Gene That Causes Childhood Cancer Neuroblastoma Is Found (Yahoo News-22/08/2008)

Scientists have discovered gene mutations that are the main cause of the inherited version of the childhood cancer neuroblastoma. In addition, the researchers found that the same mutations play a significant role in high-risk forms of non-inherited neuroblastoma, the more common form of the disease. “This discovery enables us to offer the first genetic tests to families affected by the inherited form of this disease,” said pediatric oncologist Yael P. Mossé, M.D., of The Children’s Hospital of Philadelphia, the first author of the study, published online Aug. 24 in the journal Nature. “Furthermore, because there already are drugs in development that target the same gene in adult cancers, we can soon begin testing those drugs in children with neuroblastoma.” Neuroblastoma is the most common solid cancer of early childhood. It accounts for 7 percent of all childhood cancers, but due to its often aggressive nature, causes 15 percent of all childhood cancer deaths. It arises in the developing nerves of a child, often appearing as a tumor in the chest or abdomen. Because only about 600 new cases of all forms of neuroblastoma occur annually in the U.S., familial (inherited) neuroblastoma is a very rare subset of a relatively uncommon disease. Scientists at Children’s Hospital have studied familial neuroblastoma for the past 15 years, and the current study drew on family data collected from throughout the world. John M. Maris, M.D., senior author of the current study and director of the Center for Childhood Cancer Research at Children’s Hospital, leads a laboratory with the world’s largest collection of neuroblastoma tissue samples, gathered through the multicenter Children’s Oncology Group in the U.S. and through multiple international collaborations. Maris said, “This is a very important discovery, as it not only helps us understand the genetic roots of this terrible disease, but also has led to dramatically new ideas for curative therapy.”

The study team used high-speed, automated analytic equipment at the Center for Applied Genomics at Children’s Hospital. By employing genome-wide scans to analyze DNA from the 10 most informative families with a history of neuroblastoma, Mossé and her colleagues first discovered that a region of chromosome 2 was associated with the disease. Further sequencing of that region identified mutations in the anaplastic lymphoma kinase (ALK) gene in eight families with familial neuroblastoma. “This finding means that it is possible to offer simple, non-invasive screening for patients with a family history of neuroblastoma,” said Mossé. She explained that ultrasound or a urine test could assist surveillance of children with an ALK mutation, so that if neuroblastoma appears, it can be detected at an early stage. “As we increase our knowledge of ALK mutations, we will also offer specialized diagnostic testing for all newly diagnosed patients with neuroblastoma, to eventually allow oncologists to better customize treatment to a child’s genetic profile.” After detecting ALK mutations in familial neuroblastoma, the researchers then focused on the more common sporadic (non-familial) cases of neuroblastoma, and found that ALK mutations occurred in 12 percent of 194 tumor samples from the aggressive, high-risk form of the disease. Although the normal role of the ALK gene is not well understood, other researchers had previously found that abnormalities in ALK raise a patient’s risk for lymphoma and lung cancer. “We were the first to identify mutations in ALK,” said Mossé, adding that in lymphoma and lung cancer, ALK acts through translocation, a different mechanism that involves an exchange of DNA between chromosomes to produce a new cancer-causing fusion gene.

In all three cancers, ALK acts as an oncogene, or cancer-causing gene; in fact, the current study reports the first example of a childhood cancer caused by mutations in an oncogene. Since the mutations discovered by Mossé trigger an “on” signal for neuroblastoma cells, the abnormality is an outstanding target for therapies that inhibit the ALK protein’s activity. Several pharmaceutical companies are currently developing ALK inhibitors in the laboratory, and one ALK inhibitor is already in early-phase adult clinical trials against lung cancer and lymphoma. Now Mossé and her colleagues at Children’s Hospital are planning pediatric clinical trials of ALK inhibitors in children with high-risk neuroblastoma. “It’s an advantage to be able to start with agents that have already been shown to be safe in adults,” Mossé added. Neuroblastoma has long been a puzzling disease, partly because of its broad range in outcomes. Some types of the disease strike infants but spontaneously disappear with minimal treatment, while other subtypes in older children may be relentlessly aggressive. Earlier this year, Maris’s lab reported that common DNA variations in a region of chromosome 6 raise a child’s risk of developing sporadic neuroblastoma. “Together with this current study, we are defining the genetic events that underlie this childhood cancer,” said Maris. “Better understanding of these biological pathways will guide our efforts to develop more effective treatments.” The National Institutes of Health supported the study, along with grants from the Alex’s Lemonade Stand Foundation, the American Society of Clinical Oncology, the Andrew’s Army Foundation, the Italian Neuroblastoma Foundation, Scripps Genomic Medicine, the Scripps Dickinson Scholarship, the Giulio D’Angio Endowed Chair, the Foerderer-Murray Fund and the Carly Hillman Fund. The Center for Applied Genomics at The Children’s Hospital of Philadelphia also provided support, as did the Abramson Family Cancer Research Institute of the University of Pennsylvania School of Medicine. The study could not have been done, say the authors, without the support and resources of the Children’s Oncology Group.

