Block 11 - L14-L16 Flashcards
At least ___% of patients with cancer receive radiation therapy at some point during their management.
50
Tumors grow ___ for a portion of their natural history.
Exponentially
What is the lower limit of detection of a tumor? What is the lethal volume of cancer?
Lower limit - 1E9 cells
Lethal volume - 1E12 cells
Most cancers have therefore completed about 2/3 of their natural life span before they are detected.
Who is on the cancer team?
- Surgical oncologist
- Medical oncologist
- Radiation oncologist
Support services - radiology, nuclear medicine, pathology, social work, nursing
What is the role of the radiation oncologist?
- Determine if radiation therapy is needed
- Recommend the type, dose, and fractionation schedule
- Inform patients regarding rationale, side effects, and potential late toxicities
- Follow the patient during and after treatment
What is ionizing radiation?
Energy strong enough to ionize an atom
What are gamma rays?
Photons emitted from radioactive materials as they decay
What are x-rays?
Photos produced by a machine
What is external beam radiation therapy?
Aims ionizing radiation at a tumor using beams from the outside
How are high energy photos produced?
By a linear accelerator when a tungsten target is bombarded by high energy electrons
What voltage is used in diagnostic radiology? In radiation therapy?
Diagnostic radiology - kV (25 kV-150 kV) (photoelectric effect creates sharp distinctions between tissue types)
Radiation therapy - MV (4 MV-20 MV) (intentionally ionizing, compton effect, pair production)
This type of EBRT uses simple fields, plans based on bony landmarks
Conventional EBRT
This type of EBRT develops a radiation plan based on a CT scan of the patient in the radiation position
3D conformal
What is a boost?
Additional radiation given to the region of the tumor bed that is at highest risk of recurrence
What is the unit of dosing in radiation therapy?
Gray (Gy)
1 Gy = ?
1 joule/kg (measure of energy deposited in the tissue treated)
What is the typical dose of radiation therapy per day?
2 Gy
Why is radiation therapy given in patients who receive breast conserving therapy?
To reduce the risk of cancer recurrence
What are the treatment options for operable head and neck cancers?
- Surgery followed by radiation
- Radiation followed by surgery
- Chemo-radiation with surgery reserved for incomplete response to therapy
What is IMRT?
A type of EBRT; intensity of the radiation beam varies across the radiation field, based on CT anatomy, inverse treatment planning
How is an IMRT plan designed?
Radiation oncologist defines regions to treat and doses to give, as well as regions to avoid
Radiation physicist creates the plan
The combination of chemotherapy and RT has been proven to improve cancer control rates for many tumors. What is the downside to this therapy?
Increased toxicity
What is brachytherapy?
Placement of radioactive materials into or immediately adjacent to the cancer; requires an invasive procedure; may be done alone or in combination with EBRT
What is the difference between low dose rate and high dose rate brachytherapy?
LDR - temporary or permanent, delivered over days to weeks
HDR - temporary, then removed; source is very “hot,” so high doses given in minutes
___ cancer is commonly treated with brachytherapy alone.
Prostate
What is radiosurgery?
Short course, high dose, very focused EBRT
List the ways to perform radiosurgery.
- Gamma knife
- Linear accelerator based
- Cyberknife
In this type of radiosurgery, the patient is immobilized and cross-firing tiny radiation beams give extremely high doses to small points in the brain.
Gamma knife radiosurgery
In this type of radiosurgery, a miniature linear accelerator is mounted on a robot arm and can treat tumors located anywhere in the body
Cyberknife radiosurgery
The ___ technique accurately delivers radiotherapy from within the breast in about 25 minutes.
TARGIT
Discuss the components of radiation safety.
ALARA - as low as reasonably achievable
Time - minimize amount of time you are exposed
Distance - 1/R^2 (2 times the distance is 4 times less the dose)
Shielding
What are the goals of radiation?
- Cure cancer
2. Palliation in incurable patients
When can radiation be used?
- Before surgery
- After surgery
- Alone
- In combination with chemo
List the common radiation treatments.
