage response in F-type tissues?
- All cells, including functional cells, enter the cell cycle.
- The interval b/w damage and expression of damage is a function of the dose
- The larger the dose → the less the time between damage and expression
174
What is the damage response in H-type tissues?
- The stem cells must divide and handle the damage
- The interval b/w damage and expression is a function of how long it takes clonogens to divide and form fully mature cells
175
What are some of the symptoms caused by TNF?
- Fatigue
- Anorexia
- Weight loss
- Transient Leukopenia
176
What is the role of bFGF?
- Increases growth of endothelial cells
- Protects against microvasculature damage
- Inhibits apoptosis
- Reduces late effects
177
What is the function of PDGF?
Increases damage to the vasculature
178
What is the function of TNF?
- Orchestrates inflammatory response
- Toxic to tumor cells
- Induces apoptosis
179
What is the function of interferons?
- Inhibits cell proliferation
- Immune cell activation
180
What are restorative factors?
- They restore normal function after radiation
- They belong to the GCSF, GM-CSF family
181
What factor is a radioprotector for the intestines?
Stem Cell Factor (SCM)
182
Which cells are thought to be the target cells for lung irradiation?
- Type II alveolar cells
- They manufacture TGFα and β
183
What is the order of radiosensitivity of different types of T cells?
T helper > T suppressor > T cytotoxic
All are unprimed. When primed, they become radioresistant
184
Which immune cells are highly radioresistant?
- Macrophages (upto 100 Gy)
- Plasma cells (60-90 Gy)
185
What is one of the most radiosensitive parts of a mouse's body?
Thymus
186
What is the mechanism for permanent epilation?
Loss of sebaceous gland secretions.
187
What is the dose threshold and timeline for skin cancer?
Dose unknown, > 15 yrs
188
What is the Late Effects of the Normal Tissue (LENT) system?
- It is a scoring system to evaluate late effects for different organ systems.
- It has no grade 0 or grade 5.
189
What is the Subjective Objective Management criteria with Analytic laboratory and imaging procedures (SOMA)?
- Another system for assessing toxicity
- Specifically designed for each organ.
190
What's the order of radiosensitivity of different blood vessels, from least to most?
Veins < Arteries < Capillaries
191
How many oocytes does a female have at birth and at the time of puberty, respectively?
Birth: 1,000,000
Puberty: 300,000
192
What's the α/β for CNS?
1-2 Gy
193
Is the brain or the spinal cord more radiosensitive?
The spinal cord
194
What're the most sensitive late-responding organs?
1. Lung
-- RT targets type II pneumocytes
2. Kidney
3. Liver
195
What is the formula for tumor control probability (TCP)?
- TCP = e-n
-- TCP = Tumor Control Probability
-- n = number of tumor cells remaining
196
What is TCD37?
TCD = Tumor Control Dose
37% Tumor Control Probabily
197
What is Gompertz distribution/curve?
It is a sigmoidal curve that describes the growth of a tumor. It is slowest at the beginning and the end of the time period.
198
What is tumor growth delay?
It is the delay in time for a tumor to reach the same specified size/volume that it would have if treatment was never given.
This could be the size of the tumor at the start of the tx.
Or it could be an arbitrary size.
199
What is the gold standard for measurement of the effectiveness of therapy?
Tumor Growth Delay Curves
200
What is the number of cells in a gram of tumor?
109
201
What is TD50?
TD stands for a toxic dose or tumor dilution
Within the context of a tumor, it is the number of tumor cells to get cancer in 50% of injected animals.
202
What's the potential doubling time of a human tumor?
5 days
203
What's the usual Tc for human tumors?
1-3 days
204
What is an iso-effect curve?
It is a plot of the total dose required to achieve a particular effect against dose/fx.
Isoeffect curves for late effects are very steep, while those for early effects are more shallow.
205
Which tissue, early- or late-responding, is more sensitive to fractionation?
Late
206
Why are the responses to fx so different among early- and late-responding tissues?
2/2 differences in DNA damage repair
207
What is the rationale for hypofractionation or giving multiple fx/day?
Exploit the sparing of late-tissue damage, which is low with low dose/fx
208
What is the flexure dose?
- It is the largest fx dose for which fractionation produces no significant Δ in the total dose required to achieve a certain effect.
- Graphically, it is the dose at which a dose-response curve bends.
- Flexure dose = 0.1 (α/β)
209
What is the rationale for accelerated treatment?
It improves tumor control
210
What's pure hyperfractionation?
- Dividing total dose into more fractions but keeping the overall tx time the same
-- Lower later reactions
-- Increased acute effects
-- In MARCH meta-analysis, resulted in ↑ OS benefit
211
When is hyperfractionation inferior to accelerated tx?
