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Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.
Their findings are reported online in the International Journal of Radiation Oncology,Biology,Physics.
Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.
Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.
"The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients," said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson's Kimmel Cancer Center. "Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer."
Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.
Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.
Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.
According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson's Department of Radiation Oncology and a part-time master's degree student in the Jefferson School of Population Health, the study's findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.
"Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended," Dr. Shen said. "But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients."
Saturday, January 28, 2012
Tuesday, January 24, 2012
Prostate Cancer Study Proves Drug Delays Disease Progression
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For men diagnosed with low-risk, localized prostate cancer, being treated with the drug dutasteride (“Avodart”) delays disease progression and initiating active treatment, and also reduces anxiety, show the results of a three-year international clinical trial led by Dr. Neil Fleshner, Head of the Division of Urology, University Health Network (UHN).
The findings are published online today in The Lancet. “The results prove that using active surveillance plus dutasteride is a viable, safe and effective treatment option for men who often undergo aggressive local treatment despite low risk of dying from the disease,” says Dr. Fleshner, a surgical oncologist in UHN’s Princess Margaret Cancer Program and Professor of Surgery at the University of Toronto. Dr. Fleshner also holds the Love Chair in Prostate Cancer Prevention Research.
“This is very good news for men with low-risk disease because aggressive treatment can have a major impact on their quality of life, with risks of impotence and incontinence,” says Dr. Fleshner.
The three-year clinical trial enrolled 302 men between the ages of 48 and 82 diagnosed with low-risk localized prostate cancer and regularly monitored for clinical changes – a treatment option called “active surveillance”. In the trial – known as REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management of prostate cancer) – participants were randomized 1:1 to receive dutasteride or a matching placebo daily. The men also underwent biopsies at 1.5 and three years.
The study showed a significant delay in disease progression in the men treated with dutasteride – 38% compared with 48% who received the placebo. As well, the final biopsies showed the men treated with the drug were less likely to have cancer detected – 36% compared with 23%.
“This is the first study to show that a 5a-reductase inhibitor such as dutasteride reduces the need for aggressive treatment in low-risk disease,” says Dr. Fleshner. “The drug, currently commonly used to treat enlarged prostate, works by inhibiting the male sex hormone that causes the enlargement in the first place.”
Dr. Fleshner says a small percentage of men reported drug-related side effects including sexual difficulty with either desire or erections (5%), or breast tenderness or enlargement (3%). “It’s important to realize that these drugs have been around for almost 20 years in clinical practice to treat enlarged prostates and so we have a wealth of knowledge about their side effects, which are reversible if the drug is stopped.”
Participants were also assessed for cancer-related anxiety and the men on dutasteride reported feeling much less anxious because their biopsies and PSA values improved, adds Dr. Fleshner. (PSA – or prostate-specific antigen – is a blood test used to help diagnose prostate cancer.)
For men diagnosed with low-risk, localized prostate cancer, being treated with the drug dutasteride (“Avodart”) delays disease progression and initiating active treatment, and also reduces anxiety, show the results of a three-year international clinical trial led by Dr. Neil Fleshner, Head of the Division of Urology, University Health Network (UHN).
The findings are published online today in The Lancet. “The results prove that using active surveillance plus dutasteride is a viable, safe and effective treatment option for men who often undergo aggressive local treatment despite low risk of dying from the disease,” says Dr. Fleshner, a surgical oncologist in UHN’s Princess Margaret Cancer Program and Professor of Surgery at the University of Toronto. Dr. Fleshner also holds the Love Chair in Prostate Cancer Prevention Research.
“This is very good news for men with low-risk disease because aggressive treatment can have a major impact on their quality of life, with risks of impotence and incontinence,” says Dr. Fleshner.
The three-year clinical trial enrolled 302 men between the ages of 48 and 82 diagnosed with low-risk localized prostate cancer and regularly monitored for clinical changes – a treatment option called “active surveillance”. In the trial – known as REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management of prostate cancer) – participants were randomized 1:1 to receive dutasteride or a matching placebo daily. The men also underwent biopsies at 1.5 and three years.
