Finding a Better Way to Diagnose Lung Cancer

For years, the aggressive and deadly nature of lung cancer has hampered cancer researchers from finding an effective way of screening for lung cancer. The introduction of multidetector helical computed tomography (CT) technology has changed the landscape of lung cancer screening, and physicians and researchers at Penn Medicine have been on the forefront of applying this technology in new ways to detect and characterize a wide variety of disease conditions in patients.

Penn Medicine was a participating site in the National Cancer Institute’s National Lung Screening Trial (NLST) to determine whether screening with low-dose helical CT could lower mortality rates from lung cancer. Early results of the study indicate that helical CT detects many tumors at early stages. As is the case with most types of cancer, early detection leads to more effective and more successful treatment.

“Chest CT is good for showing lung detail, allowing us to see lung nodules as small as 1 millimeter,” said Drew Torigian, MD, thoracoabdominal radiologist and principal investigator for the NLST at Penn Medicine.  “The X-ray source of CT rotates around patients as they pass through the scanner. The multiple images acquired show us the internal structure of the lung, including a 3-D view of nodules or tumors. For the first time, we have a screening test that has been shown to reduce the mortality rate of lung cancer.”

Primary results of the NLST published in June 2011 showed a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical CT versus those screened by chest X-ray.
The findings are significant, according to Dr. Torigian, because a lung cancer diagnosis is often made when the cancer is more advanced and surgery and other treatments are not as effective.

The randomized national trial involved 53,454 current and former heavy smokers between the ages of 55 and 74 who were without signs, symptoms, or history of lung cancer. Participants in the NLST were randomly assigned to receive three annual screens with either low-dose helical CT or standard chest X-ray.

Better Tools and Better Teams

Along with the latest diagnostic tools, Penn Medicine has dedicated thoracic radiologists who interpret the results of all lung imaging. Because they see many imaging studies of the chest including the lungs, they are experts at identifying and screening abnormalities in this anatomical location of the body.

“Helical CT also finds small nodules that may not be cancerous,” said John Kucharczuk, MD, chief of thoracic surgery at Penn Medicine. “Penn’s lung nodule team is dedicated to reviewing all lung nodules found by imaging and determining the best course of treatment.”

The biggest downside to using helical CT as a screening tool is the high rate of false positive screens, or the frequent detection of lung nodules that are not due to lung cancer. Dr. Torigian said that the medical community is reviewing the results of the NLST and finding the best way to implement the technology in a cost-effective manner.

Lung Cancer by the Numbers

When it comes to lung cancer, the numbers are not good. More people in the United States die from lung cancer than any other type of cancer.

• In 2011, more than 220,000 Americans will be diagnosed with lung cancer and more than 156,000 people will die of lung or bronchus cancer.
• Smokers are 10 to 20 times more likely to get lung cancer. About 90 percent of lung cancer deaths in men and almost 80 percent of lung cancer deaths in women are due to smoking.
• There are more than 94 million current or former smokers in the U.S. 
• Among both men and women in the United States, lung cancer is the second most common type of cancer, accounting for more deaths than breast cancer, prostate cancer, and colon cancer combined.

For more information about Penn Medicine’s lung cancer or smoking cessation programs or to make an appointment with a Penn lung specialist, visit PennMedicine.org/lung-cancer or call 800-789-PENN (7366).

The Fight Against Heart and Vascular Disease Gets Personal

Year after year, heart and vascular disease maintains its rank as the number one killer of Americans. Doctors at Penn Medicine are battling the epidemic through comprehensive and personalized management of cardiovascular risk factors.

There are many things people can do on their own to reduce their risk of developing heart and vascular disease, such as getting plenty of exercise and eating right. Penn Medicine’s Preventive Cardiovascular Program helps reduce that risk further using a multidisciplinary, personalized approach to treat cardiovascular risk factors. The program specializes in the treatment of complex lipid (cholesterol) and high blood pressure conditions, as well as the care of individuals with a family history of early heart attack, stroke or peripheral artery disease. The program’s expert team consists of cardiologists, vascular medicine specialists, lipid specialists, hypertension specialists, nurses and dietitians.

“We offer a wide array of preventive testing to refine cardiovascular risk assessment above and beyond traditional risk factors,” said Emil deGoma, MD, medical director of the Preventive Cardiovascular Program. “For selected individuals, advanced testing enhances our ability to personalize care for each patient; be it lifestyle changes and weight management for someone at low risk, or medication and intervention for someone at high risk.”

