Positive Health Online

Introduction

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 (blood clots 'can' signal cancer). Workup which was triggered by this presentation revealed that she did have an ovarian carcinoma for which she underwent a total abdominal hysterectomy and received Chlorambucil (Leukeren) treatment. This post-operative chemotherapy drug was among the slowest acting and least toxic of the alkylating agents (well tolerated oral drugs). Giving chemotherapy more often, and at lower doses, can prevent the re-growth of the blood vessels that feed tumours. 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. She went 24 years before experiencing any recurrent ovarian cancer.

During the early '90s in Reading, Pa., she underwent a laparotomy (a surgical procedure which involves opening the abdominal cavity for examination) as a follow-up 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 tumour marker (a blood test done to assess the amount of an antibody that recognizes an antigen in ovarian tumour cells). The rate of 'false positives' makes it inadequate for use 'by itself' for screening of high-risk patients. It should be supplemented with trans-vaginal sonography and a recto-vaginal pelvic exam all done at the same time.

Metastatic Recurrence and Treatment

It was our family doctor that found her first metastatic recurrence in 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 X-ray 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 trans-diaphragmatic tumour 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 ovarian metastasis could occur, maybe in the central nervous system (CNS), in 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 tumour from her diaphragm. My wife received post-operative chemotherapy from these medical oncologists, seven months after having that metastatic tumour surgically excised. She did not have any cancer tumour markers indicating the presence of any cancer within her system. Some tumours 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 and Carboplatin. 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 six 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. The late stage of 'recurrent ovarian cancer' makes the combination chemotherapy of Taxol and Carboplatin resistant to cancer cells and suppresses the immune system, making it possible for new tumours 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 and Carboplatin are two of the drugs that violate the blood-brain barrier (dose dependent). In essence, they it break down, damaging the blood-brain barrier to invite 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 the 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 (3.5 cm) solitary cerebellar brain tumour was found via an Enhanced CAT Scan (later confirmed by an Enhanced MRI). The tumour 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 tumour bed (which is 2 cm beyond the periphery of the excised tumour site). The treatment protocol recommended for brain metastases of large solitary tumors exceeding 2 cm in diameter is surgical resection followed by five fractions of local radiation to the tumour bed. At the same time, she should receive an MRI of the spine because of suspicions of either another tumour 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 tumour from her brain. The radiation oncologist took it upon himself to give my wife five fractions of focal radiation to the local tumour 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 metastasis, particularly when platinum drugs lower the tolerance of the CNS to radiation.

Literature of the early and mid-'80s 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 1 cm lesion. Instead of performing an Enhanced MRI to the spine to evaluate further, our local home town hospital performed a Bone Scan that showed normal bone imaging. However, a Bone Scan cannot distinguish what a lesion represents and cannot differentiate between a tumour, an infection or a fracture. 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 from a medical onocologist and a neurologist that she had Leptomeningeal Carcinomatous (remember the undiagnosed tumour of nine months prior, not further evaluated?) An Enhanced MRI showed now three metastatic tumours on her spine. Spinal metastases can grow into adjacent structures, such as into the meninges from the spine.

The largest of these tumours 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 therapeutic 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 ten 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 deterioration 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 and 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 six months to two 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 oedema, 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 ganglia 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 co-ordinated activities going wrong and things shutting down. If a cell gets too much heat or is poisoned by a toxic substance, or exposed to chemicals that damage its proteins and membranes 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 that 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 and 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 tumours 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 tumour 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 in May 2000 at Hershey Medical Center and a PET Scan in 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 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 which caused her death was primarily a result of Whole Brain Radiation, and the secondary, a result of the combination chemotherapy of Taxol and Carboplatin (Methotrexate was icing on the cake). The combination chemotherapy of Taxol and Carboplatin caused microscopic ovarian cancer cells to seed inside the CNS to form a tumour on the cerebellum and tumours on the spinal cord, with concomitant necrotizing leukoencephalopathy. Carboplatin lowered the tolerance of her CNS to any radiation treatment. The Whole Brain Radiation resulted in the death of tumour 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

I feel that my wife'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 six months after first-line chemotherapy can experience another remission following treatment with the identical first-line chemotherapy that was used previously. Aggressive treatment, like the surgical excision of the tumour, and focal radiation to the local tumour 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 benefical 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 gynaecological cancer and keeps referring to the lives of women lost 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, these treatments are 'OK'. 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.