The study showed a significant delay in disease progression in the men treated with dutasteride – 38% compared with 48% who received the placebo. As well, the final biopsies showed the men treated with the drug were less likely to have cancer detected – 36% compared with 23%.
“This is the first study to show that a 5a-reductase inhibitor such as dutasteride reduces the need for aggressive treatment in low-risk disease,” says Dr. Fleshner. “The drug, currently commonly used to treat enlarged prostate, works by inhibiting the male sex hormone that causes the enlargement in the first place.”
Dr. Fleshner says a small percentage of men reported drug-related side effects including sexual difficulty with either desire or erections (5%), or breast tenderness or enlargement (3%). “It’s important to realize that these drugs have been around for almost 20 years in clinical practice to treat enlarged prostates and so we have a wealth of knowledge about their side effects, which are reversible if the drug is stopped.”
Participants were also assessed for cancer-related anxiety and the men on dutasteride reported feeling much less anxious because their biopsies and PSA values improved, adds Dr. Fleshner. (PSA – or prostate-specific antigen – is a blood test used to help diagnose prostate cancer.)
Tuesday, January 10, 2012
Cutting-edge gene therapy for bladder cancer
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Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in men and women in the U.S. More than 70 percent of bladder cancers are diagnosed in stage T1 or less and have not invaded the muscle layer. At these early stages, standard treatment is surgery (transurethral resection) and the burning away of tumors with high energy electricity (fulguration). Many patients also may receive subsequent intravesical chemotherapy because there is often a high-risk for cancer recurrence.
The prognosis for recurrent cancer is poor, which drives clinician-scientists like William Larchian, MD, Urologic Oncologist, University Hospitals Urology Institute at University Hospitals Case Medical Center, and Associate Professor of Surgery, Case Western Reserve University School of Medicine, and his colleagues to develop an immunotherapy for bladder cancer that will stimulate the body's own natural defense mechanisms to cure the disease and prevent recurrence.
"What is interesting is that our bodies are capable of identifying, responding to and killing tumor cells naturally," explained Dr. Larchian. "We are developing a vaccination system to enhance this response and drive an effective immune response against existing and future bladder tumor cells in patients diagnosed with bladder cancer."
IL-2, a cytokine-signaling molecule, stimulates the T-cell immune response to cancer cells in the bladder. Dr. Larchian and his colleagues have developed a system that reliably introduces multiple copies of IL-2 DNA into bladder cancer cells.
"This method allows for more gene copies to enter the cells," he said, "and we are able to see higher rates of transfection compared to retroviral methods."
The enhanced IL-2 protein expression has been shown to successfully stimulate T-cell response and eliminate bladder tumors in a mouse model, particularly when followed by transfection with B7.1 gene. The addition of the B7.1 gene, which encodes an immune co-stimulatory molecule, enhanced T-cell production logarithmically and produced a 70 percent cure rate. Rechallenge with new cancer cells was also prevented. Clinical translation of this research has been submitted for Institutional Review Board approval at UH Case Medical Center.
Other research by Dr. Larchian and his colleagues aims to leverage this work to develop a gene-therapy system that can be utilized to deliver other key defense genes.
"Our future pursuits," he said, "will include using this system with very specific biological response modifiers, including anti-angiogenesis factors, and with the tumor suppressor gene, MCP3." Dr. Larchian also is developing a targeted drug delivery system using nanoparticles for bladder cancer treatment.
Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in men and women in the U.S. More than 70 percent of bladder cancers are diagnosed in stage T1 or less and have not invaded the muscle layer. At these early stages, standard treatment is surgery (transurethral resection) and the burning away of tumors with high energy electricity (fulguration). Many patients also may receive subsequent intravesical chemotherapy because there is often a high-risk for cancer recurrence.