- If doubling time ≤ 5 days, accelerated tx is better.
- It also implies that the labeling index is 10-15%
212
What is the formula for calculating BED?
- BED = nd (1 + d/(α/β))
-- n = # of fx
-- d = dose/fx
213
What is the α/β for lung tissue?
3
214
What is the formula for calculating EQD2?
EQD2 = nd ((α/β + d)/(α/β + 2))
215
How does the UK continuous hyper-fractionated accelerated radiation therapy (CHART) regimen compare w/ conventional therapy for NSCLC patients?
CHART is given as 54 Gy in 26 fx (thrice daily, 6 hrs apart) vs. 60 Gy in 30 daily fx
- CHART reduced the risk of death by 24%
- CHART increased survival at 2 years from 20-29%
- CHART a/w higher risk of dysphagia in 3 mos (19% vs. 3% (mucosa has a high α/β ratio)
- CHART a/w higher risk of transient myelitis (not seen w/ conventional radiation)
216
What's the mitotic index (MI) equation?
- MI = % of cells in mitosis
-- MI = λ Tm/Tc
-- λ = Correction factor, since cells are not uniformly distributed across all cycle phases
--- Typically, λ = 0.693
-- Tm = Time in mitosis
-- Tx = Cell cycle time
217
What is Tpot?
- Potential doubling time: Time for tumor volume doubling in the absence of cell loss.
- Tpot = Tc / GF
-- Tc = Cell cycle time
-- GF - Growth fraction
218
What's the formula for calculating the cell loss factor?
- Cell loss factor (φ) = 1 - Tpot/Td
-- Tpot = potential doubling time
-- Td = Actual/observed doubling time
219
What is volume doubling time?
- Observed time for tumor volume doubling taking into account cell loss
- Tvol = Tpot / (1 - φ)
-- φ = cell loss factor
220
How can you label the S-phase cells?
- Using BrdU, which is incorporated into synthesizing DNA
- Anti-BrdU antibodies are then used to detect BrdU
221
How can you measure the DNA content?
- Using propidium iodide (PI), which binds DNa
- It can be used to detect DNA content across different phases of the cell cycle
222
What's the formula for diameter doubling time?
Td = 3 x Tvol
223
What's the one flaw of using BED to compare a massively hypofractionated regimen to a typical 6-7 week regimen?
- BED does not factor in time
-- It's inappropriate to use for regimens that massively contract time to ≤ 5 wks
224
What is the α/β for prostate ca?
< 2 Gy
225
What's the α/β for lung ca?
- NSCLC > 10 Gy
226
What're the main flaws with using BED to compare tx regimens?
- Does not account for tx time
- Does not account for tumor proliferation
227
How much additional dose of radiation is required for every day/week of tx delay?
- +0.5 Gy per day
- +3.5 Gy per wk
228
What's the α/β ratio of skin?
9-12 Gy
229
What's the α/β ratio for the jejunum?
6-10 Gy
230
What's the α/β ratio for the colon?
10-11 Gy
231
What's the α/β for the testes?
12-13 Gy
232
What's the α/β for a callus?
9-10 Gy
233
The α/β is a mathematical descriptor of which quality of a tissue?
- Tissue sensitivity to fractionation
-- It is **not** a measure of intrinsic radiosensitivity
234
How does the toxicity of early-responding normal tissue change w/ total tx time?
- Less toxicity w/ increasing tx time, as long as they are treated to less than their tolerance dose
- Longer tx time → more time for recovery during tx
235
What's the α/β of the spinal cord?
- Cervical: 1.5-3.0
- Lumbar: 2.3-4.9
236
What's the α/β of the kidney?
1-2.4
237
What's the α/β of the lung?
2-6.3
238
What's the α/β of the bladder?
3.1-7
238
What's the α/β for breast?
2.5-4.6 (~4)
239
How large can tumors grow without establishing their own blood supply?
Diameter: 1-2 mm
240
What's the definition of Stereotactic Ablative Radiotherapy (SABR)?
- Fx dose ≥ 8 Gy (usually 8-12 Gy)
-- Overwhelms cellular division and function
-- Overwhelms tumor repair
-- More likely to cause late effects
241
What's the α/β of H&N?
13.8-23
242
What's the α/β of the lung?
3.9-8.2
243
Which dmax is a/w a 6% rate of grade 3+ tox?
Dmax = 65 Gy
243
What factors are important when determining the risk of radiation to the fetus?
1. Total Dose
2. Dose Rate
3. Gestational stage
Sex of children and adults but **not** fetuses affects radiation risk
