By Gregory D.
Pawelski, husband
Introduction:
This is an account of my wife's treatment for recurring ovarian
cancer. Her cancer treatment varied tremendously depending on
which hospital she attended and the type of treatments given at
our local hospital were responsible for her final tumor
recurrences and her depressed quality of life in her last years.
When she first got ovarian cancer in 1972, it was treated in San
Diego, post-operatively with Chlorambucil. This is one of the
slowest acting and least toxic of the oral drugs, which allows the
immune system to regenerate during the process. The cancer
recurred in 1996 on her diaphragm and was removed at the Fox Chase
Cancer Center.
It is commonplace to give the same treatment to a recurrence as
was given for the original tumor(s). However, our hometown
hospital in Pennsylvania gave her a 'hard and fast' drug
combination of Taxol and Carboplatin. This suppresses the
immune system, which can allow tumors to grow and can weaken the
blood-brain barrier, potentially inviting cancer cells into the
central nervous system.
Sure enough, the cancer turned up in her cerebellum in 1998, and
was removed at the Hershey Medical Center. Our local home town
hospital then treated her with Whole Brain Radiation. Literature
suggests that this can result in permanent side effects such as
dementia and memory loss in 90% of patients over 60. My wife was
66. Hershey suggested treatment with focal radiation to the local
tumor bed. Scans to check for a possible spinal tumor were also
suggested but never fully carried out.
In 1999, three tumors were found on her spine and were eradicated.
In the end, my wife died of the effects of Taxol and Carboplatin,
which may have caused the cerebellum tumors, and the terrible
effects of Whole Brain Radiation, which further scans revealed had
caused extensive damage to her brain.
Ann's Medical History:
In 1972, my wife had been diagnosed with ovarian cancer, when she
presented with a left DVT (deep vein thrombosis) and pulmonary
embolism at a hospital in San Diego, CA. DVT is not uncommon in
patients with ovarian cancer (it may be a presenting sign). Workup
which was triggered by this presentation revealed that she did
have an ovarian carcinoma for which she was cured with total
abdominal hysterectomy and Chlorambucil (Leukeren) treatment. This
postoperative chemotherapy drug was among the slowest acting and
least toxic of the alkylating agents (well tolerated oral-dose
drugs). By giving chemotherapy more often, at lower doses, it can
prevent the regrowth of blood vessels that feed tumors. Depression
of the immune system is slow and reversible, allowing it to
regenerate and contribute to healing. A malfunctioning immune
system can fail to stop the growth of cancer cells. When caught at
this earliest stage, ovarian cancer has a good prognosis. At Stage
I, ovarian cancer has a five-year survival rate of around 93%. She
went twenty-four years before experiencing any recurrent ovarian
cancer.
During the early 90's in Reading, Pa., she underwent a laparotomy
(a surgical procedure which involves opening the abdominal cavity
for examination) as a followup and this did not reveal any
evidence of recurrent carcinoma. This is supposed to be the most
certain way of diagnosing ovarian cancer and assessing the extent
of cancer spread (metastasis). However, negative second-look
patients have a 50% chance of disease recurrence anyway. For the
most part, her group of oncologists relied almost entirely on the
CA 125 tumor marker (a blood test done to assess the amount of an
antibody that recognizes an antigen in ovarian tumor cells). The
rate of "false positives" makes it inadequate for use
"by itself" for screening of high-risk patients. It
should be supplemented with transvaginal ultrasonography and a
rectovaginal pelvic exam all done at the same time.
Metastatic Recurrence and Treatment:
It was our family doctor that found her first metastatic
recurrence to her diaphragm in 1996 (not the medical oncologists
at our local home town hospital). She was having dry coughing
spells at first but then she began having a mucus discharge, which
eventually was bloody. A chest xray and Cat Scan had shown a
lesion inside her diaphragm. That recurrent ovarian cancer was
surgically excised at Fox Chase Cancer Center. It was a metastatic
transdiaphragmatic tumor from the original ovarian cancer (1972),
with attachment to the lung and other midline structures of the
chest. Parts of those structures were surgically resected (the
diaphragm is a common site for ovarian metastatic recurrence).