The prognosis for recurrent cancer is poor, which drives clinician-scientists like William Larchian, MD, Urologic Oncologist, University Hospitals Urology Institute at University Hospitals Case Medical Center, and Associate Professor of Surgery, Case Western Reserve University School of Medicine, and his colleagues to develop an immunotherapy for bladder cancer that will stimulate the body's own natural defense mechanisms to cure the disease and prevent recurrence.
"What is interesting is that our bodies are capable of identifying, responding to and killing tumor cells naturally," explained Dr. Larchian. "We are developing a vaccination system to enhance this response and drive an effective immune response against existing and future bladder tumor cells in patients diagnosed with bladder cancer."
IL-2, a cytokine-signaling molecule, stimulates the T-cell immune response to cancer cells in the bladder. Dr. Larchian and his colleagues have developed a system that reliably introduces multiple copies of IL-2 DNA into bladder cancer cells.
"This method allows for more gene copies to enter the cells," he said, "and we are able to see higher rates of transfection compared to retroviral methods."
The enhanced IL-2 protein expression has been shown to successfully stimulate T-cell response and eliminate bladder tumors in a mouse model, particularly when followed by transfection with B7.1 gene. The addition of the B7.1 gene, which encodes an immune co-stimulatory molecule, enhanced T-cell production logarithmically and produced a 70 percent cure rate. Rechallenge with new cancer cells was also prevented. Clinical translation of this research has been submitted for Institutional Review Board approval at UH Case Medical Center.
Other research by Dr. Larchian and his colleagues aims to leverage this work to develop a gene-therapy system that can be utilized to deliver other key defense genes.
"Our future pursuits," he said, "will include using this system with very specific biological response modifiers, including anti-angiogenesis factors, and with the tumor suppressor gene, MCP3." Dr. Larchian also is developing a targeted drug delivery system using nanoparticles for bladder cancer treatment.
Thursday, January 5, 2012
Proton therapy effective prostate cancer treatment
Proton therapy, a type of external beam radiation therapy, is a safe and effective treatment for prostate cancer, according to two new studies published in the January issue of the International Journal of Radiation Oncology•Biology•Physics (Red Journal), the American Society for Radiation Oncology's (ASTRO) official scientific journal.
In the first study, researchers at the University of Florida in Jacksonville, Fla., prospectively studied 211 men with low-, intermediate-, and high-risk prostate cancer. The men were treated with proton therapy, a specialized type of external beam radiation therapy that uses protons instead of X-rays. After a two year follow-up, the research team led by Nancy Mendenhall, MD, of the University of Florida Proton Therapy Institute, reported that the treatment was effective and that the gastrointestinal and genitourinary side effects were generally minimal.
"This study is important because it will help set normal tissue guidelines in future trials," Dr. Mendenhall, said.
In the second study, researchers from Massachusetts General Hospital in Boston, Loma Linda University Medical Center in Loma Linda, Calif., and the Radiation Therapy Oncology Group in Philadelphia performed a case-matched analysis comparing high-dose external beam radiation therapy using a combination of photons (X-rays) and protons with brachytherapy (radioactive seed implants).
Over three years, 196 patients received the external beam treatments. Their data was compared to 203 men of similar stages who received brachytherapy over the same time period. Researchers then compared the biochemical failure rates (a statistical measure of whether the cancer relapses) and determined that men who received the proton/photon therapy had the same rate of recurrence as the men who received brachytherapy.
"For men with prostate cancer, brachytherapy and external beam radiation therapy using photons and protons are both highly effective treatments with similar relapse rates," John J. Coen, MD, a radiation oncologist at Massachusetts General Hospital in Boston, said. "Based on this data, it is our belief that men with prostate cancer can reasonably choose either treatment for localized prostate cancer based on their own concerns about quality of life without fearing they are compromising their chance for a cure."
In the first study, researchers at the University of Florida in Jacksonville, Fla., prospectively studied 211 men with low-, intermediate-, and high-risk prostate cancer. The men were treated with proton therapy, a specialized type of external beam radiation therapy that uses protons instead of X-rays. After a two year follow-up, the research team led by Nancy Mendenhall, MD, of the University of Florida Proton Therapy Institute, reported that the treatment was effective and that the gastrointestinal and genitourinary side effects were generally minimal.
