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According to an article recently published in the journal Blood, patients with AML who are at a high risk of cancer progression following standard therapy may benefit from an unrelated allogeneic stem cell transplant.

Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; average age at diagnosis is more than 65 years.

Treatment of AML often begins with induction therapy (initial treatment) that includes chemotherapy to produce a complete remission (defined as the disappearance of leukemia cells in the bone marrow and normalization of the white blood cell, red blood cell, and platelet levels). After induction therapy, patients generally receive additional treatment (consolidation therapy) to reduce the likelihood of leukemia recurrence. Depending upon prognosis, age of the patient, and/or other existing medical conditions, consolidation therapy can range from extremely aggressive to less aggressive.

An allogeneic stem cell transplant, considered an extremely aggressive treatment option, involves the use of high doses of therapy, which kill a greater amount of cancer cells than standard doses. Unfortunately, the high doses of therapy also cause a significant reduction in blood cells, resulting in a patient's susceptibility to infection, bleeding, and the need for blood transfusions. Often, the infections caused by these high doses of therapy are life-threatening.

To restore levels of blood cells
stem cells, which are immature blood cells, are collected from a donor and infused into the patient following high-dose therapy. These donor stem cells can also mount an attack against the patient's cancer cells. Unfortunately, these donor cells can also attack a patient’s healthy cells, causing a potentially life-threatening condition called graft-versus-host disease (GVHD). Stem cells donated by a relative (related donor) tend to carry a lower risk of GVHD than those from an unrelated donor.

A drawback of an allogeneic stem cell transplant is that treatment-related mortality and side effects can be substantial; researchers have thus focused on curative options that are more easily tolerated. However, for patients with very aggressive AML and those who are younger, an allogeneic stem cell transplant still appears to provide optimal outcomes.

Researchers affiliated with the International Blood and Marrow Transplant Registry recently conducted a clinical study evaluating the use of allogeneic stem cell transplants with unrelated donors for patients with AML. This trial included 261 patients with AML in first remission (when disease is undetectable for the first time following treatment) or second remission (the second time following two different treatment courses that disease is undetectable) who were 60 years of age or younger. Patients in this trial were divided into three groups: those who had a high, intermediate, or low risk of developing a cancer recurrence following standard therapies.

The following results include patients in first remission:

• At five years overall survival was between 29–30% for all groups of patients.
• At five years mortality related to treatment was 47% for patients at a high risk of developing a recurrence, 53% for patients at an intermediate risk of developing a recurrence, and 63% for patients at a low risk of developing a recurrence.
• Cancer recurrence rates were 8%, 17%, and 26%, respectively for patients with low, intermediate, and high risks of developing a cancer recurrence.

The following results include patients in second remission:

• At five years overall survival was 45%, 37%, and 36%, respectively, among patients with a low, intermediate, and high risk of developing a cancer recurrence.
• At five years mortality related to treatment was 46%, 46%, and 30%, respectively among patients with a low, intermediate, and high risk of developing a cancer recurrence.
• Cancer recurrence rates were 12%, 18%, and 32%, respectively, among patients with a low, intermediate, and high risk of developing a cancer recurrence.

The researchers concluded that an unrelated allogeneic stem cell transplant can provide AML patients 60 years of age or younger who are in first remission and have a high risk of a cancer recurrence overall survival rates at five years that are comparable to those among patients with a lower risk of a recurrence. However, this trend did not seem to hold true for patients in second remission. Furthermore, mortality related to treatment was high.

Patients with AML who are at a high risk of developing a cancer recurrence and do not have a related donor for an allogeneic stem cell transplant may wish to speak with their physician regarding their individual risks and benefits of an unrelated stem cell transplant.

Reference: Tallman MS, Dewald GW, Sandham S, et al. Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission. Blood. 2007; 110:409-417.

According to an early online publication in the journal Clinical Pharmacology and Therapeutics, children of mothers who take vitamins during pregnancy have a decreased risk of pediatric brain tumors, neuroblastoma, and leukemia.

