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"The power of an aroused public is
unbeatable."
Dr. Helen Caldicott
Herman Joseph Muller wins the Nobel Prize in
Medicine.
The effects of radiation are thought of in terms of
effects on living cells.
A
typical CT scan equals 400 chest X-rays.
Equal doses of different
types or energies of radiation cause different amounts of biological damage to
living cells.
The units used to measure ionizing radiation are rather
complex.
The ionizing effects of radiation are measured by units of
exposure:
The coulomb per kilogram (C/kg) is the SI unit of ionizing
radiation exposure, and measures the amount of radiation required to create 1
coulomb of charge of each polarity in 1 kilogram of matter.
The roentgen
(R) is an older traditional unit that is almost out of use, which represented
the amount of radiation required to liberate 1 esu of charge of each polarity
in 1 cubic centimeter of dry air.
1 Roentgen = 2.58×10-4
C/kg.
However, the amount of damage done to matter (especially living
tissue) by ionizing radiation is more closely related to the amount of energy
deposited rather than the charge.
This is called the absorbed
dose.
The gray (Gy), with units J/kg, is the SI unit of absorbed dose,
which represents the amount of radiation required to deposit 1 joule of energy
in 1 kilogram of any kind of matter.
The rad (Roentgen absorbed dose),
is the corresponding traditional unit which is 0.01 J deposited per kg. 100 rad
= 1 Gy.
1 Gy of alpha radiation causes about 20 times as much damage as
1 Gy of x-rays.
The equivalent dose is defined to give an approximate
measure of the biological effect of radiation.
It is calculated by
multiplying the absorbed dose by a weighting factor WR which is different for
each type of radiation (see above table).
The sievert (Sv) is the SI
unit of equivalent dose.
Although it has the same units as grays, J/kg,
it measures something different.
It is the dose of any type of
radiation in Gy that has the same biological effect on a human as 1 Gy of
x-rays or gamma radiation.
The rem (Roentgen equivalent man) is the
traditional unit of equivalent dose.
1 sievert = 100 rem.
Because the rem is a relatively large unit, typical equivalent dose is
measured in millirem (mrem), 10-3 rem, or in microsievert (µSv), 10-6 Sv.
1 mrem = 10 µSv.
For low levels of radiation, the biological
effects are so small they may not be detected in epidemiological studies.
The body repairs many types of radiation and chemical damage.
Biological effects of radiation on living cells
may result in a variety of outcomes, including:
Cells experience DNA
damage are able to detect and repair the damage.
Cells experience DNA
damage are unable to repair the damage.
Cells may go through the
process of programmed cell death, or apoptosis, thus eliminating the
potential genetic damage from the larger tissue.
Cells experiencing nonlethal DNA
mutations pass them along.
This mutation may contribute to the formation
of a cancer.
Other observations at the tissue level are more
complicated.
These include:
In some cases, a small radiation
dose reduces the impact of a subsequent, larger radiation dose.
This has
been termed an 'adaptive
response' and is related to hypothetical mechanisms of
hormesis.
Radiation hormesis is the unproven and strange theory that a
low level of ionizing radiation helps "immunize" cells against DNA damage from
other causes thus decreasing the risk of cancer.
The theory proposes
that such low levels activate the body's DNA repair mechanisms, causing higher
levels of cellular DNA repair proteins to be present in the body, improving the
body's ability to repair DNA damage.
This allopathic theory is similar
to the theory of vaccination immunization.
This assertion is very
difficult to prove (using, for example, statistical cancer studies) because the
effects of very low ionizing radiation levels are too small to be statistically
measured amid the "noise" of normal cancer rates.
The
idea of radiation hormesis is considered unproven by regulatory bodies, which
generally use the standard "linear, no threshold" (LNT) model -
the risk of cancer is directly proportional to the
dose level of ionizing radiation.
The LNT model is safer for
regulatory purposes because it assumes worst-case damage due to ionizing
radiation; therefore, if regulations are based on it, workers might be
over-protected, but they will never be under-protected.