Among Mossé’s and Maris’s co-authors were Garrett M. Brodeur, M.D., of the Division of Oncology and Center for Childhood Cancer Research at Children’s Hospital, as well as Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at Children’s Hospital. The above co-authors are also faculty members of the University of Pennsylvania School of Medicine. Other collaborators were from the National Institute for Cancer Research, Genoa, Italy; Ghent University Hospital, Ghent, Belgium; Scripps Research Institute, La Jolla, Calif.; and the University of Rome “La Sapienza.” About The Children’s Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

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1/5 of British adult survivors of childhood cancer smoke despite hazards (Yahoo News-29/07/2008)

One-fifth of British adult survivors of childhood cancers are current smokers, and nearly a third have been regular smokers at some point in their lives, according to a study in the July 29 online issue of the Journal of the National Cancer Institute. 
Adult survivors of childhood cancer are at increased risk of developing cardiovascular disease, lung problems, and second malignancies, relative to the general public. These increased risks are due to long-term effects of the original cancer and its treatment, as well as to genetic conditions that predispose the survivors to multiple cancers. Smoking would be an additional source of risk for this population. To learn what fraction of adult survivors are current smokers or have smoked regularly in the past, Clare Frobisher, Ph.D., of the University of Birmingham, UK, and colleagues sent surveys to all those who could be contacted from among 14,836 eligible survivors of childhood cancer in the National Registry of Childhood Tumors. To be eligible for the study, survivors had to have been diagnosed with their primary cancer between 1940 and 1991 and be aged 16 years or older at the time of the survey. Of those survivors, 10,326 returned completed study questionnaires and were included in the current analysis. Of the respondents, 20 percent were current regular smokers and 29.8 percent were regular smokers at some time in their life prior to the completion of the survey. When the researchers analyzed the responses by tumor site, they found that survivors of central nervous system cancers or heritable retinoblastoma were least likely to smoke, while survivors of Wilms tumor, Hodgkin lymphoma, or soft tissue sarcomas were most likely to report being a regular current smoker. Individuals who had been treated with radiation or chemotherapy were less likely to smoke than those who had not received that type of therapy. Also, those who did not have regular hospital follow-up appointments were more likely to smoke than those who did.

The rate of current smoking in the survivors was approximately half of the rate in the general British population. The socioeconomic factors that are associated with an increased risk of smoking in the general public, though, are the same as those in the adult survivor group, including manual occupations compared with managerial or professional work, lower educational attainment, and being widowed, divorced, or separated. The relatively high rate of smoking in survivors of Wilms tumor, Hodgkin lymphoma, and soft tissue sarcomas is concerning because previous research suggests that these survivors are at a particularly high risk for second malignancies. The researchers conclude that although the rate of smoking in adult survivors of childhood cancer is lower than in the general public, further efforts are needed to reduce the smoking prevalence in this group. In general, any program of clinical follow-up for survivors of childhood cancer should include advice on the health risks of smoking, the authors assert. "Smoking cessation interventions would be more appropriate for the [British Childhood Cancer Survivor Study] cohort than smoking prevention interventions because a high proportion of the survivors were older than the age at which most individuals initiate smoking (i.e., =20 years of age)," the authors write. In an accompanying editorial, Karen Emmons, Ph.D., of the Dana-Farber Cancer Institute and Harvard School of Public Health in Boston notes that the new findings are remarkably similar to data from the U.S. Childhood Cancer Survivor Study, in which 17 percent of adult survivors reported being current smokers and 28 percent reported being ever smokers. The good news is that the rates are lower than the general public. The bad news, according to Emmons, is that for the survivors who do smoke, the habit is likely to exacerbate the already negative long-term effects of cancer treatment. 

