I am not a medical doctor.  Denise should be asking her MDs
about this.

Having said that I'd try to get an MRI immediately.  Whole
brain radiation can have a variety of side effects, but the
dizziness is worrying.  Headaches, fatigue and general loss
of "personality" are more common side effects.

Again I am not a doctor.  Tim, perhaps you could weigh in
here with another opinion.  I'm cross-posting this to
sci.med.diseases.cancer to get opinions from those folks,
too. - Tony

--
Love and light,
Tony Lima

The initial approach to using radiation postoperatively to treat brain
metastases, used to be whole brain radiation, but this was abandoned
because of the substantial neurological deficits that resulted, sometimes
appearing a considerable time after treatment. Whole brain radiation was
routinely administered to patients after craniotomy for excision of a
cerebral metastasis in an attempt to destroy any residual cancer cells at
the surgical site. However, the deleterious effects of whole brain
radiation, such as dementia and other irreversible neurotoxicities, became
evident.

This raised the question as to whether elective postoperative whole brain
radiation should be administered to patients after excision of a solitary
brain metastasis. Current clinical practice, at most leading cancer
centers, use a more focused radiation field that includes only 2-3cm
beyond the periphery of the tumor site. This begins as soon as the
surgical incision has healed.

Many metastatic brain lesions are now being treated with stereotactic
radiosurgery. In fact, some feel radiosurgery is the treatment of choice
for most brain metastases. There are a number of radiation treatments for
therapy (Stereotatic, Gamma-Knife, Brachyradiation and IMRT to name a
few). These treatments are focal and not diffuse. Unlike surgery, few
lesions are inaccessible to radiosurgical treatment because of their
location in the brain. Also, their generally small size and relative lack
of invasion into adjacent brain tissue make brain metastases ideal
candidates for radiosurgery. Multiple lesions may be treated as long as
they are small.

The risk of neurotoxicity from whole brain radiation is not insignificant
and this approach is not indicated in patients with a solitary brain
metastasis. Observation or focal radiation is a better choice in solitary
metastasis patients. Whole brain radiation can induce neurological
deterioration, dementia or both. Those at increased risk for long-term
radiation effects are adults over 50 years of age. However, whole brain
radiation therapy has been recognized to cause considerable permanent side
effects mainly in patients over 60 years of age. The side effects from
whole brain radiation therapy affect up to 90% of patients in this age
group. Focal radiation to the local tumor bed has been applied to patients
to avoid these complications.

Radiation necrosis may result from the death of tumor cells and associated
reaction in surrounding normal brain or may result from the necrosis of
normal brain tissue surrounding the previously treated metastatic brain
tumor. Such reactions tend to occur more frequently in larger lesions
(either primary brain tumors or metastatic tumors). Radiation necrosis has
been estimated to occur in 20% to 25% of patients treated for these tumors.
Some studies say it can develop in at least 40% of patients irradiated for
neoplasms following large volume or whole brain radiation and possibly 3%
to 9% of patients irradiated focally for brain tumors that developed
clinically detectable focal radiation necrosis. In the production of
radiation necrosis, the dose and time over which it is given is important,
however, the exact amounts that produce such damage cannot be stated.

Late effects of whole brain radiation can include abnormalities of
cognition (thinking ability) as well as abnormalities of hormone
production. The hypothalamus is the part of the brain that controls
pituitary function. The pituitary makes hormones that control production
os sex hormones, thyroid hormone, cortisol. Both the pituitary and the
hypothalamus will be irradiated if whole brain radiation occurs. Damage to
these structures can cause disturbances of personality, libido, thirst,
appetite, sleep and other symptoms as well. Psychiatric symptoms can be a
prominent part of the clinical picture presented when radiation necrosis
occurs.

Aggressive treatment like surgical resection 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. Within 6 months to
2 years patients can develop progressive dementia, ataxia and urinary
incontinence, causing severe disability and in some, death. Delayed
radiation injuries result in increased tissue pressure from edema,
vascular injury leading to infarction, damage to endothelial cells and
fibrinoid necrosis of small arteries and arterioles.