In biology,
radiation is mainly used for sterilization and as a
mutagen.
The 'background' dose
of natural radiation is ~ 3 mSv (300 mrem) per year.
The lethal dose of
radiation for a human is around 4 - 5 Sv (400 - 500 rem).
1898 Marie and Pierre Curie distill radium from
pitchblende.
1907 James Douglas, a
scientist and mining engineer, daughter Naomi is diagnosed with
breast cancer.
Doctors operate on her five separate
times but the cancer returns.
In a final effort, Douglas takes her to
Europe to be treated with radium.
1910
Douglas devotes his life to the promotion of radium therapy for
cancer treatment.
1911 Douglas dreams
of a method to more cheaply produce radium.
He directs research lab
chemist George Van Arsdale to experiment with various processes to extract
radium from carnotite.
Carnotite is a potassium uranium vanadate
radioactive mineral with chemical formula
K2(UO2)2(VO4)2·3H2O.
The water content can vary and small amounts of calcium, barium,
magnesium, iron, and sodium are often present.
1912 Douglas gives $100,000 to
General Memorial Hospital for the endowment of
ten beds for clinical research work, and the equipment for an X-ray plant and
clinical laboratory.
1913 With a US
government grant, Douglas forms the National Radium Institute, to mine
radium from uranium ores recently discovered in Colorado.
Douglas
donates a half million dollars of radium, three grams, to Johns Hopkins
University.
1915 Douglas, working
with Dr. James Ewing, establishes a radium department and lay the foundation in
the United States for radiation therapy.
1917
Douglas gives his entire share of the National Radium
Institute to Memorial Hospital along with the stipulation that the
hospital should return to its original mandate of serving as a cancer hospital.
The second is that radiation would be
studied and used to treat cancer.
1918
Grace Fryer starts work as a dial painter at the United States
Radium Corporation (USRC) in Orange, New Jersey.
Dial painting was "the elite job for the poor working girls".
It pays three times the average factory job, and those lucky enough to
land a position ranked in the top 5% of female workers nationally, giving the
women financial freedom in a time
of burgeoning female empowerment.
Radium's
luminosity is part of its allure,
and the dial painters soon became known as the "ghost girls" - because by the
time they finished their shifts, they themselves glow in the dark.
Radium is beneficial to health, just as
arsenic was in the Victorian
era.
People drank radium water as
a tonic, like they
drink monster drinks
now; one could buy cosmetics, butter, milk,
and toothpaste laced with radium.
Newspapers reported its use
would "add years to our lives!"
1946
Herman Joseph Muller, American, concludes low dose exposure, and
therefore even natural background radiation, is mutagenic.
There is no
harmless dose range for heritable effects or
cancer induction.
1947 Colonel EE Kirkpatrick of the US Atomic
Energy Commission issues a secret document (Document 07075001, January 8,
1947) stating the agency will administer intravenous doses of radioactive
substances to humans.
Researchers inject 4.7 micrograms of
plutonium into American soldiers
at the Oak Ridge
facility.
Plutonium Trojan Horse in the Body
Researchers give
a total of 200 doses of iodine-131, a
radioactive tracer that concentrates almost immediately in the thyroid
gland, to 85 healthy Eskimos and 17 Athapascan Indians living in
Alaska.
Laboratory workers at the University of Minnesota and
University of Chicago inject human guinea pigs with phosphorus-32.
University of
Rochester radiologist Colonel Stafford Warren injects
plutonium into human at the
teaching hospital,
Strong Memorial.
University of Rochester researchers
inject four male and two female human guinea pigs with uranium-234 and
uranium-235 in dosages ranging from 6.4 to 70.7 micrograms per one kilogram of
body weight in order to study how much uranium they could tolerate before their
kidneys fail.
Six male employees of a Chicago metallurgical laboratory are given
water contaminated with plutonium-239 to drink so that researchers can learn
how plutonium is absorbed
into the digestive tract.