More needs to be done to reduce the rate of smoking in adult cancer survivors, Emmons writes, noting that fewer than half of the survivorship programs in the U.S. currently offer smoking cessation services. Beyond just treating this issue specifically, however, Emmons argues that broader efforts are needed to improve the socioeconomic pressures and social disadvantages that encourage smoking and reduce public health. "It is time to think well beyond our disciplinary boundaries and implement inter¬ventions that we know are efficacious, such as provider-delivered counseling and pharmacotherapy, and seek solutions for the social conditions that serve as a trajectory for a lifetime of smoking," she writes.

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Kids' cancer rates highest in Northeast (Yahoo News-2/06/2008)

Surprising research suggests that childhood cancer is most common in the Northeast, results that even caught experts off guard. But some specialists say it could just reflect differences in reporting. 
The large government study is the first to find notable regional differences in pediatric cancer. Experts say it also provides important information to bolster smaller studies, confirming that cancer is rare in children, but also more common in older kids, especially among white boys. The study from the Centers for Disease Control and Prevention is based on data representing 90 percent of the U.S. population. It found that cancer affects about 166 out of every million children, a number that shows just how rare childhood cancers are. The highest rate was in the Northeast with 179 cases per million children, while the lowest was among children in the South with 159 cases per million. Some experts suggested that could mean cases were under-reported in the South and over-reported elsewhere.

The rates for the Midwest and West were nearly identical, at 166 cases per million and 165 per million, respectively. The cancer incidence in boys was 174 cases per million, compared with 157 cases per million in girls. In white children, the rate was 173 per million, versus 164 per million in Hispanics and 118 per million in blacks. Teenagers had higher rates than younger kids. A total of 36,446 cases were identified in the study, which analyzed 2001-03 data from state and federal registries. The research appears in the June edition of Pediatrics, released Monday. "It's very powerful that this study includes so much of the U.S. population so it gives us a good picture of where we are with the incidence of these childhood cancers," said Elizabeth Ward, the American Cancer Society's surveillance director. Experts said the regional differences, though small, are intriguing, but that reasons for them are uncertain. Dr. Rafael Ducos, a children's cancer physician at Ochsner Medical Center in New Orleans, said the South's low rates were perplexing and might simply reflect under-reporting there and over-reporting in other regions. "I'm at a loss to explain it," he said. Environmental factors might play a role, including exposure to radiation, said lead author Dr. Jun Li of the CDC. Radiation has been linked with the most common types of childhood cancer — leukemia, lymphoma and brain cancers.

Radiation sources include X-rays, nuclear plant emissions and natural sources such as radon gas. But Li said research is needed to determine if these sources vary enough by region to affect childhood cancer rates.Dr. Lindsay Frazier, a cancer specialist at Children's Hospital Boston and Dana Farber Cancer Institute, said pollution and housing stock that's older than anywhere else in the nation might help explain the Northeast's higher rates. But also, there could be better access to cancer centers in the Northeast, which would result in more diagnoses, she said. That could also explain why other research has shown that children's death rates from cancer are also lowest in the Northeast. While noteworthy, the differences in rates among regions shouldn't cause alarm among parents, said Dr. Adam Levy, a cancer specialist at the Children's Hospital at Montefiore Medical Center in New York. "As a parent raising a family in the Northeast, this does not at all increase my concern for my family or for my neighbors," Levy said, adding, "First and foremost, these are still very rare diseases in children." Regional differences in rates for some specific cancers have been found in adults, but these are likely due to personal habits and lifestyle factors, Ward said. For example, lung cancer rates are high in the South because smoking is generally more popular there, she said. But it generally takes years of exposure to lifestyle factors such as smoking before cancer develops, she said, so this wouldn't explain children's rates. 