Even the studies performed by Dr. Roy Patchell, et al, in the early and
late 90's have been recognized incorrectly, sometimes, in the radiation
oncology profession. The studies were thought to have been the difference
between surgical excision of brain tumor alone vs. surgical excision &
whole brain radiation. It was a study of whole brain radiation of a brain
tumor alone vs. whole brain radiation & surgical excision. The increased
success had been the surgery. And they measured "tumor recurrence", not
"long-term survival". Patients experiencing any survival could have been
dying from radiation necrosis, starting within two years of whole brain
radiation treatment and documented as "complications of cancer" not
"complications of treatment". There was less "tumor recurrence" but not
more "long-term survival". In my wife's case, tumors recurred.

Patchell's studies convincingly showed there was no survival benefit or
prolonged independence in patients who received postoperative whole brain
radiation therapy. The efficacy of postoperative radiotherapy after
complete surgical resection had not been established. It never mentioned
the incidence of dementia, alopecia, nausea, fatigue or any other numerous
side effects associated with whole brain radiation. The most interesting
part of this study were the patients who lived the longest. Patients in
the observation group who avoided neurologic deaths had an improvement in
survival, justifying the recommendation that whole brain radiation therapy
is not indicated following surgical resection of a solitary brain
metastasis.

An editorial by Drs. Arlan Pinzer Mintz and J. Gregory Cairncross (JAMA
1998;280:1527-1529) described the morbidity associated with whole brain
radiation and emphasized the importance of individualized treatment
decisions and quality-of-life outcomes.

Again, whole brain radiation is the most damaging of all types of
radiation treatments and causes the most severe side effects in the long
run to patients. In the past, patients who were candidates for whole brain
radiation were selected because they were thought to have limited survival
times of less than 1-2 years and other technology did not exist. Today,
many physicians question the use of whole brain radiation in most cases as
one-session radiosurgery treatment can be repeated for original tumors or
used for additional tumors with little or no side effects from radiation
to healthy tissues. Increasingly, major studies and research have shown
that the benefits of radiosurgery can be as effective as whole brain
radiation without the side effects.

Sometimes, symptoms of brain damage appear many months or years after
radiation therapy, a condition called late-delayed radiation damage
(radiation necrosis or radiation encephalopathy). Cerebral radiation
necrosis is a debilitating, potentially life-threatening and increasingly
frequent problem in patients with brain tumors. These symtoms can be from
progression of cancer or it can be caused by the side effects of whole
brain radiation. However, the FDG-Pet Scan can provide a reliable
technique for diagnosing tumor recurrence from necrosis. Until the new
millenium, the only treatment for patients with confirmed symptomatic
radiation-induced necrosis was pentoxifyline or heparin therapy, and it
was almost always unsuccessful. Hyperbaric Oxygen Therapy (HBO) is now a
useful terapeutic option for patients.

The most common condition treated at some Hyperbaric Oxygen Therapy
Centers is tissue injury caused by brain radiation therapy for cancer.
Wound healing requires oxygen delivery to the injured tissues. Radiation
damaged tissue has lost blood supply and is oxygen deprived. Chronic
radiation complications result from scarring and narrowing of the blood
vessels within the area which has received the treatment. Hyperbaric
Oxygen Therapy provides a better healing environment and leads to the
growth of new blood vessels in a process called re-vascularization. It
also fights infection by direct bacteriocidal effects. Using hyperbaric
treatment protocols, "most" patients with chronic radiation injuries can
be cured.

Hyperbaric oxygen therapy is administered by delivering 100 percent oxygen
at pressures greater than atmospheric (sea level) pressure to a patient in
an enclosed chamber. Hyperbaric oxygen acts as a drug, eliciting varying
levels of response at different treatment depths, durations and dosages,
and has been proven effective as adjunctive therapy for specifically
indicated conditions.