It is generally recommended that pregnant women receive vitamin supplementation during pregnancy to assure normal growth and development of the fetus. Several studies have suggested that vitamin supplementation during pregnancy can prevent birth defects. There have also been associations established between vitamin supplementation and the child’s risk of acute lymphoblastic leukemia and brain tumors. In addition, research has suggested that the widespread use of vitamin supplementation in pregnant women has helped decrease the incidence of childhood medulloblastoma and neuroblastoma.

In the current study, researchers
from the University of Toronto conducted a literature review of materials produced between 1960 and 2005. A meta-analysis was performed of data from seven studies to determine the relationship between maternal vitamin intake and childhood cancer incidence. All vitamins evaluated included folic acid. The following comparisons were made between children of women who received vitamin supplements containing folic acid during pregnancy and those who did not:

* There was a 36% reduction for pediatric leukemia; an 18% reduction in pediatric brain tumors; and a 47% reduction in neuroblastoma in children of women taking vitamin supplements.
* It was estimated that, in the U.S., vitamin supplementation during pregnancy could prevent 900 cases of pediatric leukemia and 300–400 cases of pediatric brain tumors annually.

These authors stated that it was not know specifically which vitamins were responsible for these effects. They did speculate, however, that folic acid may be responsible for this decreased risk pediatric brain tumors, neuroblastoma, and leukemia. Women who are pregnant may wish to speak with their physician regarding prenatal vitamin supplementation.

Reference: Goh YI, Bollano E, Einarson TR, et al. Prenatal multivitamin supplementation and rates of pediatric cancers: A meta-analysis. Clinical Pharmacology and Therapeutics [early online publication]. February 21, 2007. DOI: doi:10.1038/sj.clpt.6100100.

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Preoperative radiation nearly doubles the survival rate for patients with operable pancreatic cancer, according to the results of a study published in the November 15, 2008 issue of the International Journal of Radiation Oncology Biology Physics.[1]

The pancreas is an organ that is surrounded by the stomach, small intestine, bile ducts (tubes that connect the liver to the small intestine), gallbladder, liver, and spleen. The pancreas helps the body to break down food and also produces hormones, such as insulin, to regulate the body’s storage and use of food.

Pancreatic cancer has one of the highest mortality rates of all cancers. It accounts for approximately 2% of all newly diagnosed cancers in the United States each year but 5% of all cancer deaths. Pancreatic cancer is often called a “silent killer” because its symptoms are usually not recognizable until it has advanced and spread outside the pancreas. As a result the majority of pancreatic cancers are not diagnosed until they have reached advanced stages and are considered incurable.

If pancreatic cancer has not spread to surrounding or distant organs, it is usually considered operable. Historically, patients have been treated with surgery followed by chemotherapy and/or radiation to destroy any micrometastases (cancer cells that have spread outside the pancreas). New research indicates, however, that neoadjuvant radiation therapy (radiation delivered prior to surgery) might offer greater benefit to patients because it can potentially shrink the tumor prior to surgery, thereby ensuring a better chance of removal. Furthermore, because pancreatic surgery

is so invasive, many patients are in no condition to undergo radiation treatment after surgery, so neoadjuvant treatment allows them to receive radiation that they might not receive otherwise.

Researchers from the Weill Cornell Medical College used data from the Surveillance, Epidemiology, and End Results (SEER) registry database to perform a retrospective analysis on patients who had surgically resected (removed) pancreatic cancer between 1994 and 2003. The researchers compared the overall survival rates among patients who received neoadjuvant radiation, adjuvant radiation, or no radiation. Patients who received neoadjuvant radiation survived 23 months, compared with 12 months for patients who did not receive radiation and 17 months for those who received adjuvant radiation (following surgery).

The researchers concluded that neoadjuvant radiation therapy offers a significant benefit over surgery alone or surgery with adjuvant radiation therapy in treating pancreatic cancer. Research will likely be ongoing to further explore these findings.