Human guinea pigs are given one to four
injections of arsenic-76 at the University of Chicago Department of
Medicine.
The Atomic Energy Commission (AEC) sponsors iodine
studies at the University of Iowa.
In the first study,
researchers give pregnant women 100 to 200 microcuries of iodine-131 and then
study the women's aborted embryos in order to learn at what stage and to what
extent radioactive iodine crosses the placental barrier.
In the second
study, researchers give 12 male and 13 female newborns under 36 hours old and
weighing between 5.5 and 8.5 lb iodine-131 either orally or via intramuscular
injection, later measuring the concentration of iodine in the newborns'
thyroid glands.
Researchers feed 28 healthy infants at the University of Nebraska
College of Medicine iodine-131 through a gastric tube and then test
concentration of iodine in the infants'
thyroid
glands.
At the University of Tennessee, researchers inject
healthy two-to three-day-old newborns with approximately 60 rads of iodine-131.
Researchers at Harper Hospital in Detroit give oral doses of
iodine-131 to 65 premature and full-term infants weighing between 2.1 and 5.5
lb.
Eleven patients at Massachusetts General Hospital in Boston
are injected with uranium.
Researchers inject a genetic compound called
radioactive thymidine into the testicles of more than 100 Oregon State
Penitentiary inmates to learn whether sperm production is affected by
exposure to steroid hormones.
1958
The Atomic Energy Commission (AEC) drops
radioactive materials
over Point Hope, Alaska, home to the Inupiats, in a field test known under the
codename "Project Chariot."
1986
Six documented accidents occur when a high-current electron beam
generated in X-ray mode is delivered directly to patients.
Two software faults are to blame.
One, when the
operator incorrectly selected X-ray mode before quickly changing to electron
mode, which allowed the electron beam to be set for X-ray mode without the
X-ray target being in place.
A second fault allowed the electron beam
to activate during field-light mode, during which no beam scanner was active or
target was in place.
Killed By A Machine: The Therac-25
"Breast cancer is the
most common indication for chemotherapy among women in the United States, and
chemotherapy drugs are the leading cause of serious drug-related adverse
effects among women with
breast cancer." -
Michael J. Hassett, A. James O'Malley, Juliana R. Pakes, Joseph P. Newhouse,
and Craig C. Earle1885
Paul Ehrlich, a German physician and scientist working in the
fields of hematology, immunology, and antimicrobial chemotherapy develops the
first chemical to target a specific pathogen.
Ehrlich developed the
precursor technique to Gram
staining bacteria making it possible to distinguish between
different types of
blood cells leading to the capability of diagnosing numerous blood
diseases.
His laboratory discovered arsphenamine (Salvarsan), the first
effective medicinal treatment for syphilis; initiating the concept of
chemotherapy.
Paul Ehrlich popularizes the concept of 'a magic bullet'
as much as Sigmund Freud popularized the idea of a 'happy pill'.
Ehrlich
reasoned if an antigen could selectively target a disease causing organism,
then a "magic bullet" - for that organism could be delivered.
Ehrlich
elaborated the systematic testing of chemical compounds as now practiced in the
pharmaceutical industry in clinical trials.
Ehrlich's work illuminated
the existence of the blood-brain
barrier.
1942
Two pharmacologists from the Yale School of Medicine, Louis S.
Goodman and Alfred Gilman, are recruited
by the DoD to create a less volatile mustard gas.
They exchanged a
nitrogen molecule for sulfur creating a more stable compound in nitrogen
mustard.
1943 A German air raid in
Bari, Italy leads to the exposure of more than a thousand people to a secret
cargo of mustard gas bombs on the SS John Harvey.
Autopsies of the
victims suggest that profound lymphoid and myeloid suppression occurred after
exposure.
Dr. Stewart Francis Alexander theorizes that since mustard
gas all but ceased the division of certain types of somatic cells whose nature
was to divide fast, it could also potentially be put to use in helping to
suppress the division of certain types of cancerous cells.