Oxygen is a natural gas that is absolutely necessary for life and healing.
Purified oxygen is defined as a drug but is the most natural of all drugs.
Oxygen under pressure is still the same gas but is more able to penetrate
into parts of the body where the arterial flow is hindered, producing
ischemia (loss of blood flow) and hypoxia (lack of oxygen). When oxygen
under pressure is breathed by a patient in a sealed chamber, it is termed
a hyperbaric oxygen treatment (HBOT).

In addition to raising the arterial levels of oxygen 10 to 15 times higher
than that produced by normal atmospheric pressure, the pressure exerted
within the body can and does exert therapeutic benefits on acute and
chronically traumatized and swollen tissus.

The initial approach to using radiation postoperatively to treat brain
metastases, used to be whole brain radiation, but this was abandoned
because of the substantial neurological deficits that resulted, sometimes
appearing a considerable time after treatment. Whole brain radiation was
routinely administered to patients after craniotomy for excision of a
cerebral metastasis in an attempt to destroy any residual cancer cells at
the surgical site. However, the deleterious effects of whole brain
radiation, such as dementia and other irreversible neurotoxicities, became
evident.

This raised the question as to whether elective postoperative whole brain
radiation should be administered to patients after excision of a solitary
brain metastasis. Current clinical practice, at most leading cancer
centers, use a more focused radiation field that includes only 2-3cm
beyond the periphery of the tumor site. This begins as soon as the
surgical incision has healed.

Many metastatic brain lesions are now being treated with stereotactic
radiosurgery. In fact, some feel radiosurgery is the treatment of choice
for most brain metastases. There are a number of radiation treatments for
therapy (Stereotatic, Gamma-Knife, Brachyradiation and IMRT to name a
few). These treatments are focal and not diffuse. Unlike surgery, few
lesions are inaccessible to radiosurgical treatment because of their
location in the brain. Also, their generally small size and relative lack
of invasion into adjacent brain tissue make brain metastases ideal
candidates for radiosurgery. Multiple lesions may be treated as long as
they are small.

The risk of neurotoxicity from whole brain radiation is not insignificant
and this approach is not indicated in patients with a solitary brain
metastasis. Observation or focal radiation is a better choice in solitary
metastasis patients. Whole brain radiation can induce neurological
deterioration, dementia or both. Those at increased risk for long-term
radiation effects are adults over 50 years of age. However, whole brain
radiation therapy has been recognized to cause considerable permanent side
effects mainly in patients over 60 years of age. The side effects from
whole brain radiation therapy affect up to 90% of patients in this age
group. Focal radiation to the local tumor bed has been applied to patients
to avoid these complications.

Radiation necrosis may result from the death of tumor cells and associated
reaction in surrounding normal brain or may result from the necrosis of
normal brain tissue surrounding the previously treated metastatic brain
tumor. Such reactions tend to occur more frequently in larger lesions
(either primary brain tumors or metastatic tumors). Radiation necrosis has
been estimated to occur in 20% to 25% of patients treated for these tumors.
Some studies say it can develop in at least 40% of patients irradiated for
neoplasms following large volume or whole brain radiation and possibly 3%
to 9% of patients irradiated focally for brain tumors that developed
clinically detectable focal radiation necrosis. In the production of
radiation necrosis, the dose and time over which it is given is important,
however, the exact amounts that produce such damage cannot be stated.

Late effects of whole brain radiation can include abnormalities of
cognition (thinking ability) as well as abnormalities of hormone
production. The hypothalamus is the part of the brain that controls
pituitary function. The pituitary makes hormones that control production
os sex hormones, thyroid hormone, cortisol. Both the pituitary and the
hypothalamus will be irradiated if whole brain radiation occurs. Damage to
these structures can cause disturbances of personality, libido, thirst,
appetite, sleep and other symptoms as well. Psychiatric symptoms can be a
prominent part of the clinical picture presented when radiation necrosis
occurs.