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Study details heart problems after childhood cancer (Reuters Health-6/06/2008)

Survivors of childhood cancer who had aggressive chemotherapy are at increased risk of structural and functional heart problems, a new study indicates. Both chemotherapy, especially with drugs called anthracyclines, and radiation to the chest are known to increase the risk of heart damage among childhood cancer survivors, Dr. Veronika Velensek of the University Children's Hospital Ljubljana in Slovenia and colleagues note. To better understand the risk factors for cardiovascular disease among these patients, Velensek and her team performed a battery of tests of heart structure and function in 211 patients who had survived for at least five years after being diagnosed with cancer in childhood. All were treated between 1968 and 1998. More than half (53 percent) had signs of heart damage. Individuals treated most recently (1989-1998) were at greatest risk, the researchers found; nearly three-quarters of these patients had heart damage. These patients were all treated with intensive chemotherapy with several drugs, including high doses of anthracyclines, the researchers note.

Patients who underwent radiation were at increased risk of heart valve disease. Those treated for Hodgkin's disease between 1968 and 1988 were at greatest risk. "A possible explanation for this could be that in the time period higher doses of irradiation were used...older radiation therapy techniques were available and less effective shielding was used," the researchers write in the online medical journal BMC Cancer. Patients who had received a large total dose of anthracyclines and were treated with drugs called alkylating agents at the same time were most likely to have systolic dysfunction, or problems with contraction of the heart's main pumping chambers, as well as enlargement of the chambers on the left side of the heart. The researchers also found that 46 percent of the patients had below-normal exercise tolerance. While no specific type of treatment was linked to poor fitness, the researchers note, the fact that one third of the patients were sedentary and obese may have been a factor.

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Childhood Cancer Survivors Prone to Early Heart Trouble (HealthDay News-16/05/2008)

Adults who had cancer as children or teens are more likely to experience cardiovascular disease, a new study found. And the heart problems surface at a much earlier age than in people who did not suffer cancer as children. Childhood cancer survivors "have approximately a five to 10 times increased risk of having heart disease compared to their healthy siblings," said study lead author Dr. Daniel A. Mulrooney, assistant professor of pediatrics at the Masonic Cancer Center of the University of Minnesota, Minneapolis. Mulrooney was expected to present his findings Thursday night at the American Society of Clinical Oncology annual meeting, in Chicago. There are an estimated 270,000 survivors of childhood cancer in the United States, and 11 million cancer survivors total. While the cancer survivors in the new study ranged in age from 8 to 51, the average age of those with heart problems was only 27.5 years. "We're talking about a very young population that's having very significant cardiac disease and is likely not being monitored appropriately," Mulrooney added. "It is very important that they be followed and that risk factors and cardiovascular monitoring that we would think of in an older population be implemented in a younger population." 

The findings aren't entirely surprising. Previous research, much of it with the same group of survivors, has shown an increased risk of cardiovascular disease in survivors of childhood and adolescent cancer. The new analysis, the longest follow-up to date, provides updated information on 14,358 five-year survivors of childhood cancer. All the participants were diagnosed with one of eight cancers (including leukemia, lymphoma and brain malignancies) at 21 years of age or younger, between 1970 and 1986. The study participants provided information on their own heart health, which was then compared to a control group of 3,899 healthy siblings. Compared to the healthy brothers and sisters, the survivors of childhood cancer were almost six times more likely to report congestive heart failure; about five times more likely to report having had a heart attack or valvular heart disease; more than six times likelier to have pericardial disease (the pericardium is the sac that surrounds the heart); more than eight times as likely to have had an angiography; and 10 times more likely to have atherosclerosis, or hardening of the arteries. Exposure to the chemotherapy drug anthracycline increased the risk of congestive heart failure about fourfold, roughly doubled the risk of pericardial and valvular disease, and almost tripled the odds of having had an angiography, the study found.

