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Ovarian Cancer Therapy

Gregory D. Pawelski

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My wife had been diagnosed with Ovarian cancer in 1972 when she presented with a left DVT(deep vein thrombosis) and pulmonary embolism. Workup which was triggered by this presentation revealed that she did have an ovarian carcinoma for which she underwent total abdominal hysterectomy and received Chlorambucil(Leukeran) treatment. The postoperative chemotherapy drug she received was in no way as toxic as the ones given today. She was also given very limited amounts over a long period of time to allow the immune system to regenerate and contribute to healing. She went twenty-four years before she ever had a metastatic ovarian recurrence. Metastasis are cancer cells that travel to other parts of the human body from a primary cancer site and develop into a lesion(tumor). Her first metastatic recurrence was a transdiaphragmatic tumor from the original primary ovarian tumor with attachment to the lung and other midline structures of the chest. It was surgically resected at Fox Chase Cancer Center in August 1996. The Thoracic Surgical Oncologist was 100% successful and felt my wife did not need any treatment with chemotherapy. Some primary cancers like Breast and Lung can commonly metastisize to the (CNS) Central Nervous System, like the brain. However, it is very rare for Ovarian cancer cells to metastisize into the Central Nervous System. 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%. Metastasis of Ovarian cancer to the central nervous system is uncommon and was rarely seen before the use of present day chemotherapy regimens. How do Ovarian cancer cells invade the Central Nervous System? Cocktail Chemotherapy. It can do this in two ways. Some chemotherapy drugs do permeate(pass through) the blood-brain barrier(the system that protects the brain from foreign substances by blocking their passage from the blood). Unfortunately, some chemotherapeutic agents weaken the blood-brain barrier(BBB) transiently and allow CNS seeding. In essence, it breaks down, damages the blood-brain barrier to invite cancer cells into the Central Nervous System. In recent years the incidence of CNS(Central Nervous System) metastasis has increased. A NCI 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. The cerebellum was involved in two out of three patients, presenting with headache, dizziness, unsteady gait, nausea and vomiting(all symptoms and results my wife experienced). The second way cancer cells invade the Central Nervous System is that Chemotherapy suppresses the body's immune system. The body's immune system attacks and eliminates not only bacteria and other foreign substances but also cancer cells. Cancer cells are not foreign to the body but their biological function has been altered in that it doesn't respond to the body's normal mechanisms for controlling cell growth and reproduction(uncontrolled cell growth and reproduction is what causes cancerous tumors). Much of the body's protection against cancer is carried out directly by cells of the immune system rather than by antibodies circulating in the bloodstream. Cancer is 100 times more likely to occur in people who take drugs, like chemotherapy that suppress the immune system than in people with a normal immune system. My wife received postoperative Chemotherapy at the Reading Hospital & Medical Center, seven months after having that metastatic tumor resected. She did not have any cancer tumor markers indicate any cancer within her system when she received the chemotherapy treatment(she did not have any cancer). Some tumors send out microscopic outposts while others do not. However, doctors cannot tell which ones do, so they give chemotherapy in nearly every case. The hit fast, hit hard type of Chemotherapy she received was a highly neurotoxic cocktail of Taxol and Carboplatin. A group of platinum based drugs called Cisplatin, Cisplatinum and Carboplatin and a natural substance called Taxol, cross the blood brain barrier. She developed necrotizing leukoencephalopathy(a form of diffuse white matter injury that can follow this chemotherapy), confirmed by an enhanced MRI in July of 1998. 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 membranes or radiation that breaks its DNA molecules, that cell can just stop functioning. The effects of leukencephalopathy can be very severe, including mental confusion, fits and paralysis. During the Summer of 1998 a solitary cerebellar brain metastasis was found via enhanced Cat Scan and confirmed by an enhanced MRI. The 3.5cm tumor was resected in July 1998 at the Hershey Medical Center. Histologic features were consistent with metastatic papillary adenocarcinoma with "extensive necrosis" from the ovary. Necrosis means dead. Necrotic tissue means dead tissue. Tumors are not dead, they are uncontrolled cell growth and rapid reproduction. Imaging features of necrotizing leukoencephalopathy include periventricular white matter hypodensity on Cat Scan and hypo/hyperintensity on T1/T2 weighted MRI. Postoperative Chemotherapy treatment of Taxol and Carboplatin was not the proper treatment for her. She did not have any cancer at the time of treatment. The analogy of millions and millions of microscopic cancer cells(not being able to be seen), becoming billions