The thoracic surgical oncologist left us with the knowledge that a
second place an ovarian metastasis possibly could occur maybe the
Central Nervous System (CNS) like the brain and/or the spine. It
is very rare for ovarian cancer cells to metastisize to the CNS.
In fact, up until 1994 there have been only 67 well documented
cases in medical literature. A multi-institutional study of 4027
ovarian cancer patients over 30 years identified only 32 cases
while an autopsy study of ovarian cancer reported an incidence of
0.9%. The surgeon at Fox Chase did not feel that further treatment
with chemotherapy was indicated.
However, the ideas of our local home town Medical Oncologists were
different from the Thoracic Surgical Oncologist who excised the
tumor from her diaphragm. My wife received postoperative
chemotherapy by these medical oncologists, seven months after
having that metastatic tumor surgically excised. She did not have
any cancer tumor markers indicate any cancer within her system.
Some tumors send out microscopic outposts while most do not.
However, medical oncologists cannot tell which ones do, so they
want to give chemotherapy in nearly every case. The type of
chemotherapy she received was the hit fast, hit hard type
combination chemotherapy of Taxol with Carboplatin (second-line
chemotherapy). It is usually given in big doses, with breaks of
several weeks between doses to let the body try to recover (or
else it can kill a patient).
Patients who develop recurrent ovarian cancer more than 6 months
after first-line chemotherapy (in my wife's case, 24 years), can
experience another remission following treatment with the
identical first-line chemotherapy that was previously used (in her
case, Chlorambucil). It has not been shown that platinum-based
combination therapy is superior to single agent alkylator therapy.
No substantial benefit has been found in giving ovarian cancer
patients second-line chemotherapy. Clinicians have found that the
toxic effects of this treatment can cause a lower quality of life
for these patients. Plus, the late stage of "recurrent
ovarian cancer" makes the combination chemotherapy of Taxol
& Carboplatin drug resistent to cancer cells and suppresses
the immune system, making it possible new tumors to grow because
the patient has been rendered unable to resist them.
In recent years the incidence of central nervous system (CNS)
metastasis has increased. Unfortunately, some chemotherapeutic
agents can weaken the blood-brain barrier (BBB) transiently and
allow CNS seeding. Taxol & Carboplatin are two of the drugs
that violate the blood-brain barrier (dose dependent). In essence,
it breaks down, damages the blood-brain barrier (BBB) to invite
microscopic cancer cells into the CNS. A NCI observational study
in 1995 reported experience in their clinic where recurrent
systemic disease occurred in all patients for which they received
dose intense paclitaxel (Taxol) therapy. Brain metastasis was the
only site of disease recurrence, presenting with headache,
dizziness, unsteady gait, nausea and vomiting.
It was our family doctor that found her second metastatic
recurrence to her cerebellum in 1998 (not the medical oncologists
at our local home town hospital). She was presenting with headache,
dizziness, unsteady gait, nausea and vomiting. A large
(3.5cm) solitary cerebellar brain tumor was found via enchanced
Cat Scan (later confirmed by an enhanced MRI). The tumor was
excised from her brain by a Neurosurgeon at Hershey Medical
Center. Histologic features were consistent with metastatic
papillary adenocarcinoma with extensive necrosis from the
ovary.
The Neurosurgeon stated that he was 99% successful and felt that
she should go back to our local home town hospital and receive
focal radiation to the local tumor bed (which is 2cm beyond the
periphery of the excised tumor site). The treatment protocol
recommended for brain metastases of large solitary tumors
exceeding 2cm in diameter is surgical resection followed by 5
fractions of local radiation to the tumor bed. At the same time,
she should receive an MRI of the spine because of suspicions of
either another tumor, on her spine or a herniated disc, causing
her leg problems. However, the ideas of our local home town
Radiation Oncologist were different from the Neurosurgeon who
excised the tumor from her brain. The Radiation Oncologist took it
upon himself to give my wife 5 fractions of focal radiation to the
local tumor bed, plus 20 fractions of Whole Brain Radiation over a
35 day period. The risk of neurotoxicity from Whole Brain
Radiation is not insignificant and this approach is not indicated
in all patients with a solitary brain metastases, particularly
when platinum drugs lower the tolerance of the CNS to radiation.
