hCG and LDH concentrations above the normal range can occur with any germ cell tumor histology
June 11, 2010 (Chicago, Illinois) — The American Society of Clinical Oncology (ASCO) has issued a guideline on the use of serum tumor markers in the diagnosis, treatment, and management of germ cell tumors in men, which include, most commonly, testicular cancer.
The germ cell tumors clinical practice guideline was announced at a press conference here at the organization's 2010 Annual Meeting.
This is the newest guideline on the use of biomarkers for specific cancers from ASCO — with more to come as part of an "expanded series" of guidelines on biomarkers.
The initial 2 guidelines on biomarkers were on breast (2007) and gastrointestinal cancers (2006).
Why has ASCO chosen germ cell tumors, which are rare — with fewer than 9000 cases annually in the United States — for their third tumor marker guideline?
According to the panel of authors of the guideline, which was published online June 7 in the Journal of Clinical Oncology, it is "because of the large volume of publications and the long history of using serum concentrations of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) to guide management decisions for patients with GCT."
In short, there is clinical value in using biomarkers to help manage patients with germ cell tumors, the authors explain
At the press conference, the new guideline's lead author, Timothy D. Gilligan, MD, from the Cleveland Clinic in Ohio, said that these 3 biomarkers for germ cell tumors "play a critical role in the management of these tumors."
He also hinted that some tumor markers might not be as clinically useful as the germ cell tumor markers.
Medical tests that measure tumor biomarkers are not as rigorously examined by the US Food and Drug Administration (FDA) as drugs are, he explained.
"The FDA doesn't require that marker products improve outcome. The products are only required to measure what they claim to measure," he told reporters at the press conference.
He called for "better evidence about whether tumor markers for other cancers help provide better care for patients." Specifically, he called for proof that the tumor-marker products "improve medical outcomes or quality of life."
The stakes can be high when patients undergo biomarker tests, Dr. Gilligan noted.
"Medical tests are dangerous," he said. "They can lead to a waterfall of further tests and unnecessary treatment."
Dr. Gilligan cited the use of prostate-specific antigen (PSA) as a screening test for prostate cancer as an example of a problematic biomarker that has produced overdiagnosis and overtreatment of disease. The introduction of the PSA screening test in the mid-1980s led to an estimated 1 million cases of overdiagnosis of prostate cancer by 2009, as reported by Medscape Oncology.
Dr. Gilligan called for improved tests to detect cancer. "We need better tests to detect treatable cancers earlier so that treatment will be more effective."
The future of tumor biomarkers promises to be busy, suggested Dr. Gilligan. "This is a big area of research. There are a lot of new products coming out along these lines," he said.
What's New in Germ Cell Tumor Markers
The expert panel convened by ASCO, which included Dr. Gilligan, conducted a systematic review of medical research literature, in partnership with Cancer Care Ontario, to develop the new recommendations on germ cell tumors and related serum tumor markers.
Germ cell tumors might be rare but they are also among the most curable cancers, with more than 90% of men cured, according to Dr. Gilligan. Germ cell tumors most commonly start in sperm-producing cells in the testicles. Testicular cancers are typically detected when the patient notices a swelling or irregularity in the shower or when dressing, Dr. Gilligan explained.
"Testicular cancer is curable in most cases, but proper management is key because the stakes are high, both for survival and quality of life," said Dr. Gilligan in a press statement.
AFP, hCG, and LDH should not be used to screen for germ cell tumors, to help decide whether orchiectomy is needed, or to make treatment decisions for patients with cancer of unknown origin, notes the guideline.
This news about the latter practice — using germ cell tumor markers to choose a chemotherapy regimen for patients with a cancer of unknown primary — is worth highlighting, noted Dr. Gilligan "This has been the practice, but the literature does not support use of tumor markers for this," he said.
The other most notable new recommendation, said Dr. Gilligan, is about serum tumor markers: they should not be used as part of "surveillance for stage I seminomas."