[1] Stessin AM, Meyer JE, Sherr DL. Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer: An analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Registry. International Journal of Radiation Oncology Biology Physics. 2008; 72: 1128-1133.

A UK company has launched a new genetic risk assessment service which they claim will allow doctors to draw up personalised breast cancer screening and prevention programmes.

The test combines information about a woman's lifestyle with a DNA test. The results are combined to calculate her overall 'absolute risk' of breast cancer, according to the company, BreastHealthUK.

The gene test is provided by Icelandic company deCODE genetics and is carried out using a sample of DNA extracted from a mouth swab.

*With more and more commercial genetic screens emerging, there's an urgent need for well-designed studies evaluating these types of tests.*

- Dr Lesley Walker, director of cancer information, Cancer Research UK

It looks at seven gene variations - or SNPs - that are associated with an increased risk of breast cancer, several of which were discovered by Cancer Research UK scientists.

It combines these with results from a lifestyle risk calculation programme called the Tyrer-Cuzick model, also developed by Cancer Research UK-funded scientists.

Women are then presented with the results in consultation with an experienced breast surgeon or genetic counsellor, so that
their genetic and lifestyle risk factors can be discussed and the implications fully explained.

The test is not available on the NHS but can be obtained privately for ?700.

Breast surgeon Professor Gordon Wishart, medical director of BreastHealth UK, commented: "Although genetic testing is still a relatively young technique, when combined with proven methods to elicit lifestyle and family history factors, it can provide breast surgeons with new insights into detection and prevention of this disease."

However, experts pointed out that there is still a long way to go before the genetics of breast cancer is fully understood, and that research is needed to prove that these commercial tests will actually reduce cancer death rates.

Dr Lesley Walker, Cancer Research UK's director of cancer information, commented: "Assessing your risk of cancer and interpreting the results of genetic tests is a very complex matter. With more and more commercial genetic screens emerging, there's an urgent need for well-designed studies evaluating these types of tests - we need to know more about their clinical and psychological impacts, and their current scientific value."

Dr Walker continued: "We've still only got a few pieces of the genetic puzzle. Genetic testing without this missing information means we risk worrying women who may never develop the disease. The commercial market for genetic testing should be properly regulated and appropriate information on the pros and cons should be conveyed to customers.

"At this stage, Cancer Research UK would recommend that women worried about their risk of cancer visit their GP or contact Cancer Research UK's information nurses on 0808 800 4040. Women with a strong family history of breast cancer will be offered genetic testing on the NHS."

Women with a strong family history of breast cancer are already eligible for genetic testing on the NHS. According to guidelines published by the National Institute for Health and Clinical Excellence (NICE), women can be referred to specialist genetics services if they have a high risk of developing breast cancer.

This risk is usually determined by looking at a number of factors, including the age at which close relatives were diagnosed with breast cancer; whether a relative had cancer in both breasts; and whether any men in the family have had breast cancer.

US scientists have discovered a previously unknown way by which a cancer-causing version of the Myc gene speeds up the progression of the disease.

A faulty version of Myc is already known to interfere with the early stages of DNA activity in the nucleus of the cell. It prevents DNA from being 'transcribed' into RNA, which is an essential first step in making proteins for cell growth and function.

However, scientists at the University of California San Francisco (UCSF) have now found that the faulty Myc gene can also act directly on the final stage of protein production.

*Genes like Myc contribute to cancer in many different ways and every time we discover a new one, we give ourselves another potential avenue for beating the disease.*

- Ed Yong, health information manager, Cancer Research UK

Dr Maria Barna, a faculty fellow in the university's Biochemistry and Biophysics Department and one of the study's senior authors, explained that cancer-causing genes such as Myc regulate a number of distinct cellular processes.

"The key to our studies was the ability to generate novel genetic tools to halt Myc's action on protein production. This demonstrates how essential this process is for cancer formation," she revealed.

Co-senior author Dr Davide Ruggero, assistant professor of urology at the UCSF Helen Diller Family Comprehensive Cancer Centre, commented: "Control of protein production rapidly affects cell behaviour, and in a robust manner.