Literature of the early and mid-80's on morbidity of Whole Brain
Radiation, is flooded with papers reporting long-term side
effects, such as dementia, memory loss, radiation induced
necrosis, leukoencephalopathy, in up to 50% of two year
survivors. Whole Brain Radiation Therapy has been recognized to
cause considerable permanent side effects in patients over 60
years of age. The side effects from WBR Therapy affect up to 90%
of patients in this age group. My wife was 66 years of age while
receiving Whole Brain Radiation Therapy.
During radiation treatment, my wife received an Unenhanced MRI to
the spine that showed a 1cm lesion. Instead of performing an
Enhanced MRI to the spine or a Triple Phase Bone Scan to further
evaluate, our local home town hospital performed a Regular Bone
Scan that showed normal bone imaging. However, a Regular Bone Scan
cannot distinguish what a lesion represents and cannot
differentiate between a tumor, an infection or a fracture (a
Triple Phase Bone Scan may occasionally be helpful in determining
benign from malignant lesions). Enhanced (contrast) agents
increase the sensitivity, conspicuity and accuracy of an exam. The
agent most commonly used is Gadolinium. The proper medical
protocol for all Brain and Spinal MRI's for metastatic diseases is
Enhanced with contrast (today, it is the Pet Scan). An Enhanced
MRI was not performed and the Radiation Oncologist told us the
lesion was nothing and not to worry about it. He also ignored
my complaints about her having seizures during radiation
therapy.
Nine months later, my wife was admitted to our local home town
hospital during the Memorial Day Weekend of 1999, for a week of
testing and evaluation for unexplained falls and
light-headiness. After two weeks of failing to find out what
was wrong with her, I took her by ambulance to Hershey Medical
Center for proper medical treatment. At Hershey Medical Center, we
found out by a medical onocologist and a neurologist that she had
Leptomeningeal Carcinomatous (remember the undiagnose tumor of
nine months prior, not further evaluated?). An Enhanced MRI showed
now three (3) metastatic tumors on her spine. Spinal metastases
can grow into adjacent structures, such as into the meninges from
the spine. The largest of these tumors grew into the meninges on
the spine into the spinal fluid, hence Leptomeningeal
Carcinomatous. This was confirmed by a spinal tap.
With the damage already done to her by our local home town
hospital, the doctors at Hershey Medical (in order to save her
life or at least give her some time) had to administer Intrathecal
Methotrexate along with systemic radiation to the spine (Admitted
June 19,1999). When both therapies are performed at the same time
it doubles the theraputic dosages of each therapy (increasing the
neuro-toxic effects on the brain). However, the cancer cells were
eradicated completely from her central nervous system by this
protocol. Ever since the second spinal tap at Hershey (when
methotrexate was already being administered), all of her spinal
taps were negative for 10 consecutive times up until January 14,
2000. A Whole Body Bone Scan (November 3, 1999) indicated that the
skeletal system demonstrated normal uptake and an Enhanced Brain
MRI (November 3, 1999) showed no new areas of abnormal
enhancement.
Adverse Side Effects of Treatments:
My first experience with the side effects of combination
chemotherapy and whole brain radiation was when she was at Hershey
Medical Center in 1999. The doctors showed me the Enhanced Brain
MRI from her previous year's cerebellum excision and the one done
in 1999. The scans showed the progressive deteriation of her white
matter (white matter disease). Late delayed effects, occurring
several months to many years later, are classified into diffuse
white-matter injury, radiation-induced arteriopathy &
stroke, and late delayed Radiation Necrosis. These reactions are
due to changes in the white matter and death of brain tissue
caused by radiation-damaged blood vessels. This clinical syndrome
generally occurs 6 months to 2 years after radiation therapy.