The diagnosis of germ cell tumors in men is divided into 2 different types — seminoma and nonseminoma, said Dr. Gilligan.
Generally, seminomas are relatively slow-growing; nonseminomas tend to grow and spread more quickly and are treated differently.
Seminoma cells do not produce AFP. As a result, concentrations above the normal range of AFP can occur in patients with nonseminomas but not in those with pure seminoma. In contrast, hCG and LDH concentrations above the normal range can occur with any germ cell tumor histology, write the authors of the new guideline.
A rise in these markers generally indicates disease relapse in patients who have been treated, said Dr. Gilligan.
However, as noted above, Dr. Gilligan and his colleagues recommend against using these markers as part of surveillance in stage I seminomas.
Dr. Gilligan has disclosed no relevant financial relationships.
J Clin Oncol. Published online June 7, 2010. Abstract
Showing posts with label cancer. Show all posts
Showing posts with label cancer. Show all posts
Monday
HAPTOGLOBIN
Haptoglobin is a blood protein made by the liver. Haptoglobin (abbreviated as Hp) is a protein in the blood plasma that binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. Haptoglobin is produced mostly by hepatocytes but also by other tissues: e.g. skin, lung, and kidney. Haptoglobin, in its simplest form, consists of two α- and two β-chains, connected by disulfide bridges. The chains originate from a common precursor protein which is proteolytically cleaved during protein synthesis according to published reports.
Haptoglobin exists in two allelic forms in the human population, so called Hp1 and Hp2; the latter one having arisen due to the partial duplication of Hp1 gene. Three phenotypes of Hp, therefore are found in humans: Hp1-1, Hp2-1, and Hp2-2. Hp of different phenotypes have been shown to bind hemoglobin with different affinities, with Hp2-2 being the weakest binder
Clinical Significance: Decreased values can indicate a slower type of red cell destruction unrelated to anemia. For example, destruction can be caused by mechanical heart valves or abnormal hemoglobin , such as sickle cell disease or thalassemia.
Haptoglobin is known as an acute phase reactant. Haptoglobin level increases during acute conditions such as infection, injury, tissue destruction, some cancers, burns, surgery, or trauma. Haptoglobins purpose is to remove damaged cells and debris and rescue important material such as iron. Haptoglobin levels can be used to monitor the course of these conditions.
Hemoglobin is the protein in the red blood cell that carries oxygen throughout the body. Iron is an essential part of hemoglobin; without iron, hemoglobin can not function. Haptoglobin's main role is to save iron by attaching itself to any hemoglobin released from a red cell.
When red blood cells are destroyed, the hemoglobin is released. Haptoglobin is always present in the blood waiting to bind to released hemoglobin. White blood cells (called macrophages) bring the haptoglobin-hemoglobin complex to the liver, where the haptoglobin and hemoglobin are separated and the iron is recycled.
In hemolytic anemia, so many red cells are destroyed that most of the available haptoglobin is needed to bind the released hemoglobin. The more severe the hemolysis, the less haptoglobin remains in the blood.
Decreased haptoglobin levels usually indicates hemolytic anemia. Other causes of red cell destruction also decrease haptoglobin: a blood transfusion reaction; mechanical heart valve; abnormally shaped red cells; or abnormal hemoglobin, such as thalassemia or sickle cell anemia.
Haptoglobin levels are low in liver disease, because the liver can not manufacture normal amounts of haptoglobin. Low levels may also indicate an inherited lack of haptoglobin, a condition found particularly in African Americans.
Haptoglobin increases as a reaction to illness, trauma, or rheumatoid disease. High haptoglobin values should be followed-up with additional tests. Drugs can also effect haptoglobin levels.