and billions of cancer cells and eventually becoming a tumor, medical oncologists cannot tell. So, chemotherapy is given after surgery just in case tumors would occur. This does promote chemotherapy! My wife received postoperative Whole Brain Radiation therapy for that large solitary brain metastasis at the Reading Hospital & Medical Center. She began developing brain radiation necrosis within 6-10 months after Whole Brain Radiation, confirmed by an enhanced MRI in June of 1999. Her radiation-induced brain necrosis could have been focal or diffuse, depending on the modality of treatment. The five fractions of focal radiation to the local tumor bed that she received could have resulted in focal necrosis around the tumor bed or she could have developed metastatic recurrence. Her additional twenty fractions of Whole Brain Radiation resulted in diffuse necrotic effects. An EEG of December 1999 showed generalized diffuse slowing that was significant with global encephalopathy. It is most commonly seen in toxic metabolic and degenerative conditions(my wife received five of six intended treatments of the highly neurotoxic chemo cocktails of Taxol and Carboplatin from March until July of 1997). There appeared to be a real amount of focal right sided slowing which would indicate cortical dysfunction on that side. A number of MRI's showed the ventricles overall were prominent and there was widening of the sulci consistent with atropy. 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 in August 2000 showed globally decreased radiotracer uptake within the brain, bilaterally, consistent with involutional change and prior radiation therapy. 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(my wife suffered a stroke to the left basal ganlia area of the brain in January 2000, confirmed by an enhanced MRI). There are a number of radiation treatments for therapy(Stereotatic, Gamma-Knife & Brachyradiation to name a few). The Whole Brain Radiation treatment my wife received was not the proper treatment for her. In her case, tumors greater than 2cm in size should be resected(if possible) and depending on the surgeon's success(her's was 99%) focal radiation to the local tumor bed is indicated. Her radiation oncologist's ideas were different from those of the neurosurgeon and gave her twenty fractions of Whole Brain Radiation to a perfectly good brain. The radiation oncologist had not told us of any of the late-delayed reactions that could happen from Whole Brain Radiation(the Pennsylvania State Board of Medicine and the Department of Health are presently investigating my wife's case). 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 develope progressive dementia, ataxia and urinary incontinence causing severe disability and in some, death(all symtoms my wife developed). A recurrence of the cerebral metastasis was very likely to happen in the future. It did, observed via an Enhanced MRI of May 2000 and that Pet Scan of August 2000. Four, mm-sized metastatic tumors were found in and around the previously resected cerebeller tumor and because of Ann's weakened condition, Gamma-Knife would be the only best medical course of success. 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(Radiation Necrosis), as if she may too far advanced in that injury to survive much longer. My wife died on 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 Ann experienced and caused her death was primarily a result of Whole Brain Radiation and secondary a result of Cocktail Chemotherapy of Taxol & Carboplatin. I never came across the idea of radiation necrosis, much less chemo-induced necrosis, until the doctors at Hershey Medical Center pointed it out to me in June 1999. I've spent two years with many a sleepless night researching what really happened to my wife and how she was killed. Death by "side effects of treatment" is not the same as "complications of cancer". A lot of cancer patients who succumb to their disease, get the wrong information on their death certificates. They die with incorrect, incomplete or misleading diagnoses. Often it will say they died of heart failure, kidney failure, liver failure, etc. These can be side effects of cancer treatment as well as the progression of the cancer. They are lumped together reducing the general understanding of the impact of cancer. We need to reinvent the death certificate, rewritten to include things like death from side effects of treatment, death from advanced age, etc. with more information so we can figure out trends and what contributed to the death. The sad idea I found out over my two years of research was that cancer patients do die from chemo-radiation treatments. The very sad idea I found out that this is the "norm", a common occurrence. I just can't believe this and refuse to accept this adage. Yes, I'm bitter and angered, so was my wife. She wanted me to put my anger and bitterness into constructive research, education and exposure of the conventional way patients are being treated for cancer. So much conventional cancer treatments have been available for such a short period of time that it has not yet been determined all of the truely long term side effects of some of these treatments. One can learn from someone else's mistakes or one can learn from their own mistakes. They have a choice.


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