Aggressive treatment like surgical resection 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. Within 6 months to
2 years patients can develop progressive dementia, ataxia and urinary
incontinence, causing severe disability and in some, death. Delayed
radiation injuries result in increased tissue pressure from edema,
vascular injury leading to infarction, damage to endothelial cells and
fibrinoid necrosis of small arteries and arterioles.

Even the studies performed by Dr. Roy Patchell, et al, in the early and
late 90's have been recognized incorrectly, sometimes, in the radiation
oncology profession. The studies were thought to have been the difference
between surgical excision of brain tumor alone vs. surgical excision &
whole brain radiation. It was a study of whole brain radiation of a brain
tumor alone vs. whole brain radiation & surgical excision. The increased
success had been the surgery. And they measured "tumor recurrence", not
"long-term survival". Patients experiencing any survival could have been
dying from radiation necrosis, starting within two years of whole brain
radiation treatment and documented as "complications of cancer" not
"complications of treatment". There was less "tumor recurrence" but not
more "long-term survival". In my wife's case, tumors recurred.

Patchell's studies convincingly showed there was no survival benefit or
prolonged independence in patients who received postoperative whole brain
radiation therapy. The efficacy of postoperative radiotherapy after
complete surgical resection had not been established. It never mentioned
the incidence of dementia, alopecia, nausea, fatigue or any other numerous
side effects associated with whole brain radiation. The most interesting
part of this study were the patients who lived the longest. Patients in
the observation group who avoided neurologic deaths had an improvement in
survival, justifying the recommendation that whole brain radiation therapy
is not indicated following surgical resection of a solitary brain
metastasis.

An editorial by Drs. Arlan Pinzer Mintz and J. Gregory Cairncross (JAMA
1998;280:1527-1529) described the morbidity associated with whole brain
radiation and emphasized the importance of individualized treatment
decisions and quality-of-life outcomes.

Again, whole brain radiation is the most damaging of all types of
radiation treatments and causes the most severe side effects in the long
run to patients. In the past, patients who were candidates for whole brain
radiation were selected because they were thought to have limited survival
times of less than 1-2 years and other technology did not exist. Today,
many physicians question the use of whole brain radiation in most cases as
one-session radiosurgery treatment can be repeated for original tumors or
used for additional tumors with little or no side effects from radiation
to healthy tissues. Increasingly, major studies and research have shown
that the benefits of radiosurgery can be as effective as whole brain
radiation without the side effects.

Sometimes, symptoms of brain damage appear many months or years after
radiation therapy, a condition called late-delayed radiation damage
(radiation necrosis or radiation encephalopathy). Cerebral radiation
necrosis is a debilitating, potentially life-threatening and increasingly
frequent problem in patients with brain tumors. These symtoms can be from
progression of cancer or it can be caused by the side effects of whole
brain radiation. However, the FDG-Pet Scan can provide a reliable
technique for diagnosing tumor recurrence from necrosis. Until the new
millenium, the only treatment for patients with confirmed symptomatic
radiation-induced necrosis was pentoxifyline or heparin therapy, and it
was almost always unsuccessful. Hyperbaric Oxygen Therapy (HBO) is now a
useful terapeutic option for patients.

The most common condition treated at some Hyperbaric Oxygen Therapy
Centers is tissue injury caused by brain radiation therapy for cancer.
Wound healing requires oxygen delivery to the injured tissues. Radiation
damaged tissue has lost blood supply and is oxygen deprived. Chronic
radiation complications result from scarring and narrowing of the blood
vessels within the area which has received the treatment. Hyperbaric
Oxygen Therapy provides a better healing environment and leads to the
growth of new blood vessels in a process called re-vascularization. It
also fights infection by direct bacteriocidal effects. Using hyperbaric
treatment protocols, "most" patients with chronic radiation injuries can
be cured.