"The ability of the Myc oncogene to directly alter this process may well explain the rapid progression of cancer formation."

In order to find out whether Myc-induced protein production plays a role in cancer, the researchers bred two types of mice - one of which was prone to cancer and over-expressed the Myc oncogene, while
the other had lowered protein production.

This resulted in mice which had the destructive Myc traits as well as an enhanced ability to suppress protein production.

The researchers found that in these mice, cell growth, division and death - which is required to counter cancer - were restored to near-normal levels.

This also helped to counter Myc-induced damage to chromosome function, indicating that Myc causes changes in the genetic integrity of cells through control of protein production and that it may disrupt a number of genes.

Dr Ruggero said: "We discovered a previously unrecognised link between alterations in protein synthesis and the mechanism by which cells maintain the integrity of the genome.

"We found that when Myc is overexpressed, this leads to changes in protein levels of a key gene that is essential for normal distribution of genetic material between daughter cells during cell division."

The discovery, which appears in Nature, suggests that existing drugs which counter increased protein production could slow down tumour growth in cancers where Myc is overactive.

Ed Yong, Cancer Research UK's health information manager, said: "Genes like Myc contribute to cancer in many different ways and every time we discover a new one, we give ourselves another potential avenue for beating the disease."

Ref: Barna et al. Nature 456, 971-975 (18 December 2008)

Ovarian cancer has often been referred to as a 'silent killer', but new preliminary findings from an Australian study show the disease is in fact not silent - these latest data show most women (83 per cent) experience at least one symptom of ovarian cancer in the year prior to their diagnosis.

The study also revealed 17 per cent of women waited more than three months after the onset of their symptoms before visiting their doctor, with 8 per cent waiting more than six months.

"The most common reason for the delay was an assumption that the symptoms were not serious, with many women attributing them to another medical condition or the natural process of ageing," said Dr Helen Zorbas, CEO, National Breast and Ovarian Cancer Centre.

The study by National Breast and Ovarian Cancer Centre in collaboration with the Queensland Institute of Medical Research, examined the pathways taken by 1500 Australian women to their diagnosis of ovarian cancer, strengthening the case for women to be aware of the symptoms of the disease.

"As there is no screening test for ovarian cancer, the first step to diagnosis is a woman identifying symptoms which are persistent and unusual for her and seeking medical attention. It is therefore vital that women are aware of the symptoms to look out for," said Dr Zorbas.

The symptoms of ovarian cancer include:

- abdominal bloating
- abdominal or back pain
- appetite loss or feeling full quickly
- changes in toilet habits
- unexplained weight loss or gain
- indigestion or heartburn
- fatigue

  The most common symptoms, experienced by half of the study participants, were abdominal symptoms such as fullness and pain. Bloating, bowel or urinary symptoms were reported by approximately one third of participants.

"We know many women will experience these symptoms as part of everyday life," said Dr Zorbas. "But if any of these symptoms are unusual for you and they persist, it is important to see your doctor. No one knows your body like you do."

This year about 1300 women will be diagnosed with ovarian cancer in Australia. More than half of women diagnosed do not survive five years after their diagnosis. More than 70 per cent of women are diagnosed at an advanced stage, where the cancer has spread and is difficult to treat successfully.

National Breast and Ovarian Cancer Centre is funded by the Australian Government and works with consumers, health professionals, cancer organisations, researchers and governments to improve care and cancer control in breast and ovarian cancer. Queensland Institute of Medical Research coordinates the Epidemiology core of the Australian Ovarian Cancer Study. The Australian Ovarian Cancer Study is a collaborative research program between clinicians, scientists, patients and advocacy groups aimed at improving the prevention, diagnosis, and treatment of ovarian cancer.

Bree Stevens
Senior Communications & Policy Officer
National Breast and Ovarian Cancer Centre
Level 1, Suite 103, 355 Crown Street SURRY HILLS NSW 2010
Telephone + 61 2 9357 9402 Mobile 0438 209 833 Facsimile + 61 2 9357 9477

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