Symptoms include decreased intellect, memory impairment,
confusion, personality changes and alteration of the normal
function of the area irradiated (all symptoms my wife had over the
past year).
Radiation Necrosis can be fatal! It causes pathological changes
that impair vascular integrity. Delayed radiation injuries result
in increased tissue pressure from edema, vascular injury leading
to infarction (stroke), damage to endothelial cells and fibrinoid
necrosis of small arteries and arterioles. My wife suffered a
stroke to the left basal ganlia area of the brain in January 2000,
confirmed by an enhanced MRI. My wife had developed necrotizing
leukoencephalopathy (a form of diffuse white matter injury that
can follow combination chemotherapy), confirmed by an enhanced MRI
in July of 1998 at Hershey. The white matter is the covering of
the nerves within the brain. Its function is to speed up the
passage of impulses along the nerves. Necrosis is simply a cell
dying, all of its coordinated activities going wrong and things
shut down. If a cell gets too much heat or is poisoned by a toxic
substance or exposed to chemicals that damage its proteins and
membraines or radiation that breaks its DNA molecules, that
cell can just stop functioning.
An EEG showed generalized diffuse slowing that was significant
with global encephalopathy. It is most commonly seen in toxic
metabolic and degenerative conditions. There appeared to be a real
amount of focal right sided slowing which would indicate cortical
dysfunction on that side. Her MRI's showed the ventricles overall
were prominent and there was widening of the sulci consistent with
cerebral atrophy (wasting away of brain cells and tissues). There
was diffuse, abnormal signal intensity within the periventricular
white matter, consistent with post radiation changes. The signal
abnormality within the white matter appeared slightly increased
compared to her prior studies. A Pet Scan showed globally
decreased radiotracer uptake within the brain, bilaterally,
consistent with involutional change and prior radiation therapy.
Because of the previous chemo-radiation treatments, a recurrence
of the cerebral metastasis was very likely to happen in the
future. Some long-term effects can include development of
secondary maligancies (the risk is 16 times greater).
Resistance to standard chemotherapy regimens of Carboplatin with
Taxol ultimately develops in nearly all adenocarcinoma cancer
patients (mainly because of the late stages of the cancer).
Recurrent ovarian cancer being such a late stage cancer, can be
resistant to the combination chemotherapy of Taxol/Carboplatin. It
can actually spread the cancerous cells rather than the cancer
itself spreading. Since both radiation and chemotherapy
suppress the immune system, it is possible that new tumors are
allowed to grow because the patient has been rendered unable to
resist them. A person who is cured of cancer by these drastic
means may find himself struggling with a new, drug-induced tumor a
few years later. A malfunctioning immune system can fail to
stop the growth of cancer cells. Recurrence of the cerebral
metastasis was observed via an Enhanced MRI of May 2000 at Hershey
Medical Center and a Pet Scan of August 2000 at the University of
Pennsylvania. Four, mm-sized metastatic tumors were found in and
around the previously resected cerebeller tumor and because of my
wife's weakened condition, Gamma-Knife would be the only
best medical protocol. She received Gamma-Knife treatment at
University of Maryland Medical Center on September 12, 2000.
During the whole time of her admission at the hospital, the
doctors kept referring to her continued diffuse white-matter
injury (brain necrosis), as if she may be too far advanced in that
injury to survive much longer. She died at home on Thursday,
September 21, 2000 at the age of 68 from Cardio-Pulmonary
Failure. Minutes before she expired, her temperature was normal,
her blood pressure was normal but her pulse was 150 (tachycardia).
Her heart was racing to keep up with the lack of brain function
and finally quit. The white matter disease that my wife
experienced and caused her death was primarily a result of Whole
Brain Radiation and secondary a result of Combination Chemotherapy
of Taxol & Carboplatin (Methotrexate was icing on the cake).