Hyperbaric oxygen therapy is administered by delivering 100 percent oxygen
at pressures greater than atmospheric (sea level) pressure to a patient in
an enclosed chamber. Hyperbaric oxygen acts as a drug, eliciting varying
levels of response at different treatment depths, durations and dosages,
and has been proven effective as adjunctive therapy for specifically
indicated conditions.

Oxygen is a natural gas that is absolutely necessary for life and healing.
Purified oxygen is defined as a drug but is the most natural of all drugs.
Oxygen under pressure is still the same gas but is more able to penetrate
into parts of the body where the arterial flow is hindered, producing
ischemia (loss of blood flow) and hypoxia (lack of oxygen). When oxygen
under pressure is breathed by a patient in a sealed chamber, it is termed
a hyperbaric oxygen treatment (HBOT).

In addition to raising the arterial levels of oxygen 10 to 15 times higher
than that produced by normal atmospheric pressure, the pressure exerted
within the body can and does exert therapeutic benefits on acute and
chronically traumatized and swollen tissus.

Leptomeningeal Carcinomatous (Carcinomatous Meningitis)

The most common cancers to involve the leptomeninges are breast cancer,
lung cancer and melanomas, and now, because of dose-intense combination
chemotherapies, even ovarian cancer is more common.

Unfortunately, cancer cells are too small to find on any scans unless they
have grown into a lump. There can still be cancer cells in the body even
though scans may have indicated that all the cancer had gone.
Leptomeningeal metastasis (Lepteomeningeal Carcinomatous or Carcinomatous
Meningitis) is a condition caused by cancer cells getting into the thin
sheets of body tissue that surround and protect the brain and spine. These
sheets are called the meninges. Meningitis means inflammation of the
meninges. Carcinomatous just means acting like a cancer. Most people are
familiar with the type of meningitis caused by an infection, but with
carcinomatous meningitis, it is the cancer cells in the meninges that
cause the inflammation, not an outside infection.

Cancer cells do not always develop into an active secondary tumor when
they have spread to a new site. Sometimes they stay inactive for many
years. Even after a cancer appears to have been successfully treated, some
cancer cells may still be elsewhere in the body. No one knows why some
cancer cells stay inactive or what triggers them to form a secondary
cancer.

Tumor cells reach the meninges by hematogenous (blood) spread or by direct
extension from pre-existing lesions and are then disseminated throughout
the neuroaxis by the flow of the cerebrospinal fluid. Patients present
with signs and symptoms from injury to nerves that traverse the
subarachnoid space, direct tumor invasion into the brain or spinal cord,
alterations in blood supply to the nervous system, obstruction of normal
cerebrospinal fluid (CSF) flow pathways or general interference with brain
function.

Secondary cancers from a primary cancer can develop in different parts of
the body, including the brain or spine. Cancer cells do not always develop
into an active secondary tumor when they have spread to a new site.
Sometimes they stay inactive for many years. So, even after a cancer
appears to have been successfully treated, some cancer cells may still be
elsewhere in the body. No one knows why some cancer cells stay inactive or
what triggers them to form a secondary cancer.

Symptoms from neoplastic meningitis include pain, headaches, mental status
decline, loss of sensation in the face or elsewhere on the body, or
difficulties with vision, hearing, or swallowing, among others. Diagnosis
is most commonly made by lumbar puncture, although the CSF cytology is
persistently negative in about 10% of patients with leptomeningeal
carcinomatosis. Radiology studies may reveal subarachnoid masses, diffuse
contrast enhancement of the meninges or hydrocephalus without a mass
lesion.

Doctors estimate that about 5 out of every 100 patients who have cancer
develop carcinomatous meningitis. It is most common in breast cancer, but
it can occur with any type of cancer. The cancer cells in the meninges can
cause a range of symptoms, including confusion, headaches and weakness.

The condition is very difficult to treat. The main aim is to help control
symptoms and not cure the disease. Chemotherapy injected into the spinal
fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are
both treatments for Carcinomatous meningitis. Some patients respond to
these treatments, but the prognosis is generally poor. There are no set
guidelines for treating this condition as oncologists don't really know
which treatments work best.