Radiation treatment to the heart doubled the risk of congestive heart failure, heart attack and pericardial disease, almost tripled the risk of valvular disease, and increased the risk of atherosclerosis by a factor of more than five, according to the study. Dr. Karen Burns is clinical director of the ATP5+ Clinic for Childhood Cancer Survivors at Cincinnati Children's Hospital. She said most of the heart problems seen in survivors of childhood cancer come from the class of chemotherapy drugs called anthrocyclines, which cause problems with cardiac muscle, and from radiation, if the radiation field included the heart. Although monitoring for heart disease in childhood cancer survivors is already in place in many specialized facilities, Burns said she hoped that, "if this study is available to the general public, it will encourage people who are survivors to get closer follow-up." Mulrooney added: "We see this in our long-term follow-up clinic. We identify patients who are at risk based on this analysis and may do an echocardiogram or a lipid panel, things we might not typically do in a 20-year-old. There are tools out there, and getting this knowledge out there as well would be helpful so primary-care physicians will be more aware, oncologists and cardiologists will be aware, and patients as well." 

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Gene Variation Linked to Neuroblastoma, a Childhood Cancer (Yahoo News-7/05/2008)

For the first time, a gene linked to the often fatal childhood cancer neuroblastoma has been identified, researchers report."This is the first paper that helps us understand what causes this childhood cancer," said lead researcher Dr. John M. Maris, director of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia. "We expected for decades that this cancer was a genetic disease, but we have had a hard time understanding what abnormalities in our genetic makeup lead to this cancer." Neuroblastoma, a cancer of the peripheral nervous system that usually appears as a solid tumor in the chest or abdomen, is the most common solid tumor malignancy seen in early childhood. Among infants, it can disappear with minimal treatment, but in older children, it can be an aggressive cancer spreading throughout the body. Neuroblastoma accounts for 7 percent of all childhood cancers but causes 15 percent of all childhood cancer deaths. There are about 700 new cases diagnosed each year in the United States, the researchers said. Maris' team found a common genetic variation of the gene 6p22 on chromosome 6, which doubles the risk of getting this disease. "This finding supports our assumption that there are a number of minor variations that work together -- in sort of a perfect storm -- to give a child this disease," he said. "This finding is the discovery of the first of these genetic variants." Maris noted that this is the first time a childhood cancer has been found to be influenced by rather common genetic changes "that can be in you or me or anyone." In addition, Maris said that having this particular genetic variation not only increases the risk of developing neuroblastoma, but also increases the risk of developing the more aggressive form of the disease. "This leads us to believe that the disease we call high-risk or low-risk neuroblastoma are really different diseases," he said. 


The findings were published in the May 7 online edition of the New England Journal of Medicine.For the study, Maris' team analyzed blood samples from 1,032 children with neuroblastoma and 2,043 children without the disease. The researchers honed in on three single nucleotide polymorphisms (SNPs) -- which are variations in DNA -- that were more common in patients with neuroblastoma than in patients without the disease. The three SNPs were clustered in the 6p22 region of chromosome 6. There are two genes in this region, but exactly what they do is unknown, the researchers said. To confirm their findings, Maris' group analyzed blood samples from additional neuroblastoma patients and children without the disease. Among these additional patients, the researchers also found that variants in the 6p22 region were associated with increased risk for neuroblastoma. "This finding gives us the motivation to continue this line of research to discover all of the different genetic variations that work together," Maris said. "We have already discovered additional variations." Knowing the complete genetic influences on neuroblastoma may eventually lead to new treatments, he said. Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, said that the new findings could one day lead to better diagnosis and treatment of the malignancy. "We still need to understand what these genes do, because little is known about these genes," he said. Lichtenfeld added that, while the new research is important, it's still very preliminary. "Ultimately, what you want to do is to analyze the cancer and gain clues as to what the prognosis may be and what the appropriate treatment may be," he said. "This does not get us there, but it is one step along that pathway." 

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Better care eases suffering of kids with cancer (Reuters Health-23/04/2008)

Increasing attention to palliative care has reduced suffering for children with cancer in recent years, according to a new report. "When we first published our original study in 2000, I think there was a more passive approach to caring for children with cancer at the end of life," Dr. Joanne Wolfe from the Dana-Farber Cancer Institute, Boston, told Reuters Health. "In our current study, we have shown that through an active and intensive focus on the needs of children with advanced cancer and their families, care can be improved upon." Wolfe and her colleagues determined whether efforts to improve communication, symptoms, and quality of life in children with advanced cancer have changed patterns of care for children at the end of life. The researchers reviewed the medical records of 119 children treated at Dana-Farber or Children's Hospital and who died of cancer between 1997 and 2004. From the 1990s to the early 2000s, there was a 22 percentage point increase in the documentation of discussion about hospice care, the authors report in the Journal of Clinical Oncology. Furthermore, hospice discussions and do-not-resuscitate orders were documented earlier in the course of care.