The Combination Chemotherapy of Taxol & Carboplatin caused
microscopic ovarian cancer cells to seed inside the CNS to form a
tumor on the cerebellum and tumors on the spinal cord, with
concomitant necrotizing leukoencephalopathy. Carboplatin lowered
the tolerance of her Central Nervous System to any radiation
treatment.The Whole Brain Radiation resulted in the death of tumor
cells and associated reaction in surrounding normal brain. Such
reactions tend to occur more frequently in larger metastatic
lesions. Late delayed Radiation Necrosis (also known as Radiation
Encephalopathy) is often irreversible and progressive, leading to
severe disability or death (all symptoms my wife experienced).
Cancer Treatments as Killers:
Ann's life was greatly shortened and neurologically
deteriorated by the chemo and radiation treatment received at our
local home town hospital. Patients who develop recurrent
ovarian cancer more than 6 months after first-line chemotherapy
can experience another remission following treatment with the
identical first-line chemotherapy that was previously used.
Aggressive treatment, like surgical excision of tumor and focal
radiation to the local tumor bed, in patients with limited or no
systemic disease can yield long-term survival. In such patients,
delayed deleterious side effects of whole brain radiation therapy
are particularly tragic and there is no survival benefit or
prolonged independence. The patient cannot experience the beneficial
improvement in quality of life.
If more people researched how and why their loved-one died after
being treated by orthodox cancer therapies then I believe there
would be a movement to have more effective and less toxic
treatments available. Ideally, we would conduct such research
before the treatments were administered but we usually don't have
the luxury of time to learn what the oncologists are not telling
us when it matters most. It is scary when we try to give
oncologists the benefits of doing what needs to be done but we
have to learn to ask more questions and seek more answers.
It seems the medical profession doesn't want to hear about the
side effects of treatment for gynological cancer and keeps
referring to the lives of women loss this way as "rare".
If it was their lives, they might not call it "rare".
Some people would have you believe that because "their"
bodies didn't give out after receiving chemotherapy or radiation
that these treatments are "o.k.". Cancer patients who
die, having undergone toxic treatments which sap their energy and
harm their immune systems are heralded as brave souls. Sometimes
it is good for the soul to hear what others in similar
circumstances have to say.
The quality of life must be considered as a major decision point
in cancer care. That element, so long missing in most clinics,
hopefully will be brought to the fore especially in the many
cancer clinical trials. I hope that quality of life soon becomes a
major outcome issue for all involved in the treatment of patients
with cancer. I will continue to be an advocate for my loved ones
and help others in their own journeys with cancer.
Because of the experience with my wife, I spent three years on
cancer research. I've written to over 3,000 medical professionals
and institutions all over the United States and across the globe.
I have studied over 500 medical web sites (like MedLine, Pub Med,
Oncololink, Johns-Hopkins, NCI, NIH, etc.). I have all of my
wife's medical records to relay first hand experience. I even
retained a medical expert (a retired surgeon of 25 years at our
local home town hospital) to concur my findings. I had to learn
the how and why, what happened to my wife.
There are three main points that I've found out in my three years
of cancer research.
- An understanding of the doctors involved with my wife's
medical care at our local home town hospital.
- An understanding of the lack of uniformed cancer care being
practiced here in the United States.
- Cancer patients frequently die from their cancer
treatments and not from the cancer itself.
Cancer chemotherapy and radiation therapy almost without
exception, will damage some normal tissue and diminish the immune
system. Radiation has been known for a long time to both enhance
cancer growth and to halt cancer growth. Damaging the immune
system in turn is known to foster the growth of some kinds of
other cancer. We do not yet have really outstanding treatments for
most cancers. Modern medicine in general and cancer treatment
in particular, is very imperfect. In the hopes of curing
disease or helping patients, the medical profession uses rather
drastic treatments for devastating diseases they know will kill
someone in a short time. Many oncologists don't make the families
aware enough that these treatments are drastic and can have
serious side effects.
It takes time for doctors to sit down with patients and truly
explain the benefits and the risks of treatment. In an ideal
world, patients would consider the benefits and the risks of each
treatment and make an informed decision with the guidance of a
wise doctor. But, hurried doctors seldom spend much time
discussing the benefits and the risks and few patients ever
question whether treatment may do more harm than good.
|
Ann
Lory Pawelski