Without treatment, the median survival of patients is 4 - 6 weeks and
death occurs from progressive neurologic dysfunction. Radiation therapy to
symptomatic sites and disease visible on neuroimaging studies and
intrathecal chemotherapy increases the median survival to 3 - 6 months.
Major favorable prognostic factors include excellent performance status,
absence of serious fixed neurologic deficits, normal CSF flow scans and
absent or responsive systemic tumor.

Oncologists have been looking at using different combinations of
chemotherapy drugs to treat Leptomenigeal Carcinomatous secondary to the
primary cancer (Chemosensitivity Testing may help in this process). They
found that giving both chemotherapy injected into the bloodstream and
chemotherapy given directly into the spinal fluid may improve the outlook
for some people. However, current available therapies are toxic though,
and provide limited benefits.

Approximately 50% of lung and breast cancer patients who survive more than
one year with Leptomeningeal metastasis treated with repeated injections of
intrathecal methotrexate develop leukoencephalopathy which includes
confusion, dementia, somnolence or focal neurologic signs. This usually
occurs when intrathecal methotrexate is combined with irradiation and this
combination should be avoided if possible. The leukoencephalopathy may
improve if intrathecal methotrexate is discontinued, although it may also
progress to coma and death.

A medical oncologist involved with Chemosensitivity Testing has stated
that their lab has only received maybe four Lepomeningeal Carcinomatous
specimens over the years. Of those, only one specimen had sufficient tumor
cells for testing. The problem is that it requires a specimen of
cerebrospinal fluid, and it's not safe (with LC) to take more than a few
ml of spinal fluid, and there are typically not enough cells to test more
than one drug, if that. If there would be another site of the disease
(lymph node, pleural fluid, etc.), then that could be biopsied. The
biology of the disease, in all probability, would be similar to that of
the lymph node, pleural fluid, etc. tumor.

If an assay test could not be performed and the disease had to be treated
empirically, one protocol could be giving intrathecal thiotepa plus
systemic gemcitabine (the gemcitabine given prior to the thiotepa).
Thiotepa may be safely given intrathecally. Gemcitabine can probably be
given intrathecally (it is somewhat similar to cytarabine), but it is
thought that no one has ever done a clinical trial to prove that this is
feasible and safe. In principal, the best shot would be to give
intrathecal gemcitabine + intrathecal thiotepa.

Leptomeningeal Carcinomatous (Carcinomatous Meningitis)

The most common cancers to involve the leptomeninges are breast cancer,
lung cancer and melanomas, and now, because of dose-intense combination
chemotherapies, even ovarian cancer is more common.

Unfortunately, cancer cells are too small to find on any scans unless they
have grown into a lump. There can still be cancer cells in the body even
though scans may have indicated that all the cancer had gone.
Leptomeningeal metastasis (Lepteomeningeal Carcinomatous or Carcinomatous
Meningitis) is a condition caused by cancer cells getting into the thin
sheets of body tissue that surround and protect the brain and spine. These
sheets are called the meninges. Meningitis means inflammation of the
meninges. Carcinomatous just means acting like a cancer. Most people are
familiar with the type of meningitis caused by an infection, but with
carcinomatous meningitis, it is the cancer cells in the meninges that
cause the inflammation, not an outside infection.

Cancer cells do not always develop into an active secondary tumor when
they have spread to a new site. Sometimes they stay inactive for many
years. Even after a cancer appears to have been successfully treated, some
cancer cells may still be elsewhere in the body. No one knows why some
cancer cells stay inactive or what triggers them to form a secondary
cancer.

Tumor cells reach the meninges by hematogenous (blood) spread or by direct
extension from pre-existing lesions and are then disseminated throughout
the neuroaxis by the flow of the cerebrospinal fluid. Patients present
with signs and symptoms from injury to nerves that traverse the
subarachnoid space, direct tumor invasion into the brain or spinal cord,
alterations in blood supply to the nervous system, obstruction of normal
cerebrospinal fluid (CSF) flow pathways or general interference with brain
function.