"This study is important because it will help set normal tissue guidelines in future trials," Dr. Mendenhall, said.
In the second study, researchers from Massachusetts General Hospital in Boston, Loma Linda University Medical Center in Loma Linda, Calif., and the Radiation Therapy Oncology Group in Philadelphia performed a case-matched analysis comparing high-dose external beam radiation therapy using a combination of photons (X-rays) and protons with brachytherapy (radioactive seed implants).
Over three years, 196 patients received the external beam treatments. Their data was compared to 203 men of similar stages who received brachytherapy over the same time period. Researchers then compared the biochemical failure rates (a statistical measure of whether the cancer relapses) and determined that men who received the proton/photon therapy had the same rate of recurrence as the men who received brachytherapy.
"For men with prostate cancer, brachytherapy and external beam radiation therapy using photons and protons are both highly effective treatments with similar relapse rates," John J. Coen, MD, a radiation oncologist at Massachusetts General Hospital in Boston, said. "Based on this data, it is our belief that men with prostate cancer can reasonably choose either treatment for localized prostate cancer based on their own concerns about quality of life without fearing they are compromising their chance for a cure."
Thursday, December 8, 2011
PSA Testing, Combined With Other Relevant Patient Data Can Reduce Unnecessary Prostate Biopsies
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Separate study suggests combining urine test with PSA can aid cancer diagnosis
Prostate cancer screening that combines an adjusted blood test with other factors including the size of the gland, the patient’s overall weight and family history, can help up to one-quarter of men avoid biopsies and the risks associated with them, a Beth Israel Deaconess Medical Center-led research team says.
Writing in a study published online by the journal Cancer, the team led by Martin G. Sanda, MD, Director of the Prostate Center at Beth Israel Deaconess Medical Center and Professor of Urology at Harvard Medical School, suggests that instead of using “one-size-fits-all” levels of PSA to determine who should have a biopsy, considering other factors such as prostate size can substantially improve the ability of PSA testing to identify aggressive prostate cancers for which treatment is warranted, while avoiding detection of indolent cancers that are better undiagnosed because they do not require treatment.
A second study led by Sanda, and published online in the journal Urologic Oncology, suggests the presence or absence of genes commonly found in the urine of men, when combined with a PSA test, can also be used to determine whether a biopsy is necessary.
The new suggested approaches come as the United States Preventive Services Task Force expert panel concluded that current PSA-based prostate cancer screening saves few or no lives, but causes harm through treatment or further invasive testing such as biopsies. That’s because prostate cancers can vary in aggressiveness and more men die of other causes aside from that cancer – and because the PSA test alone cannot determine how dangerous any particular cancer may be.
“The US Preventative Services Task Force threw the baby out with the bathwater by their blanket recommendation against prostate cancer screening,” says Sanda, noting that PSA screening can instead be refined to more selectively identify only aggressive cancer for which treatment is indicated by adjusting PSA results for other considerations such as family history, obesity, and prostate size.
Results from the multi-center study that suggest that PSAD levels of less than 0.1 – in contrast to the unadjusted level of between 2.5 and 4 – can be a better benchmark of a potential cancer. The density, determined by a digital rectal exam, enables physicians to take into account other factors like benign prostatic hyperplasia, an enlargement of the gland that affects all men as they age.
Combining the PSAD with the digital exam, a look at the patient’s family history and a body mass index of 25 of less – the calculation used to define obesity – would avoid biopsy in approximately one-quarter of biopsy-eligible men, the researchers found.
“Urological practice, patient outcome and cost-effectiveness of health care would each benefit from new targeted strategies, such as nomograms (a predictive tool) that improve prediction of aggressive cancers, to enable selective identification of candidate for prostate biopsy that would improve the yield of clinically significant, histologically aggressive cancers warranting subsequent definitive treatment,” researchers wrote.
