Patients Lose More than Their Health

The cost of this disease to its victims can be unrelenting. According to a study by the National Brian Tumor Foundation, of patients with brain cancer, 59% said their medical expenses were a financial hardship. Many families felt financially drained and had to borrow money (42%), increase their credit card debt (47%), accept a second or third mortgage (15%) or went completely bankrupt (7%). The cost of prescriptions, deductibles, increased insurance premiums and delayed disability funding exacerbated their medical costs and made expenses more difficult to pay. In fact, 15% of the patients assessed paid more than $1,000 each month for treatment. Making things more difficult, while 91% of patients were able to work before their diagnosis, only 33% were able to work afterwards. Furthermore, the disability insurance which was intended to help patients only makes things worse due to long, complicated forms that usually assure an initial denial. Even after acceptance, patients were required to wait two years before any benefits would take effect. During this interlude, patients were left to scrape by as best they could. Of the patients interviewed, 62% lacked disability insurance. The medical debt never failed to grow however, as it was found that a significant correlation existed between the time since diagnosis and the patient’s credit card debt.

Hope for Help in the Near Future

Brain cancer is notoriously difficult to diagnose and treat due to its location in the body. Usually, patients are forced to undergo invasive biopsy procedures for doctors to assess which type of cancer the patient has. This increases medical costs by increasing the time spent in the hospital during the operation and recovery, the drugs used for sedation and pain afterwards, and of course, the number of doctors required for such a procedure. However, it may soon be possible to find the same answers through a simple blood test.

Cancer cells, like other cells, “talk” to each other. Often a cell will accomplish this by secreting a protein that is recognized and acted upon by another cell. Cancer cells, for example, can send signals in this way to cause blood vessels to alter their normal route and instead, grow near the cancer cell. This redirection of blood vessels is what feeds the cell and allows it to grow. In cancer cells, these signaling factors are called microvesicles.

After the discovery of these signals as imperative for breast cancer cell growth, Dr. Johan Skog of Harvard Medical School began studying the microvesicles secreted by brain tumor cells. What turned this into a potential diagnostic method were the small bits of RNA found in the microvesicles. Previously, neither DNA nor RNA had been observed which made any diagnosis based on these signaling secretions impossible. However, when RNA was found, it opened the door to a blood-based genetic test. Skog and Dr. Xandra Breakefied, a neurologist also at Harvard Medical School, hypothesized that if the brain tumors were releasing signaling factors with RNA, they might be found in the blood where sensitive tests could detect them and distinguish between the types of brain cancers.

To test their idea, Skog and Breakefield collected the secretions from 30 tumors that had been frozen for long-term storage. They also examined blood samples from the same patients the tumors had been extracted from. In 28% of the blood samples, RNA from the microvesicles was found. In the tumors, RNA was found in almost 50%. Although this may seem to leave a lot of room for misdiagnosis, it is significant since RNA is very fragile and unstable and can degrade very quickly. The fact that RNA was found at all is rather amazing. It is believed that if these same tests were run on fresh samples, rather than those that had been frozen, a much higher number would test positive for the tumor-specific RNA. The RNA released from these tumors could even help doctors determine the genetic abnormalities of the cancer, allowing for a more tumor-specific therapy.

Although doctors do not expect this new method to completely replace the need for other diagnostic procedures, it could lend a way to extract valuable information in a relatively non-painful and inexpensive way.

Cryopreservation, which uses temperatures as low as -196°C for tissue storage, has been successful in small trials to preserve ovarian tissue of young cancer patients. Dr. Donnez has been researching a way to preserve this tissue without delaying cancer treatment. In May 2008, Donnez and his team published an article* in Reproductive BioMedicine Online which could extend hope to young women dealing with cancer and infertility. This article described the cryopreservation process, which included removing tissue samples from the ovaries of five women diagnosed with cancer prior to their treatment as well as the cryopreservation protocol.