Parents reported no difference in the proportion of children who experienced fatigue, pain, breathing difficulty, or anxiety between the earlier and later periods, the researchers note, but reports of "a great deal" or "a lot" of suffering decreased in the later period for all symptoms except fatigue. Moreover, a significantly greater proportion of parents in the later period felt "very prepared" for the medical problems experienced by their child at the end of life and for the circumstances at the time of death. "Our results suggest that increased focus on the palliative care needs of children with advanced cancer and their families creates an environment that fosters significantly improved end-of-life care, with parents reporting better preparedness for the end-of-life course and decreased suffering in their children," the investigators conclude. "This finding is really important in the sense that it suggests that child and family suffering can be further eased, especially with more targeted interventions," Wolfe added.

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Gene blockage may help treat childhood cancer (Reuters Health - 14/04/2008) 

Overactivity of a gene called ODC1 is associated with poor survival of neuroblastoma, a common, often fatal cancer seen mostly in young children, according to research presented Sunday at the American Association for Cancer Research 2008 meeting in San Diego. The good news, however, is that blocking this gene may improve outcomes. In the study, the researchers gave an ODC1-blocking drug called DFMO to mice with the disease and actually 
cured some of them. Dr. Michelle Haber of the Children's Cancer Institute Australia in Sydney and colleagues analyzed neuroblastoma specimens from 209 patients before treatment and found that ODC1 overactivity predicted poor outcomes. "Patients with low levels of ODC1 in their tumors had significantly better survival," Haber told the conference. Moreover, patients with a variant of ODC1 associated with lower activity had better outcomes than patients without this variant, she reported. "We've shown that ODC1 is a good target in primary neuroblastoma because the higher the levels of this gene, the worse the patients do," Haber said.
Haber's team also showed that inhibition of ODC1 with DFMO delayed or prevented the development of neuroblastoma in mice. "Most importantly," Haber said, the findings demonstrate that the effectiveness of standard chemotherapy drugs can be substantially improved by adding DFMO. In fact, when DFMO was 
combined with the chemotherapy drug cyclophosphamide, a number of the mice were cured of their cancer. These findings suggest there is a new treatment approach for this childhood cancer, which has a very high relapse rate, she concluded.

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Cancer survivors' follow-up care falls short -(USA Today) 

A new study shows that most pediatric cancer survivors aren't getting key follow-up treatment as adults. 12% Haven't seen a doctor in the past two years
68% Got no follow-up care related to their pediatric cancer. Top cancer researchers are gathered at the American Society of Clinical Oncology annual meeting in Chicago. Most childhood cancer survivors aren't getting important follow-up care to prevent serious long-term side effects of their treatment, a new study shows.Experts note that progress against pediatric cancers has come at a high price. Although about 80% of children with cancer are cured of their disease, nearly two-thirds later develop a chronic health problem related to their tumors or therapy, says Paul Nathan, an oncologist at the Hospital for Sick Children in Toronto and the study's lead author.

Certain patients face especially high risks. Up to 20% of girls and young women treated with chest radiation — a common treatment for Hodgkin's disease — will develop breast cancer as a result, says Nathan, who presented his research Sunday at the American Society of Clinical Oncology meeting in Chicago. And up to half of children treated with high doses of anthracycline-based chemotherapy will develop heart problems, Nathan says. For these reasons, experts recommend all cancer survivors at risk of heart disease have a test called an echocardiogram every one to two years, Nathan says. Those at risk of breast cancer should have yearly mammograms beginning at age 25, which is 15 to 25 years earlier than typically recommended. 