In a separate multicenter study published in Urologic Oncology, researchers said a test looking for two specific genetic biomarkers – TMPRSS2:ERG and PCA3 – taken after a digital rectal exam, could help limit biopsies to men who possess both genes and whose PSA readings range between 2 and 10, potentially sparing one-third of men from biopsies.
“Urine testing for prostate cancer is in its infancy,” says Sanda, noting next steps are underway as a result of study funded by a $3.1 million grant from the National Institutes of Health , that is evaluating new urine and blood test for prostate cancer in more 2,400 men over the next five years with a goal of improving upon the problems of over-diagnosis and over-treatment.
A focal point of the proposed work involves a community outreach effort led by BIDMC primary care physician J. Jacques Carter, MD, MPH, Medical Director of the Dana Farber Cancer Institute Prostate Cancer Screening and Education Program and an Assistant Professor of Medicine at Harvard Medical School. A key component of this study will be African-American men, who appear to develop prostate cancer more frequently, and who are at increased risk of dying from prostate cancer.
Separate study suggests combining urine test with PSA can aid cancer diagnosis
Prostate cancer screening that combines an adjusted blood test with other factors including the size of the gland, the patient’s overall weight and family history, can help up to one-quarter of men avoid biopsies and the risks associated with them, a Beth Israel Deaconess Medical Center-led research team says.
Writing in a study published online by the journal Cancer, the team led by Martin G. Sanda, MD, Director of the Prostate Center at Beth Israel Deaconess Medical Center and Professor of Urology at Harvard Medical School, suggests that instead of using “one-size-fits-all” levels of PSA to determine who should have a biopsy, considering other factors such as prostate size can substantially improve the ability of PSA testing to identify aggressive prostate cancers for which treatment is warranted, while avoiding detection of indolent cancers that are better undiagnosed because they do not require treatment.
A second study led by Sanda, and published online in the journal Urologic Oncology, suggests the presence or absence of genes commonly found in the urine of men, when combined with a PSA test, can also be used to determine whether a biopsy is necessary.
The new suggested approaches come as the United States Preventive Services Task Force expert panel concluded that current PSA-based prostate cancer screening saves few or no lives, but causes harm through treatment or further invasive testing such as biopsies. That’s because prostate cancers can vary in aggressiveness and more men die of other causes aside from that cancer – and because the PSA test alone cannot determine how dangerous any particular cancer may be.
“The US Preventative Services Task Force threw the baby out with the bathwater by their blanket recommendation against prostate cancer screening,” says Sanda, noting that PSA screening can instead be refined to more selectively identify only aggressive cancer for which treatment is indicated by adjusting PSA results for other considerations such as family history, obesity, and prostate size.
Results from the multi-center study that suggest that PSAD levels of less than 0.1 – in contrast to the unadjusted level of between 2.5 and 4 – can be a better benchmark of a potential cancer. The density, determined by a digital rectal exam, enables physicians to take into account other factors like benign prostatic hyperplasia, an enlargement of the gland that affects all men as they age.
Combining the PSAD with the digital exam, a look at the patient’s family history and a body mass index of 25 of less – the calculation used to define obesity – would avoid biopsy in approximately one-quarter of biopsy-eligible men, the researchers found.
“Urological practice, patient outcome and cost-effectiveness of health care would each benefit from new targeted strategies, such as nomograms (a predictive tool) that improve prediction of aggressive cancers, to enable selective identification of candidate for prostate biopsy that would improve the yield of clinically significant, histologically aggressive cancers warranting subsequent definitive treatment,” researchers wrote.
In a separate multicenter study published in Urologic Oncology, researchers said a test looking for two specific genetic biomarkers – TMPRSS2:ERG and PCA3 – taken after a digital rectal exam, could help limit biopsies to men who possess both genes and whose PSA readings range between 2 and 10, potentially sparing one-third of men from biopsies.