- EBRT (conventional, 3D conformal, IMRT)
- Brachytherapy (HDR, LDR)
- Radiosurgery
True or false - Radiation toxicity only occurs if radiotherapy has been delivered.
True
True or false - Radiation toxicity only occurs if radiotherapy has been delivered to the area in question.
True
The most important factors to determine if a patient is having a radiation toxicity is determining the ___ and the ___.
Area radiated; dose
What three methods can be used to decrease exposure to radiation?
- Time (linear relationship)
- Distance (geometric relationship)
- Shielding (half value layers)
Which radiation injuries are dose-related (non-stochastic)?
- Decrease in sperm count
- Hematologic effects
- GI effects
- CNS effects
Which radiation injuries are non-dose-related (stochastic)?
- Increase in cancer risk
2. Genetic abnormalities
How should total body exposure to radiation be treated?
The damage is already done - provide supportive care, reconstruct the accident to estimate the exposure level, reverse isolation may be needed (protect them from you because they are immunocompromised), fluid/electrolyte maintenance, follow blood levels of platelets and WBCs, consider BMT if exposure is high
Name the mutation:
TCT (Ser) > TCA (Ser)
Silent (no change in product)
Name the mutation:
CAT (His) > CCT (Pro)
Missense (change in product)
Name the mutation:
AGNNN-NNNGT>ACNNNN-NNNGT
Splice site (insertion, deletion or change in a number of nucleotides in the specific site at which splicing takes place)
Name the mutation:
-20T>A
Promoter
Name the mutation:
TCAGCC>TAGCC
Deletion
Name the mutation:
TCAGCC>TCAACCGCC
Insertion
Name the mutation:
CAGCAG>CAGCAGCAGCAG
Repeat
What are three types of chromosome mutations and an example of each?
- Amplification (Her2Neu amplification in breast cancer)
- Deletion (Cri-du-Chat Chromosome 5 deletion in Cat’s Cry Syndrome)
- Translocation (Philadelphia chromosome - t(9;22)(q34;q11) in CML)
This trisomy presents with flattened nose and face, upward slanting eyes, widely separated first and second toes, increased skin creases, single palmar crease, short fifth finger that curves forward
Trisomy 21 (Down Syndrome)
This trisomy presents with a prominent occiput, dysplastic ears, clenched hands with overlapping fingers, flexed big toe, prominent heels, small mouth, small jaw, short neck, shiled chest or short and prominent sternum, wide-set nipples
Trisomy 18 (Edwards syndrome)
This trisomy presents with small head, absent eyebrows, cleft lip/palate, dysplastic ears, clenched hands and polydactyly, and undescended or abnormal testes
Trisomy 13 (Patau syndrome)
This trisomy presents with absent frontal baldness, poor beard growth, breast development, osteoporosis, small testes, female-type pubic hair pattern, tall stature, slightly feminized physique, mildly impaired IQ, tendency to lose chest hair
Triple X (Klinefelter syndrome)
Which monosomy is compatible with life?
Turner syndrome (X)
How can cytogenetic disorders be detected?
- Karyotyping
- FISH
- CGH (comparative genomic hybridiziation) analysis
- Next generation sequencing
Identify the pedigree symbols.
Look up image.
This type of inheritance is encoded on the X or Y chromosome and is conferred with gender
Sex-linked
This type of inheritance is encoded on numeric chromosomes
Autosomal
Both alleles must be affected for the trait to be displayed
Recessive
A single mutant allele confers a phenotype
Dominant
What are the key features of autosomal dominant inheritance?
- Parents pass the disease on to half of their offspring regardless of gender
- Family members that do not exhibit the disease do not carry an affected allele
Among mutations in genes encoding enzymes, regulatory gene products such as transcription factors, and structural gene products, which are more likely to be recessively inherited and which are more likely to be dominantly inherited?
Recessive - enzymes
Dominant - gene products
Define haploinsufficiency.
1 functional allele is not enough
What is a dominant negative mutation?
