Chemo-Radiation Necrosis

gdpawel

Brain metastasis is a rare complication of ovarian cancer with only 67 well documented cases in 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%. Leptomeningeal metastasis is also a rare complication of ovarian cancer with only 14 cases reported by 1994.

The treatment method recommended for brain metastases of large solitary tumors exceeding 2cm in diameter is surgical resection followed by 5 fractions(at 2.0gy per) of focal radiation to the local tumor bed. My wife received the 5 fractions plus an additional 20 fractions of Whole Brain radiation(at 2.0gy per). Mindful, these were well within the tolerable limits of up to 55gy but radiated to the whole brain. The optimal dose of radiation necessary to destroy microscopic foci of tumor after surgical resection of a single brain metastasis is unknown.

Whole Brain Radiation induces neurological deterioration that is progressive and often irreversible. It results from direct injury to brain tissue and blood vessels. The risk increases with higher total dose, higher dose per fraction and with concomitant use of neurotoxic chemotherapeutic agents. Chemotherapy affects both normal and tumor cells. The effect on normal cells is the cause of side effects from chemotherapy. Some chemotherapy drugs do permeate(pass through) the blood brain barier(the system that protects the brain from foreign substances by blocking their passage from the blood). The group of drugs called nitrosoureas like Cisplatin, Cisplatinum or Carboplatin are such drugs and natural substances such as Taxol, also cross the barrier. My wife had previous chemotherapy treatments of Taxol and Carboplatin.

Necrotizing leukoencephalopathy is the form of diffuse white matter injury that follows chemotherapy, as well as a suppressed 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. Cancer is 100 times more likely to occur in people who take drugs that suppress the immune system than in people with normal immune systems. My wife almost didn't make it through her chemotherapy treatments. She could only receive five of the six intended treatments. We met a number of other patients that didn't make it through their chemotherapy treatments.

The clinical manifestations of Radiation Necrosis range from mild cognitive neurological impairment to dementia to death. Radiation Necrosis occurs more commonly after radiosurgery but can occur after conventional Whole Brain Radiation therapy as well. The major complication of radiosurgery is the development of symptomatic Radiation Necrosis requiring prolonged administration of steroids and reoperation. The rate of reoperation is 30%-40%, usually within six months. Radiation Necrosis is common with Whole Brain Radiation dosages beginning at 50gy, although frequency of Radiation Necrosis is anywhere from 2%-50% at dosages beginning at 30gy(depending who's research you read).

As if my wife's complications with Radiation Necrosis, brought on by Whole Brain Radiation and Taxol/Carboplatin chemotherapy weren't enough, she was subjected to improper medical protocol for brain and spinal MRI's for metastatic disease(unenhanced instead of enchanced-contrast), which left an undiagnosed tumor on her spine. After nine months, while admitted to the hospital for testing and evaluation for unexplained falls and light-headiness, the oncologists failed to perform a Spinal Tap and/or enhanced MRI and failed to diagnose three spinal metastases. They let her go home to fall and break her hip in four places.

With the damage already done to her, oncologists at another hospital(in order to save her life or at least give her some time) had to administer intrathecal(to the brain) Methotrexate along with systemic radiation(15 fractions at 2.0gy) to the spine. This is when I came across for the first time, the idea of Radiation Necrosis. The oncologists showed me her enhanced brain MRI's from the previous year and the one performed then. It showed the progressive deteriation of her white matter(white matter disease). Late delayed effects, occuring several months to many years later are classified into diffuse white-matter injury, radiation-induced arteriopathy & stroke and late delayed radiation necrosis. Late delayed Radiation Necrosis is often irreversible and progressive, leading to stroke, severe disability or death.

The most recent enhanced brain MRI's, Pet Scan and EEG showed even more diffuse white-matter injury. The Pet Scan showed globally decreased radiotracer uptake withing the brain, bilaterally, consistent with involutional change and prior radiation therapy. The 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 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.

My wife died at the age of 68 from Cardiopulmonary Failure(almost two years from the day she finished Whole Brain Radiation Therapy). 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 a result of Whole Brain Radiation and Chemotherapy(Taxol & Carboplatin). Believe me, a slow, arduous, neurological death is not preferable to a cancerous one.

Even the infamous study performed by Dr. Roy Patchell, et al, in the early '90's was recognized incorrectly in the radiation oncology profession. The study was thought to have been the difference between surgical resection of brain tumor alone, vs. surgical resection & whole brain radiation. It was not. It was a study of whole brain radiation of a brain tumor alone, vs. whole brain radiation & surgical resection. The increased success had been the surgery. And they measured "tumor recurrance", not "long term survival". Patients experiencing any survival were 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 recurrance" but not more "long term survival". In my wife's case, tumors recurred.