“Urine testing for prostate cancer is in its infancy,” says Sanda, noting next steps are underway as a result of study funded by a $3.1 million grant from the National Institutes of Health , that is evaluating new urine and blood test for prostate cancer in more 2,400 men over the next five years with a goal of improving upon the problems of over-diagnosis and over-treatment.
A focal point of the proposed work involves a community outreach effort led by BIDMC primary care physician J. Jacques Carter, MD, MPH, Medical Director of the Dana Farber Cancer Institute Prostate Cancer Screening and Education Program and an Assistant Professor of Medicine at Harvard Medical School. A key component of this study will be African-American men, who appear to develop prostate cancer more frequently, and who are at increased risk of dying from prostate cancer.
Panel endorses active monitoring and delay of treatment for low-risk prostate cancer
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An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.
“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.
Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.
Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.
The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.
Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease,” stated Dr. Ganz.
The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.
The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.
With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.
An updated version of the panel's draft statement, which incorporates public comments received in an open conference session this morning, will be posted later today at http://consensus.nih.gov.
The panel will hold a press telebriefing to discuss their findings today at 2 p.m. eastern time. To participate, call 888-428-7458(inside the United States) or 201-604-5177 (International) and reference the NIH State-of-the-Science Conference. Audio playback will be available shortly after conclusion of the telebriefing and can be accessed by calling 888-632-8973 (US) or 201-499-0429(International) and entering replay code 11996437.
The state-of-the-science conference was sponsored by the NIH Office of Medical Applications of Research, the National Cancer Institute, and the Centers for Disease Control and Prevention, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement. Additional materials, including panel biographies, photos, and other related resources, are available at http://consensus.nih.gov/2011/prostatemedia.htm. Interviews with panel members can be arranged by contacting Elizabeth Neilson at 301-496-4999 or NeilsonE@od.nih.gov.
The conference was webcast live and will be archived shortly. Links to the archived webcast will be available at http://consensus.nih.gov/2011/prostate.htm.
An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.
“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.
Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.
Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.
The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.
Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease,” stated Dr. Ganz.
The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.
The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.
With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.
An updated version of the panel's draft statement, which incorporates public comments received in an open conference session this morning, will be posted later today at http://consensus.nih.gov.
The panel will hold a press telebriefing to discuss their findings today at 2 p.m. eastern time. To participate, call 888-428-7458(inside the United States) or 201-604-5177 (International) and reference the NIH State-of-the-Science Conference. Audio playback will be available shortly after conclusion of the telebriefing and can be accessed by calling 888-632-8973 (US) or 201-499-0429(International) and entering replay code 11996437.
The state-of-the-science conference was sponsored by the NIH Office of Medical Applications of Research, the National Cancer Institute, and the Centers for Disease Control and Prevention, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement. Additional materials, including panel biographies, photos, and other related resources, are available at http://consensus.nih.gov/2011/prostatemedia.htm. Interviews with panel members can be arranged by contacting Elizabeth Neilson at 301-496-4999 or NeilsonE@od.nih.gov.
The conference was webcast live and will be archived shortly. Links to the archived webcast will be available at http://consensus.nih.gov/2011/prostate.htm.
Wednesday, October 19, 2011
IQ can rise or fall significantly during adolescence
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The findings may have implications for testing and streaming of children during their school years
IQ, the standard measure of intelligence, can increase or fall significantly during our teenage years, according to research funded by the Wellcome Trust, and these changes are associated with changes to the structure of our brains. The findings may have implications for testing and streaming of children during their school years.
Across our lifetime, our intellectual ability is considered to be stable, with Intelligence Quotient (IQ) scores taken at one point in time used to predict educational achievement and employment prospects later in life. However, in a study published today in the journal Nature, researchers at the Wellcome Trust Centre for Neuroimaging at UCL (University College London) and the Centre for Educational Neuroscience show for the first time that in fact our IQ is not constant.
The researchers, led by Professor Cathy Price, tested thirty-three healthy adolescents in 2004 when they were between the ages of 12 and 16 years. They then repeated the tests four years later when the same subjects were between 15 and 20 years old. On both occasions, the researchers took structural brains scans of the subjects using magnetic resonance imaging (MRI).