In Nathan's study, however, 28% of those at risk of heart disease got recommended echocardiograms. Only 49% of women at risk of breast cancer received recommended mammograms. Men were less likely than women to get cancer-related screenings; uninsured patients were three times as likely to miss suggested tests, according to his analysis of the 8,522 patients in the Childhood Cancer Survivor Study, which tracks adults who were treated for pediatric cancer between 1970 and 1986. Patients in the study had a median age of 7 when they were diagnosed with cancer. Their median age today is 31. Nathan says he was disappointed in the findings. And he notes that his study actually may present an overly optimistic picture. Because study participants are more aware than others of long-term effects of cancer, they may be more likely than the average survivor to seek follow-up care. Nathan says the country needs to better educate patients and doctors, many of whom see too few pediatric cancer survivors to be familiar with the latest guidelines for follow-up care. It also would help if insurers paid for crucial follow-up tests for cancer survivors, who need exams more frequently and at younger ages, he says. 

Second cancers are a serious problem in the USA; they account for about 15% of the 1.4 million cancers diagnosed each year, says Patricia Ganz, a professor at the Jonsson Comprehensive Cancer Center at the University of California-Los Angeles. Oncology society president Nancy Davidson, a professor at the Johns Hopkins University School of Medicine in Baltimore, expects the health problems of childhood cancer survivors to increase as patients age. "We're happy with our success, but we have a lot to do to improve our care," Davidson says. 

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Skin cells 'fight child cancer'  

One in 500 children develops some form of cancer. Genetically modified skin cells could be used to fight a cancer which strikes the very young, a UK study suggests. Scientists at UCL said they were able to stimulate the immune system of mice by injecting the animals' skin cells into a neuroblastoma tumour. This type of tumour accounts for 15% of childhood cancer deaths. It is most frequently found in the under-fives. But the authors, writing in the British Journal of Cancer, said clinical trials in humans were at least five years off. 

Nerve cells 

Once the skin cells were genetically modified they became "little factories" producing a sort of protein which helped the immune system, said lead researcher Dr Stephen Hart. This study in mice adds to the growing body of evidence that kick-starting the immune system can work successfully against neuroblastoma 

Dr Bruce Morland 

When they were injected into the tumour site, these cells apparently helped the mouse fight the cancer - with a treated mouse living 90 days or more longer than an untreated mouse. Research in the past has show that genetically modified tumour cells can be turned against the tumour they came from, "but use of the patient's own skin cells would be much easier", Dr Hart wrote. "These cells can be taken by a routine skin punch biopsy, grown in the lab then genetically modified before injecting into the tumour site."  Neuroblastoma is a cancer of specialised nerve cells, called neural crest cells. These cells are involved in the development of the nervous system and other tissues. Prognosis for children diagnosed in the first 12-18 months of life is good, but if it comes back in older children it can be very hard to cure. 

Fewer than 100 new cases are diagnosed each year, according to Cancerbackup. 
Dr Bruce Morland, head of the Children's Cancer and Leukaemia Group, said: "we are delighted that scientists are finding out how to harness the potential of immunotherapy for this childhood cancer. "This study in mice adds to the growing body of evidence that kick-starting the immune system can work successfully against neuroblastoma. "However, we need to learn much more about this approach before we can be sure that it is a safe and effective treatment for children." 

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Gleevec, The Targeted Cancer Pill, Delivers More Good News To Patients- (ScienceDaily - 2/1/2008) 
 

Gleevec, the targeted cancer pill that has saved more than 100,000 lives, now is saving more children with a dire leukemia, as well as preventing disease progression with long term use in adults with chronic myeloid leukemia. "Data at this weekend's meeting continues to show how much Gleevec has completely changed the outlook for so many, many patients facing cancer," said Brian Druker, M.D., director of the OHSU Cancer Institute. At the plenary session of the annual meeting of the American Society of Hematology researchers delivered news that Gleevec has been shown to improve outcomes for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Ph+ ALL is the childhood leukemia with the worst prognosis and the Children's Oncology Group study shows that adding Gleevec to the treatment almost completely reverses this poor prognosis. The Children's Oncology Group is a worldwide clinical trial cooperative supported by the National Cancer Institute, a branch of the National Institutes of Health.

Also released at the conference is new data from the largest clinical trial in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that showed Gleevec, with long-term use, can prevent progression to advanced stages of the disease. Six-year results of the International Randomized Interferon versus STI571 (IRIS) study for which Druker served as principal investigator, demonstrated that continuous treatment with Gleevec produced a declining rate of relapse over time. The downward trend in the risk of disease progression while on Gleevec has continued since year two of the study. Remarkably, between years five and six, no patients progressed to an advanced phase of the disease.