Encodes an altered gene product that acts antagonistically to the wild-type allele
List several common diseases inherited in an AD fashion.
- Osteogenesis Imperfecta
- Marfan Syndrome
- Ehlers Danlos Syndrome
- Familial hypercholesterolemia
What mutation causes Marfan syndrome?
FBN1 (encodes for fibrillin)
What protein is affected in Ehlers-Danlos syndrome?
Collagen
What is mutated in familial hypercholesterolemia?
LDL receptor (lack of receptor causes buildup of cholesterol, xanthomas of the skin)
What are features of X-linked dominant inheritence?
- Affected males always pass it to their daughters, never to their sons
- Females pass it to half of their children regardless of gender
What are features of AR inheritance?
- Appears in more than one sibling of the proband, but not in the parents, offspring, or other relatives
- Males and females are equally affected
- Parents are asymptomatic carriers
- Parents may be consanguineous
Risk to each sibling of the proband is 25%
What is the Hardy-Weinberg equation?
(p+q)^2 = p^2 + 2pq + q^2 = 1
p = frequency of allele A q = frequency of allele a p^2 = frequency of individual AA q^2 = frequency of individual aa 2pq = frequency of individual Aa
What are two examples of AR inheritance?
CF
Phenylkeotnuria
What is mutated in CF?
CFTR gene on chromosome 7
What happens in phenylketonuria?
Phenylalanine accumulates due to mutations of the PAH enzyme that normally converts it to tyrosine
What are the features of X-linked recessive inheritance?
- Affected fathers transmit the disease to their grandsons through their daughters but not through their sons
- All daughters of affected fathers are carriers and have a 50% chance of transmitting the mutation to their children. With 1 affected allele, females are carriers and males express the disease.
What are 2 examples of X-linked recessive inheritance?
- Duchenne’s muscular dystrophy
2. Incontinentia pigmenti
What is mutated in incontinentia pigmenti?
Patients lack a functional IKBKG gene (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) which regulates NFkappaB activation (cell death); presents with a blistering rash at birth
What is an example of X-linked dominant inheritance?
Rett syndrome
What is the mutation in Rett syndrome?
MECP2 (methyl CpG binding protein 2)
What are two examples of mutations that can affect non-coding RNA?
- HOTAIR expression leads to silencing of HOX genes, increasing cancer invasiveness
- BACE1-AS stabilizes BACE-1 expression, increasing amyloid formation in Alzheimers
What is genomic imprinting?
Different phenotypes occur depending on the parental source o the mutation
What are modifier genes and what is an example?
Phenotype of a mutation depends on the level of expression of a different (set of) genes; CF (severity depends on other genes)
What is reduced penetrance?
Not all patients with the disease genotype express symptoms
What is variable expressivity?
The severity, signs, and symptoms of the disease differ in patients due to different mutations in the same gene (allelic heterogeneity)
What is mosaicism?
Some cells have the mutations whereas others do not; can be gonadal or somatic (part of body affected, but not all of it)
What happens with expanding trinucleotide repeats?
Disease gets worse with increasing generations
What happens in mitochondrial disease?
Maternally inherited, as the egg contributes the mitochondria
What is consanguinity?
When related people have offspring, 2 otherwise rare recessive alleles can come together
Explain imprinting with respect for Angelman and Prader-Willi Syndrome.
If you inherit the gene deletion from Mom, you develop Angelman syndrome. If you inherit the gene deletion from dad, you develop Prader-Willi syndrome (regardless of your sex).
What is a classic repeat disorder?
Huntington’s disease (uncontrolled limb movements, mood alterations, decline in reasoning skills, obsessive-compulsive behavior, AD inheritance, chromosome 4)
What is anticipation?
Severity increases in subsequent generations (example - myotonic dystrophy)
What are the features of mitochondrial DNA disorders?
- Disease is passed on from mother to children of either gender
- Father does not transmit the diseased allele
- Phenotype can vary due to different copy numbers of diseased mito per cell
What is an example of mitochondrial inheritance?
Leber hereditary optic neuropathy