Professor Price and colleagues found significant changes in the IQ scores measured in 2008 compared to the 2004 scores. Some subjects had improved their performance relative to people of a similar age by as much as 20 points on the standardised IQ scale; in other cases, however, performance had fallen by a similar amount. In order to test whether these changes were meaningful, the researchers analysed the MRI scans to see if there was a correlation with changes in the structure of the subjects' brains.
"We found a considerable amount of change in how our subjects performed on the IQ tests in 2008 compared to four years earlier," explains Sue Ramsden, first author of the study. "Some subjects performed markedly better but some performed considerably worse. We found a clear correlation between this change in performance and changes in the structure of their brains and so can say with some certainty that these changes in IQ are real."
The researchers measured each subject's verbal IQ, which includes measurements of language, arithmetic, general knowledge and memory, and their non-verbal IQ, such as identifying the missing elements of a picture or solving visual puzzles. They found a clear correlation with particular regions of the brain. An increase in verbal IQ score correlated with an increase in the density of grey matter – the nerve cells where the processing takes place – in an area of the left motor cortex of the brain that is activated when articulating speech. Similarly, an increase in non-verbal IQ score correlated with an increase in the density of grey matter in the anterior cerebellum, which is associated with movements of the hand. However, an increase in verbal IQ did not necessarily go hand-in-hand with an increase in non-verbal IQ.
According to Professor Price, a Wellcome Trust Senior Research Fellow, it is not clear why IQ should have changed so much and why some people's performance improved whilst others' decline. It is possible that the differences are due to some of the subjects being early or late developers, but it is equally possible that education played a role in changing IQ, and this has implications for how schoolchildren are assessed.
"We have a tendency to assess children and determine their course of education relatively early in life, but here we have shown that their intelligence is likely to be still developing," says Professor Price. "We have to be careful not to write off poorer performers at an early stage when in fact their IQ may improve significantly given a few more years.
"It's analogous to fitness. A teenager who is athletically fit at 14 could be less fit at 18 if they stopped exercising. Conversely, an unfit teenager can become much fitter with exercise. "
Other studies from the Wellcome Trust Centre for Neuroimaging and other research groups have provided strong evidence that the structure of the brain remains 'plastic' even throughout adult life. For example, Professor Price showed recently that guerrillas in Columbia who had learned to read as adults had a higher density of grey matter in several areas of the left hemisphere of the brain than those who had not learned to read. Professor Eleanor Maguire, also from the Wellcome Trust Centre, showed that part of a brain structure called the hippocampus, which plays an important role in memory and navigation, has greater volume in licensed London taxi drivers.
"The question is, if our brain structure can change throughout our adult lives, can our IQ also change?" adds Professor Price. "My guess is yes. There is plenty of evidence to suggest that our brains can adapt and their structure changes, even in adulthood."
'Understanding the brain' is one of the Wellcome Trust's key strategic challenges. It funds a significant portfolio of neuroscience and mental health research, ranging from studies of molecular and cellular components to work on cognition and higher systems. At the Wellcome Trust Centre for Neuroimaging, clinicians and scientists study higher cognitive function to understand how thought and perception arise from brain activity, and how such processes break down in neurological and psychiatric disease.
"This interesting study highlights how 'plastic' the human brain is," said Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust. "It will be interesting to see whether structural changes as we grow and develop extend beyond IQ to other cognitive functions. This study challenges us to think about these observations and how they may be applied to gain insight into what might happen when individuals succumb to mental health disorders."
The findings may have implications for testing and streaming of children during their school years
IQ, the standard measure of intelligence, can increase or fall significantly during our teenage years, according to research funded by the Wellcome Trust, and these changes are associated with changes to the structure of our brains. The findings may have implications for testing and streaming of children during their school years.