The British
and US governments cover up the presence of mustard gas.
"Oncologists
take for granted response to therapy prolongs
survival, an opinion
based on fallacy and not supported by
clinical studies." -
Ulrich Abel
carmustine, cisplatin, cytarabine
Carmustine is a mustard
gas-related compound;
Carmustine, also called BCNU
(1,3[bis]-2-chloroethyl-nitrosourea), decomposes spontaneously into a
chloroethyl hydroxide that can alkylate the DNA and into
an isocyanide molecule, which may
produce carbamylation of proteins. Cytotoxicity is caused by DNA
cross-links.
Cisplatin is a platinum-based compound;
Cisplatin, mode of action has been linked to its ability to crosslink
with the purine bases on the DNA; interfering with DNA repair mechanisms,
causing DNA damage, and subsequently
inducing apoptosis in cancer cells.
Cytarabine is an
antimetabolite antineoplastic agent that inhibits the synthesis of DNA with
immunosuppressant properties.
Cytarabine is metabolized
intracellularly into its active triphosphate form (cytosine arabinoside
triphosphate). Cytosine arabinoside interferes with the synthesis of DNA. Its
mode of action is due to its rapid conversion into cytosine arabinoside
triphosphate, which damages DNA when the cell cycle holds in the S phase
(synthesis of DNA). Rapidly dividing cells, which require DNA replication for
mitosis, are therefore most affected. Cytosine arabinoside also inhibits both
DNA and RNA polymerases and nucleotide reductase enzymes needed for DNA
synthesis.
Cancer
Treatment-Induced Neurotoxicity
Hodgkin
Lymphoma Treatment Regimens
Cancer therapy
selection, dosing, administration, and the management of related adverse events
can be a complex process that should be handled by an experienced health care
team. Clinicians must choose and verify treatment options based on the
individual patient; drug dose modifications and supportive care interventions
should be administered accordingly. The cancer treatment
regimens below may include both U.S. Food and Drug Administration-approved and
unapproved indications/regimens. These regimens are provided only to
supplement the latest treatment strategies. These Guidelines are a work in
progress that may be refined as often as new significant data become available.
The NCCN Guidelines® are a consensus statement of its authors regarding
their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult any NCCN Guidelines® is expected to use
independent medical judgment in the context of individual clinical
circumstances to determine any patient's care or treatment. The NCCN makes no
warranties of any kind whatsoever regarding their content, use, or application
and disclaims any responsibility for their application or use in any
way.
Ocular
side effects of systemically administered chemotherapy
Tables
of Possible Side Effects for Commonly-Used Oncology Drugs
"The
overall contribution of curative and adjuvant cytotoxic chemotherapy to 5-year
survival in adults was estimated to be 2.1% in the USA . It is clear that
cytotoxic chemotherapy only makes a minor contribution to cancer survival." -
Graeme Morgan, Robyn Ward, and Michael Barton
2006 Chemotherapy impairs
the brain, killing
crucial neural cells and
causing key parts of the
brain to shrink.
New findings add to a growing body of evidence
suggesting that the mental fuzziness,
memory loss and
cognitive impairment often reported by
cancer patients but often
dismissed by oncologists - is a serious problem.
Key areas of the brain
including the prefrontal, parahippocampus and cingulate gyri shrink during and
after chemotherapy for several months.
MRI scans show cause of chemobrain
"Chemotherapy
patients experience short
term problems with memory .
About 15% suffer permenant medically
induced cognitive impairment.
The symptoms are consistent:
a mental fogginess that
may include problems with memory, word retrieval, concentration, processing
numbers, following instructions,
multitasking and setting
priorities." - Jane E. Brody
"Those of us on the front lines have known
this for a long time, now we have neuropathological evidence that
what we are seeing involves
an anatomic change." - Dr. Stewart Fleishman*, director of cancer
supportive services at Beth Israel Medical Center and St. Luke's-Roosevelt
Hospital Center |
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