Normal results vary widely from person to person. Unless the level is very high or very low, haptoglobin levels are most valuable when the results of several tests done on different days are compared. Reference: HealthAtoZ.com
Haptoglobin exists in two allelic forms in the human population, so called Hp1 and Hp2; the latter one having arisen due to the partial duplication of Hp1 gene. Three phenotypes of Hp, therefore are found in humans: Hp1-1, Hp2-1, and Hp2-2. Hp of different phenotypes have been shown to bind hemoglobin with different affinities, with Hp2-2 being the weakest binder
Clinical Significance: Decreased values can indicate a slower type of red cell destruction unrelated to anemia. For example, destruction can be caused by mechanical heart valves or abnormal hemoglobin , such as sickle cell disease or thalassemia.
Haptoglobin is known as an acute phase reactant. Haptoglobin level increases during acute conditions such as infection, injury, tissue destruction, some cancers, burns, surgery, or trauma. Haptoglobins purpose is to remove damaged cells and debris and rescue important material such as iron. Haptoglobin levels can be used to monitor the course of these conditions.
Hemoglobin is the protein in the red blood cell that carries oxygen throughout the body. Iron is an essential part of hemoglobin; without iron, hemoglobin can not function. Haptoglobin's main role is to save iron by attaching itself to any hemoglobin released from a red cell.
When red blood cells are destroyed, the hemoglobin is released. Haptoglobin is always present in the blood waiting to bind to released hemoglobin. White blood cells (called macrophages) bring the haptoglobin-hemoglobin complex to the liver, where the haptoglobin and hemoglobin are separated and the iron is recycled.
In hemolytic anemia, so many red cells are destroyed that most of the available haptoglobin is needed to bind the released hemoglobin. The more severe the hemolysis, the less haptoglobin remains in the blood.
Decreased haptoglobin levels usually indicates hemolytic anemia. Other causes of red cell destruction also decrease haptoglobin: a blood transfusion reaction; mechanical heart valve; abnormally shaped red cells; or abnormal hemoglobin, such as thalassemia or sickle cell anemia.
Haptoglobin levels are low in liver disease, because the liver can not manufacture normal amounts of haptoglobin. Low levels may also indicate an inherited lack of haptoglobin, a condition found particularly in African Americans.
Haptoglobin increases as a reaction to illness, trauma, or rheumatoid disease. High haptoglobin values should be followed-up with additional tests. Drugs can also effect haptoglobin levels.
Normal results vary widely from person to person. Unless the level is very high or very low, haptoglobin levels are most valuable when the results of several tests done on different days are compared. Reference: HealthAtoZ.com
Thursday
HUMAN C- REACTIVE PROTEIN (CRP)
THE LATEST IN HUMAN C-REACTIVE PROTEIN (CRP) Research:
Transgenic expression of human C-Reactive Protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury.These in vivo observations support the hypothesis that CRP modulates NO metabolism and may have implications regarding the mechanisms by which CRP modulates vascular disease.Source: Am J Physiol Heart Circ Physiol 293: H489-H495, 2007
human C-Reactive Protein Binds Activating Fcγ Receptors and Protects Myeloma Tumor Cells from Apoptosis.CRP also enhanced myeloma cell secretion of IL-6 and synergized with IL-6 to protect myeloma cells from chemotherapy drug-induced apoptosis. Thus, our results implicate CRP as a potential target for cancer treatment.Source: Cancer Cell, Vol 12, 252-265, 11 September 2007
Transgenic expression of human C-Reactive Protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury.These in vivo observations support the hypothesis that CRP modulates NO metabolism and may have implications regarding the mechanisms by which CRP modulates vascular disease.Source: Am J Physiol Heart Circ Physiol 293: H489-H495, 2007
human C-Reactive Protein Binds Activating Fcγ Receptors and Protects Myeloma Tumor Cells from Apoptosis.CRP also enhanced myeloma cell secretion of IL-6 and synergized with IL-6 to protect myeloma cells from chemotherapy drug-induced apoptosis. Thus, our results implicate CRP as a potential target for cancer treatment.Source: Cancer Cell, Vol 12, 252-265, 11 September 2007
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