Across our lifetime, our intellectual ability is considered to be stable, with Intelligence Quotient (IQ) scores taken at one point in time used to predict educational achievement and employment prospects later in life. However, in a study published today in the journal Nature, researchers at the Wellcome Trust Centre for Neuroimaging at UCL (University College London) and the Centre for Educational Neuroscience show for the first time that in fact our IQ is not constant.
The researchers, led by Professor Cathy Price, tested thirty-three healthy adolescents in 2004 when they were between the ages of 12 and 16 years. They then repeated the tests four years later when the same subjects were between 15 and 20 years old. On both occasions, the researchers took structural brains scans of the subjects using magnetic resonance imaging (MRI).
Professor Price and colleagues found significant changes in the IQ scores measured in 2008 compared to the 2004 scores. Some subjects had improved their performance relative to people of a similar age by as much as 20 points on the standardised IQ scale; in other cases, however, performance had fallen by a similar amount. In order to test whether these changes were meaningful, the researchers analysed the MRI scans to see if there was a correlation with changes in the structure of the subjects' brains.
"We found a considerable amount of change in how our subjects performed on the IQ tests in 2008 compared to four years earlier," explains Sue Ramsden, first author of the study. "Some subjects performed markedly better but some performed considerably worse. We found a clear correlation between this change in performance and changes in the structure of their brains and so can say with some certainty that these changes in IQ are real."
The researchers measured each subject's verbal IQ, which includes measurements of language, arithmetic, general knowledge and memory, and their non-verbal IQ, such as identifying the missing elements of a picture or solving visual puzzles. They found a clear correlation with particular regions of the brain. An increase in verbal IQ score correlated with an increase in the density of grey matter – the nerve cells where the processing takes place – in an area of the left motor cortex of the brain that is activated when articulating speech. Similarly, an increase in non-verbal IQ score correlated with an increase in the density of grey matter in the anterior cerebellum, which is associated with movements of the hand. However, an increase in verbal IQ did not necessarily go hand-in-hand with an increase in non-verbal IQ.
According to Professor Price, a Wellcome Trust Senior Research Fellow, it is not clear why IQ should have changed so much and why some people's performance improved whilst others' decline. It is possible that the differences are due to some of the subjects being early or late developers, but it is equally possible that education played a role in changing IQ, and this has implications for how schoolchildren are assessed.
"We have a tendency to assess children and determine their course of education relatively early in life, but here we have shown that their intelligence is likely to be still developing," says Professor Price. "We have to be careful not to write off poorer performers at an early stage when in fact their IQ may improve significantly given a few more years.
"It's analogous to fitness. A teenager who is athletically fit at 14 could be less fit at 18 if they stopped exercising. Conversely, an unfit teenager can become much fitter with exercise. "
Other studies from the Wellcome Trust Centre for Neuroimaging and other research groups have provided strong evidence that the structure of the brain remains 'plastic' even throughout adult life. For example, Professor Price showed recently that guerrillas in Columbia who had learned to read as adults had a higher density of grey matter in several areas of the left hemisphere of the brain than those who had not learned to read. Professor Eleanor Maguire, also from the Wellcome Trust Centre, showed that part of a brain structure called the hippocampus, which plays an important role in memory and navigation, has greater volume in licensed London taxi drivers.
"The question is, if our brain structure can change throughout our adult lives, can our IQ also change?" adds Professor Price. "My guess is yes. There is plenty of evidence to suggest that our brains can adapt and their structure changes, even in adulthood."
'Understanding the brain' is one of the Wellcome Trust's key strategic challenges. It funds a significant portfolio of neuroscience and mental health research, ranging from studies of molecular and cellular components to work on cognition and higher systems. At the Wellcome Trust Centre for Neuroimaging, clinicians and scientists study higher cognitive function to understand how thought and perception arise from brain activity, and how such processes break down in neurological and psychiatric disease.
"This interesting study highlights how 'plastic' the human brain is," said Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust. "It will be interesting to see whether structural changes as we grow and develop extend beyond IQ to other cognitive functions. This study challenges us to think about these observations and how they may be applied to gain insight into what might happen when individuals succumb to mental health disorders."
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