Advanced Risk Refinement Services

According to Dr. deGoma, the Preventive Cardiovascular Program uses innovative technologies and imaging capabilities to assess the risk of heart and vascular disease, including:

• Genetic testing for heart attack risk: This blood test identifies someone’s risk for heart attack by examining variations in the sequence of their inherited genetic material, also known as DNA. Certain variations are associated with an increased risk of having a heart attack, while others can mean a decreased risk.
• Vascular ultrasound screening (carotid intima-media thickness assessment): A non-invasive ultrasound evaluation examines the health of the carotid arteries, looking for warning signs such as the accumulation of plaque or thickening of the blood vessel wall.
• Coronary artery calcium scanning: Another non-invasive test, this “heart scan” evaluates the coronary arteries for the buildup of calcium. Higher coronary artery calcium scores are associated with a higher risk for heart attack.
• Advanced lipid laboratory testing:  Testing beyond the standard fasting cholesterol panel can help diagnose lipid diseases, assess cardiovascular risk assessment, and identify the most appropriate treatment options.
• Ambulatory 24-hour blood pressure monitoring. Continuous blood pressure monitoring provides a comprehensive assessment of blood pressure changes throughout the day and night. It is a valuable tool for diagnosing hypertension and ensuring the effectiveness and safety of treatment.

The wide range of risk refinement services offered by Penn Medicine’s Preventive Cardiovascular Program is located at the Ruth and Raymond Perelman Center for Advanced Medicine.  For more information or to schedule an appointment, please visit PennMedicine.org/heart/prevention or call 800-789-PENN (7366).

Identifying Alzheimer’s Disease

There has never been a definitive test for diagnosing Alzheimer’s disease. Doctors usually know if someone has dementia, and based on symptoms and testing they can predict whether the dementia is caused by Alzheimer’s. But a diagnosis can only be confirmed by examining the brain for the specific plaques and tangles that indicate Alzheimer’s.  Doctors are close to being able to predict which patients will develop cognitive disease.

Alzheimer’s disease is the most common cause of dementia. It is different from other causes of cognitive impairment and dementia because it is defined by the abundance of the two hallmark deposits found in the brains of patients with Alzheimer’s disease: neurofibrillary tangles formed by tau amyloid fibrils and senile plaques formed by beta amyloid (Aβ) fibrils.  It causes progressive loss of intellectual and social skills severe enough to interfere with day-to-day life. The brain cells degenerate and die due to the damaging effects of the tangles and plaques thereby causing a steady decline in memory and mental function. Current medications and management strategies can temporarily improve Alzheimer’s symptoms, maximize function and maintain independence.

Researchers at Penn are involved in several studies designed to develop an easy test that can find the disease early on. With an easy and accurate diagnosis in the early stages of development, doctors can gain a better understanding of Alzheimer’s disease and look at more effective treatments for this disease.

Searching for Biomarkers

For more than 20 years, Penn researchers have investigated methods for diagnosing Alzheimer’s disease. Early success came from the development of a radioactive tracer that could detect the beta amyloid plaques associated with Alzheimer’s in the brain.  The tell-tale chemical and physical indicators of the changes in the brain are known as “biomarkers.” Studies under way in Penn’s Alzheimer’s Disease Core Center  use and compare different diagnostic technologies to detect these biomarkers of changes in the brain.

Penn researchers identify, measure and store the specific biomarkers found in proteins and fluids to better understand the physiological changes that occur over time in Alzheimer’s disease.  “We look for consistency in these tests so that we can accurately interpret these biomarkers,” said John Q. Trojanowski, MD, PhD, co-director of Penn’s Center for Neurodegenerative Disease Research and director of the Alzheimer’s Disease Core Center. “We are close to being able to predict which patients will develop cognitive disease.”

Cerebrospinal Fluid Sampling

Cerebrospinal fluid (CSF) is the fluid that circulates through the brain and the spinal cord. It acts as a “shock absorber” for protection of these areas and contains proteins and other important biomarkers that may indicate existence of diseases such as Alzheimer’s.  By analyzing CSF, Penn researchers can pinpoint the biomarkers that may signal an increased risk of developing disease. The CSF is obtained through a simple and safe process known as a lumbar puncture or spinal tap. The procedure is quick and involves no, or only slight discomfort.

Neuroimaging

Neuroimaging studies compare different diagnostic technologies to detect changes in the brains of patients with Alzheimer’s.  PET scanners look at how the various brain regions use glucose. Doctors can tell by the pattern of glucose use whether a brain is developing Alzheimer’s because nerve cells use less glucose when they are beginning to fail. But PET can be expensive and the radioactive tracers used to create the images carry some risks for patient needing repeated testing.

New Penn Medicine studies examining MRI imaging of blood flow in each brain region mirrors the glucose use seen in the PET scans.  The studies, published in November 2011 in Alzheimer’s and Dementia and Neurology, show MRI may be a useful way of diagnosing the disease and managing therapy.  “This can become a useful way of diagnosing the disease and managing therapy,” said study co-author John Detre, MD, Penn neurologist.

Dr. Trojanowski and Leslie Shaw, PhD, also co-lead the Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a public-private partnership launched in 2004 at 58 sites in the U.S. and Canada. Several hundred investigators are following more than 1,000 subjects over time to assess how the biomarkers change to reflect the onset and progression of cognitive impairment and dementia.  The partnership extends through 2016 and is funded by grant support from the National Institute on Aging, pharmaceutical companies and foundations to identify, standardize and validate informative biomarkers for Alzheimer’s disease.