There are three main points that I've found out in my three years of cancer research. One, is an understanding of the doctors involved with my wife's medical care at our local home town hospital. Two, is an understanding of the lack of uniform cancer care being practised here in the United States (even among a few of the leading cancer centres). Three, cancer patients do frequently die from their cancer treatments (it is not really 'rare') and not from the cancer itself.

I receive hundreds of emails from other cancer treatment victims and their loved ones because of my postings on numerous websites on the internet. They, as well as myself, thought we were alone. I found out that there are too many of us out there needing more information that should have been given 'before' cancer treatment.

I didn't get to be with Ann for all that 28 year ride, from her first ovarian cancer experience in 1972 until her demise in 2000. I met Ann in 1990 when she moved back East to be near her only brother (after her first husband died suddenly of a heart attack in 1989). She moved across the street from my parents in Reading, Pennsylvania, USA. In 1993, I bought the house next door to her. Little did we both know that we would become an item (it was mostly her doing). She sold her house and I sold mine and we bought 'our' house out in the middle of the woods (and of course, married). I went through all of her ovarian cancer recurrences from 1996-2000.

Towards the end, my wife didn't seem to feel much of anything. Her daughter's comment to me about two weeks before her demise was: "I look into mom's eyes and I do not see anything in there, anymore. She's not inside there." That scared me! I spent three years watching her be slowly tortured to death (ever since she began combination chemotherapy). A slow, arduous, neurological death was not easy to take (for her and for me).

I did get an extra 14 more months to be with her to let her know unequivocally that she was loved! She knew it! While she was up at Hershey Medical Center during the summer of 1999, to try and save her life or to at least get her some more time, I bought the home edition of the Merck Manual. It had a very, very good chapter on death and dying (what to expect) although, when the time came, I still wasn't prepared for it. She died in my arms and I tried CPR while summoning the paramedics on the phone. People have told me, "at least she died in your arms". Well, it doesn't cut it! Almost weekly, I suffer some flashback of the final event and it still scares me.

Notes

1.    Giving chemotherapy more often, and at lower doses, can prevent the re-growth of the blood vessels that feed tumours. 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.
2.    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 tumour marker (a blood test done to assess the amount of an antibody that recognizes an antigen in ovarian tumour cells). The rate of ‘false positives’ makes it inadequate for use ‘by itself’ for screening of high-risk patients. It should be supplemented with trans-vaginal sonography and a recto-vaginal pelvic exam all done at the same time.
3.    It was a metastatic trans-diaphragmatic tumour 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).
4.    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%.
5.    A National Cancer Institute (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.
6.    Histologic features were consistent with metastatic papillary adenocarcinoma with extensive necrosis from the ovary.
7.    Literature of the early and mid-’80s on morbidity of Whole Brain Radiation (WBR) 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.
8.    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 MRIs for metastatic diseases is ‘enhanced with contrast’ (today, it is the PET Scan).
9.    Spinal metastases can grow into adjacent structures, such as into the meninges from the spine.
10.    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 co-ordinated activities going wrong and things shutting down. If a cell gets too much heat or is poisoned by a toxic substance, or exposed to chemicals that damage its proteins and membranes or radiation that breaks its DNA molecules, that cell can just stop functioning.
11.    Her MRIs showed that 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.

Further Information

During my three years of research, I've written to over 3,000 medical professionals and institutions all over the United States and across the globe. Much of the information you'll read in my article is from these. Some have been from over 500 medical websites that I've studied (like MedLine, Pub Med, Oncololink, Johns-Hopkins, NCI, NIH, etc.). I have all of my wife's medical records to relay first-hand experience.