These women, from 21 to 28 years old, underwent surgery to re-implant their cryopreserved tissue after they remained disease-free for at least five years. All of these women faced infertility after their cancer treatments caused ovarian failure. Within 16-26 weeks of re-implanting the tissue, it began to function normally, restoring the possibility of children. Although Dr. Donnez has been conducting this type of work for 10 years, he has reported that only five women have had their ovarian tissue preserved and later replaced because “…it was often hard to convince oncologists and pediatricians of [ovarian preservation’s] worth in early years.” He has, however, stated that after 2000-2001, there was a definitive rise in the number of requests for ovarian tissue storage.

A Motherhood Restored

In an October 2004 publication of Lancet, Dr. Donnez’s goal was fully realized. Using ovarian tissue preserved from a 25-year-old Hodgkin’s lymphoma patient for seven years, he re-implanted several samples when she was 32 years old. Like many other women, her cancer treatments had left her infertile. Within five months of the surgery, the ovarian tissue was functioning; at 11 months she became pregnant through natural means. In September 2004, she gave birth to a healthy baby girl. Donnez and others hope this will become the standard procedure for young cancer patients in the future. He does caution, however, that there are limits to this technique. He points out that “we should keep in mind that if we cryopreserve ovarian tissue, [we] should do [it]…before the patient hits 35 years. After that, the ovarian reserve [is]…lower, and we know we will lose about 60%-80% of the follicles.”

Although there have been positive results with this method of fertility rescue, the ethics of performing such a procedure, especially on children and adolescents, has been hotly debated. According to the Ethics Committee of the American Society for Reproductive Medicine in 2005, embryo cryopreservation, which uses a woman’s fertilized egg, was the only established method. According to Dr. Tommaso Falcone, Chairman of the Department of Obstetrics-Gynecology at the Cleveland Clinic, “This technique is considered experimental at all American sites.” Dr. Falcone also notes that the local bioethics department usually gets involved when this procedure is considered. This outlook made acceptance of ovarian tissue preservation slow.

However, favoring embryo cryopreservation over ovarian tissue preservation presents a number of problems. The main one is that, unlike ovarian tissue preservation, it requires the adolescent or young woman to both have a partner or sperm donor as well as undergo ovarian stimulation. Most adolescents and young women do not have a partner for this. Moreover, when cancer treatment is imperative, delaying it to undergo ovarian stimulation and embryo preservation can be detrimental. In children who have not reached puberty, embryos are impossible, leaving ovarian tissue preservation the only option for fertility. A final problem with embryo storage is that many people believe life begins at conception. For those with this view, embryo preservation is unacceptable, leaving ovarian tissue preservation their only true option. In a review article by Dr. Donnez in 2006, he responded to the controversy by stating that “it is our ethical responsibility to propose ovarian tissue cryopreservation…to all adolescents and young women having to undergo chemotherapy. Respecting the code of good practice, all patients who may become infertile have the right to receive proper consideration of their interests.”

Limited Success

While some U.S. centers such as the Center for Reproductive Medicine at the Cleveland Clinic offer ovarian tissue cryopreservation, their website states that they have only re-implanted a few ovarian pieces and that they functioned for only a matter of weeks. While transplanted ovarian tissue may function for weeks or years, there is always the possibility that it will become dysfunctional. For this reason, many women wait until they are ready for children before reintroducing their saved tissue. It is important to remember that although the freezing and storage of this tissue is less than $1,000, the surgery required to remove the tissue and replace it is significantly more. While insurance may cover a portion of the surgical cost, in many cases it doesn’t.

Regardless of this, interest and awareness regarding ovarian tissue preservation has increased in the last several years even though only six healthy pregnancies using this method have been reported worldwide. Although initially used for cancer patients, it has seeped into the mainstream. Many worry that this procedure will become increasingly commonplace and that it will eventually be viewed as normal. If this technique were normalized for the public, the pressure to have a family and career simultaneously could be lifted. A woman of 25 could save her tissue, solidify her career and choose to become pregnant at whatever age she wished. Even if she waited until she was 50, the ovarian tissue would act as if she were only 25. It is unclear what the consequences of this would be; however, it seems delaying the next generation in this way could significantly change our society, what is expected of women and what is perceived as normal.

*“Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: a pilot experience.”