Biomarker for Tau-Related Brain Disorders

Penn researchers led by Virginia M.-Y. Lee, PhD, MBA, recently determined that a well-known chemical process called acetylation is associated with one of the biological processes related to Alzheimer’s disease and related disorders, and they seek to exploit this finding in their biomarker and drug discovery research in the near future.

Tau is one of the primary disease proteins associated with neurodegenerative diseases including Alzheimer’s. Tau proteins are expressed primarily in the central nervous system where they help with the assembly and stability of microtubules, the protein structures that are the backbone of the nerve-cell communication system.

“Cerebrospinal fluid sampling can measure these tau proteins that are the building block proteins of Alzheimer’s disease tangles, which correlate with the severity of the disease at autopsy. The hope is that by measuring tau in CSF, one can diagnose Alzheimer’s disease with more certainty during life. Indeed, our bold, long-term goal is to convert the current ‘gold standard’ for the definite diagnosis of Alzheimer’s disease. We hope to move from an autopsy evaluation to one that is done with living patients early in the disease process by developing a new biomarker standard for the definite diagnosis of Alzheimer’s disease and using a panel of biomarkers that includes measuring the levels of CSF tau,” said Dr. Trojanowksi. “Patients with Alzheimer’s and other dementias have an increased level of neurofibrillary tangles made up of tau proteins. By understanding the role of plaques and tangles we move closer to understanding and treating Alzheimer’s disease.”

For more information, or to schedule an appointment visit PennMedicine.org or call 800-789-PENN (7366). 

Correct Diagnosis is Key to Successful Treatment

Penn Medicine’s excellent diagnostics and expert physicians provide patients with the best chance of a successful outcome.  Effective medical treatment is based on an accurate diagnosis of each patient’s disease.  As one of the nation’s top medical centers, Penn Medicine offers patients the latest, state-of-the-art diagnostic tools and tests. But technology is only as good as the people using it, and Penn physicians are experts at reviewing and interpreting test results. In fact, Penn physicians and researchers invented much of the current diagnostic technology and continue to look for ways to expand its uses.

Advances in Imaging

Medical care and treatment depends on the ability to see inside the body quickly and accurately. At Penn, the radiologists interpreting these images often specialize in just one field—such as heart images, brain images, or gastrointestinal images. Because Penn radiologists specialize in a specific area, readings are more accurate. In addition, because of this specialization, Penn radiologists are looking for physiological and molecular changes in the body, such as blood flow and glucose metabolism, as well as anatomical changes.   Penn has a long history of excellence in imaging. The Hospital of the University of Pennsylvania is home to the first department of radiology in the United States. Many imaging technologies now in use were developed and perfected at Penn.

Radiologists continue to look for new ways to see what is happening inside the body—and why.  Right now, Penn radiologists are working to advance several technologies.

• Arterial spin labeling (ASL). This technology developed at Penn is now being licensed around the world as a non-invasive method for viewing cerebral blood flow in the brain.
• Spiral CT (see related article about diagnosing lung cancer on page 4).  Helical CT images provide high-resolution views with less radiation exposure to patients. Along with lung cancer, this technology is being used to diagnose vascular abnormalities and diseases. 
• Positron emission tomography (PET) for detecting Alzheimer’s disease (see related story on page X). A compound developed at Penn helps detect brain plaques associated with Alzheimer’s disease.

“Penn has traditionally emphasized research in addition to clinical care,” said R. Nick Bryan, MD, PhD, chair of Penn Radiology. “As one of the leading research institutes in the country, we are leaders in developing new imaging technology as well as bringing in the latest technological advances to help make difficult diagnosis in our patients.”

Developing Personalized Diagnostics

The Human Genome Project, an international scientific research project, identified and mapped the approximately 20,000 to 25,000 genes in human DNA, and determined the sequences of the 3 billion chemical base pairs that make up the human genome. The project ushered in a revolution in personalized medicine, and nowhere is that more apparent that at Penn Pathology and Laboratory Medicine.
“By finding and studying gene mutations, we will eventually have information that helps us identify cancer causing mutations and how they react to treatment for every cancer patient. It will be a terrific resource,” said David B. Roth, MD, PhD, chair of pathology and laboratory medicine at Penn. Additionally, predictive testing for mutations in genes that may predispose individuals to disease will provide more accurate risk assessment and has the potential for great impact on prevention, early detection and early intervention.
The Penn laboratory where the Philadelphia Chromosome was discovered is expanding to include a new Center for Personalized Diagnostics. Both a research and patient care center, its plans are to provide diagnostic gene sequencing and other genome-wide diagnostic tools for patients.  The goal is to provide clinicians with information regarding their patient’s disease, so that a customized treatment regimen can be directed to the driving mutations specific for their patient.

“Personalized diagnostics are an important part of personalized medicine,” said Dr. Roth, “and Penn has the vision to see that this is next step in providing the best outcomes for patients. Large-scale gene sequencing is a laborious process, but the enormous results are worth it.”

For more information or to schedule an appointment with a Penn Medicine physician, visit PennMedicine.org or call 800-789-PENN (7366).