Secondary cancers from a primary cancer can develop in different parts of
the body, including the brain or spine. Cancer cells do not always develop
into an active secondary tumor when they have spread to a new site.
Sometimes they stay inactive for many years. So, even after a cancer
appears to have been successfully treated, some cancer cells may still be
elsewhere in the body. No one knows why some cancer cells stay inactive or
what triggers them to form a secondary cancer.

Symptoms from neoplastic meningitis include pain, headaches, mental status
decline, loss of sensation in the face or elsewhere on the body, or
difficulties with vision, hearing, or swallowing, among others. Diagnosis
is most commonly made by lumbar puncture, although the CSF cytology is
persistently negative in about 10% of patients with leptomeningeal
carcinomatosis. Radiology studies may reveal subarachnoid masses, diffuse
contrast enhancement of the meninges or hydrocephalus without a mass
lesion.

Doctors estimate that about 5 out of every 100 patients who have cancer
develop carcinomatous meningitis. It is most common in breast cancer, but
it can occur with any type of cancer. The cancer cells in the meninges can
cause a range of symptoms, including confusion, headaches and weakness.

The condition is very difficult to treat. The main aim is to help control
symptoms and not cure the disease. Chemotherapy injected into the spinal
fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are
both treatments for Carcinomatous meningitis. Some patients respond to
these treatments, but the prognosis is generally poor. There are no set
guidelines for treating this condition as oncologists don't really know
which treatments work best.

Without treatment, the median survival of patients is 4 - 6 weeks and
death occurs from progressive neurologic dysfunction. Radiation therapy to
symptomatic sites and disease visible on neuroimaging studies and
intrathecal chemotherapy increases the median survival to 3 - 6 months.
Major favorable prognostic factors include excellent performance status,
absence of serious fixed neurologic deficits, normal CSF flow scans and
absent or responsive systemic tumor.

Oncologists have been looking at using different combinations of
chemotherapy drugs to treat Leptomenigeal Carcinomatous secondary to the
primary cancer (Chemosensitivity Testing may help in this process). They
found that giving both chemotherapy injected into the bloodstream and
chemotherapy given directly into the spinal fluid may improve the outlook
for some people. However, current available therapies are toxic though,
and provide limited benefits.

Approximately 50% of lung and breast cancer patients who survive more than
one year with Leptomeningeal metastasis treated with repeated injections of
intrathecal methotrexate develop leukoencephalopathy which includes
confusion, dementia, somnolence or focal neurologic signs. This usually
occurs when intrathecal methotrexate is combined with irradiation and this
combination should be avoided if possible. The leukoencephalopathy may
improve if intrathecal methotrexate is discontinued, although it may also
progress to coma and death.

A medical oncologist involved with Chemosensitivity Testing has stated
that their lab has only received maybe four Lepomeningeal Carcinomatous
specimens over the years. Of those, only one specimen had sufficient tumor
cells for testing. The problem is that it requires a specimen of
cerebrospinal fluid, and it's not safe (with LC) to take more than a few
ml of spinal fluid, and there are typically not enough cells to test more
than one drug, if that. If there would be another site of the disease
(lymph node, pleural fluid, etc.), then that could be biopsied. The
biology of the disease, in all probability, would be similar to that of
the lymph node, pleural fluid, etc. tumor.

If an assay test could not be performed and the disease had to be treated
empirically, one protocol could be giving intrathecal thiotepa plus
systemic gemcitabine (the gemcitabine given prior to the thiotepa).
Thiotepa may be safely given intrathecally. Gemcitabine can probably be
given intrathecally (it is somewhat similar to cytarabine), but it is
thought that no one has ever done a clinical trial to prove that this is
feasible and safe. In principal, the best shot would be to give
intrathecal gemcitabine + intrathecal thiotepa.