Chemotherapy Resources

http://www.brain-tumour.net/neurosurgery/chemotherapy/index.htm (The American Brain Tumor Assn.) http://www.cancernetwork.com/home/frames.htm
http://www.cancernetwork.com/handbook/chemotherapy.htm&3 (cancernetwork.com)
http://weisenthal.org/ (Larry Weisenthal, MD, PhD)
http://www.moffitt.usf.edu/pubs/ccj/v6n5/article4.htm (H. Lee Moffitt Cancer Center & Research Inst.)
http://www.unc.edu/news/newsserv/research/may99/judson051799.htm (University of North Carolina School of Medicine)
http://www.merck.com/pubs/mmanual_home/sec15/166.htm (The Merck Manual)
http://www.slip.net/~mcdavis/dbas7395/95609207.htm (Ovarian Cancer Research Notebook)
http://www.jwci.org/researchbreastcancer.htm (John Wayne Cancer Institute)
http://www.australianprescriber.com/magazines/vol18no4/cytotoxic.htm (Mater Misericordiae Hospital)
http://www.members.aol.com/afipinfo/critrevonchem.html (Armed Forces Institute of Pathology)
http://www.members.aol.com/afipinfo/xpcslab.html (Armed Forces Institute of Pathology)
http://www.commonweal.org/choiceschap5.html (commonwealth.org)
http://www.ehendrick.org/healthy/00042290.html (ehendrick.org)
http://www.cancer.gov/cancerinfo/chemo-and-you (National Cancer Institute)
http://www.cancerguide.org/medline.html (Cancer Guide to Medline)
http://www.parliament.the-stationery-office.co.uk/pa/cm199900/cmselect/cmsctech/332/0062150.htm (The Society of Academic Surgeons & The Surgical Research Society)
http://www.cancerhelp.org.uk/help/default.asp?page=5078 (Cancer Research UK)
http://www.ovarian-news.com (International Ovarian Cancer Connection) http://www-personal.si.umich.edu/~jgourdji/TREAT.HTML (University of Michigan School of Information & Library Studies)
http://www.nlm.nih.gov/medlineplus/ovariancancer.html (MedLine Plus)
http://weisenthal.org/ovataxol.htm (Larry Weisenthal, MD, PhD)
http://www.nanonline.org/ (Dana Farber Cancer Institute)
http://www.slip.net/~mcdavis/ovarian.html (National Ovarian Cancer Association)
http://www.oncolink.com/ (OncoLink)

Radiation Therapy Resources

http://www.umm.edu/nervous/brain.htm (Uiversity of Maryland Medicine) http://www.brain-tumour.net/neurosurgery/radiation/index.htm (The Brain Tumor Society)
http://www.cancer.gov/cancerinfo/radiation-therapy-and-you (National Cancer Institute)
http://www.cancernetwork.com/home/frames.htm (cancernetwork.com)
http://www.commonweal.org/choiceschap5.html (commonweal.org)
http://www.members.aol.com/afipinfo/critrevonchem.html (Armed Forces Institute of Pathology)
http://www.emedicine.com/NEURO/topic625.htm (emedicine.com)
http://www.emedicine.com/neuro/topic330.htm (emedicine.com)
http://www.baromedical.com/newsletter/hbosladearticle.html (Ben Slade, M.D. Hyperbaric Medicine)
http://www.members.aol.com/afipinfo/xpcslab.html (Armed Forces Institute of Pathology) http://jama.ama-assn.org/issues/v281n18/ffull/jlt0512-3.html (Journal of the American Medical Assn.)
http://www.soc-neuro-onc.org/newsletterfeatures/brainmetpaper.htm (MD Anderson Cancer Center)
http://www.merck.com/pubs/mmanual_home/sec15/166.htm (The Merck Manual)
http://www.moffitt.usf.edu/pubs/ccj/v6n5/dept6.htm (H. Lee Moffitt Cancer Center & Research Inst.)
http://www.australianprescriber.com/magazines/vol18no4/cytotoxic.htm (Mater Misericordiae Hospital)
http://www.med.jhu.edu/radiosurgery/williams/nf_williams.html (Johns Hopkins Medicine)
http://www.brain-tumour.net/neurosurgery/gammaknife/gamm1.htm (The Brain Tumor Society)
http://www.cancerguide.org/medline.html (Cancer Guide)
http://www.ehendrick.org/healthy/00063040.html (ehendrick.org)
http://www.parliament.the-stationery-office.co.uk/pa/cm199900/cmselect/cmsctech/332/0062150.htm (The Society of Academic Surgeons & Surgical Research Society)
http://www.spine-health.com/topics/diag/diag09.html (Spine-Health.com)
http://www.21stcenturyoncology.com/cancer/cancer_specific_brain.html (21st Century Oncology)
http://www.nlm.nih.gov/medlineplus/radiationexposure.html (MedLine Plus)
http://www.nanonline.org/ (National Academy of Neuropsychology)
http://www.oncolink.com/ (OncoLink)