"The news about Gleevec and the childhood leukemia study as well as the six-year IRIS study that shows there is no progression to advanced phase in CML means that more and more patients are surviving, despite being diagnosed with these cancers," said Druker, JELD-WEN Chair of Leukemia Research, Howard Hughes Medical Institute Investigator and member of the National Academy of Sciences. He also is a professor of medicine (hematology and medical oncology), cell and developmental biology, and biochemistry and molecular biology in the OHSU School of Medicine. Gleevec has also been approved for the treatment of gastrointestinal stromal tumors, pediatric CML, as well as five additional rare cancers. Michael Heinrich, M.D., professor of medicine (hematology/medical oncology) in the OHSU School of Medicine and the Portland Veteran's Affairs medical Center, and a member of the OHSU Cancer Institute, has been the principal investigator in research studies involving GIST and Gleevec.

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Officials backpedal on Pa. cancer study- An abstract making an environmental link to the disease was released by mistake, they say.-(AP) 


Officials yesterday abruptly backpedaled on a federally funded health study that suggested an environmental link to a cluster of rare blood cancer cases in Northeastern Pennsylvania, saying an abstract that made the claim was mistakenly released to the public. The research is to be presented Monday at a medical conference in Atlanta. An abstract released in advance of the meeting said there was "significant evidence" that something in the environment caused an unusually large number of cases of polycythemia vera in Luzerne, Carbon and Schuylkill Counties. The abstract, submitted to the American Society of Hematology, also said people who had lived within 13 miles of a former toxic waste dump in northern Schuylkill County developed the blood cancer at a rate 4.5 times higher than people living in other parts of the three counties.

Steve Dearwent, a government epidemiologist, said that the abstract was written early in the summer and that subsequent analysis of the data did not support the conclusion of an environmental link, although he added that it still was a possibility. He said the abstract should have been revised before it was submitted. "We're going to have to retract the abstract to correct the record because it is erroneous information," said Dearwent, chief of health investigations for the Agency for Toxic Substances and Disease Registry, the federal agency that oversaw the study. "It was preliminary and hadn't been vetted, and unfortunately, it got submitted, unbeknownst to most people here." 

Dearwent said additional research might prove an environmental link. And the study's lead researcher, Dr. Ronald Hoffman of the Mount Sinai School of Medicine in New York, said yesterday that the data do point to something in the environment. "Based upon the data, there's significant concern that there is something in the environment leading to the development of polycythemia vera in that area. The nature of what's causing it is unknown at the moment and is going to require further study," he said. Dante Picciano, a lawyer and geneticist who is active in local environmental issues, said the data indicate a much larger problem than polycythemia vera. He wants study of a wide range of cancers and other diseases in the region. 

"This is the tip of the iceberg. It's inconceivable that you're going to have environmental exposures cause an increase in [only] one type of rare cancer," he said. Polycythemia vera, classified as a cancer, can lead to heart attack or stroke. About one case of polycythemia vera occurs each year for every 100,000 Americans. The cause is unknown. Local activists have raised suspicions about McAdoo Associates, about 80 miles northwest of Philadelphia, where a hazardous waste recycling business operated from 1975 to 1979 and accepted hundreds of thousands of gallons of paint sludge, waste oils, used solvents, PCBs, cyanide, pesticides, and many other known or suspected carcinogens. Environmental officials shut down the site in 1979, and it was later placed on the federal Superfund list and cleaned up. 

Residents fear that chemicals leached into the region's water supplies and polluted private wells and public reservoirs. State and federal environmental officials have said for years that the McAdoo site does not pose a health threat. Activists have also raised concerns about five power plants in Schuylkill County fueled by waste coal and about the practice of filling abandoned coal mines with ash created by coal-burning power plants. In October, officials from the Agency for Toxic Substances confirmed 38 cases of polycythemia vera in the region and said the rate was elevated. At the time, federal officials said there was no proof of an environmental cause, and that cases were scattered throughout the area in no predictable pattern - making the assertions in the abstract surprising.

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